今日の臨床サポート

腎盂・尿管腫瘍

著者: 横溝晃 医療法人 原三信病院 泌尿器科

監修: 中川昌之 公益財団法人 慈愛会 今村総合病院 泌尿器科顧問

著者校正/監修レビュー済:2021/09/29
患者向け説明資料
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:
横溝晃 : 特に申告事項無し[2021年]
監修:中川昌之 : 研究費・助成金など(武田薬品工業株式会社)[2021年]

改訂のポイント:
  1. 定期レビューを行い、化学療法や新しいガイドラインについて加筆した。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 腎盂・尿管腫瘍は、腎盂尿管という上部尿路に生じる腫瘍の総称で、その多くは癌である。
  1. 腎盂尿管癌は腎盂、尿管の尿路上皮由来の悪性腫瘍で、以前は組織型として「移行上皮癌」と称されていたが、現在は腎盂尿管癌と膀胱癌を併せて「尿路上皮癌」と呼ばれる。
  1. 尿路上皮癌のなかで、多くは膀胱癌であり、腎盂尿管癌はその5~10%を占める。
  1. 欧米諸国での年間新患発生率は10万人当たり1~2人と推定されるが、日本の患者数は、正確な集計が行われていないため不明である。
  1. 男女比は3対1で、膀胱癌と同じ男女比である。
  1. 膀胱癌は診断時に浸潤癌である率は15%であるのに対し、腎盂尿管癌は60%と高い[1]
  1. 腎盂尿管癌患者の約10%に同時に膀胱癌が存在し、過去もしくは将来の膀胱内再発は30~51%に生じる[2]
  1. 膀胱癌と同じように喫煙が最も重要なリスク因子であり、芳香族アミンなど有機溶媒曝露もリスク因子である。
 
下部尿管癌の摘出標本写真

尿管下端に乳頭状広基性腫瘍が認められた。

出典

img1:  著者提供
 
 
 
腎盂癌

腎盂に充満し、腎実質に浸潤する腎盂癌の摘出標本の写真。

出典

img1:  著者提供
 
 
 
  1. 左尿管癌の症例
  1. 主訴:無症候性肉眼的血尿
  1. 病歴:67歳、女性。受診の1年6カ月前より、ときどき無症候性肉眼的血尿が出現することに気づいたが、その後、血尿は消失したため、受診せず放置。1カ月前に、健診のエコーにて、左水腎症を指摘され、当科紹介初診。背部痛など、症状はなし。喫煙:20本/日を20歳から53歳まで。
  1. 診断のためのテストとその結果:検尿では尿潜血2+、沈渣RBC50/H、WBC4/H。尿細胞診class V。エコーで左水腎水尿管症、左萎縮腎を認める。膀胱鏡では膀胱内に異常なし。血清Cr値1.2mg/mL(eGFR 48mL/min)。CTにて、左中部尿管に造影効果のある腫瘤を認め、一部周囲に浸潤を疑う所見あり。腫大リンパ節なし、胸部CT、骨シンチでは異常なく、左尿管癌T3N0M0、stageⅢの診断となった。
  1. 治療:尿管周囲浸潤も疑われたため、開腹による左腎尿管全摘除術、同時に腎門部から、大動脈分岐部までリンパ節郭清術を施行した。
  1. 転帰:病理診断は尿路上皮癌、high grade、G2、pT3、pN0。術後血清Cr値1.5mg/mL(eGFR 34mL/min)。腎機能障害はあるが、術後補助化学療法の有用性が最近明らかになり、カルボプラチンとゲムシタビンによるアジュバント化学療法を予定している。
 
左尿管癌のCT所見

a:腎内部リンパ節腫大を認める。
b:左水腎症と左腎萎縮を認める。

出典

img1:  著者提供
 
 
 
  1. 左腎盂癌の症例
  1. 主訴:無症候性肉眼的血尿
  1. 病歴:2010年9月より、無症候性肉眼的血尿出現。近医総合病院受診。CTにて、左腎盂癌の診断にて当科紹介初診。
  1. 治療:後腹膜鏡下左腎尿管全摘除術を施行。
  1. 転帰:術後1年で再発転移なし。
 
左腎盂癌患者の造影(早期)CT

造影早期で、左腎盂に造影効果のある腫瘤陰影を認める。

出典

img1:  著者提供
 
 
 
CT(造影排泄相)

造影排泄層で、左腎盂に陰影欠損を認める。

出典

img1:  著者提供
 
 
 
CT Urography

左腎盂に陰影欠損を認める。

出典

img1:  著者提供
 
 
 
