今日の臨床サポート

精巣腫瘍

著者: 川喜田睦司 神戸市立医療センター中央市民病院 泌尿器科

監修: 松田公志 関西医科大学 泌尿器科学教室

著者校正/監修レビュー済:2018/01/31
患者向け説明資料

概要・推奨   

疾患のポイント:
  1. 精巣腫瘍は、臨床的にセミノーマと非セミノーマに分類される。非セミノーマには胎児性癌、卵黄嚢腫瘍、奇形腫、絨毛癌があり、胎児性癌と奇形腫の混合を奇形癌と呼ぶ。なお、精巣腫瘍の約50%は転移を認めないStageIのセミノーマである。セミノーマは放射線感受性があることが特徴である。精巣腫瘍の治癒率は高く、進行例でも化学療法を受けた患者の70~80%が治癒に至る。
 
診断:
  1. ポイント:
  1. 診断には、超音波断層検査とMRIが有用である。これらの画像検査にて充実性腫瘤を認めた場合は、高位精巣摘除術を行い、病理組織検査をして最終診断とする。
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
川喜田睦司 : 報酬額(メディカロイド)[2021年]
監修:松田公志 : 講演料(アステラス製薬株式会社),奨学(奨励)寄付など(小野薬品工業株式会社)[2021年]

病態・疫学・診察

疾患情報  
  1. 精巣腫瘍は、臨床的にセミノーマと非セミノーマに分類される。非セミノーマには胎児性癌、卵黄嚢腫瘍、奇形腫、絨毛癌があり、胎児性癌と奇形腫の混合を奇形癌と呼ぶ。
  1. 若年者に多く発生し、20~34歳にピークがあり、白人に多く、アジア人、黒人に少ない。
  1. 治癒率は90%以上で、進行例でも化学療法を受けた患者の70~80%が治癒に至る。
問診・診察のポイント  
臨床症状:
  1. 陰嚢内容の無痛性腫大で発症する。10%は有痛性。hCG高値例では女性化乳房を来す(5~7%)。腰痛・側腹部痛を11%で認める[1]
  1. 転移巣による症状として、腹部腫瘤、腹痛、腰痛、下肢浮腫、頚部・鎖骨上腫瘤、呼吸困難、血痰、咳、骨痛、中枢神経症状などがある。10%は転移巣の症状で発見される。

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最新のエビデンスに基づいた二次文献データベース「今日の臨床サポート」。
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文献 

著者: C La Vecchia, C Bosetti, F Lucchini, P Bertuccio, E Negri, P Boyle, F Levi
雑誌名: Ann Oncol. 2010 Jun;21(6):1323-60. doi: 10.1093/annonc/mdp530. Epub 2009 Nov 30.
Abstract/Text BACKGROUND: To update the pattern of cancer mortality in Europe. Materials and methods: We analysed cancer mortality in 34 European countries during 2000-2004, with an overview of trends in 1975-2004 using data from the World Health Organization.
RESULTS: From 1990-1994 to 2000-2004, overall cancer mortality in the European Union declined from 185.2 to 168.0/100 000 (world standard, -9%) in men and from 104.8 to 96.9 (-8%) in women, with larger falls in middle age. Total cancer mortality trends were favourable, though to a variable degree, in all major European countries, including Russia, but not in Romania. The major determinants of these favourable trends were the decline of lung (-16%) and other tobacco-related cancers in men, together with the persistent falls in gastric cancer, and the recent appreciable falls in colorectal cancer. In women, relevant contributions came from the persistent decline in cervical cancer and the recent falls in breast cancer mortality, particularly in northern and western Europe. Favourable trends were also observed for testicular cancer, Hodgkin lymphomas, leukaemias, and other neoplasms amenable to treatment, though the reductions were still appreciably smaller in eastern Europe.
CONCLUSION: This updated analysis of cancer mortality in Europe showed a persistent favourable trend over the last years.

PMID 19948741  Ann Oncol. 2010 Jun;21(6):1323-60. doi: 10.1093/annonc/・・・
著者: Michael J Garner, Michelle C Turner, Parviz Ghadirian, Daniel Krewski
雑誌名: Int J Cancer. 2005 Sep 1;116(3):331-9. doi: 10.1002/ijc.21032.
Abstract/Text Testicular cancer is a rare disease, accounting for 1.1% of all malignant neoplasms in Canadian males. Despite the low overall incidence of testicular cancer, it is the most common malignancy among young men. The incidence rate of testicular cancer has been increasing since the middle of the 20th century in many western countries. However, the etiology of testicular cancer is not well understood. A search of the peer-reviewed literature was conducted to identify important articles for review and inclusion in this overview of the epidemiology of testicular cancer. Most of the established risk factors are related to early life events, including cryptorchidism, carcinoma in situ and in utero exposure to estrogens. Occupational, lifestyle, socioeconomic and other risk factors have demonstrated mixed associations with testicular cancer. Although there are few established risk factors for testicular cancer, some appear to be related to hormonal balance at various life stages. Lifestyle and occupational exposures occurring later in life may play a role in promoting the disease, although they are not likely involved in cancer initiation. In addition to summarizing the current epidemiologic evidence on risk factors for testicular cancer, we suggest future research directions that may elucidate the etiology of testicular cancer.

PMID 15818625  Int J Cancer. 2005 Sep 1;116(3):331-9. doi: 10.1002/ijc・・・
著者: Lorenzo Richiardi, Andreas Pettersson, Olof Akre
雑誌名: Int J Androl. 2007 Aug;30(4):230-40; discussion 240-1. doi: 10.1111/j.1365-2605.2007.00760.x.
Abstract/Text Germ-cell testicular cancer has a well-characterized descriptive epidemiology, whereas the aetiology remains largely unknown. It is believed that exposures acting prenatally are instrumental to germ-cell cancer development, although no specific exposure has been identified. Several epidemiological studies have investigated a number of indicators of prenatal exposures, such as birth order, gestational duration, birth weight, maternal age and nausea during pregnancy, but results are inconsistent. This paper briefly reviews the current support for genetic and environmental factors in testicular cancer aetiology. In particular, we have summarized the evidence suggesting a strong role of inherited susceptibility, which is probably carried by the effect of several unknown moderate-risk genes. We have illustrated inconsistencies in the previous studies on prenatal factors by estimating the heterogeneity and pooled odds ratios among twelve studies investigating the association between low birth weight and testicular cancer. We have discussed the possibility that puberty is another time window during which environmental factors may increase the risk of testicular cancer. Finally, we have reviewed the results from studies on cryptorchidism and impaired fertility in relation to risk for testicular cancer. In conclusion, we propose that future aetiological studies on testicular cancer should take postnatal exposures acting during puberty into account and, whenever possible, investigate both main effects and interactions among prenatal factors, genetic factors and postnatal factors.

PMID 17488341  Int J Androl. 2007 Aug;30(4):230-40; discussion 240-1. ・・・
著者: V Paul Doria-Rose, Mary Lou Biggs, Noel S Weiss
雑誌名: Cancer Causes Control. 2005 Aug;16(6):651-6. doi: 10.1007/s10552-005-0169-x.
Abstract/Text OBJECTIVES: Previous studies have reported an association between subfertility and the risk of testicular germ cell tumors. We examined fertility, measured by number of children fathered and prior diagnosis of infertility, as a risk factor for testicular cancer, while accounting for the influence of occult cancer and cryptorchidism.
METHODS: Tumor registry data were used to identify 329 cases of testicular cancer in white men aged 20 to 69 years, diagnosed in western Washington State from 1977 to 1983; 672 cancer-free controls were identified by random-digit dialing. Telephone interviews ascertained reproductive histories and basic demographic information. Logistic regression was used to estimate the relative risk of testicular cancer associated with fertility.
RESULTS: Testicular cancer risk was decreased among men who had previously fathered a child (age-adjusted odds ratio (OR) 0.76, 95% confidence interval (CI): 0.54-1.06). Inverse associations were seen for seminomas and non-seminomas, and only slight attenuations in the ORs were observed when men with a history of cryptorchidism were excluded. Prior diagnosis of infertility was associated with an increased risk of testicular cancer (OR 2.40, 95% CI: 1.00-5.77).
CONCLUSIONS: These results are consistent with an increased risk of testicular cancer among men with reduced fertility that goes beyond the effects of cryptorchidism.

PMID 16049803  Cancer Causes Control. 2005 Aug;16(6):651-6. doi: 10.10・・・
著者: K-P Dieckmann, U Pichlmeier
雑誌名: World J Urol. 2004 Apr;22(1):2-14. doi: 10.1007/s00345-004-0398-8. Epub 2004 Mar 18.
Abstract/Text Clinical epidemiology is sometimes called the basic science of clinical medicine. In terms of the pathogenesis of testicular germ cell tumors (GCTs), clinical epidemiology analyzes suspected risk factors. The present review highlights the risk factors established so far and briefly summarizes those factors currently under investigation. In analogy to the methods of evidence based medicine, this review attributes levels of evidence to each of the putative risk factors. Level I represents highest quality of evidence while level V denotes the lowest level. So far, undescended testis (UDT), contralateral testicular GCT and familial testis cancer are established risk factors attaining high levels of evidence (levels I-III a). In a meta-analysis of 21 studies exploring the association of UDT with GCT risk, an over-all relative risk (RR) of 4.8 (95% confidence interval 4.0-5.7) was found. Contralateral testicular GCT involves a roughly 25-fold increased RR of GCT, while familial testis cancer constitutes a RR of 3-10. Infertility, testicular atrophy, and twin-ship represent risk factors with lesser levels of evidence (level III a). There is also some evidence for HIV infection being a predisposing factor for GCT (level IV a). Scrotal trauma is probably not associated with GCT risk. The estrogen excess theory implies high estrogen levels during the first trimester of pregnancy. As a consequence, primordial germ cells lose track of the normal developmental line and transform into premalignant cells that later become testicular intraepithelial neoplasia (TIN), the precursor of full-blown testicular GCT. Surrogate parameters for high gestational estrogen levels are investigated in case control studies. Such factors are maternal age >30 years, first-born, low birth weight, maternal breast cancer, high sex-ratio of siblings. So far, the sum of evidence is promising but still conflicting (especially for level III b). Another novel theory is the childhood nutrition hypothesis. This concept postulates a modulating or "catalyzing" effect by high dietary intake during childhood on the pathogenesis of testicular GCT. A surrogate parameter of early childhood nutrition is adult height. So far, 12 controlled studies have looked to the possible association of attained height and GCT risk of which six demonstrated a significant association. Thus, the sum of evidence corresponds to level III b. This concept is appealing because it would explain several hitherto unexplained epidemiological features of GCT.

PMID 15034740  World J Urol. 2004 Apr;22(1):2-14. doi: 10.1007/s00345-・・・
著者: Jay D Raman, Craig F Nobert, Marc Goldstein
雑誌名: J Urol. 2005 Nov;174(5):1819-22; discussion 1822. doi: 10.1097/01.ju.0000177491.98461.aa.
Abstract/Text PURPOSE: We determined the standardized incidence ratio of testicular cancer in infertile men presenting with an abnormal semen analysis compared to the general population.
MATERIALS AND METHODS: The charts from more than 3,800 men presenting with infertility and abnormal semen analysis during a 10-year period were retrospectively reviewed. The incidence of testicular tumors diagnosed in this group was compared to that of race and age matched controls during the same period from the general population (as reported by the Surveillance, Epidemiology and End Results [SEER] database).
RESULTS: Of 3,847 men 10 (0.3%) with infertility and abnormal semen analysis were diagnosed with testicular tumors. Mean patient age was 32.6 years (range 25 to 52) and all 10 men were diagnosed with a seminomatous germ cell tumor. Two men had a history of cryptorchidism while the remaining 8 had no identifiable risk factors for testicular cancer. The SEER database reported an incidence of 10.6 cases of testicular cancer (95% CI 10.3-10.8) per 100,000 men of similar age group and racial composition during the same period. The standardized incidence ratio of testicular cancer was 22.9 (95% CI 22.4-23.5) when comparing our infertile group to the control population. Exclusion from analysis of the 2 patients with a history of cryptorchidism decreased the standardized incidence ratio to 18.3 (95% CI 18.0-18.8).
CONCLUSIONS: Infertile men with abnormal semen analyses have a 20-fold greater incidence of testicular cancer compared to the general population. Patients and physicians should be aware that one of the causes of infertility could be cancer, particularly testicular cancer.

PMID 16217294  J Urol. 2005 Nov;174(5):1819-22; discussion 1822. doi: ・・・
著者: Andreas Stang, Wolfgang Ahrens, Cornelia Baumgardt-Elms, Christa Stegmaier, Hiltrud Merzenich, Michael de Vrese, Jürgen Schrezenmeir, Karl-Heinz Jöckel
雑誌名: Cancer Epidemiol Biomarkers Prev. 2006 Nov;15(11):2189-95. doi: 10.1158/1055-9965.EPI-06-0372.
Abstract/Text Recent case-control studies suggested that dairy product consumption is an important risk factor for testicular cancer. We examined the association between consumption of dairy products, especially milk, milk fat, and galactose, and testicular cancer in a population-based case-control study including 269 case and 797 controls (response proportions of 76% and 46%, respectively). Dietary history was assessed by food frequency questions for the index persons and through their mothers including diet 1 year before interview and diet at age 17 years. We used conditional logistic regression to calculate odds ratios as estimates of the relative risk (RR), 95% confidence intervals (95% CI), and to control for social status and height. The RR of testicular cancer was 1.37 (95% CI, 1.12-1.68) per additional 20 servings of milk per month (each 200 mL) in adolescence. This elevated overall risk was mainly due to an increased risk for seminoma (RR, 1.66; 95% CI, 1.30-2.12) per additional 20 milk servings per month. The RR for seminoma was 1.30 (95% CI, 1.15-1.48) for each additional 200 g milk fat per month and was 2.01 (95% CI, 1.41-2.86) for each additional 200 g galactose per month during adolescence. Our results suggest that milk fat and/or galactose may explain the association between milk and dairy product consumption and seminomatous testicular cancer.

PMID 17119045  Cancer Epidemiol Biomarkers Prev. 2006 Nov;15(11):2189-・・・
著者: Klaus-Peter Dieckmann, Uwe Pichlmeier
雑誌名: Eur Urol. 2002 Dec;42(6):564-9.
Abstract/Text BACKGROUND AND OBJECTIVES: The incidence of testicular germ cell tumors (GCT) has been increasing since decades but cohorts of men born during war-time and immediately thereafter had a lower incidence. Based on this epidemiological observation, a hypothesis was generated that postulated nutritional factors in early life to be involved in the pathogenesis of GCT. To support this hypothesis biomarkers for early life nutrition were analyzed.
PATIENTS AND METHODS: In a case control study, 353 prospectively enrolled patients with GCT and 259 hospital-based controls with bone fractures and with nephrolithiasis were assessed for adult height, weight and body mass index (BMI). All of the patients and controls were aged between 15 and 45 years. Evaluation was done by descriptive tabulation of data, by calculating univariate odds-ratios for potential risk factors, by calculating p-values for trend-tests and by multivariate logistic regression analysis. In addition, the literature was surveyed with respect to the suspected association of anthropometric measures with GCT-risk.
RESULTS: No significant associations were found with respect to BMI and weight. However, height was significantly associated with GCT-risk (p<0.001). The multivariate analysis strengthened this association showing an increased risk of GCT with an odds-ratio of 2.11 (95% confidence interval 1.25; 3.55) for body height of at least 185 cm when compared to base-line height of 175-179 cm. Eleven previous studies with data on body size and GCT-risk were found in the literature.
CONCLUSION: Tallness appears to be significantly associated with risk of germ cell cancer. As adult height is a proxy for energy intake during early life it is probable that the pathogenesis of GCT is promoted by childhood nutrition. It is conceivable that the increase in GCT incidence and the secular trend of increasing adult stature are interrelated. Increasing availability and increasing awareness of protein-rich food in early childhood could be the common denominator to these observations.

PMID 12477651  Eur Urol. 2002 Dec;42(6):564-9.
著者: Carol A C Coupland, David Forman, Clair E D Chilvers, Gwyneth Davey, Malcolm C Pike, R Tim D Oliver
雑誌名: Cancer Causes Control. 2004 Apr;15(3):277-83. doi: 10.1023/B:CACO.0000024257.49409.1f.
Abstract/Text OBJECTIVE: To investigate the role of a range of maternal and pre-natal characteristics as potential risk factors for testicular cancer.
METHODS: A population-based case-control study of testicular cancer. Mothers of participants completed a questionnaire about their reproductive and obstetric history.
RESULTS: The risk of testicular cancer was approximately doubled for sons of mothers aged 15-19 years at conception compared with mothers with older ages at conception. Nausea or vomiting during the first trimester of pregnancy was associated with a reduced risk of testicular cancer (odds ratio of 0.73, 95% confidence interval 0.53-1.00). There was also a borderline reduction in risk in men who had been breastfed for 6 months or more (odds ratio 0.65, 95% confidence interval 0.41-1.04). Men who had low birthweights (< 2500 g) or had been born two or more weeks early had slightly increased risks, as did men whose mothers had used oral contraception in the 12 months before their conception.
CONCLUSIONS: These findings support previous reports of increased risks in men born early or with low birthweight, but the direction of the association with maternal age is contrary to some other studies. The suggestion of a protective effect of breastfeeding requires further confirmation.

Copyright 2004 Kluwer Academic Publishers
PMID 15090722  Cancer Causes Control. 2004 Apr;15(3):277-83. doi: 10.1・・・
著者: Casey Crump, Kristina Sundquist, Marilyn A Winkleby, Weiva Sieh, Jan Sundquist
雑誌名: Int J Cancer. 2012 Jul 15;131(2):446-51. doi: 10.1002/ijc.26371. Epub 2011 Sep 14.
Abstract/Text Most testicular germ cell tumors originate from carcinoma in situ cells in fetal life, possibly related to sex hormone imbalances in early pregnancy. Previous studies of association between gestational age at birth and testicular cancer have yielded discrepant results and have not examined extreme preterm birth. Our objective was to determine whether low gestational age at birth is independently associated with testicular cancer in later life. We conducted a national cohort study of 354,860 men born in Sweden in 1973-1979, including 19,214 born preterm (gestational age < 37 weeks) of whom 1,279 were born extremely preterm (22-29 weeks), followed for testicular cancer incidence through 2008. A total of 767 testicular cancers (296 seminomas and 471 nonseminomatous germ cell tumors) were identified in 11.2 million person-years of follow-up. Extreme preterm birth was associated with an increased risk of testicular cancer (hazard ratio = 3.95; 95% confidence interval = 1.67-9.34) after adjusting for other perinatal factors, family history of testicular cancer and cryptorchidism. Only five cases (three seminomas and two nonseminomas) occurred among men born extremely preterm, limiting the precision of risk estimates. No association was found between later preterm birth, post-term birth or low or high fetal growth and testicular cancer. These findings suggest that extreme but not later preterm birth may be independently associated with testicular cancer in later life. They are based on a small number of cases and will need confirmation in other large cohorts. Elucidation of the key prenatal etiologic factors may potentially lead to preventive interventions in early life.

Copyright © 2011 UICC.
PMID 22314417  Int J Cancer. 2012 Jul 15;131(2):446-51. doi: 10.1002/i・・・
著者: Joel Shaw
雑誌名: Am Fam Physician. 2008 Feb 15;77(4):469-74.
Abstract/Text Testicular cancer is the most common malignancy in men 20 to 35 years of age and has an annual incidence of four per 100,000. If diagnosed early, the cure rate is nearly 99 percent. Risk factors for testicular cancer include cryptorchidism (i.e., undescended testicles), family history, infertility, tobacco use, and white race. Routine self-examination and physician screening have not been shown to improve outcomes, and the U.S. Preventive Services Task Force and American Cancer Society do not recommend them in asymptomatic men. Patients presenting with a painless testicular mass, scrotal heaviness, a dull ache, or acute pain should receive a thorough examination. Testicular masses should be examined with scrotal ultrasonography. If ultrasonography shows an intratesticular mass, the patient should be referred to a urologist for definitive diagnosis, orchiectomy, and further evaluation with abdominal computed tomography and chest radiography. The family physician's role after diagnosis of testicular cancer includes encouraging the patient to bank sperm because of possible infertility and evaluating for recurrence and future complications, especially cardiovascular disease.

PMID 18326165  Am Fam Physician. 2008 Feb 15;77(4):469-74.
著者: Javier C Angulo, Javier González, Nuria Rodríguez, Emilio Hernández, Carlos Núñez, Jose M Rodríguez-Barbero, Alicia Santana, José I López
雑誌名: J Urol. 2009 Nov;182(5):2303-10. doi: 10.1016/j.juro.2009.07.045. Epub 2009 Sep 16.
Abstract/Text PURPOSE: Testicular germ cell tumors sometimes regress spontaneously and manifest exclusively by metastasis. We report our experience with extragonadal germ cell tumors of probable testicular origin to study the frequency of this entity, and clinical, ultrasound and histopathological correlations in a series of patients.
MATERIALS AND METHODS: A retrospective 16-year review of 1.2 million inhabitants in Spain revealed 17 with regressed testicular tumors treated at a total of 4 institutions. We analyzed clinical information, ultrasound features and histopathological characteristics of testicular lesions and metastasis, and highlight the main findings.
RESULTS: A primary testicular origin was confirmed in all cases. This entity is more common than initially suspected since it accounts for 4% of consecutive germ cell tumors. Clinical manifestations varied according to metastatic site with an abdominal palpable mass (47% of cases), loin pain (35%) and transient testicular pain (29%) the most common complaints. No evidence of testicular neoplasms was found on physical examination in any case. Metastasis histology was nonseminomatous in 53% of cases, pure seminoma in 29% and mixed in 18%. The most common ultrasound features were calcifications in 65% of cases, hyperechogenic linear images in 59% and hypoechogenic nodular areas in 41%. Histological findings consisted of fibrotic areas in 100% of cases, hemosiderin deposits in 65%, seminiferous tubule atrophy in 59% and psammoma bodies in 29%. In testicular parenchyma or spermatic chord intratubular neoplasms and viable tumor foci were also noted (47% and 41% of cases, respectively).
CONCLUSIONS: Spontaneous regression of a germ cell testicular tumor should be considered in each patient with extragonadal germ cell neoplasms. Ultrasound diagnosis of and surgical treatment for these primary testicular tumors appear critical to prevent relapse because residual disease develops in a significant proportion of cases.

PMID 19762049  J Urol. 2009 Nov;182(5):2303-10. doi: 10.1016/j.juro.20・・・
著者: M Mancini, L Carmignani, G Gazzano, P Sagone, F Gadda, S Bosari, F Rocco, G M Colpi
雑誌名: Hum Reprod. 2007 Apr;22(4):1042-6. doi: 10.1093/humrep/del500. Epub 2007 Jan 12.
Abstract/Text BACKGROUND: An increased risk of testicular cancer in men with infertility and poor semen quality has been reported. Our aim was to investigate the prevalence of testicular nodules and cancer in azoospermic subjects with different spermatogenetic patterns.
METHODS: A total of 1443 consecutive infertile men were investigated, out of which 145 (10.0%) were found to be azoospermic. By using clinical examination and testicular ultrasound, 11 out of the 145 patients showed testicular nodules (2.8-26 mm). To obtain spermatozoa for assisted reproduction, 97 subjects required testicular sperm extraction (TESE) and biopsy, including the 11 patients with nodules. They were divided into two groups according to biopsy results: Group A (n = 38) with complete Sertoli cell-only syndrome (SCOS) and Group B (n = 59) with varying spermatogenetic patterns. Ten nodules were found in Group A and one in Group B.
RESULTS: In azoospermic men, the overall prevalence of nodules was 7.5%. In complete SCOS, the prevalence of nodules and cancer was 10/38 (26.3%) and 4/38 (10.5%), respectively. Amongst the cancers, one embryonal carcinoma, one seminoma and two in-situ carcinomas were found.
CONCLUSION: The prevalence of testicular nodules and cancer in azoospermic men with complete SCOS is very high. In these subjects, the role of clinical evaluation, ultrasound and biopsy should be emphasized.

PMID 17220165  Hum Reprod. 2007 Apr;22(4):1042-6. doi: 10.1093/humrep/・・・
著者: Josep Tabernero, Luís Paz-Ares, Ramon Salazar, Pilar Lianes, José Guerra, Joan Borrás, Humberto Villavicencio, Oscar Leiva, Hernán Cortés-Funes
雑誌名: J Urol. 2004 Jan;171(1):164-7. doi: 10.1097/01.ju.0000099893.79138.55.
Abstract/Text PURPOSE: The crude and cumulative incidence of contralateral germ cell testicular tumors (GCTTs) is between 1% to 5% and 3% to 6% at 10 to 15 years in previously reported studies. To evaluate the real incidence of a second GCTT in a southern European population the medical records of 623 patients with GCTT successfully treated between 1976 and 1993 at 2 university hospitals were reviewed.
MATERIALS AND METHODS: All patients had been treated with standard treatment strategies according to disease stage and diagnosis year. Contralateral biopsy at GCTT diagnosis was not performed in any patient. Only those with a survival of 1 year or greater were included. In addition to the imaging and biochemical (tumor markers) procedures used to diagnose disease relapse, physical examination of the contralateral testis and/or testicular ultrasound was done yearly.
RESULTS: At a median followup of 8.6 years (range 2 to 19.7) 6 patients (1%) had a contralateral GCTT, which was synchronous in 1 and metachronous in 5. The cumulative risk of a contralateral GCTT was 1.2% (95% CI 0.1% to 2.3%) at 15 years and it did not depend on the treatment for the first GCTT.
CONCLUSIONS: The incidence of contralateral GCTT in our series was lower than expected compared with other published series. This finding mirrors the lower incidence of GCTT in the general population in our country than in other areas with a higher incidence of contralateral GCTT. Therefore, contralateral testicular biopsy at initial diagnosis is not mandatory in our experience.

PMID 14665868  J Urol. 2004 Jan;171(1):164-7. doi: 10.1097/01.ju.00000・・・
著者: S Basu, D C Howlett
雑誌名: Abdom Imaging. 2001 Jul-Aug;26(4):425-32.
Abstract/Text Ultrasound is the initial imaging modality used in the evaluation of the symptomatic testis. Ultrasound is painless and quick and supplements clinical examination of the testis. In this review, a range of testicular pathologies are discussed and sonographic examples illustrated. Particular attention is drawn to testicular microlithiasis and its relation to germ cell neoplasia and also to the sonographic features of epidermoid cysts that may allow testis-sparing surgery.

PMID 11441559  Abdom Imaging. 2001 Jul-Aug;26(4):425-32.
著者: J T Atchley, K C Dewbury
雑誌名: Clin Radiol. 2000 Jul;55(7):493-502. doi: 10.1053/crad.1999.0472.
Abstract/Text Benign testicular tumours are uncommon but if recognized can enable a conservative approach to surgery to be recommended. This pictorial review demonstrates the variety of sonographic appearances of testicular epidermoid cysts correlating them with pathological findings in 19 lesions, the largest reported imaged series to date. Atchley, J. T. M., Dewbury, K. C. (2000). Clinical Radiology 55, 493-502.

Copyright 2000 The Royal College of Radiologists.
PMID 10924372  Clin Radiol. 2000 Jul;55(7):493-502. doi: 10.1053/crad.・・・
著者: Y Watanabe, M Dohke, K Ohkubo, T Ishimori, Y Amoh, A Okumura, K Oda, T Hayashi, Y Dodo, Y Arai
雑誌名: Radiology. 2000 Oct;217(1):219-27.
Abstract/Text PURPOSE: To evaluate testicular enhancement patterns in various scrotal disorders at dynamic contrast medium-enhanced subtraction magnetic resonance (MR) imaging.
MATERIALS AND METHODS: Forty-two patients with scrotal symptoms (22 testicular diseases, 20 extratesticular scrotal disorders) underwent three-dimensional (3D) fast field-echo or fast spin-echo dynamic subtraction MR imaging after injection of paramagnetic contrast medium. The relative percentages of peak height and mean slope of the testes on the affected side were compared with those on the unaffected side by using time-signal intensity curves.
RESULTS: Extratesticular scrotal disorders (time-signal intensity curve mean peak height, 93.1%; mean slope, 89.8%) showed gradual and progressive increase in homogeneous testicular contrast enhancement in all normal testes. Relative percentages of peak height and mean slope of testicular torsion (mean peak height, 17.3%; mean slope, 10.6%), infarction (mean peak height, 30.4%; mean slope, 19.8%), traumatic hemorrhagic necrosis (mean peak height, -3.5%; mean slope, -12.0%), and epidermoid cyst (mean peak height, -6.6%; mean slope, -14.2%) were significantly lower than those of extratesticular scrotal disorders. Acute mumps orchitis (mean peak height, 135.1%; mean slope, 307.5%) and malignant testicular tumor (mean peak height, 178.7%; mean slope, 467.6%) showed higher relative percentages of peak height and mean slope.
CONCLUSION: Dynamic contrast-enhanced subtraction MR imaging can provide information about testicular perfusion on the basis of contrast enhancement and can be used to differentiate testicular diseases from scrotal disorders.

PMID 11012448  Radiology. 2000 Oct;217(1):219-27.
著者: L Leibovitch, R S Foster, K K Kopecky, J P Donohue
雑誌名: J Urol. 1995 Nov;154(5):1759-63.
Abstract/Text PURPOSE: We evaluated the significance of retroperitoneal lymph nodes detected by computerized tomography (CT) of low stage nonseminomatous germ cell tumor patients.
MATERIALS AND METHODS: A blind retrospective review of 143 CTs of low stage nonseminomatous germ cell tumor revealed pathological stage A disease on 89 (62.2%) and pathological stage B disease on 54 (37.8%). A multivariate logistic regression model was used to evaluate the relationships between diameter of the retroperitoneal nodes detected in these CTs and pathological stage.
RESULTS: Based on this model, as the diameter of the nodes increased within a 0 to 25 mm. range, the likelihood of pathological stage B disease increased in a continuous fashion. Using a 3 mm. threshold to define nonmetastatic nodes the sensitivity and negative predictive value of CT based staging was 90%.
CONCLUSIONS: This measurement scheme improves the accuracy of staging compared to conventional methods.

PMID 7563341  J Urol. 1995 Nov;154(5):1759-63.
著者: S Hilton, H W Herr, J B Teitcher, C B Begg, R A Castéllino
雑誌名: AJR Am J Roentgenol. 1997 Aug;169(2):521-5. doi: 10.2214/ajr.169.2.9242768.
Abstract/Text OBJECTIVE: Patients with nonseminomatous germ cell cancer of the testis with no evidence of metastatic disease after orchiectomy may be managed with either retroperitoneal lymph node dissection or surveillance. The present retrospective study was undertaken to determine the accuracy of CT for revealing retroperitoneal lymph node metastases in patients with newly diagnosed clinical stage 1 testicular nonseminomatous germ cell cancer of the testis when smaller size criteria (smaller than 10 mm) are applied and to test the hypothesis that CT-revealed anterior retroperitoneal lymph nodes are more likely to correlate with metastases than are posterior lymph nodes.
MATERIALS AND METHODS: Abdominal CT scans obtained before surgery in 70 patients were reviewed by three observers who were unaware of the results of retroperitoneal lymphadenectomy. The sizes and sites of all lymph nodes measuring larger than or equal to 4 mm were recorded. Each CT scan was judged as positive or negative for retroperitoneal metastasis on the basis of the size of the largest measured lymph node at the expected metastatic site. Diameters of 4, 6, 8, and 10 mm were successively applied to each case as the criteria for a positive scan.
RESULTS: Using a criterion of 10 mm or larger for metastases, we calculated a sensitivity of 37% and a specificity of 100%; with a 4-mm criterion, the sensitivity was 93% and the specificity was 58%. Receiver operating characteristic curves comparing the accuracy of CT for revealing similar-sized lymph nodes located anterior or posterior to a line bisecting the aorta differed significantly (p = .04) when the same criteria were applied to lymph nodes in both regions.
CONCLUSION: False-negative rates were decreased from 63% using a size criterion of 10 mm to as low as 7% using a size criterion of 4 mm, with a corresponding decrease in specificity. Lymph nodes measuring larger than or equal to 4 mm, especially those located anterior to the mid portion of the aorta, should raise a suspicion of metastases.

PMID 9242768  AJR Am J Roentgenol. 1997 Aug;169(2):521-5. doi: 10.221・・・
著者: P M White, D J Adamson, G C Howard, A R Wright
雑誌名: Clin Radiol. 1999 Apr;54(4):207-11.
Abstract/Text AIM: To evaluate role of chest computed tomography (CTC) and chest radiography (CXR) in management of patients with testicular germ cell tumours (GCT).
PATIENTS AND METHODS: An analysis was undertaken of staging and re-assessment CTC and CXR examinations performed on patients with GCT over a 4.5-year period. Data were obtained on clinical presentation, tumour histology, tumour marker levels and clinical course. Consensus review interpretation was combined with these data to obtain a 'standard of reference'. Sensitivity, specificity and predictive values were derived by comparison of original imaging reports to 'standard of reference'.
RESULTS: Six hundred and twenty-three CTC examinations on 207 patients with GCT were included. Intrathoracic metastases were identified in 1% of seminoma patients compared with 20% of non-seminoma (NSGCT) patients. CTC was more accurate than CXR in the detection of intrathoracic metastases at 0.97, 0.96-0.98 (95% CI) compared with 0.91, 0.89-0.93. The agreement between imaging techniques and the standard of reference (determined by Kappa statistic) was respectively 0.96 for CTC and 0.65 for CXR. In GCT patients undergoing re-assessment with both CXR and CTC, CXR never detected unknown intrathoracic metastatic disease. Abdominopelvic lymphadenopathy was associated with intrathoracic metastases (P < 0.001), however re-assessment CTC did identify intrathoracic metastases in 27 cases without concurrent abdominopelvic disease. CXR was negative in 19 of these.
CONCLUSION: Routine interval CXRs are unnecessary in NSGCT patients undergoing regular re-assessment CTC due to the low additional yield and limited effect on management. Re-assessment should still include CTC. In low risk, pure seminoma patients (abdominal CT and marker negative) re-assessment CTC can be safely avoided. Baseline CTC is advocated with CXR alone for re-assessment.

PMID 10210337  Clin Radiol. 1999 Apr;54(4):207-11.
著者: B Hamm, M Taupitz, P Hussmann, S Wagner, K J Wolf
雑誌名: AJR Am J Roentgenol. 1992 Jan;158(1):183-90. doi: 10.2214/ajr.158.1.1727343.
Abstract/Text Superparamagnetic iron oxide (SPIO) particles are a promising contrast agent for MR lymphography. The effect of SPIO on MR imaging of normal lymph nodes and the impact of the size of the dose have not yet been investigated in detail. Therefore, we performed dose-response and pulse sequence optimization studies. MR images of the iliac lymph nodes of 15 normal rabbits were obtained at 1.5 T with 12 different spin-echo (SE) and gradient-echo (GRE) sequences before and after SPIO administration. The contrast agent was injected into a femoral lymph vessel at five different doses (0.02-2.0 mumol Fe/animal). The dose that reduced signal intensity by half (ED50) was determined for each sequence, and images were evaluated qualitatively. Doses of 0.2 and 1.0 mumol Fe caused a complete signal loss throughout the lymph node. In this dose range, proton density-weighted SE sequences showed a profound signal loss (ED50, 0.132 mumol Fe), and lymph nodes were sharply demarcated. The GRE sequences (ED50, 0.027-0.070 mumol Fe) and the T2-weighted SE sequence (ED50, 0.014 mumol Fe) showed an even more pronounced signal loss but insufficient anatomic resolution. Underdosing (less than or equal to 0.1 mumol Fe) caused only a focal signal loss in the lymph nodes. Oversaturation (2.0 mumol Fe for SE sequences, greater than or equal to 1.0 mumol Fe for GRE sequences) led to image distortion and did not allow assessment of lymph node morphology. Our results show that optimal contrast enhancement of normal lymph nodes with SPIO can be achieved in the dose range of 0.2-1.0 mumol Fe on proton density-weighted SE sequences. Our results may serve as a basis for further development of noninvasive MR lymphography.

PMID 1727343  AJR Am J Roentgenol. 1992 Jan;158(1):183-90. doi: 10.22・・・
著者: C Bokemeyer, P Nowak, A Haupt, B Metzner, H Köhne, J T Hartmann, L Kanz, H J Schmoll
雑誌名: J Clin Oncol. 1997 Apr;15(4):1449-54.
Abstract/Text PURPOSE: Despite improved cure rates for patients with metastatic testicular cancer with cisplatin-based combination chemotherapy, patients who develop brain metastases are generally considered to possess a poor prognosis. This report summarizes the long-term results in 44 patients with brain metastases from testicular cancer treated between 1978 and 1995 at Hannover University Medical School.
PATIENTS AND METHODS: Histologically, 42 patients (95%) had a nonseminomatous germ cell cancer and two patients (5%) a seminoma. Thirty-nine patients (89%) had lung metastases and 37 (84%) fulfilled the criteria for advanced disease according to the Indiana University classification even without considering the brain metastases. Eighteen patients (41%) presented with brain metastases at primary diagnosis (group 1), four (9%) developed brain metastases at relapse after a previous favorable response to combination chemotherapy (group 2), and 22 (50%) developed brain metastases during or directly after cisplatin-based chemotherapy. Chemotherapy consisted of cisplatin-based combination treatment and radiotherapy was given as whole-brain irradiation of 30 to 40 Gy and in single cases combined with a boost of 10 Gy to single lesions.
RESULTS: Overall, 10 patients achieved long-term survival (23%; 95% confidence interval [CI], 10.1% to 35.4%). The prognosis was significantly better for patients in groups 1 and 2, with six of 18 (33%) and three of four (75%) patients alive, compared with only one of 22 (5%) in group 3 (P < .01). Patients treated with either chemotherapy or radiotherapy alone did not achieve long-term survival, while nine of 28 (32%) who received treatment with both modalities with or without surgery achieved sustained long-term survival. During univariate analysis, patients with the diagnosis of brain metastases at first presentation (P < .01), patients with a single brain lesion (P < .02), and patients who received combined chemotherapy and radiotherapy (P < .03) had a significantly improved outcome.
CONCLUSIONS: Long-term survival can be achieved in approximately 25% of patients with brain metastases from testicular cancer by combined treatment with brain irradiation and aggressive cisplatin-based chemotherapy. Patients who develop brain metastases during systemic treatment should receive only palliative radiation therapy, since sustained survival will not be reached.