CT 排泄相の冠状断画像

左腎盂に陰影欠損を認める。

出典

img1:  著者提供
 
 
問診・診察のポイント  
  1. 最も多い症状は、無症候性肉眼的血尿である。

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文献 

著者: M C Hall, S Womack, A I Sagalowsky, T Carmody, M D Erickstad, C G Roehrborn
雑誌名: Urology. 1998 Oct;52(4):594-601.
Abstract/Text OBJECTIVES: To review a large single-center experience of patients treated for upper tract transitional cell carcinoma (TCC) with extended follow-up in order to identify patterns of recurrence, assess patient outcomes, and determine the impact of traditional prognostic factors.
METHODS: We reviewed 252 patients treated surgically for upper tract TCC with a median follow-up of 64 months. Most patients (77%) underwent nephroureterectomy, whereas 17% were treated with a parenchymal sparing approach. Traditional prognostic factors including age, sex, tumor stage, grade, location, and type of surgical treatment were analyzed with respect to disease recurrence and survival.
RESULTS: Disease relapse occurred in 67 patients (27%) at a median time of 12.0 months. Recurrences were local in the retroperitoneum (9%), the bladder (51%), remaining upper tract (18%), or distant in the lung, bone, or liver (22%). The 6 patients with local relapse were among the 73 patients with pT3 or pT4 tumors, and all died of TCC at a median time from diagnosis of 37 months. Significant prognostic factors for recurrence by univariate analysis were tumor grade (P = 0.0014) and stage (P = 0.0001). On multivariate analysis, only tumor stage (P = 0.017) and treatment modality (P = 0.020) were predictors of recurrence. Actuarial 5-year disease-specific survival rates by primary tumor stage were 100% for Ta/cis, 91.7% for T1, 72.6% for T2, and 40.5% for T3. Patients with primary Stage T4 tumors had a median survival of 6 months. Although tumor stage and grade correlated with disease-specific survival on univariate analysis, only patient age (P = 0.042) and stage (P = 0.0001) were significant on multivariate analysis with the type of surgical procedure performed approaching significance (P = 0.0504).
CONCLUSIONS: Primary tumor stage and surgical procedure performed (radical versus parenchymal sparing) are important predictors of disease recurrence. Patient age and tumor stage were the only predictors of disease-specific survival on multivariate analysis with the type of surgical procedure approaching significance. Radical nephroureterectomy achieves excellent local control even in the setting of locally advanced (pT3 or T4) disease. The major clinical feature in this setting is distant failure, and the development of effective systemic therapy is needed to improve the outcome in these patients.

PMID 9763077  Urology. 1998 Oct;52(4):594-601.
著者: Jay D Raman, Casey K Ng, Douglas S Scherr, Vitaly Margulis, Yair Lotan, Karim Bensalah, Jean-Jacques Patard, Eiji Kikuchi, Francesco Montorsi, Richard Zigeuner, Alon Weizer, Christian Bolenz, Theresa M Koppie, Hendrik Isbarn, Claudio Jeldres, Wareef Kabbani, Mesut Remzi, Mathias Waldert, Christopher G Wood, Marco Roscigno, Mototsuga Oya, Cord Langner, J Stuart Wolf, Philipp Ströbel, Mario Fernández, Pierre Karakiewcz, Shahrokh F Shariat
雑誌名: Eur Urol. 2010 Jun;57(6):1072-9. doi: 10.1016/j.eururo.2009.07.002. Epub 2009 Jul 15.
Abstract/Text BACKGROUND: There is a lack of consensus regarding the prognostic significance of ureteral versus renal pelvic upper tract urothelial carcinoma (UTUC).
OBJECTIVE: To investigate the association of tumor location on outcomes for UTUC in an international cohort of patients managed by radical nephroureterectomy (RNU).
DESIGN, SETTING, AND PARTICIPANTS: A retrospective review of institutional databases from 10 institutions worldwide identified patients with UTUC.
INTERVENTION: The 1249 patients in the study underwent RNU with ipsilateral bladder cuff resection between 1987 and 2007.
MEASUREMENTS: Data accrued included age, gender, race, surgical approach (open vs laparoscopic), tumor pathology (stage, grade, lymph node status), tumor location, use of perioperative chemotherapy, prior endoscopic therapy, urothelial carcinoma recurrence, and mortality from urothelial carcinoma. Tumor location was divided into two groups (renal pelvis and ureter) based on the location of the dominant tumor.
RESULTS AND LIMITATIONS: The 5-yr recurrence-free and cancer-specific survival estimates for this cohort were 75% and 78%, respectively. On multivariate analysis, only pathologic tumor (pT) classification (p<0.001), grade (p<0.02), and lymph node status (p<0.001) were associated with disease recurrence and cancer-specific survival. When adjusting for these variables, there was no difference in the probability of disease recurrence (hazard ratio [HR]: 1.22; p=0.133) or cancer death (HR: 1.23; p=0.25) between ureteral and renal pelvic tumors. Adding tumor location to a base prognostic model for disease recurrence and cancer death that included pT stage, tumor grade, and lymph node status only improved the predictive accuracy of this model by 0.1%. This study is limited by biases associated with its retrospective design.
CONCLUSIONS: There is no difference in outcomes between patients with renal pelvic tumors and with ureteral tumors following nephroureterectomy. These data support the current TNM staging system, whereby renal pelvic and ureteral carcinomas are classified as one integral group of tumors.