PMID 9193339  J Clin Oncol. 1997 Apr;15(4):1449-54.
著者: S D Fosså, C Bokemeyer, A Gerl, S Culine, W G Jones, G M Mead, J R Germa-Luch, J Pont, H J Schmoll, S Tjulandin
雑誌名: Cancer. 1999 Feb 15;85(4):988-97.
Abstract/Text BACKGROUND: Multiinstitutional experience with the management of cerebral metastases from malignant germ cell tumors (MGCT) is presented.
METHODS: Clinical data regarding brain metastases from MGCT at diagnosis (Group 1 [56 patients]) or after cisplatin-based chemotherapy (Group 2 [83 patients]) were collected retrospectively. All patients in Group 1 received "conventional" cisplatin-based chemotherapy supplemented by cerebral radiotherapy (36 patients) and/or neurosurgery (10 patients). In the patients in Group 2 cerebral metastases were detected a median of 9 months after the initiation of chemotherapy. Thirty-five patients received chemotherapy, 59 patients received radiotherapy, and 25 patients underwent neurosurgery.
RESULTS: The 5-year cause specific survival rate in Group 1 was 45% (95% confidence interval [CI], 31-59%). Neurosurgery and the absence of extracerebral, nonpulmonary visceral disease, but not cerebral radiotherapy, were independent predictors of good prognosis. The 5-year cause specific survival rate in Group 2 was 12% (95% CI, 4-20%), but was 39% among patients with an isolated brain recurrence (24 patients). Radiotherapy, but not chemotherapy, represented an independent predictor of good prognosis together with brain metastases at first recurrence and the absence of extracerebral recurrence.
CONCLUSIONS: Among patients with brain metastases at the time of diagnosis of an MGCT, cisplatin-based chemotherapy resulted in a 5-year cause specific survival rate of 45%, with cerebral radiotherapy having limited impact. The 5-year cause specific survival rate for all patients with brain metastases after cisplatin-based chemotherapy was 12%, but increased to 39% in patients with an isolated brain recurrence. Cerebral radiotherapy (and neurosurgery) represent essential treatment modalities for patients in whom brain metastases are diagnosed after induction chemotherapy.

PMID 10091779  Cancer. 1999 Feb 15;85(4):988-97.
著者: J R Spermon, L F De Geus-Oei, L A L M Kiemeney, J A Witjes, W J G Oyen
雑誌名: BJU Int. 2002 Apr;89(6):549-56.
Abstract/Text OBJECTIVE: To investigate the role of 18fluoro-2-deoxyglucose positron emission tomography (FDG-PET) in the initial staging of clinical stage I and II nonseminomatous germ cell tumours (NSGCTs) and in re-staging (non)seminomatous GCTs after chemotherapy.
PATIENTS AND METHODS: FDG-PET studies were undertaken in 50 patients. FDG uptake was interpreted visually and when possible the standardized uptake value was determined. A FDG-PET scan was taken in five patients with clinical stage I and in seven with stage II NSGCT. The scans were validated by histology. Stage I patients underwent a retroperitoneal lymph node dissection because of vascular invasion in the primary tumour. Thirty-eight scans were taken after completing chemotherapy (28 NSGCTs and 10 seminomatous GCTs), and validated by histology or clinical follow-up.
RESULTS: In stage I NSGCT, FDG-PET staging was equivalent to computed tomography (CT) staging. One small lesion, consisting of mature teratoma, was missed by both FDG-PET and CT. In stage II NSGCT, FDG-PET missed two lesions (mature teratoma and retroperitoneal mass with a small component of embryonal cell carcinoma) whereas CT correctly classified all. In 20 of 28 patients with NSGCT, histology was obtained after chemotherapy. In one of three patients with viable tumorous residual mass the FDG-PET scan was clearly positive; in four of 12 with mature teratoma and inflammation components retroperitoneally, the FDG-PET was also positive. In contrast, eight patients with solitary mature teratoma had a negative PET result. In four of five patients with necrosis after chemotherapy the PET result was correctly negative. All eight patients on surveillance had a negative PET scan and were free of disease at median (range) of 14 (8-18) months. Interestingly, of the 12 patients with a correct negative PET result, 11 had no mature teratoma in their primary tumour. Nine of 10 patients with SGCT were correctly staged. Two FDG-PET studies showed increased uptake; in one, a viable seminomatous mass was found and in the other there was inflammation in the residual mass. In all other patients the FDG-PET scan correctly predicted absence of viability in the residual mass.
CONCLUSIONS: In primary staging, FDG-PET has no benefit over CT. In re-staging, a negative FDG-PET result predicts fibrotic residual mass in seminomatous GCT. Moreover, it could be useful to predict fibrotic residual mass in NSGCT in those patients with no teratoma component in their primary tumour.

PMID 11942962  BJU Int. 2002 Apr;89(6):549-56.
著者: U Lassen, G Daugaard, A Eigtved, L Højgaard, K Damgaard, M Rørth
雑誌名: Eur J Nucl Med Mol Imaging. 2003 Mar;30(3):396-402. doi: 10.1007/s00259-002-1075-z. Epub 2003 Jan 9.
Abstract/Text Relapse occurs in 30% of patients with stage I non-seminomatous germ cell tumours (NSGCT) within 1 year after orchiectomy. Whole-body positron emission tomography with fluorine-18 fluorodeoxyglucose (FDG-PET) may detect small metastases when standard staging with computed tomography (CT) and tumour markers is negative. In this study, 46 patients underwent FDG-PET after staging with normal CT and tumour markers. To exclude diagnostic test bias and workup bias, all patients had routine follow-up with repeated CT and tumour marker evaluation, even though the initial FDG-PET was positive. Thirty-six patients have remained disease free with a median follow-up of 48 months (range 24-76). Ten patients (22%) suffered disease relapse after a median of 2 months (range 1-8), and of these, seven had a true positive initial PET with increased uptake of FDG indicating metastatic disease. There were three false negative and no false positive PET scans. The sensitivity, specificity and accuracy of PET were 70%, 100% and 93%, respectively. The sensitivity of detecting small retroperitoneal metastases was 88%. The negative and positive predictive values were 92% and 100%, respectively, whereas the negative predictive value of standard staging procedures was 78%. FDG-PET thus seems to be superior to conventional staging (P=0.06) in stage I NSGCT. This non-invasive method may improve the overall management of patients with NSGCT.

PMID 12634968  Eur J Nucl Med Mol Imaging. 2003 Mar;30(3):396-402. doi・・・
著者: Maria De Santis, Alexander Becherer, Carsten Bokemeyer, Franz Stoiber, Karin Oechsle, Franz Sellner, Alois Lang, Kurt Kletter, Bernhard M Dohmen, Christian Dittrich, Jörg Pont
雑誌名: J Clin Oncol. 2004 Mar 15;22(6):1034-9. doi: 10.1200/JCO.2004.07.188.
Abstract/Text PURPOSE: To define the clinical value of 2-18fluoro-deoxy-D-glucose positron emission tomography (FDG PET) as a predictor for viable residual tumor in postchemotherapy seminoma residuals in a prospective multicentric trial.
PATIENTS AND METHODS: FDG PET studies in patients with metastatic pure seminoma who had radiographically defined postchemotherapy residual masses were correlated with either the histology of the resected lesion or the clinical outcome documented by computer tomography (CT), tumor markers, and/or physical examination during follow-up. The size of the residual lesions on CT, either >3 cm or < or =3 cm, was correlated with the presence or absence of viable residual tumor.
RESULTS: Fifty-six FDG PET scans of 51 patients were assessable. All 19 cases with residual lesions >3 cm and 35 (95%) of 37 with residual lesions < or =3 cm were correctly predicted by FDG PET. The specificity, sensitivity, positive predictive value, and negative predictive value of FDG PET were 100% (95% CI, 92% to 100%), 80% (95% CI, 44% to 95%), 100%, and 96%, respectively, versus 74% (95% CI, 58% to 85%), 70% (95% CI, 34% to 90%), 37%, and 92%, respectively, for CT discrimination of the residual tumor by size (>3 cm/< or =3 cm).
CONCLUSION: This investigation confirms that FDG PET is the best predictor of viable residual tumor in postchemotherapy seminoma residuals and should be used as a standard tool for clinical decision making in this patient group.

PMID 15020605  J Clin Oncol. 2004 Mar 15;22(6):1034-9. doi: 10.1200/JC・・・
著者: Arduino Verdecchia, Silvia Francisci, Hermann Brenner, Gemma Gatta, Andrea Micheli, Lucia Mangone, Ian Kunkler, EUROCARE-4 Working Group
雑誌名: Lancet Oncol. 2007 Sep;8(9):784-96. doi: 10.1016/S1470-2045(07)70246-2.
Abstract/Text BACKGROUND: Traditional cancer-survival analyses provide data on cancer management at the beginning of a study period, and are often not relevant to current practice because they refer to survival of patients treated with older regimens that might no longer be used. Therefore, shortening the delay in providing survival estimates is desirable. Period analysis can estimate cancer survival by the use of recent data. We aimed to apply the period-analysis method to data that were collected by European cancer registries to estimate recent survival by country and cancer site, and to assess survival changes in Europe. We also compared our findings with data on cancer survival in the USA from the US SEER (Surveillance, Epidemiology, and End Results) programme.
METHODS: We analysed survival data for patients diagnosed with cancer in 2000-02, collected from 47 of the European cancer registries participating in the EUROCARE-4 study. 5-year period relative survival for patients diagnosed in 2000-02 was estimated as the product of interval-specific relative survival values of cohorts with different lengths of follow-up. 5-year survival profiles for patients diagnosed in 2000-02 were estimated for the European mean and for five European regions, and findings were compared with US SEER registry data for patients diagnosed in 2000-02. A 5-year survival profile for patients diagnosed in 1991-2002 and a 10-year survival profile for patients diagnosed in 1997-2002 were also estimated by the period method for all malignancies, by geographical area, and by cancer site.
FINDINGS: For all cancers, age-adjusted 5-year period survival improved for patients diagnosed in 2000-02, especially for patients with colorectal, breast, prostate, and thyroid cancer, Hodgkin's disease, and non-Hodgkin lymphoma. The European mean age-adjusted 5-year survival calculated by the period method for 2000-02 was high for testicular cancer (97.3% [95% CI 96.4-98.2]), melanoma (86.1% [84.3-88.0]), thyroid cancer (83.2% [80.9-85.6]), Hodgkin's disease (81.4% [78.9-84.1]), female breast cancer (79.0% [78.1-80.0]), corpus uteri (78.0% [76.2-79.9]), and prostate cancer (77.5% [76.5-78.6]); and low for stomach cancer (24.9% [23.7-26.2]), chronic myeloid leukaemia (32.2% [29.0-35.7]), acute myeloid leukaemia (14.8% [13.4-16.4]), and lung cancer (10.9% [10.5-11.4]). Survival for patients diagnosed in 2000-02 was generally highest for those in northern European countries and lowest for those in eastern European countries, although, patients in eastern European had the highest improvement in survival for major cancer sites during 1991-2002 (colorectal cancer from 30.3% [28.3-32.5] to 44.7% [42.8-46.7]; breast cancer from 60% [57.2-63.0] to 73.9% [71.7-76.2]; for prostate cancer from 39.5% [35.0-44.6] to 68.0% [64.2-72.1]). For all solid tumours, with the exception of stomach, testicular, and soft-tissue cancers, survival for patients diagnosed in 2000-02 was higher in the US SEER registries than for the European mean. For haematological malignancies, data from US SEER registries and the European mean were comparable in 2000-02, except for non-Hodgkin lymphoma.
INTERPRETATION: Cancer-service infrastructure, prevention and screening programmes, access to diagnostic and treatment facilities, tumour-site-specific protocols, multidisciplinary management, application of evidence-based clinical guidelines, and recruitment to clinical trials probably account for most of the differences that we noted in outcomes.

PMID 17714993  Lancet Oncol. 2007 Sep;8(9):784-96. doi: 10.1016/S1470-・・・
著者: H J Schmoll, R Souchon, S Krege, P Albers, J Beyer, C Kollmannsberger, S D Fossa, N E Skakkebaek, R de Wit, K Fizazi, J P Droz, G Pizzocaro, G Daugaard, P H M de Mulder, A Horwich, T Oliver, R Huddart, G Rosti, L Paz Ares, O Pont, J T Hartmann, N Aass, F Algaba, M Bamberg, I Bodrogi, C Bokemeyer, J Classen, S Clemm, S Culine, M de Wit, H G Derigs, K P Dieckmann, M Flasshove, X Garcia del Muro, A Gerl, J R Germa-Lluch, M Hartmann, A Heidenreich, W Hoeltl, J Joffe, W Jones, G Kaiser, O Klepp, S Kliesch, L Kisbenedek, K U Koehrmann, M Kuczyk, M P Laguna, O Leiva, V Loy, M D Mason, G M Mead, R P Mueller, N Nicolai, G O N Oosterhof, T Pottek, O Rick, H Schmidberger, F Sedlmayer, W Siegert, U Studer, S Tjulandin, H von der Maase, P Walz, S Weinknecht, L Weissbach, E Winter, C Wittekind, European Germ Cell Cancer Consensus Group
雑誌名: Ann Oncol. 2004 Sep;15(9):1377-99. doi: 10.1093/annonc/mdh301.
Abstract/Text Germ cell tumour is the most frequent malignant tumour type in young men with a 100% rise in the incidence every 20 years. Despite this, the high sensitivity of germ cell tumours to platinum-based chemotherapy, together with radiation and surgical measures, leads to the high cure rate of > or = 99% in early stages and 90%, 75-80% and 50% in advanced disease with 'good', 'intermediate' and 'poor' prognostic criteria (IGCCCG classification), respectively. The high cure rate in patients with limited metastatic disease allows the reduction of overall treatment load, and therefore less acute and long-term toxicity, e.g. organ sparing surgery for specific cases, reduced dose and treatment volume of irradiation or substitution of node dissection by surveillance or adjuvant chemotherapy according to the presence or absence of vascular invasion. Thus, different treatment options according to prognostic factors including histology, stage and patient factors and possibilities of the treating centre as well may be used to define the treatment strategy which is definitively chosen for an individual patient. However, this strategy of reduction of treatment load as well as the treatment itself require very high expertise of the treating physician with careful management and follow-up and thorough cooperation by the patient as well to maintain the high rate for cure. Treatment decisions must be based on the available evidence which has been the basis for this consensus guideline delivering a clear proposal for diagnostic and treatment measures in each stage of gonadal and extragonadal germ cell tumour and individual clinical situations. Since this guideline is based on the highest evidence level available today, a deviation from these proposals should be a rare and justified exception.

PMID 15319245  Ann Oncol. 2004 Sep;15(9):1377-99. doi: 10.1093/annonc/・・・
著者: International Prognostic Factors Study Group, Anja Lorch, Jörg Beyer, Caroline Bascoul-Mollevi, Andrew Kramar, Lawrence H Einhorn, Andrea Necchi, Christophe Massard, Ugo De Giorgi, Aude Fléchon, Kim A Margolin, Jean-Pierre Lotz, Jose Ramon Germa Lluch, Thomas Powles, Christian K Kollmannsberger
雑誌名: J Clin Oncol. 2010 Nov 20;28(33):4906-11. doi: 10.1200/JCO.2009.26.8128. Epub 2010 Oct 18.
Abstract/Text PURPOSE: To develop a prognostic model in patients with germ cell tumors (GCT) who experience treatment failure with cisplatin-based first-line chemotherapy.
PATIENTS AND METHODS: Data from 1,984 patients with GCT who progressed after at least three cisplatin-based cycles and were treated with cisplatin-based conventional-dose or carboplatin-based high-dose salvage chemotherapy was retrospectively collected from 38 centers/groups worldwide. One thousand five hundred ninety-four (80%) of 1,984 eligible patients were randomly divided into a training set of 1,067 patients (67%) and a validation set of 527 patients (33%). Seminomas were set aside for posthoc analyses. Primary end point was the 2-year progression-free survival after salvage treatment.
RESULTS: Overall, 990 patients (62%) relapsed and 604 patients (38%) remained relapse free. Histology, primary tumor location, response, and progression-free interval after first-line treatment, as well as levels of alpha fetoprotein, human chorionic gonadotrophin, and the presence of liver, bone, or brain metastases at salvage were identified as independent prognostic variables and used to build a prognostic model in the training set. Survival rates in the training and validation set were very similar. The estimated 2-year progression-free survival rates in patients not included in the training set was 75% in very low risk, 51% in low risk, 40% in intermediate risk, 26% in high risk, and only 6% in very high-risk patients. Due to missing values in individual variables, 69 patients could not reliably be classified into one of these categories.
CONCLUSION: Prognostic variables are important in patients with GCT who experienced treatment failure with cisplatin-based first-line chemotherapy and can be used to construct a prognostic model to guide salvage strategies.

PMID 20956623  J Clin Oncol. 2010 Nov 20;28(33):4906-11. doi: 10.1200/・・・
著者: Peter Albers, Walter Albrecht, Ferran Algaba, Carsten Bokemeyer, Gabriella Cohn-Cedermark, Karim Fizazi, Alan Horwich, Maria Pilar Laguna, European Association of Urology
雑誌名: Eur Urol. 2011 Aug;60(2):304-19. doi: 10.1016/j.eururo.2011.05.038. Epub 2011 May 25.
Abstract/Text CONTEXT: On behalf of the European Association of Urology (EAU), guidelines for the diagnosis, therapy, and follow-up of testicular cancer were established.
OBJECTIVE: This article is a short version of the EAU testicular cancer guidelines and summarises the main conclusions from the guidelines on the management of testicular cancer.
EVIDENCE ACQUISITION: Guidelines were compiled by a multidisciplinary guidelines working group. A systematic review was carried out using Medline and Embase, also taking Cochrane evidence and data from the European Germ Cell Cancer Consensus Group into consideration. A panel of experts weighted the references, and a level of evidence and grade of recommendation were assigned.
RESULTS: There is a paucity of literature especially regarding longer term follow-up, and results from a number of ongoing trials are awaited. The choice of treatment centre is of the utmost importance, and treatment in reference centres within clinical trials, especially for poor-prognosis nonseminomatous germ cell tumours, provides better outcomes. For patients with clinical stage I seminoma, based on recently published data on long-term toxicity, adjuvant radiotherapy is no longer recommended as first-line adjuvant treatment. The TNM classification 2009 is recommended.
CONCLUSIONS: These guidelines contain information for the standardised management of patients with testicular cancer based on the latest scientific insights. Cure rates are generally excellent, but because testicular cancer mainly affects men in their third or fourth decade of life, treatment effects on fertility require careful counselling of patients, and treatment must be tailored taking individual circumstances and patient preferences into account.

Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.
PMID 21632173  Eur Urol. 2011 Aug;60(2):304-19. doi: 10.1016/j.eururo.・・・
著者: P Chung, C Parker, T Panzarella, M K Gospodarowicz, S Jewett, M F Milosevic, C N Catton, A J Bayley, B Tew-George, M Moore, J F G Sturgeon, P Warde
雑誌名: Can J Urol. 2002 Oct;9(5):1637-40.
Abstract/Text INTRODUCTION: Surveillance is an alternative to adjuvant radiotherapy for stage I testicular seminoma. We present the long-term results of seminoma surveillance, with emphasis on quantifying the risk of late relapse beyond 5 years.
METHODS: From 1981 to 1993, of 431 men with stage I testicular seminoma, 203 were managed by surveillance following radical orchidectomy. The surveillance protocol comprised a combination of clinical examination, CT scans of abdomen and pelvis, chest x-rays and serum markers, at defined intervals.
RESULTS: At a median follow-up of 9.2 years, 35 men have relapsed. Five of the relapses occurred more than 5 years after orchidectomy (at 5.1, 6.9, 7.3, 7.3, and 9.0 years). The actuarial risk of relapse at 5 and 10 years was 15% (standard error [SE] 1.1%) and 18% (SE 1.8%) respectively. One hundred sixty one men were free of relapse at 5 years, and have been followed beyond this point for a median of 4.3 years. The actuarial risk of relapse between 5 and 10 years was 4% (SE 0.5%).
CONCLUSIONS: These results demonstrate that there is a small but clinically significant risk of relapse more than 5 years after orchidectomy for stage I seminoma. These data support the need for long term surveillance.

PMID 12431325  Can J Urol. 2002 Oct;9(5):1637-40.
著者: Padraig Warde, Lena Specht, Alan Horwich, Tim Oliver, Tony Panzarella, Mary Gospodarowicz, Hans von der Maase
雑誌名: J Clin Oncol. 2002 Nov 15;20(22):4448-52.
Abstract/Text PURPOSE: Several management options are available to patients with stage I seminoma, including adjuvant radiotherapy, surveillance, and adjuvant chemotherapy. We performed a pooled analysis of patients from the four largest surveillance studies to better delineate prognostic factors associated with disease progression.
PATIENTS AND METHODS: Individual patient data were obtained from each center (Princess Margaret Hospital, Danish Testicular Cancer Study Group, Royal Marsden Hospital, and Royal London Hospital) for 638 patients. Tumor characteristics (size, histologic subtype, invasion of rete testis, and tumor invasion into small vessels [SVI]) as well as age at diagnosis were analyzed for prognostic importance for relapse.
RESULTS: With a median follow-up of 7.0 years (range, 0.02 to 17.5 years), 121 relapses were observed for an actuarial 5-year relapse-free rate (RFR) of 82.3%. On univariate analysis, tumor size (RFR: 4 cm, 76%; P =.003), rete testis invasion (RFR: 86% [absent] v 77% [present], P =.003), and the presence of SVI (RFR: 86% [absent] v 77% [present], P =.038) were predictive of relapse. On multivariate analysis, tumor size ( 4 cm, hazard ratio 2.0; 95% confidence interval [CI], 1.3 to 3.2) and invasion of the rete testis (hazard ratio 1.7; 95% CI, 1.1 to 2.6) remained as important predictors for relapse.
CONCLUSION: We have identified size of primary tumor and rete testis invasion as important prognostic factors for relapse in patients with stage I seminoma managed with surveillance. This information will allow patients and clinicians to choose management based on a more accurate assessment of an individual patient's risk of relapse. In addition, it will allow clinicians to tailor follow-up protocols based on risk of occult disease.

PMID 12431967  J Clin Oncol. 2002 Nov 15;20(22):4448-52.
著者: Jorge Aparicio, José R Germà, Xavier García del Muro, Pablo Maroto, José A Arranz, Alberto Sáenz, Agustín Barnadas, Joan Dorca, Josep Gumà, David Olmos, Romá Bastús, Joan Carles, Daniel Almenar, Miguel Sánchez, Luis Paz-Ares, Juan J Satrústegui, Begoña Mellado, Ana Balil, Marta López-Brea, Alfredo Sánchez, Second Spanish Germ Cell Cancer Cooperative Group
雑誌名: J Clin Oncol. 2005 Dec 1;23(34):8717-23. doi: 10.1200/JCO.2005.01.9810. Epub 2005 Oct 31.
Abstract/Text PURPOSE: To assess the efficacy of a risk-adapted treatment policy for patients with stage I seminoma by using universally accepted risk criteria.
PATIENTS AND METHODS: Between 1999 and 2003, 314 patients with clinical stage I seminoma after orchiectomy were prospectively included. One hundred patients (31.8%) presented no risk factors and were managed with surveillance. In contrast, 131 patients (41.7%) had tumors larger than 4 cm, 33 patients (10.5%) had rete testis involvement, and 50 patients (15.9%) had both risk factors. All the latter received two courses of adjuvant carboplatin.
RESULTS: Chemotherapy was well tolerated, as only 17 patients (7.9%) presented grade 3 to 4 toxicity. Relapses were observed in six patients (6.0%) on surveillance and in seven patients (3.3%) treated with carboplatin (0.8% of tumors larger than 4 cm, 9.1% of those involving the rete testis, and 6.0% of patients with both risk criteria). All were located at the retroperitoneum, except for one at the spermatic cord. Median tumor size was 25 mm (range, 11 to 70 mm), and median time to relapse was 9 months (range, 4 to 28 months). All patients were rendered disease-free with chemotherapy (etoposide plus cisplatin). Median follow-up was 34 months (range, 12 to 72 months). The actuarial 5-year disease-free survival rate was 93.4% for patients on surveillance and 96.2% for patients treated with adjuvant chemotherapy. Overall 5-year survival was 100%.
CONCLUSION: Adjuvant carboplatin is effective in reducing the relapse rate in patients with stage I seminoma and risk factors. A risk-adapted strategy is safe and feasible and should be considered an alternative to systematic approaches, such as irradiation, chemotherapy, or surveillance.

PMID 16260698  J Clin Oncol. 2005 Dec 1;23(34):8717-23. doi: 10.1200/J・・・
著者: Peter Chung, Padraig Warde
雑誌名: J Natl Cancer Inst. 2011 Feb 2;103(3):194-6. doi: 10.1093/jnci/djq535. Epub 2011 Jan 6.
Abstract/Text
PMID 21212383  J Natl Cancer Inst. 2011 Feb 2;103(3):194-6. doi: 10.10・・・
著者: S D Fosså, A Horwich, J M Russell, J T Roberts, M H Cullen, N J Hodson, W G Jones, H Yosef, G M Duchesne, J R Owen, E J Grosch, A D Chetiyawardana, N S Reed, B Widmer, S P Stenning
雑誌名: J Clin Oncol. 1999 Apr;17(4):1146.
Abstract/Text PURPOSE: To compare relapse rates and toxicity associated with para-aortic (PA) strip or PA and ipsilateral iliac lymph node irradiation (dogleg [DL] field) (30 Gy/15 fractions/3 weeks) for stage I testicular seminoma.
PATIENTS AND METHODS: Between July 1989 and May 1993, 478 men with testicular seminoma stage I (T1 to T3; no ipsilateral inguinoscrotal operation before orchiectomy) were randomized (PA, 236 patients; DL, 242 patients).
RESULTS: Median follow-up time is 4.5 years. Eighteen relapses, nine in each treatment group, have occurred 4 to 35 months after radiotherapy; among these, four were pelvic relapses, all occurring after PA radiotherapy. However, the 95% confidence interval (CI) for the difference in pelvic relapse rates excludes differences of more than 4%. The 3-year relapse-free survival was 96% (95% CI, 94% to 99%) after PA radiotherapy and 96.6% (95% CI, 94% to 99%) after DL (difference, 0.6%; 95% confidence limits, -3.4%, +4.6%). One patient (PA field) has died from seminoma. Survival at 3 years was 99.3% for PA and 100% for DL radiotherapy. Acute toxicity (nausea, vomiting, leukopenia) was less frequent and less pronounced in patients in the PA arm. Within the first 18 months of follow-up, the sperm counts were significantly higher after PA than after DL irradiation.
CONCLUSION: In patients with testicular seminoma stage I (T1 to T3) and with undisturbed lymphatic drainage, adjuvant radiotherapy confined to the PA lymph nodes is associated with reduced hematologic, gastrointestinal, and gonadal toxicity, but with a higher risk of pelvic recurrence, compared with DL radiotherapy. The recurrence rate is low with either treatment. PA radiotherapy is recommended as standard treatment in these patients.

PMID 10561173  J Clin Oncol. 1999 Apr;17(4):1146.
著者: Robert H Jones, Paul A Vasey
雑誌名: Lancet Oncol. 2003 Dec;4(12):730-7.
Abstract/Text For patients diagnosed with early-stage testicular cancer radical orchidectomy is the primary therapeutic intervention. The major pathological types of testicular cancer are seminoma and non-seminomatous germ-cell cancer. After orchidectomy, most patients with seminoma receive adjuvant radiotherapy as standard of care, although surveillance and adjuvant chemotherapy protocols are being developed. For patients with non-seminomatous tumours there are three therapeutic options; surveillance, adjuvant chemotherapy, or retroperitoneal lymph-node dissection. These patients are classified into groups with high-risk or low-risk of recurrence by presence of vascular invasion in the surgical specimen. After orchidectomy, about 50% of patients with high-risk disease will relapse but this risk is reduced to less than 5% with adjuvant therapy. Surveillance of patients with low-risk disease is acceptable because testicular cancer is still curable if metastatic recurrence occurs. There is no consensus about the management of early non-seminomatous testicular cancer because survival is almost 100% irrespective of the initial treatment decision.

PMID 14662429  Lancet Oncol. 2003 Dec;4(12):730-7.
著者: William G Jones, Sophie D Fossa, Graham M Mead, J Trevor Roberts, Michael Sokal, Alan Horwich, Sally P Stenning
雑誌名: J Clin Oncol. 2005 Feb 20;23(6):1200-8. doi: 10.1200/JCO.2005.08.003.
Abstract/Text PURPOSE: To assess the possibility of reducing radiotherapy doses without compromising efficacy in the management of patients with stage I seminoma.
PATIENTS AND METHODS: Patients were randomly assigned 20 Gy/10 fractions over 2 weeks or 30 Gy/15 fractions during 3 weeks after orchidectomy. They completed a symptom diary card during treatment and quality-of-life forms pre- and post-treatment. The trial was powered to exclude absolute differences in 2-year relapse rates of 3% to 4% (alpha = .05 [one sided]; 90% power).
RESULTS: From 1995 to 1998, 625 patients were randomly assigned to treatment. Four weeks after starting radiotherapy, significantly more patients receiving 30 Gy reported moderate or severe lethargy (20% v 5%) and an inability to carry out their normal work (46% v 28%). However, by 12 weeks, levels in both groups were similar. With a median follow-up of 61 months, 10 and 11 relapses, respectively, have been reported in the 30- and 20-Gy groups (hazard ratio, 1.11; 90% CI, 0.54 to 2.28). The absolute difference in 2-year relapse rates is 0.7%; the lower 90% confidence limit is 2.9%. Only one patient has died from seminoma (allocated to the 20-Gy treatment group).
CONCLUSION: Treatment with 20 Gy in 10 fractions is unlikely to produce relapse rates more than 3% higher than for standard 30 Gy radiation therapy, and data on an additional 469 patients randomly assigned in a subsequent trial support and strengthen these results. Reductions in morbidity enable patients to return to work more rapidly. Prolonged follow-up is required before any inference can be made about any impact of allocated treatment on new primary cancer diagnoses.

PMID 15718317  J Clin Oncol. 2005 Feb 20;23(6):1200-8. doi: 10.1200/JC・・・
著者: K P Dieckmann, B Brüggeboes, U Pichlmeier, J Küster, U Müllerleile, H Bartels
雑誌名: Urology. 2000 Jan;55(1):102-6.
Abstract/Text OBJECTIVES: Adjuvant radiotherapy produces excellent disease-free rates in clinical Stage I seminoma. However, concern is growing about side effects and late hazards of this treatment. Carboplatin has been suggested to supplant radiotherapy. To date, there is little experience with this drug in the adjuvant treatment of seminoma. In particular, it is unclear whether one or two courses should be administered.
METHODS: In a nonrandomized study, 125 patients with pure clinical Stage I seminoma were given adjuvant carboplatin treatment (400 mg/m2). Ninety-three patients received one course and 32 two courses. The median follow-up time was 48 months. To assess gonadal toxicity, serial measurements of follicle-stimulating hormone (FSH) levels were done. To assess myelotoxicity, platelet counts at 3 and 4 weeks after treatment were monitored.
RESULTS: There were no relapses after two courses of carboplatin. After one course of carboplatin, eight relapses occurred (8.6%; 95% confidence interval [CI] 3.79% to 16.2%). All the relapses were located in the para-aortic region, and all the patients were rescued with cisplatin-based chemotherapy. The median time to recurrence was 16 months. The 5-year actuarial progression-free survival rate after one course was 91.1% (95% CI 85.25% to 97.01%). Younger patients (age groups: less than 30 years and 31 to 38 years) had relapses more frequently (P = 0.038) than those in the older age group (greater than 38 years). After 3 weeks, 32% of the patients had platelet counts below 150/nL. The median FSH level increased immediately after treatment, reaching a peak of 13.6 U/L. After 20 months, the median FSH level had returned to the normal range.
CONCLUSIONS: One adjuvant course of carboplatin was associated with low myelotoxicity and low gonadal toxicity; however, the recurrence rate was almost 9% and thus unsatisfactory. After two courses of carboplatin, no relapse was observed. Thus, the two-course regimen of carboplatin appears to be equivalent to radiotherapy, and because of its favorable toxicity profile, this regimen should be investigated in randomized trials.

PMID 10654903  Urology. 2000 Jan;55(1):102-6.
著者: Peter W M Chung, Mary K Gospodarowicz, Tony Panzarella, Michael A S Jewett, Jeremy F G Sturgeon, Betty Tew-George, Andrew J S Bayley, Charles N Catton, Michael F Milosevic, Malcolm Moore, Padraig R Warde
雑誌名: Eur Urol. 2004 Jun;45(6):754-59; discussion 759-60. doi: 10.1016/j.eururo.2004.01.020.
Abstract/Text OBJECTIVES: To review treatment outcome and patterns of failure for patients with stage II testicular seminoma and to identify prognostic factors for relapse.
METHODS: From 1981 to 1999, 126 men with stage II seminoma were treated at Princess Margaret Hospital. Of these, 95 were treated with radiotherapy (RT) and 31 with chemotherapy (ChT). Patient and tumour characteristics were analyzed for prognostic significance for subsequent relapse.
RESULTS: At median follow-up of 8.5 years, the 5- and 10-year overall survival were both 93%, the 5- and 10-year cause-specific survival were both 94% and the 5- and 10-year relapse-free rates were both 85%. Patients with stage IIA and IIB disease treated with RT and stage IIB treated with chemotherapy had 5-year relapse-free rates of 91.7%, 89.7% and 83.3%, respectively. Seventeen percent of patients treated with radiotherapy and 6% of those treated with chemotherapy have relapsed. Of the RT patients the commonest sites of relapse were left supraclavicular fossa, lung/mediastinum, bone, para-aortics and liver; nine patients had a solitary site of relapse. Two patients treated with chemotherapy had recurrence in the para-aortic and iliac nodes. For RT patients, larger primary tumour size was associated with a reduction in relapse rate. Age, rete testis invasion and lymphovascular invasion were found not to be of prognostic significance.
CONCLUSIONS: In stage IIA/B seminoma, radiotherapy continues to provide excellent results, as the majority of patients will be cured with this treatment alone. Chemotherapy is the treatment of choice for stage IIC seminoma.

PMID 15149748  Eur Urol. 2004 Jun;45(6):754-59; discussion 759-60. doi・・・
著者: Xavier Garcia-del-Muro, Pablo Maroto, Josep Gumà, Javier Sastre, Marta López Brea, José A Arranz, Nuria Lainez, Diego Soto de Prado, Jorge Aparicio, José M Piulats, Xavier Pérez, Josep R Germá-Lluch
雑誌名: J Clin Oncol. 2008 Nov 20;26(33):5416-21. doi: 10.1200/JCO.2007.15.9103. Epub 2008 Oct 20.
Abstract/Text PURPOSE: To assess the long-term efficacy and toxicity of front-line cisplatin-based chemotherapy in patients with stage IIA or IIB testicular seminoma.
PATIENTS AND METHODS: Untreated patients with pure seminoma of the testis after orchiectomy, with clinical stage IIA or IIB, were considered eligible for this prospective observational study. Chemotherapy consisted of either four cycles of cisplatin and etoposide or three cycles of cisplatin, etoposide, and bleomycin.
RESULTS: Between April 1994 and March 2003, 72 patients were entered onto the study at 26 participating centers. Eighteen patients had stage IIA disease, and 54 patients had stage IIB disease. Eighty-three percent of patients achieved complete response, and 17% achieved partial response with residual mass. After a median follow-up time of 71.5 months, six patients with stage IIB disease experienced relapse, and one of these patients died as a result of seminoma. Three patients experienced non-seminoma-related deaths (two died from a further esophageal carcinoma, and one died from an upper digestive hemorrhage). The estimated 5-year progression-free survival rates for patients with stage IIA or IIB disease were 100% and 87% (95% CI, 77.5% to 97%), respectively. Five-year progression-free and overall survival rates for the whole group were 90% (95% CI, 82% to 98%) and 95% (95% CI, 89% to 100%), respectively. Severe granulocytopenia and thrombocytopenia were observed in eight and two patients, respectively. Mild to moderate emesis, stomatitis, and diarrhea were the most common nonhematologic effects.
CONCLUSION: Chemotherapy is a highly effective and well-tolerated treatment for patients with stage IIA or IIB seminoma and represents an available alternative that could avoid some of the serious late effects associated with radiotherapy. Further studies focusing on long-term toxicities of different treatment modalities are needed.

PMID 18936476  J Clin Oncol. 2008 Nov 20;26(33):5416-21. doi: 10.1200/・・・
著者: Ashraf A Mosharafa, Richard S Foster, Bradley C Leibovich, Richard Bihrle, Cynthia Johnson, John P Donohue
雑誌名: J Urol. 2003 Jun;169(6):2126-8. doi: 10.1097/01.ju.0000060121.33899.4b.
Abstract/Text PURPOSE: A seminomatous element in patients undergoing retroperitoneal lymph node dissection for testicular cancer is associated with a desmoplastic reaction that renders retroperitoneal surgery more challenging. We examined the impact of seminomatous elements on the rate of complications and the need for additional intraoperative procedures in patients undergoing post-chemotherapy retroperitoneal lymph node dissection.
MATERIALS AND METHODS: The testis cancer data base at our institution was retrospectively reviewed and 1,366 patients were identified who underwent post-chemotherapy retroperitoneal lymph node dissection between 1973 and 2001. In 97 patients there was an element of seminoma in the dissection specimen and/or pure seminoma in the testicular primary specimen (seminoma group). The remaining 1,269 patients underwent post-chemotherapy retroperitoneal lymph node dissection for nonseminomatous testicular tumors. The rates of intraoperative complications and additional procedures as well as postoperative complications were analyzed.
RESULTS: Of the 97 patients in the seminoma group 37 (38.1%) required a total of 47 additional intraoperative procedures, including 25 nephrectomies, 9 inferior vena caval resections, 5 arterial grafts, 5 bowel resections and 3 hepatic resections/biopsies, compared with 340 of the 1,269 patients (26.8%) in the group without seminomatous elements (p = 0.02). Postoperatively complications occurred in 24 of 97 patients (24.7%) in the seminoma group versus 257 of 1,269 (20.3%) in the group without seminomatous elements (p = 0.29). One of the 97 patients in the seminoma group died secondary to postoperative complications.
CONCLUSIONS: A seminomatous element in patients undergoing post-chemotherapy retroperitoneal lymph node dissection is associated with a higher rate of additional intraoperative procedures and postoperative complications than in patients without seminomatous elements. However, resection is still possible with acceptable morbidity when indicated in appropriately selected patients.

PMID 12771733  J Urol. 2003 Jun;169(6):2126-8. doi: 10.1097/01.ju.0000・・・
著者: H S Puc, R Heelan, M Mazumdar, H Herr, J Scheinfeld, V Vlamis, D F Bajorin, G J Bosl, P Mencel, R J Motzer
雑誌名: J Clin Oncol. 1996 Feb;14(2):454-60.
Abstract/Text PURPOSE: Guidelines for management of postchemotherapy residual mass in patients with advanced seminoma remain controversial. We sought to characterize independent prognostic factor(s) for persistence of tumor to identify patients with a high risk of residual carcinoma.
PATIENTS AND METHODS: One hundred four patients with advanced seminoma were assessed. All had achieved a complete response or partial response with normal markers to induction cisplatin-based chemotherapy and had radiographs available for review. Selected prechemotherapy and postchemotherapy characteristics were compared for patients who had either germ cell tumor histology at surgery or relapsed at the assessed site (defined as site failure) versus those who had only necrosis or fibrosis found at surgery and did not relapse at the assessed site (defined as site nonfailure).
RESULTS: At a median follow-up time of 47 months (range, 5 to 153), 94 patients (90%) were designated as site nonfailures and 10 (10%) as site failures. Site failure correlated only with size of the residual mass (< 3 cm or normal v > or = 3 cm; P = .0006). Two of 74 patients (3%) with residual masses less than 3 cm were considered site failures, compared with eight of 30 (27%) with residual masses > or = 3 cm.
CONCLUSION: Patients with advanced seminoma who have normal radiographs or residual masses less than 3 cm after chemotherapy can be observed without further intervention. The following three options exist for patients with a residual mass > or = 3 cm: observation, radiotherapy, or surgical intervention. We prefer the latter to define response, resect viable tumor when possible, and direct further treatment.

PMID 8636757  J Clin Oncol. 1996 Feb;14(2):454-60.
著者: H W Herr, J Sheinfeld, H S Puc, R Heelan, D F Bajorin, P Mencel, G J Bosl, R J Motzer
雑誌名: J Urol. 1997 Mar;157(3):860-2.
Abstract/Text PURPOSE: We attempted to select patients for surgery of post-chemotherapy residual mass in advanced seminoma.
MATERIALS AND METHODS: A total of 55 patients with advanced seminoma underwent surgical exploration of a mass seen on computerized tomography (CT) after chemotherapy. Residual masses were defined radiographically as smaller or larger than 3 cm. and as well defined or poorly defined. Surgery consisted of complete resection of the mass and surrounding lymph nodes or multiple biopsies at sites of disease.
RESULTS: Of the 55 patients 32 (58%) had masses resected and 23 (42%) underwent multiple biopsies. Of 27 patients with a post-chemotherapy 3 cm. or larger mass on CT 8 (30%) had residual tumor (seminoma in 6 and teratoma in 2), whereas necrotic tissue was found in the other 28 patients having a mass smaller than 3 cm. Well defined masses on CT were resected in 78% of patients and poorly defined masses could be resected in only 44%. Of the 8 patients with positive histology 6 remain alive and disease-free after complete resection of a well defined, larger than 3 cm. mass containing viable tumor, and 2 with a poorly defined mass died after biopsy only of residual seminoma despite salvage therapy. Three other patients who underwent complete resection of necrotic masses subsequently had relapse at distant sites and died. Median followup was 47 months (range 5 +/- 153+ months).
CONCLUSIONS: Patients with advanced seminoma who have a residual mass smaller than 3 cm. after chemotherapy do not benefit from surgery. For patients with a residual mass 3 cm. or larger we prefer surgery to define response, resect viable tumor when possible and direct further treatment.

PMID 9072586  J Urol. 1997 Mar;157(3):860-2.
著者: Stefania Gori, Stella Porrozzi, Fausto Roila, Gemma Gatta, Ugo De Giorgi, Maurizio Marangolo
雑誌名: Crit Rev Oncol Hematol. 2005 Feb;53(2):141-64. doi: 10.1016/j.critrevonc.2004.05.006.
Abstract/Text Cancer of the testis is a relatively rare disease, accounting for about 1% of all cancers in men. Cryptorchidism is the only confirmed risk factor for testicular germ cell tumour. The majority of GCT are clinically detectable at initial presentation. Any nodular, hard, or fixed area discovered in the testis, must be considered neoplastic until proved otherwise. The appropriate surgical procedure to make the diagnosis is a radical orchidectomy through an inguinal incision. Many GCT produce tumoural markers (AFP, HCG, LDH), who are useful in the diagnosis and staging of disease; to monitor the therapeutic response and to detect tumour recurrence. In 1997 a prognostic factor-based classification for the metastatic germ cell tumours was developed by the IGCCCG: good, intermediate and poor prognosis, with 5-year survival of 91, 79 and 48%, respectively. GCT of the testis is a highly table, often curable, cancer. Germ cell testicular cancers are divided into seminoma and non-seminoma types for treatment planning because seminomatous testicular cancers are more sensitive to radiotherapy. Seminoma (all stages combined) has a cure rate of greater than 90%. For patients with low-stage disease, the cure approaches 100%. For patients with non-seminoma tumours, the cure rate is >95% in stages I and II; it is approximately 70% with standard chemotherapy and resection of residual disease, if necessary, in stages III and IV. Minimum guidelines for clinical, biochemical, and radiological follow-up have been reported by ESMO in 2001.

PMID 15661565  Crit Rev Oncol Hematol. 2005 Feb;53(2):141-64. doi: 10.・・・
著者: Timothy D Gilligan, Jerome Seidenfeld, Ethan M Basch, Lawrence H Einhorn, Timothy Fancher, David C Smith, Andrew J Stephenson, David J Vaughn, Roxanne Cosby, Daniel F Hayes, American Society of Clinical Oncology
雑誌名: J Clin Oncol. 2010 Jul 10;28(20):3388-404. doi: 10.1200/JCO.2009.26.4481. Epub 2010 Jun 7.
Abstract/Text PURPOSE: To provide recommendations on appropriate uses for serum markers of germ cell tumors (GCTs).
METHODS: Searches of MEDLINE and EMBASE identified relevant studies published in English. Primary outcomes included marker accuracy to predict the impact of decisions on outcomes. Secondary outcomes included proportions of patients with elevated markers and statistical tests of elevations as prognostic factors. An expert panel developed consensus guidelines based on data from 82 reports.
RESULTS: No studies directly compared outcomes of decisions with versus without marker assays. The search identified few prospective studies and no randomized controlled trials; most were retrospective series. Lacking data on primary outcomes, most Panel recommendations are based on secondary outcomes (relapse rates and time to relapse).
RECOMMENDATIONS: The Panel recommended against using markers to screen for GCTs, to decide whether orchiectomy is indicated, or to select treatment for patients with cancer of unknown primary. To stage patients with testicular nonseminomas, the Panel recommended measuring three markers (alpha-fetoprotein [AFP], human chorionic gonadotropin [hCG], and lactate dehydrogenase [LDH]) before and after orchiectomy and before chemotherapy for those with extragonadal nonseminomas. They also recommended measuring AFP and hCG shortly before retroperitoneal lymph node dissection and at the start of each chemotherapy cycle for nonseminoma, and periodically to monitor for relapse. The Panel recommended measuring postorchiectomy hCG and LDH for patients with seminoma and preorchiectomy elevations. They recommended against using markers to guide or monitor treatment for seminoma or to detect relapse in those treated for stage I. However, they recommended measuring hCG and AFP to monitor for relapse in patients treated for advanced seminoma.

PMID 20530278  J Clin Oncol. 2010 Jul 10;28(20):3388-404. doi: 10.1200・・・
著者: R T D Oliver, J Ong, J Shamash, R Ravi, V Nagund, P Harper, M J Ostrowski, B Sizer, J Levay, A Robinson, D E Neal, M Williams, Anglian Germ Cell Cancer Group
雑誌名: Urology. 2004 Mar;63(3):556-61. doi: 10.1016/j.urology.2003.10.023.
Abstract/Text OBJECTIVES: To study survival and late events after adjuvant chemotherapy in Stage 1 nonseminoma.
METHODS: From 1978 to 1986, all patients had surveillance. From 1986, adjuvant chemotherapy (initially a 3-day regimen of etoposide, bleomycin, and cisplatin, but, more recently, bleomycin, Oncovin, and cisplatin) was offered to patients at a high risk of relapse (greater than 30%).
RESULTS: A total of 382 patients with Stage 1 nonseminoma treated between 1978 and 2000 were reviewed. Of the 234 patients treated by surveillance, 71 (30%) had relapses (5 after 2 years), 6 died (2.6%) of germ cell cancer, and 3 developed second primary testicular cancer. Of the 148 men treated with adjuvant chemotherapy, 6 (4%) had relapses and 2 (1.4%) died of chemoresistant cancer. After one course of etoposide, bleomycin, and cisplatin, 3 (6.5%) of 46 developed a relapse; after two courses, 1 (3.6%) of 28 did so; and after bleomycin, Oncovin, and cisplatin every 10 days x2, 2 (2.7%) of 74 patients did so. Of the high-risk patients who were offered adjuvant treatment, 24% declined. As a consequence, the relapse rate of the surveillance patients only fell from 36% to 27% after the introduction of adjuvant therapy, although for the total cohort treated in the adjuvant era, the relapse rate was 16%.
CONCLUSIONS: Adjuvant chemotherapy is more effective than retroperitoneal lymph node dissection for reducing the relapse risk in high-risk Stage 1 nonseminoma. However, given the uncertainty about the incidence of postchemotherapy late events, surveillance and retroperitoneal lymph node dissection remain justified alternatives. With positron emission tomography and laparoscopy showing increasing promise in these cases, quality-of-life studies and greater patient involvement in treatment selection are needed.

PMID 15028457  Urology. 2004 Mar;63(3):556-61. doi: 10.1016/j.urology.・・・
著者: Alvaro Zuniga, David Kakiashvili, Michael A S Jewett
雑誌名: BJU Int. 2009 Nov;104(9 Pt B):1351-6. doi: 10.1111/j.1464-410X.2009.08858.x.
Abstract/Text
PMID 19840012  BJU Int. 2009 Nov;104(9 Pt B):1351-6. doi: 10.1111/j.14・・・
著者: G Read, S P Stenning, M H Cullen, M C Parkinson, A Horwich, S B Kaye, P A Cook
雑誌名: J Clin Oncol. 1992 Nov;10(11):1762-8.
Abstract/Text PURPOSE: A prospective study of surveillance after orchidectomy alone in patients with stage I nonseminomatous germ cell testicular tumor (NSGCT) was performed to determine the relapse-free rate and to identify the histologic criteria that predict for relapse.
PATIENTS AND METHODS: Three hundred ninety-six patients from 16 United Kingdom and one Norwegian centers were entered onto the study between January 1, 1984 and October 1, 1987 of whom 373 were eligible for analysis. In a previous retrospective study, we defined a prognostic index based on histologic criteria that identified a group of patients with a high risk of relapse. This index was based on the presence of venous and lymphatic invasion, undifferentiated cells, and the absence of yolk sac elements in the primary tumor.
RESULTS: The 2-year actuarial relapse-free rate after orchidectomy was 75% (95% confidence interval, 71% to 79%), and the rate at 5 years was 73%. Five patients died of tumor or treatment-related complications, which resulted in a 5-year survival of 98%. The relapse-free rate in patients with three or four risk factors was 54%.
CONCLUSIONS: This study confirms the safety of surveillance as a method of management and identifies a group of patients with a high risk of relapse. A prospective phase II study has been initiated to determine whether two courses of platinum-based adjuvant chemotherapy will prevent relapse in these high-risk patients.

PMID 1403057  J Clin Oncol. 1992 Nov;10(11):1762-8.
著者: Michael Scholz, Wolfgang Höltl
雑誌名: Curr Opin Urol. 2003 Nov;13(6):473-6. doi: 10.1097/01.mou.0000098069.73234.61.
Abstract/Text PURPOSE OF REVIEW: To review current developments in the management of patients with testicular cancer, with special emphasis on risk factors for the primary tumour and treatment options for clinical stage I testicular germ cell tumours.
RECENT FINDINGS: The management of patients with testicular cancer has substantially improved over the past 25 years. Current concepts for treating localized and regional disease have been influenced by effective systematic chemotherapy. At present, cure rates approach nearly 100% for low-stage disease and more than 80% for advanced disease.
SUMMARY: Retroperitoneal lymph node dissection is still favoured as the therapy of choice for clinical stage I non-seminomatous germ cell tumours in many centres, but as risk factors for the primary tumour have become better understood, surveillance and risk-adapted therapy, including surveillance for low-risk patients and adjuvant chemotherapy for the high-risk group, is now being considered a therapeutic option particularly in European centres. Adjuvant radiotherapy is still the gold standard for the treatment of patients with clinical stage I seminoma, but the relapse rate of 19% and a 5-year overall survival of 97.7% make surveillance a possible therapeutic option. The results of phase II and III trials should soon provide additional information on carboplatin for single-agent adjuvant chemotherapy.

PMID 14560141  Curr Opin Urol. 2003 Nov;13(6):473-6. doi: 10.1097/01.m・・・
著者: M H Cullen, S P Stenning, M C Parkinson, S D Fossa, S B Kaye, A H Horwich, S J Harland, M V Williams, R Jakes
雑誌名: J Clin Oncol. 1996 Apr;14(4):1106-13.
Abstract/Text PURPOSE: This United Kingdom Medical Research Council (UK-MRC) study prospectively evaluated efficacy and long-term toxicity of adjuvant chemotherapy in high-risk stage I nonseminomatous germ cell tumors of the testis (NSGCTT).
PATIENTS AND METHODS: Eligible patients were those identified by the local histopathologist as having features confirmed in MRC surveillance studies to indicate an approximate 50% risk of relapse. Central histopathology review was undertaken. Chemotherapy consisted of two courses of cisplatin 100 mg/m2, bleomycin 30 mg weekly x 3, and etoposide 120 mg/m2 x 3, every 21 days (BEP).
RESULTS: One hundred fourteen eligible cases were enrolled. Median time of follow-up was 4 years, with 93 patients followed-up for at least 2 years. There have been two relapses, including one patient who did not have a germ cell tumor (GCT), according to the reference histopathologist. This patient is alive with active disease, the other has died. There was one death after a cerebrovascular accident during treatment. Assessment of fertility, lung function, and audiometry pretreatment and more than 9 months posttreatment indicated no clinically significant changes. A mean decrease in transfer factor coefficient (KCO) of 15% of the predicted value was noted, but no patient had symptomatic respiratory dysfunction.
CONCLUSION: There have been only two relapses among 114 cases of high-risk stage I NSGCTT treated with two courses of adjuvant BEP chemotherapy. The 95% confidence interval (CI) excludes a true relapse rate of more than 5%. Of 104 patients confirmed on histopathology review to have GCT, there has been only one relapse. Adjuvant chemotherapy is free from significant long-term toxicity, offering an effective alternative to surveillance or retroperitoneal lymph node dissection (RPLND) followed by surveillance, and may be preferred by some patients.

PMID 8648364  J Clin Oncol. 1996 Apr;14(4):1106-13.
著者: Christine Chevreau, Catherine Mazerolles, Michel Soulié, Marie-Hélène Gaspard, Loïc Mourey, Louis Bujan, Pierre Plante, Pascal Rischmann, Jean-Marc Bachaud, Bernard Malavaud
雑誌名: Eur Urol. 2004 Aug;46(2):209-14; discussion 214-5. doi: 10.1016/j.eururo.2004.03.022.
Abstract/Text OBJECTIVES: To report the long-term impact of two cycles of adjuvant chemotherapy on relapse rates and treatment-related morbidity in high-risk stage I nonseminomatous testicular germ cell tumors (NSGCTT I).
MATERIAL AND METHODS: From April 1987 to September 1997, 40 stage I NSGCTT patients with evidence of vascular invasion and/or embryonal carcinoma (EC) in the orchidectomy specimen were treated with two courses of bleomycin, cisplatin, and etoposide (BEP).
RESULTS: All patients but one (incidental death) were alive after an extended follow-up (median 113.2 months, range 63-189). No patients relapsed but two patients presented a second cancer in the remaining testis. Short-term toxicity was minimal and no long-term toxicity was observed.
CONCLUSION: The present series, with extensive follow-up, demonstrated that the efficacy and toxicity of two cycles of BEP compared well with the results of surveillance strategies or RPLND in high-risk stage I NSGCTT.

PMID 15245815  Eur Urol. 2004 Aug;46(2):209-14; discussion 214-5. doi:・・・
著者: R A Huddart, A Norman, M Shahidi, A Horwich, D Coward, J Nicholls, D P Dearnaley
雑誌名: J Clin Oncol. 2003 Apr 15;21(8):1513-23. doi: 10.1200/JCO.2003.04.173.
Abstract/Text PURPOSE: To assess the risk of cardiovascular morbidity and cardiac risk factors in long-term survivors of testicular cancer according to treatment received.
PATIENTS AND METHODS: All resident male patients registered in the United Kingdom between 1982 and 1992 attending for follow-up were eligible for recruitment. Patients completed a current health questionnaire and underwent clinical review, along with hematologic, biochemical, and hormonal profiles. For patients not under routine review, follow-up information was sought from their general practitioner and mortality data were sought from the Office of National Statistics. Descriptive analysis was performed on all variables and comparisons were made among patients treated by orchidectomy and follow-up only, chemotherapy alone (C), radiotherapy alone (RT), and radiotherapy and chemotherapy (C/RT).
RESULTS: Data on cardiovascular events were available on 992 patients. After a median follow-up of 10.2 years, 68 events had been reported, including 18 deaths. After adjusting for age, increased risk for cardiac events was seen after C (relative risk [RR] = 2.59; 95% confidence interval [CI], 1.15 to 5.84; P =.022), RT (RR = 2.40; 95% CI, 1.04 to 5.45; P =.036), and C/RT (RR = 2.78; 95% CI, 1.09 to 7.07; P =.032). There were no significant differences in cardiac risk factors. On multivariate analysis, age, treatment group, free thyroxine, protein, and magnesium levels were associated with cardiovascular disease.
CONCLUSION: In long-term survivors of testicular cancer, we observed a two-fold or greater risk of developing cardiovascular disease. This was not due to increases in cardiac risk factors, which suggests a direct or indirect treatment effect. These data support the continued research into the minimization of treatment in good-prognosis testicular cancer.

PMID 12697875  J Clin Oncol. 2003 Apr 15;21(8):1513-23. doi: 10.1200/J・・・
著者: Axel Heidenreich, Peter Albers, Michael Hartmann, Sabine Kliesch, Kai-Uwe Kohrmann, Susanne Krege, Philipp Lossin, Lothar Weissbach, German Testicular Cancer Study Group
雑誌名: J Urol. 2003 May;169(5):1710-4. doi: 10.1097/01.ju.0000060960.18092.54.
Abstract/Text PURPOSE: Nerve sparing retroperitoneal lymph node dissection has been the standard diagnostic and therapeutic approach to clinical stage I nonseminoma. However, the application of prognostic risk factors and introduction of laparoscopy have recently called into question the clinical usefulness of nerve sparing retroperitoneal lymph node dissection. We assessed the therapeutic efficacy and associated complications of this procedure in patients with clinical stage I nonseminomatous germ cell tumor treated at 7 tertiary referral centers to evaluate its role in the modern management of low stage testis cancer.
MATERIALS AND METHODS: Between January 1995 and September 2000, 239 patients with clinical stage I nonseminomatous germ cell tumor underwent nerve sparing retroperitoneal lymph node dissection in standardized fields of dissection. For retrospective analysis patient charts were reviewed. A minor complication did not prolong hospital stay and a major complication prolonged hospitalization for at least 2 days. Early complications developed within the first 30 days after retroperitoneal lymph node dissection and late complications occurred from postoperative day 31 and thereafter.
RESULTS: Nerve sparing retroperitoneal lymph node dissection was performed unilaterally in 209 patients (88.2%) and bilaterally in 30 (11.8%). Median operative time was 214 minutes (range 90 to 395), mean hospital stay was 8 days (range 4 to 39) and mean blood loss was less than 150 ml. A mean of 18.5 lymph nodes (range 9 to 57) were dissected with metastases detected in 67 patients (28%). An average of 2.9 lymph nodes (range 1 to 14) with a mean diameter of 2.6 cm. (range 0.3 to 6.0) showed metastasis. Disease was pathological stage I in 172 patients (71.7%), 52 (17.6%) had 3 or fewer metastatic lymph nodes, and 15 (6.3%) had 4 to 5 and 10 (4.2%) had greater than 5 positive lymph nodes. Minor complications occurred in 14.2% of the cases and major complications were observed in 5.4%. Antegrade ejaculation was preserved in 93.3% of the patients, recurrence developed in 14 (5.8%) and retroperitoneal recurrence was observed in 3 (1.2%), including 1 in field and 2 out field.
CONCLUSIONS: Primary diagnostic and therapeutic nerve sparing retroperitoneal lymph node dissection still has a role in the primary management of clinical stage I nonseminomatous germ cell tumor. Surgery is associated with low morbidity and patient followup is easy and cost-effective due to the concentration on extraretroperitoneal locations. Primary nerve sparing retroperitoneal lymph node dissection is curative in about 70% of clinical stage I nonseminoma cases with a maximum of 3 positive lymph nodes.

PMID 12686815  J Urol. 2003 May;169(5):1710-4. doi: 10.1097/01.ju.0000・・・
著者: J P Donohue, J A Thornhill, R S Foster, R G Rowland, R Bihrle
雑誌名: J Urol. 1993 Feb;149(2):237-43.
Abstract/Text Results with primary retroperitoneal lymphadenectomy in 464 patients with clinical stage A nonseminomatous germ cell testis cancer (1965 to 1989) were reviewed. The false-negative staging error by clinical methods remains at 30%. The relapse rate in pathological stage A cancer patients was 11% (37 of 323), with 2 deaths. For pathological stage B disease 64% of the patients were cured by retroperitoneal lymphadenectomy alone. With modern adjuvant chemotherapy no stage B tumor relapsed since 1979 and the survival rate was 100%. For all 25 years (464 patients) the relapse rate was 14% and the survival rate was 98.9% (3 cancer and 2 noncancer deaths). Because these results are based on preoperative clinical staging, they are directly comparable with series using radiotherapy or surveillance.

PMID 8381190  J Urol. 1993 Feb;149(2):237-43.
著者: D B Lashley, B A Lowe
雑誌名: Urol Clin North Am. 1998 Aug;25(3):405-23.
Abstract/Text Regardless of the treatment option selected for management of low-stage germ cell cancer, ultimate survival is nearly identical. Treatment-related morbidity is very low regardless of management modality and the individual patient can expect similar physical limitations owing to therapy. The overall difference in loss of productivity between treatment programs varies by little more than 1 week. The cost of treatment is similar for all methods, although there is a definite financial advantage to surveillance, less so for selective surveillance, when compared with other forms of management. Socioeconomic factors are of importance when managing limited resources for a large population, but are of less concern to an individual, especially when the mean differences in per patient costs vary by only $5000. Because of these close similarities in efficacy, morbidity, and costs treatment decisions should be individualized. A responsible and reliable patient can be managed safely by selective surveillance. Those individuals considered to be less self-motivated to pursue intensive care should be managed by primary therapy. Without more information regarding the long-term outcomes associated with primary adjuvant chemotherapy, primary adjuvant RPLND, where experienced surgical support is available, is the preferred management for low-stage germ cell cancer in patients selected for, or electing, active treatment rather than surveillance. Active investigations examining the role of medical management in this population should be continued. Our preferred choice of initial management is to offer selective surveillance to appropriate patients and modified RPLND to the remainder.

PMID 9728211  Urol Clin North Am. 1998 Aug;25(3):405-23.
著者: P C Sogani, M Perrotti, H W Herr, W R Fair, H T Thaler, G Bosl
雑誌名: J Urol. 1998 Mar;159(3):855-8.
Abstract/Text PURPOSE: The long-term outcome results of a prospective surveillance trial for clinical stage I nonseminomatous germ cell tumors of the testis (NSGCT) are reported in an effort to define the natural history of clinical stage I testis cancer treated with orchiectomy alone, and to determine if a subset of patients exists that may be suitable for surveillance.
MATERIALS AND METHODS: Between September 1979 and December 1987, 105 patients were entered into the study. Patients with persistent elevation of serum tumor markers (AFP, BHCG, and LDH) following orchiectomy, stage T2-T4 primary tumors, any evidence of metastases and pure choriocarcinoma or pure seminoma on histology were excluded from study. Enrolled patients underwent periodic physical examination, serological testing and radiological imaging according to an established protocol.
RESULTS: Median followup was 11.3 years. Of the patients 78 (74.3%) have remained disease-free and 27 (25.7%) have experienced relapse. Of the patients with relapse 24 are currently disease-free after treatment for relapse for a median duration of 10.8 years and 3 (2.8%) died of disease. All relapses occurred within 24 months of orchiectomy (median 5 months). Significant predictors of relapse during surveillance were a predominant embryonal carcinoma histology (p = 0.016) and vascular invasion (p = 0.0005). In patients with neither embryonal carcinoma nor vascular invasion the relapse rate was 12%, and no patients died of disease.
CONCLUSIONS: With extended followup 74% of men with clinical stage I (T1) nonseminomatous germ cell tumor of the testis were cured by orchiectomy alone, and cure rates approached 90% when patients with predominant embryonal carcinoma histology or vascular invasion were excluded from surveillance. These findings support management by surveillance alone in a highly select cohort of men who have clinical stage I (T1) nonseminomatous germ cell tumor of the testis, normal serum markers following orchiectomy and neither predominant embryonal carcinoma or vascular invasion on histology.

PMID 9474168  J Urol. 1998 Mar;159(3):855-8.
著者: Peter Albers, Roswitha Siener, Sabine Kliesch, Lothar Weissbach, Susanne Krege, Christoph Sparwasser, Harald Schulze, Axel Heidenreich, Werner de Riese, Volker Loy, Erhard Bierhoff, Christian Wittekind, Rolf Fimmers, Michael Hartmann, German Testicular Cancer Study Group
雑誌名: J Clin Oncol. 2003 Apr 15;21(8):1505-12. doi: 10.1200/JCO.2003.07.169.
Abstract/Text PURPOSE: To prospectively assess potential risk factors for relapse in clinical stage I nonseminomatous germ cell tumors of the testis (CS I NSGCT).
PATIENTS AND METHODS: From September 1996 to May 2002, 200 patients with CS I NSGCT were prospectively assigned to retroperitoneal lymph node dissection (RPLND), and risk factor assessment was performed within a multicenter protocol. One hundred sixty-five patients had an adequate minimum follow-up of 12 months (mean, 34.5 months) or had pathologic stage II.
RESULTS: Pathologic stage II disease was found in 27.9% of patients. Only 0.6% of patients relapsed in the retroperitoneum after confirmation of pathologic stage I disease. With reference pathology, vascular invasion (VI) was most predictive of stage in multifactorial analysis (accuracy, 65.1%). However, the positive predictive value (PPV) of VI to predict patients who have metastatic disease or relapse during follow-up was only 52.7%. With absent VI, low-risk patients had a negative predictive value (NPV) of 76.9%. With a combination of several risk factors, the PPV increased to 63.6% and the negative predictive value increased to 86.5%.
CONCLUSION: Even with an optimal combination of prognostic factors and reference pathology, more than one third of patients predicted to have pathologic stage II or relapse during follow-up will not harbor metastatic disease and, therefore, would be overtreated with adjuvant therapy. However, patients at low risk may be predicted at an 86.5% level, and thus, surveillance in highly compliant patients would be a valuable option. For high-risk patients, further reduction of adjuvant treatment is necessary.

PMID 12697874  J Clin Oncol. 2003 Apr 15;21(8):1505-12. doi: 10.1200/J・・・
著者: L S Freedman, M C Parkinson, W G Jones, R T Oliver, M J Peckham, G Read, E S Newlands, C J Williams
雑誌名: Lancet. 1987 Aug 8;2(8554):294-8.
Abstract/Text 259 patients with stage I non-seminomatous germ-cell testicular teratoma who were treated by orchidectomy alone and monitored at one often centres in the United Kingdom were followed for a median of 30 months. 62 of the 70 relapses occurred in the first 18 months after orchidectomy. The 2-year relapse-free rate was 74%, falling to 68% at 4 years. Histological sections from 233 of the orchidectomy specimens were reviewed centrally. Four features independently predicted relapses: invasion of testicular veins, invasion of testicular lymphatics, absence of yolk-sac elements, and presence of undifferentiated tumour. An index, based on the number of these features observed, identified a high-risk subgroup of 55 patients who had a 42% relapse-free rate at 2 years.

PMID 2886764  Lancet. 1987 Aug 8;2(8554):294-8.
著者: A Heidenreich, N S Schenkmann, I A Sesterhenn, F K Mostofi, W F McCarthy, B Heidenreich, J W Moul
雑誌名: J Urol. 1997 Aug;158(2):620-5.
Abstract/Text PURPOSE: Primary archival tumor tissues of 89 patients with clinical stage I nonseminomatous germ cell tumors were analyzed for MIB-1 expression and histological parameters such as percentage embryonal carcinoma and presence of vascular invasion to determine the value of these parameters to predict absence or presence of occult lymph node disease.
MATERIALS AND METHODS: A monoclonal antibody (MIB-1) developed for application in paraffin-embedded tissues was used to measure immunohistochemical expression of Ki-67 for the overall tumor (total MIB-1) and for each malignant cell type present. In addition, the primary tumors were examined for the presence of vascular invasion and determination of quantitative histology. Univariate and multivariate logistic regression models were used for statistical analysis.
RESULTS: Univariate analysis neither revealed total MIB-1 score nor MIB-1 score in the highest area of staining of the different cell types to significantly predict pathological stage I or stage II disease. However, the presence of vascular invasion (p < 0.0001) and the percentage of embryonal carcinoma (p < 0.0001) were significant risk factors for occult nodal disease. Multivariate logistic regression analysis revealed the combination of vascular invasion and the percentage of embryonal carcinoma to be the best model to predict pathological stage II correctly (86.5%).
DISCUSSION: The determination of immunohistochemical MIB-1 expression did not correlate with pathological stage in clinical stage I nonseminomatous germ cell tumors (NSGCT). We were not able to define high risk or low risk groups for occult nodal disease based on MIB-1 staining results. However, percentage of embryonal carcinoma and presence of vascular invasion accurately predicted absence or presence of lymph node metastasis in clinical stage I NSGCT. Our study underlines that a prospective multicenter trial is urgently needed to accurately assess the role of MIB-1 staining in management of clinical stage I NSGCT.

PMID 9224380  J Urol. 1997 Aug;158(2):620-5.
著者: J Pont, W Höltl, D Kosak, E Machacek, H Kienzer, H Julcher, N Honetz
雑誌名: J Clin Oncol. 1990 Jan;8(1):16-20.
Abstract/Text Based on the results of a retrospective study, which found blood vessel invasion to be the most important prognostic factor in clinical stage I nonseminomatous testicular germ cell cancer (NSTGCC I), a prospective study was started in 1985 which assigned NSTGCC I patients without evidence of vascular invasion to surveillance and patients with vascular invasion to two cycles of adjuvant chemotherapy with cisplatin, etoposide, and bleomycin. Twenty-two patients entered the surveillance group and 18 patients received adjuvant chemotherapy. Median follow-up is 30 months (3 to 50 months). Relapses occurred in three patients (7.5%), one in the surveillance group (4.5%), two in the chemotherapy group (11%). Thirty-eight patients (95%) are alive and without evidence of disease. Two patients of the adjuvant-treated group died, one of progressive germ cell cancer and one of lung cancer. We conclude that low- and high-risk NSTGCC I patients can be identified by considering blood vessel invasion. The presence of embryonal carcinoma and vascular invasion seem to be interrelated prognostic factors, because in 94% of vessel invasion the invading element was embryonal carcinoma. The exclusion of patients with vascular invasion from surveillance decreases relapse rates remarkably. Adjuvant chemotherapy diminishes relapse rates in high-risk patients but does not entirely prevent relapse.

PMID 1688613  J Clin Oncol. 1990 Jan;8(1):16-20.
著者: O Klepp, O Dahl, P Flodgren, U Stierner, A M Olsson, J Oldbring, S Nilsson, L Daehlin, M Tørnblom, R Småland, H Starkhammar, L Abramsson, E Wist, N Raabe, T Edekling, E Cavallin-Ståhl
雑誌名: Eur J Cancer. 1997 Jun;33(7):1038-44.
Abstract/Text 250 patients with clinical stage 1 non-seminomatous germ cell tumours of the testis (NSGCT 1) were included into a prospective multicentre protocol during 1990-1994 and treated according to three risk strata: patients without tumour cell invasion of vascular structures in the testis (VASC-) and elevated serum AFP levels (AFP+) at orchiectomy were considered low risk (LR) and only observed closely. VASC- and AFP- or VASC+ and AFP+ patients were presumed intermediate risk (IR) and pathologically staged (PS) by retroperitoneal lymph node dissection (RPLND). VASC+ and AFP-patients were regarded as high risk (HR) and received adjuvant chemotherapy (PEB x 3). At a median observation time of 40 (7-68) months, all patients were alive and without evidence of active germ cell cancer. The actuarial relapse rate in the 106 LR patients was 22%, and 70% (14/20) had elevated serum tumour markers at relapse. One of 32 (3%) HR patients relapsed with a resectable retroperitoneal mature teratoma despite adjuvant chemotherapy. Only 14% of the 99 IR patients who underwent RPLND had PS2 disease, and the actuarial relapse rate in 85 PS1 patients was 18%. This multicentre study demonstrated that excellent therapeutic outcome is possible when 18 comparatively small urological and oncological centres follow a strict and formal cancer care programme. The useful prognostic effect of VASC was once again verified. Pathological staging by RPLND in NSGCT1 is, in our opinion, not necessary, with presumed low-risk patients offered surveillance and high-risk patients offered adjuvant chemotherapy.

PMID 9376184  Eur J Cancer. 1997 Jun;33(7):1038-44.
著者: D Ondrus, J Matoska, V Belan, J Kausitz, F Goncalves, M Hornák
雑誌名: Eur Urol. 1998;33(6):562-6.
Abstract/Text OBJECTIVE: Surveillance after orchiectomy alone becomes popular for the management of clinical stage I nonseminomatous germ cell testicular tumours (CS I NSGCTT). Effort to identify patients at high risk of relapse leads to searching prognostic factors of CS I NSGCTT. The aim of this study was to identify those patients in whom a surveillance policy is less likely to be successful.
PATIENTS AND RESULTS: Seventy-two CS I NSGCTT patients were stratified to different risk-adapted therapeutic approaches according to histopathologic findings of primary tumor removed by inguinal orchiectomy. Eighteen patients (group A) with vascular invasion and majority of embryonal carcinoma component in the primary tumor were treated with adjuvant BEP chemotherapy. None of them experienced disease progression after a median follow-up period of 36 months after orchiectomy. Five patients (group B) with vascular invasion and the majority of teratomatous elements in the primary tumor have been followed up 56 months after orchiectomy. They were treated with primary retroperitoneal lymph node dissection (RPLND). Two of them (40%) had pathologic stage II after RPLND and underwent subsequent chemotherapy. One of them died due to disease progression 29 months following orchiectomy. Another one lives with no evidence of disease (NED). Three patients in pathologic stage I are alive with NED. Forth-nine patients (group C) without vascular invasion have been followed up for a median duration of 37 months after orchiectomy. They were kept under close surveillance, consisted of regular follow-up with tumor markers, chest x-ray and CT of the retroperitoneum. Disease progression was observed in 7 (14.3%) patients after a median duration of 8 months after orchiectomy. They were treated with BEP chemotherapy and live with disease-free median survival of 22 months after completion of therapy. The overall survival rate of all 72 patients was 98.6%. The median survival for all patients was 37 months (range 7-73).
CONCLUSIONS: The authors will continue to use surveillance policy only in patients without vascular invasion in the primary tumor.

PMID 9743698  Eur Urol. 1998;33(6):562-6.
著者: P Maroto, X García del Muro, J Aparicio, L Paz-Ares, J A Arranz, J Guma, J Terrassa, J Barnadas, J Dorta, J R Germà-Lluch
雑誌名: Ann Oncol. 2005 Dec;16(12):1915-20. doi: 10.1093/annonc/mdi397. Epub 2005 Aug 26.
Abstract/Text BACKGROUND: The Spanish Germ Cell Group is composed of 60 centres. Our challenge was to define a surveillance protocol that would be safe and suitable regardless of population size or geographic coverage.
METHODS: From January 1994 to January 2004, 589 patients with stage I non-seminomatous germ cell tumours entered a risk-adapted surveillance protocol after orchiectomy. Patients with vascular or local invasion of adjacent structures (231/589; 39%) received two cycles of BE400P (bleomycin 30 U/week, etoposide 100 mg/m2 x4, cisplatinum 25 mg/m2 x4). Other patients (358/589; 61%) were kept on close follow-up (chest X-ray; serum tumour markers: first year every 2 months, second year every 3 months, third year every 4 months; abdominal computed tomography scans at every other outpatient control). The outcomes selected for the study were feasibility, relapse rate and number of patients lost to follow-up and mortality.
RESULTS: Median follow-up was 40 months. In the surveillance group, 21 patients were lost to follow-up. In the chemotherapy group, two patients relapsed at 12 and 14.5 months and they are presently free of disease. In the surveillance group, 71 (19%) patients relapsed, of which 55 (71%) relapsed within the first year. Five (1.4%) patients died of their cancer. Factors associated with relapse were embryonal carcinoma and vascular invasion in patients who refused chemotherapy.
CONCLUSIONS: Our risk-adapted surveillance protocol provided a low rate of recurrences.

PMID 16126737  Ann Oncol. 2005 Dec;16(12):1915-20. doi: 10.1093/annonc・・・
著者: P Albers, T M Ulbright, J Albers, G A Miller, A Orazi, W N Crabtree, J Baniel, T Reister, R A Sidner, R S Foster, J P Donohue
雑誌名: J Urol. 1996 Feb;155(2):579-86.
Abstract/Text PURPOSE: Traditional histopathological features have failed to predict accurately the pathological stage of clinical stage A nonseminomatous germ cell tumors of the testis. Based on pilot studies in nonconsecutive patients at our university, we evaluated nontraditional risk factors (cell cycle analysis by flow cytometry, deoxyribonucleic acid analysis by single cell cytophotometry [image analysis] and assessment of proliferative activity by immunohistochemistry) combined with histopathological features in consecutive patients with clinical stage A nonseminomatous testis cancer.
MATERIALS AND METHODS: Orchiectomy specimens from 105 consecutive patients with clinical stage A nonseminomatous germ cell tumors who underwent retroperitoneal lymph node dissection (76 with pathological stage A disease and 29 with proved metastasis) were recut, histopathologically reviewed, immunohistochemically stained with proliferation markers (for example Ki-67/MIB-1), and examined by flow cytometry and image analysis.
RESULTS: After multiple logistic regression analysis, the G2M+S cell cycle fraction of the aneuploid tumor stemline was the most predictive parameter of pathological stage (p = 0.0004). Using a cutoff of 41%, patients with metastasis were predicted with a sensitivity of 71%. Of 61 patients with a G2M+S value of less than 41%, 53 had pathological stage A cancer (negative predictive value 87%). A low volume of embryonal carcinoma was predominant in patients at low risk for metastasis and MIB-1 immunohistochemical staining identified 23% of patients with pathological stage A tumor who were at extremely low risk for metastatic disease.
CONCLUSIONS: Assessment of tumor cell proliferation cannot classify accurately high risk patients at a clinically applicable level. However, identification of patients at low risk for metastasis by flow cytometry, immunohistochemical proliferation markers and volume of embryonal carcinoma may be possible at the 90% level. MIB-1 staining is able to classify patients at extremely low risk for metastasis. These parameters deserve further study, since identification of patients at extremely low risk for metastasis could potentially decrease overall morbidity in the management of clinical stage A nonseminomatous testis cancer.

PMID 8558664  J Urol. 1996 Feb;155(2):579-86.
著者: Roanne Segal
雑誌名: Urol Oncol. 2006 Jan-Feb;24(1):68-74. doi: 10.1016/j.urolonc.2005.07.006.
Abstract/Text Germ cell tumors of the testes constitute approximately 1-2% of all tumors in males 15-35 years of age. Half of those present as clinical stage I disease. The traditional approach was either a retroperitoneal node dissection or radiotherapy. A historical review of the literature suggested that 70% of these patients were cured and did not benefit from further therapy. This coupled with the advent of tumor markers, advanced diagnostic techniques, and cisplatin based chemotherapy led to the consideration for surveillance programs, thereby offering therapy only to those who required it. This article reviews the surveillance programs described in the literature to date with respect to both suitability and program design.

PMID 16414498  Urol Oncol. 2006 Jan-Feb;24(1):68-74. doi: 10.1016/j.ur・・・
著者: Gordon J Rustin, Graham M Mead, Sally P Stenning, Paul A Vasey, Nina Aass, Robert A Huddart, Michael P Sokal, Jonathan K Joffe, Stephen J Harland, Sarah J Kirk, National Cancer Research Institute Testis Cancer Clinical Studies Group
雑誌名: J Clin Oncol. 2007 Apr 10;25(11):1310-5. doi: 10.1200/JCO.2006.08.4889.
Abstract/Text PURPOSE: Surveillance is a standard management approach for stage I nonseminomatous germ cell tumors (NSGCT). A randomized trial of two versus five computed tomography (CT) scans was performed to determine whether the number of scans influenced the proportion of patients relapsing with intermediate- or poor-prognosis disease at relapse.
METHODS: Patients with clinical stage I NSGCT opting for surveillance were randomly assigned to chest and abdominal CT scans at either 3 and 12 or 3, 6, 9, 12, and 24 months, with all other investigations identical in the two arms. Three of five patients were allocated to the two-scan schedule. Four hundred patients were required.
RESULTS: Two hundred forty-seven patients were allocated to a two-scan and 167 to five-scan policy. With a median follow-up of 40 months, 37 relapses (15%) have occurred in the two-scan arm and 33 (20%) in the five-scan arm. No patients had poor prognosis at relapse, but two (0.8%) of those relapsing in the two-scan arm had intermediate prognosis compared with 1 (0.6%) in the five-scan arm, a difference of 0.2% (90% CI, -1.2% to 1.6%). No deaths have been reported.
CONCLUSION: This study can rule out with 95% probability an increase in the proportion of patients relapsing with intermediate- or poor-prognosis disease of more than 1.6% if they have two rather than five CT scans as part of their surveillance protocol. CT scans at 3 and 12 months after orchidectomy should be considered a reasonable option in low-risk patients.

PMID 17416851  J Clin Oncol. 2007 Apr 10;25(11):1310-5. doi: 10.1200/J・・・
著者: Susanne Krege, Jörg Beyer, Rainer Souchon, Peter Albers, Walter Albrecht, Ferran Algaba, Michael Bamberg, István Bodrogi, Carsten Bokemeyer, Eva Cavallin-Ståhl, Johannes Classen, Christoph Clemm, Gabriella Cohn-Cedermark, Stéphane Culine, Gedske Daugaard, Pieter H M De Mulder, Maria De Santis, Maike de Wit, Ronald de Wit, Hans Günter Derigs, Klaus-Peter Dieckmann, Annette Dieing, Jean-Pierre Droz, Martin Fenner, Karim Fizazi, Aude Flechon, Sophie D Fosså, Xavier Garcia del Muro, Thomas Gauler, Lajos Geczi, Arthur Gerl, Jose Ramon Germa-Lluch, Silke Gillessen, Jörg T Hartmann, Michael Hartmann, Axel Heidenreich, Wolfgang Hoeltl, Alan Horwich, Robert Huddart, Michael Jewett, Johnathan Joffe, William G Jones, László Kisbenedek, Olbjørn Klepp, Sabine Kliesch, Kai Uwe Koehrmann, Christian Kollmannsberger, Markus Kuczyk, Pilar Laguna, Oscar Leiva Galvis, Volker Loy, Malcolm D Mason, Graham M Mead, Rolf Mueller, Craig Nichols, Nicola Nicolai, Tim Oliver, Dalibor Ondrus, Gosse O N Oosterhof, Luis Paz Ares, Giorgio Pizzocaro, Jörg Pont, Tobias Pottek, Tom Powles, Oliver Rick, Giovanni Rosti, Roberto Salvioni, Jutta Scheiderbauer, Hans-Ulrich Schmelz, Heinz Schmidberger, Hans-Joachim Schmoll, Mark Schrader, Felix Sedlmayer, Niels E Skakkebaek, Aslam Sohaib, Sergei Tjulandin, Padraig Warde, Stefan Weinknecht, Lothar Weissbach, Christian Wittekind, Eva Winter, Lori Wood, Hans von der Maase
雑誌名: Eur Urol. 2008 Mar;53(3):478-96. doi: 10.1016/j.eururo.2007.12.024. Epub 2007 Dec 26.
Abstract/Text OBJECTIVES: The first consensus report presented by the European Germ Cell Cancer Consensus Group (EGCCCG) in the year 2004 has found widespread approval by many colleagues throughout the world. In November 2006, the group met a second time under the auspices of the Department of Urology of the Amsterdam Medical Center, Amsterdam, The Netherlands.
METHODS: Medical oncologists, urological surgeons, radiation oncologists as well as pathologists from several European countries reviewed and discussed the data that had emerged since the 2002 conference, and incorporated the new data into updated and revised guidelines. As for the first meeting, the methodology of evidence-based medicine (EBM) was applied. The results of the discussion were compiled by the writing committee. All participants have agreed to this final update.
RESULTS: The first part of the consensus paper describes the clinical presentation of the primary tumor, its treatment, the importance and treatment of testicular intraepithelial neoplasia (TIN), histological classification, staging and prognostic factors, and treatment of stage I seminoma and non-seminoma.
CONCLUSIONS: Whereas the vast majority of the recommendations made in 2004 remain valid 3 yr later, refinements in the treatment of early- and advanced-stage testicular cancer have emerged from clinical trials. Despite technical improvements, expert clinical skills will continue to be one of the major determinants for the prognosis of patients with germ cell cancer. In addition, the particular needs of testicular cancer survivors have been acknowledged.

PMID 18191324  Eur Urol. 2008 Mar;53(3):478-96. doi: 10.1016/j.eururo.・・・
著者: Susanne Krege, Jörg Beyer, Rainer Souchon, Peter Albers, Walter Albrecht, Ferran Algaba, Michael Bamberg, István Bodrogi, Carsten Bokemeyer, Eva Cavallin-Ståhl, Johannes Classen, Christoph Clemm, Gabriella Cohn-Cedermark, Stéphane Culine, Gedske Daugaard, Pieter H M De Mulder, Maria De Santis, Maike de Wit, Ronald de Wit, Hans Günter Derigs, Klaus-Peter Dieckmann, Annette Dieing, Jean-Pierre Droz, Martin Fenner, Karim Fizazi, Aude Flechon, Sophie D Fosså, Xavier Garcia del Muro, Thomas Gauler, Lajos Geczi, Arthur Gerl, Jose Ramon Germa-Lluch, Silke Gillessen, Jörg T Hartmann, Michael Hartmann, Axel Heidenreich, Wolfgang Hoeltl, Alan Horwich, Robert Huddart, Michael Jewett, Johnathan Joffe, William G Jones, László Kisbenedek, Olbjørn Klepp, Sabine Kliesch, Kai Uwe Koehrmann, Christian Kollmannsberger, Markus Kuczyk, Pilar Laguna, Oscar Leiva Galvis, Volker Loy, Malcolm D Mason, Graham M Mead, Rolf Mueller, Craig Nichols, Nicola Nicolai, Tim Oliver, Dalibor Ondrus, Gosse O N Oosterhof, Luis Paz-Ares, Giorgio Pizzocaro, Jörg Pont, Tobias Pottek, Tom Powles, Oliver Rick, Giovanni Rosti, Roberto Salvioni, Jutta Scheiderbauer, Hans-Ulrich Schmelz, Heinz Schmidberger, Hans-Joachim Schmoll, Mark Schrader, Felix Sedlmayer, Niels E Skakkebaek, Aslam Sohaib, Sergei Tjulandin, Padraig Warde, Stefan Weinknecht, Lothar Weissbach, Christian Wittekind, Eva Winter, Lori Wood, Hans von der Maase
雑誌名: Eur Urol. 2008 Mar;53(3):497-513. doi: 10.1016/j.eururo.2007.12.025. Epub 2007 Dec 26.
Abstract/Text OBJECTIVES: The first consensus report that had been presented by the European Germ Cell Cancer Consensus Group (EGCCCG) in 2004 has found widespread approval by many colleagues throughout the world. In November 2006, the group met a second time under the auspices of the Department of Urology of the Amsterdam Medical Center, The Netherlands.
METHODS: Medical oncologists, urologic surgeons, radiation oncologists as well as pathologists from several European countries reviewed and discussed the data that had emerged since the 2002 conference and incorporated the new data into updated and revised guidelines. As for the first meeting the methodology of evidence-based medicine (EBM) was applied. The results of the discussion were compiled by the writing committee. All participants have agreed to this final update.
RESULTS: The second part of the consensus paper includes the treatment of metastasised disease, residual tumour resection, salvage therapy, follow-up, and late toxicities.
CONCLUSIONS: Whereas the vast majority of the recommendations made in 2004 remain valid 3 yr later, refinements in the treatment of early-stage as well as of advanced-stage testicular cancer have emerged from clinical trials. Despite technical improvements, expert clinical skills will continue to be one of the major determinants for the prognosis of patients with germ cell cancer. In addition, the particular needs of testicular cancer survivors have been acknowledged.

PMID 18191015  Eur Urol. 2008 Mar;53(3):497-513. doi: 10.1016/j.eururo・・・
著者: C J Logothetis, M L Samuels, D E Selig, D E Johnson, D A Swanson, A C von Eschenbach
雑誌名: J Urol. 1985 Dec;134(6):1127-30.
Abstract/Text In 28 patients with primary clinical stage II testicular carcinoma (retroperitoneal mass of less than 10 cm. in diameter) or persistently elevated levels of serum biomarkers after orchiectomy primary chemotherapy was administered followed by selective lymphadenectomy for patients with a persistent retroperitoneal mass. Of the patients 21 were treated with cyclophosphamide, doxorubicin, cisplatin/vinblastine and bleomycin, and 7 who were not candidates for this regimen received less aggressive chemotherapy. All 28 patients were free of disease after a mean followup of 93.6 weeks and a median of 89 weeks (range 28 to 199.5 weeks). No patient who achieved complete remission has had relapse. Of the 28 patients 1 had a seminoma and an elevated alpha-fetoprotein level, 15 had embryonal carcinoma (Dixon-Moore category II) and 12 had teratocarcinomas (Dixon-Moore category IV). Only 1 of the 15 patients with embryonal carcinoma required surgical exploration for a persistent radiographic abnormality, whereas 6 of the 12 patients with Dixon-Moore category IV tumors required surgical exploration (p less than 0.0147). This delayed approach did not increase surgical complications. Our experience with primary chemotherapy followed by selective lymphadenectomy for stage II testicular carcinoma resulted in universal survival. Only 8 of the 28 patients (29 per cent) required lymphadenectomy.

PMID 2414470  J Urol. 1985 Dec;134(6):1127-30.
著者: C Massard, A Plantade, M Gross-Goupil, Y Loriot, B Besse, B Raynard, F Blot, S Antoun, G Nitenberg, B Escudier, K Fizazi
雑誌名: Ann Oncol. 2010 Aug;21(8):1585-8. doi: 10.1093/annonc/mdq021. Epub 2010 Feb 24.
Abstract/Text BACKGROUND: Patients with extensive lung metastases from nonseminomatous germ-cell tumours (NSGCTs) and dyspnoea at presentation are at high risk of acute respiratory distress syndrome (ARDS) and death within the first weeks after chemotherapy induction. This syndrome is linked to acute intra-alveolar haemorrhage related to early tumour necrosis, which in turn, can be complicated by pulmonary infection promoted by neutropenia. The management of these patients was modified at Institut Gustave Roussy in 1997 to try to avoid this complication.
PATIENTS AND METHODS: Data concerning all patients with lung metastases from NSGCT and dyspnoea or a partial pressure of oxygen (pO(2)) <80 mmHg treated from 1980 to 2006 in our institution were collected. Patients were treated in a specialised intensive care unit. From 1980 to 1997, the first chemotherapy cycle consisted in a full-dose regimen. After 1997, a 3-day reduced induction regimen of EP (cisplatin 20 mg/m(2)/day and etoposide 100 mg/m(2)/day) was used, with bleomycin and two additional days of EP being postponed to day 15, with the regular BEP regimen being started at day 21.
RESULTS: Twenty-five patients with poor-risk disseminated NSGCT according to the International Germ Cell Consensus Classification Group had extensive lung metastases plus dyspnoea at presentation (n = 6), a pO(2) <80 mmHg (n = 2), or both criteria (n = 17). Median human chorionic gonadotrophin was 200 000 UI (range 11-8 920 000), and 18 of 25 (72%) patients also had nonpulmonary visceral metastases. During the 1980-1997 period, 13 of 15 patients (87%) developed ARDS, 10 of whom died, and only 4 of 15 (27%) patients were long-term survivors. In contrast, during the 1997-2006 period, only 3 of 10 patients (30%) developed ARDS (P = 0.01), 2 of whom died, and 4 of 10 (40%) eventually survived.
CONCLUSION: Initial reduction of chemotherapy doses during the first cycle of chemotherapy for poor prognosis NSGCT with extensive lung metastases seems to prevent the risk of early death due to ARDS.

PMID 20181575  Ann Oncol. 2010 Aug;21(8):1585-8. doi: 10.1093/annonc/m・・・
著者: K D Miller, P J Loehrer, R Gonin, L H Einhorn
雑誌名: J Clin Oncol. 1997 Apr;15(4):1427-31.
Abstract/Text PURPOSE: Salvage therapy for disseminated germ cell tumors of all histologic subtypes with vinblastine, ifosfamide, and cisplatin (VeIP) will cure approximately 25% of patients. The purpose of this study was to evaluate the activity of VeIP in patients with recurrent seminoma.
PATIENTS AND METHODS: We conducted a retrospective review of 24 patients with recurrent seminoma who were treated at Indiana University with VeIP as second-line chemotherapy. All patients had received cisplatin-containing regimens as primary chemotherapy and seven had also received prior pelvic radiotherapy. All patients received four courses of VeIP.
RESULTS: The minimum follow-up duration was 2 years (range, 2 to 9.1), with a median follow-up time of 7 years. Twenty of 24 patients (83%) achieved a complete remission (CR) following VeIP alone. One additional patient was rendered disease-free (NED) with the resection of residual carcinoma. Eight patients have relapsed. Four of six patients with extragonadal primary tumors and two of four who failed to achieve CR with initial chemotherapy are continuously NED with VeIP. Overall, 13 of 24 (54%) are long-term survivors with VeIP salvage chemotherapy.
CONCLUSION: VeIP has significant curative potential in patients with recurrent seminoma and appears to produce a higher CR rate and more long-term survivors than is achieved in patients with nonseminomatous disease.

PMID 9193335  J Clin Oncol. 1997 Apr;15(4):1427-31.
著者: S D Fosså, S P Stenning, A Gerl, A Horwich, P I Clark, P M Wilkinson, W G Jones, M V Williams, R T Oliver, E S Newlands, G M Mead, M H Cullen, S B Kaye, G J Rustin, P A Cook
雑誌名: Br J Cancer. 1999 Jul;80(9):1392-9. doi: 10.1038/sj.bjc.6690534.
Abstract/Text The aim of this study was to define prognostic parameters for survival in patients with malignant germ cell tumours progressing after platinum-based induction chemotherapy with or without surgery. A total of 164 progressing patients (testicular: 83%, extragonadal: 17%) were identified out of 795 patients treated with platinum-based induction chemotherapy for metastatic germ cell malignancy with or without surgery. 'Progressive disease' included patients who had progressed after a previous partial or complete remission as well as patients who failed primary therapy. Salvage chemotherapy consisted of 'conventional' platinum-based chemotherapy. Prognostic factors for survival were assessed by uni- and multivariate analyses. The resulting prognostic model was validated in an independent data set of 66 similar patients. For all 164 patients the median time from start of induction chemotherapy to progression was 10 months (range: 0-99). Thirty-eight (23%) patients relapsed after 2 years. The 5-year survival rate for all progressing patients was 30% (95% confidence interval 23-38%). In the univariate analysis the following factors most importantly predicted a poor prognosis: progression-free interval < 2 years: initial poor prognosis category (MRC criteria), < CR to induction chemotherapy, initial treatment early in the 1980s and treatment given at a 'small' centre. Three prognostic factors remained in the multivariate analysis: progression-free interval, response to induction treatment and the level of serum human chronic gonadotrophin (hCG) and alpha fetoprotein (AFP) at relapse. One hundred and twenty-four patients could be classified on the basis of these characteristics, Those patients with progression-free interval < 2 years, < CR to induction chemotherapy and high markers at relapse (AFP >100 kU l(-1) or hCG >100 IU l(-1)) formed a poor prognosis group of 30 patients, none of whom survived after 3 years. Patients with at most two of these three risk factors formed a good prognosis group of 94 patients (76%) with a 47% (37-56%) 5-year survival. Thirty-eight patients from the good prognosis group with a progression-free interval of >2 years had a 2-year survival of 74% (60-88%) and 5-year survival of 61%. These prognostic groups were validated in the independent data set, in which 5-year survival rates in the good and poor risk groups were 51% and 0% respectively. One-third of patients progressing during or after platinum-based induction chemotherapy for metastatic germ cell malignancy may be cured by repeated 'conventional' platinum-based chemotherapy. Good prognosis parameters are: progression-free interval of > 2 years, CR to induction treatment and normal or low serum markers at relapse (hCG < 100 IU l(-1) and AFP < 100 kU l(-1)). The results of high-dose salvage chemotherapy should be interpreted on the background of these prognostic factors.

PMID 10424741  Br J Cancer. 1999 Jul;80(9):1392-9. doi: 10.1038/sj.bjc・・・
著者: H J Schmoll, J Beyer
雑誌名: Semin Oncol. 1998 Apr;25(2):174-85.
Abstract/Text Metastatic germ cell cancer is a very heterogeneous group with respect to prognosis under cisplatinum-based chemotherapy. The main determinants of complete response and survival are not only the extension of the metastases but much more the biology of the underlying tumor which is represented by the location of the metastases (pulmonary versus nonpulmonary visceral metastases (liver, bone, central nervous system) and the level of the marker elevation (AFG, HCG, LDH). Using these parameters patients with seminoma can be in two or three prognostic divided groups, depending on the model used; nonseminomatous germ cell cancer can be divided in three prognostic groups (good, intermediate and poor prognosis) with a 5 year survival of 90%, 70%, and 50%, respectively. The rate of marker decline and AFP- "surge" are not proven to be significant indicators of prognosis after the start of chemotherapy. Also, molecular markers i12p, p53, Rb, DNA-repair-capacity, etc, currently do not contribute to the prognostic models. In conclusion, with the present available prognostic models the patients with seminomatous as well as nonseminomatous cancer can be attributed to different prognostic groups for first-line as well as salvage treatment. This allows to the selection of patients for a risk adapted treatment and for the investigation of less toxic regimen for good prognosis patients and more aggressive protocols for intermediate and in particular poor risk patients.

PMID 9562450  Semin Oncol. 1998 Apr;25(2):174-85.
著者: Anja Lorch, Oliver Rick, Thomas Wündisch, Jörg-Thomas Hartmann, Carsten Bokemeyer, Jörg Beyer
雑誌名: J Urol. 2010 Jul;184(1):168-73. doi: 10.1016/j.juro.2010.03.017. Epub 2010 May 16.
Abstract/Text PURPOSE: We assessed the activity of high dose chemotherapy in patients with unresectable late relapse germ cell tumors.
MATERIALS AND METHODS: A total of 35 patients with late relapse were included in a group of 216 treated with high dose chemotherapy as first or subsequent salvage treatment in a prospective, randomized, multicenter phase III trial comparing single vs sequential high dose chemotherapy. Late relapse was defined as unequivocal evidence of relapse more than 2 years after completion of cisplatin based chemotherapy. All patients were considered to have unresectable, progressive, late relapse germ cell tumors. Responders were scheduled for surgical resection of all residual lesions when technically feasible.
RESULTS: We identified 4 late relapse groups, including late relapse in 20 of 35 patients (57%) after first line treatment (group 1), in 4 (11%) after first salvage treatment (group 2), in 4 (11%) after initial and after first salvage treatment (group 3), and in 7 (20%) after first line treatment and salvage treatment with rapid progression thereafter who were randomized to a high dose chemotherapy trial (group 4). Median time to late relapse was 4.7 years (range 2.1 to 18.3) in all groups. Resection of all residual lesions could be done in 15 of 35 patients (43%). At a median followup of 5.6 years (range 1.9 to 8.5) 5 of 35 patients (14%) had no progression, resulting in 15% projected progression-free survival.
CONCLUSIONS: Management for unresectable late relapse germ cell tumors remains controversial. High dose chemotherapy followed by resection of all residual lesions can result in long-term remission in individuals.

Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
PMID 20483152  J Urol. 2010 Jul;184(1):168-73. doi: 10.1016/j.juro.201・・・
著者: R J Motzer, J Sheinfeld, M Mazumdar, M Bains, T Mariani, J Bacik, D Bajorin, G J Bosl
雑誌名: J Clin Oncol. 2000 Jun;18(12):2413-8.
Abstract/Text PURPOSE: To evaluate the dose, toxicity, and efficacy of paclitaxel in combination with ifosfamide and cisplatin as salvage therapy for patients with relapsed testicular germ cell tumors (GCTs).
PATIENTS AND METHODS: Thirty patients with previously treated GCTs were treated with paclitaxel and ifosfamide plus cisplatin (TIP) as second-line therapy. All had favorable prognostic features for response (testis primary tumor site and prior complete response to first-line chemotherapy program). Four cycles of paclitaxel, ifosfamide 5 g/m(2), and cisplatin 100 mg/m(2) were given 21 days apart with granulocyte colony-stimulating factor support, followed by resection of radiographic residua. The dose of paclitaxel was increased among cohorts with dose levels of 175, 215, and 250 mg/m(2); the largest dose was selected for the phase II part of the trial.
RESULTS: Twenty-three (77%) of 30 patients achieved a complete response to chemotherapy alone, and one patient achieved a durable partial response with normal tumor markers. Therefore, 24 (80%) achieved a favorable response. Eleven patients with normalized markers after chemotherapy underwent resection of residual tissue, with only necrosis found in 10 and mature teratoma in one. Two patients relapsed, and 22 (73%) of the favorable responses remain durable at a median follow-up duration of 33 months. Myelosuppression was the major toxicity, and two patients had grade 3 neurotoxicity.
CONCLUSION: Four cycles of TIP was associated with a high proportion of patients who achieved a complete response, a lack of relapse, and relative tolerability as an ifosfamide-containing salvage regimen for testicular GCTs. The high durable complete response proportion emphasizes the importance of patient selection according to prognostic factors for a favorable outcome to conventional-dose salvage therapy.

PMID 10856101  J Clin Oncol. 2000 Jun;18(12):2413-8.
著者: L H Einhorn, S D Williams, P J Loehrer, R Birch, R Drasga, G Omura, F A Greco
雑誌名: J Clin Oncol. 1989 Mar;7(3):387-91.
Abstract/Text Four courses of PVP16B (cisplatin plus etoposide [VP-16] plus bleomycin) has been standard chemotherapy for disseminated germ cell tumors at Indiana University and the Southeastern Cancer Study Group (SECSG) since 1984. We began a random prospective phase III study in patients with favorable-prognosis (minimal and moderate extent) disseminated germ cell tumors comparing four courses of PVP16B over 12 weeks to the identical dose PVP16B administered in three courses over 9 weeks. The categories of minimal and moderate disease constitute approximately two thirds of all disseminated germ cell tumors that require chemotherapy. One hundred eighty-four patients entered this trial, and all patients have a minimal follow-up of 1 year. Overall, 106 of 107 (99%) minimal extent and 73 of 77 moderate patients (95%) achieved an initial disease-free status (NED), confirming the favorable prognostic categories. Eighty-six of 88 patients (98%) randomized to three courses and 93 of 96 randomized to four courses (97%) of PVP16B achieved disease-free status. There have been ten relapses (5%), with five on each arm. Currently, 81 of 88 (92%) and 88 of 96 (92%) patients randomized to three v four courses of PVP16B are continuously disease-free. This study confirms the high cure rate with PVP16B in favorable-prognosis germ cell tumors. The deletion of the fourth course of PVP16B significantly reduces the toxicity, cost, and inconvenience of this curative regimen. We conclude that three courses of PVP16B is the preferred regimen for favorable-prognosis germ cell tumors.

PMID 2465391  J Clin Oncol. 1989 Mar;7(3):387-91.
著者: A B Simpson, J Paul, J Graham, S B Kaye
雑誌名: Br J Cancer. 1998 Oct;78(8):1061-6.
Abstract/Text We conducted a retrospective review of fatal bleomycin pulmonary toxicity in patients treated for germ cell tumours during 1991-95 at the Beatson Oncology Centre, Glasgow. Case notes of patients treated with bleomycin were reviewed with respect to cumulative bleomycin dose, renal impairment, exposure to supplemental oxygen, thoracic radiotherapy and age. A total of 194 patients underwent chemotherapy, of whom 180 received bleomycin-containing regimens. Five fatal cases of pulmonary toxicity were identified, an incidence of 2.8%. These cases were older than the remaining patients (P < 0.001), with a median age at diagnosis of 55 vs 33 years. The incidence of fatal pulmonary toxicity increased with each decade of life above age 30. Renal function also differed between the two groups, with the worst glomerular filtration rate recorded at the time of bleomycin administration for each patient, lower in the fatal group, median 69 vs 107 ml min(-1) (P < 0.001). There was no difference with respect to cumulative bleomycin dose or exposure to supplemental oxygen. For patients aged over 40 years, especially those with renal function in the lower range of normal, the risk of developing fatal toxicity may exceed 10%. The benefits of bleomycin could be questioned for this age group.

PMID 9792151  Br J Cancer. 1998 Oct;78(8):1061-6.
著者: Lawrence H Einhorn, Richard S Foster
雑誌名: J Clin Oncol. 2006 Jun 1;24(16):2597-8; author reply 2598-9. doi: 10.1200/JCO.2006.05.6184.
Abstract/Text
PMID 16735718  J Clin Oncol. 2006 Jun 1;24(16):2597-8; author reply 25・・・
著者: Hans-Joachim Schmoll, Susanne Osanto, Koji Kawai, Lawrence Einhorn, Karim Fizazi
雑誌名: Urology. 2011 Oct;78(4 Suppl):S456-68. doi: 10.1016/j.urology.2011.08.001.
Abstract/Text The use of cisplatin-based combination chemotherapy has led to a dramatic improvement in the cure rate of patients with metastatic germ cell tumors (GCTs). With high complete response (CR) rates achieved in approximately 80% of patients with advanced testicular cancer after standard first-line cisplatin-based chemotherapy. Thereafter, the goals of various trials were to reduce the chemotherapy toxicity by limiting the number of chemotherapy cycles, the duration of therapy, and reducing the doses of, or even omitting, individual cytotoxic drugs, while maintaining efficacy, or to investigate the potential role of carboplatin as single agent or combined with etoposide and bleomycin for advanced seminoma. From prospective randomized trials and available data from additional sources, a European standard has been defined in several consensus conferences,(1-3) with the most recent consensus conference published by the European Society for Medical Oncology Consensus Group.(4,5) These international guidelines were developed from the previous published guidelines and data from available current trials. The principles of evidence-based medicine were scored (score 1-4) using a modified version of the Oxford levels of evidence and are listed in the present report in brackets. Draft guidelines were presented at an International Consensus in Urological Disease (ICUD) meeting (Shanghai, November 2009). The writing committee compiled the results of the discussion. All participants agreed to this final update.

Copyright © 2011 Elsevier Inc. All rights reserved.
PMID 21986225  Urology. 2011 Oct;78(4 Suppl):S456-68. doi: 10.1016/j.u・・・
著者: S Culine, P Kerbrat, A Kramar, C Théodore, C Chevreau, L Geoffrois, N B Bui, J Pény, A Caty, R Delva, P Biron, K Fizazi, J Bouzy, J P Droz, Genito-Urinary Group of the French Federation of Cancer Center (GETUG T93BP)
雑誌名: Ann Oncol. 2007 May;18(5):917-24. doi: 10.1093/annonc/mdm062. Epub 2007 Mar 9.
Abstract/Text BACKGROUND: High cure rates are expected in good-risk metastatic nonseminomatous germ-cell tumor (NSGCT) patients with bleomycin, etoposide and cisplatin.
PATIENTS AND METHODS: Patients received either three cycles of BE500P or four cycles of E500P every 3 weeks. Disease was defined according to the Institut Gustave Roussy prognostic model. Patients were retrospectively assigned into the International Germ Cell Cancer Collaborative Group (IGCCCG) classification. A sample size of 250 patients was necessary for an expected favorable response rate (primary end point) of 90% and not more than a 10% difference between the two arms.
RESULTS: Among 257 assessable patients, 124 and 122 patients achieved a favorable response in the 3BE500P and 4E500P arms, respectively (P = 0.34). Median follow-up was 53 months. The 4-year event-free survival rates were 91% and 86%, respectively (P = 0.135). The 4-year overall survival rates were not significantly different [five deaths versus 12 deaths, respectively (P = 0.096)]. Similar nonsignificant trends were observed in good IGCCCG prognosis patients.
CONCLUSIONS: Both regimens produced similar results in terms of favorable response rates. As the trial was underpowered for survival analyses, conclusive data would require a larger randomized trial. Unless such a study is done, 3BE500P is the treatment of choice for metastatic NSGCT patients.

PMID 17351252  Ann Oncol. 2007 May;18(5):917-24. doi: 10.1093/annonc/m・・・
著者: C R Nichols, P J Catalano, E D Crawford, N J Vogelzang, L H Einhorn, P J Loehrer
雑誌名: J Clin Oncol. 1998 Apr;16(4):1287-93.
Abstract/Text PURPOSE: To compare standard therapy with bleomycin, etoposide, and cisplatin (BEP) to experimental therapy with etoposide, ifosfamide, and cisplatin (VIP) as primary treatment of men with advanced, disseminated germ cell tumors.
PATIENTS AND METHODS: A total of 304 men with advanced disseminated germ cell tumors were randomly allocated to receive four courses of BEP or VIP. Two hundred ninety-nine patients were assessable for toxicity and 286 were assessable for response. Complete response rates, favorable response (complete remission, surgical free of disease, continuous partial remission for 2+ years), time to treatment failure, and overall survival were assessed.
RESULTS: Overall complete remission rate (VIP, 37%; BEP, 31%), favorable response rate (VIP, 63%; BEP, 60%), failure-free at 2 years (VIP, 64%; BEP, 60%), and 2-year overall survival (VIP, 74%; BEP, 71%) were not significantly different between the two treatments. Grade 3 or worse toxicity, particularly hematologic and genitourinary toxicity, was significantly more common in patients who received VIP.
CONCLUSION: BEP and VIP produce comparable favorable response rate and survival in patients with poor-risk germ cell tumors. The substitution of ifosfamide for bleomycin, however, was associated with significantly greater toxicity. Four courses of BEP remain the standard treatment for advanced disseminated germ cell tumors.

PMID 9552027  J Clin Oncol. 1998 Apr;16(4):1287-93.
著者: T Powles, D Robinson, J Shamash, H Moller, N Tranter, T Oliver
雑誌名: Ann Oncol. 2008 Mar;19(3):443-7. doi: 10.1093/annonc/mdm540. Epub 2007 Nov 28.
Abstract/Text BACKGROUND: The use of adjuvant carboplatin in the management of stage I seminoma of the testis has been limited by the lack of long-term data. In this study, we address this issue for the first time.
PATIENTS AND METHODS: Data on 199 patients treated with single-agent carboplatin for stage I seminoma of the testis were prospectively collected. Overall mortality, deaths from circulatory disease and the incidence of second cancers were compared with expected values derived from the UK general population.
RESULTS: The median follow-up for the cohort was 9.0 years (range 0.1-20.1). There has been no excess in overall mortality [standardised mortality ratio (SMR) 0.89; 95% CI 0.36-1.83], death from circulatory diseases (SMR 1.44; 95% CI 0.39-3.69) or the incidence of second nontestis cancers (standardised incidence ratio 0.96; 95% CI 0.26-2.45) in this group of patients. These findings also applied to specific follow-up periods of >5 or 10 years. Specifically, neither haematological nor solid nontestis tumours occurred in excess. There was an increase in the long-term development of contralateral testis cancers.
CONCLUSIONS: This study addresses some of the concerns surrounding the long-term safety of single-agent carboplatin. It also helps in planning long-term follow-up for patients receiving this form of treatment.

PMID 18048383  Ann Oncol. 2008 Mar;19(3):443-7. doi: 10.1093/annonc/md・・・

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