Copyright © 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.
PMID 19619934  Eur Urol. 2010 Jun;57(6):1072-9. doi: 10.1016/j.eururo.・・・
著者: Soichiro Yoshida, Hitoshi Masuda, Chikako Ishii, Hiroshi Tanaka, Yasuhisa Fujii, Satoru Kawakami, Kazunori Kihara
雑誌名: AJR Am J Roentgenol. 2011 Jan;196(1):110-6. doi: 10.2214/AJR.10.4632.
Abstract/Text OBJECTIVE: The purpose of this study was to prospectively evaluate the diagnostic ability of diffusion-weighted MRI (DWI) for detecting upper urinary tract cancer.
SUBJECTS AND METHODS: Seventy-six patients (36 women, 40 men; median age, 70 years) suspected of having upper urinary tract cancer underwent T1- and T2-weighted imaging and DWI (b values, 0 and 800 s/mm(2)) with or without T1-weighted dynamic contrast-enhanced MRI (DCE-MRI). Two radiologists independently interpreted the images.
RESULTS: Of the 76 patients suspected of having upper urinary tract cancer, 49 were diagnosed with upper urinary tract cancer and the remaining 27 were diagnosed as not having upper urinary tract cancer. The sensitivity, specificity, and accuracy of DWI interpretation for each reviewer was 92%, 96%, and 93% and 94%, 81%, and 89%, respectively. The sensitivity and accuracy of DWI were significantly higher than those of T1- and T2-weighted imaging (p < 0.01 and p = 0.03 for reviewer 1 and p < 0.01 for both values for reviewer 2), although the specificity did not change. The diagnostic abilities of DWI and DCE-MRI were not significantly different. The interobserver agreement of DWI between the two reviewers was excellent (κ score = 0.801). The apparent diffusion coefficient values of upper urinary tract cancer with grade 3 were significantly lower than those of upper urinary tract cancer with grades 2 and 1 (p < 0.028).
CONCLUSION: DWI provides accurate information for the diagnosis of upper urinary tract cancer in a noninvasive manner. The additional use of DWI to T1- and T2-weighted imaging increases the sensitivity of MRI in identifying upper urinary tract cancer with excellent interobserver agreement. Furthermore, DWI could be a useful adjunct to preoperative assessment of histologic grade.

PMID 21178054  AJR Am J Roentgenol. 2011 Jan;196(1):110-6. doi: 10.221・・・
著者: Seyed Amirhossein Razavi, Gelareh Sadigh, Aine M Kelly, Paul Cronin
雑誌名: Acad Radiol. 2012 Sep;19(9):1134-40. doi: 10.1016/j.acra.2012.05.004. Epub 2012 Jun 19.
Abstract/Text RATIONALE AND OBJECTIVES: The purpose of this study was to critically appraise and compare the diagnostic performance of imaging modalities that are used for the diagnosis of upper and lower/bladder urinary tract cancer, transitional cell carcinoma (TCC).
METHODS: A focused clinical question was constructed and the literature was searched using the patient, intervention, comparison, outcome (PICO) method comparing computed tomography (CT) urography, magnetic resonance (MR) urography, excretory urography, and retrograde urography in the detection of TCC of the upper urinary tract. The same methods were used to compare CT cystography, MR cystography, and ultrasonography in the diagnosis of bladder cancer. Retrieved articles were appraised and assigned a level of evidence based on the Oxford University Centre for Evidence-Based Medicine hierarchy of validity for diagnostic studies.
RESULTS: The retrieved sensitivity/specificity for the detection of TCC of upper urinary tract for CT urography, MR urography, excretory urography, and retrograde urography were 96%/99%, 69%/97%, 80%/81%, and 96%/96%, respectively. For detecting bladder cancer, the retrieved sensitivity/specificity for CT cystography, MR cystography, and ultrasonography were 94%/98%, 91%/95%, and 78%/96%, respectively.
CONCLUSIONS: CT urography is the best imaging technique for confirming or excluding malignancy in the upper urinary tract, whereas CT cystography has the best diagnostic performance for diagnosing bladder cancer.

Copyright © 2012 AUR. All rights reserved.
PMID 22717592  Acad Radiol. 2012 Sep;19(9):1134-40. doi: 10.1016/j.acr・・・
著者: Brian R Lane, Armine K Smith, Benjamin T Larson, Michael C Gong, Steven C Campbell, Derek Raghavan, Robert Dreicer, Donna E Hansel, Andrew J Stephenson
雑誌名: Cancer. 2010 Jun 15;116(12):2967-73. doi: 10.1002/cncr.25043.
Abstract/Text BACKGROUND: The prevalence of chronic kidney disease (CKD) in patients with upper tract urothelial carcinoma (UTUC) is poorly defined, both before and after nephrouretectomy. Although multimodal treatment paradigms for UTUC are under-developed, this has important implications on patients' ability to receive cisplatin-based combination chemotherapy (CBCC).
METHODS: Estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease formula in 336 patients with UTUC, who were treated at the Cleveland Clinic by nephroureterectomy since 1992. An eGFR cutoff of 60 mL/min/1.73 m(2) was used to determine the presence of CKD and eligibility for CBCC.
RESULTS: Median age was 72 years and median preoperative eGFR was 59 mL/min/1.73m(2). Before nephroureterectomy, only 48% of patients were eligible to receive CBCC and this decreased to 22% postoperatively (P < .001). In the 144 patients with pT2-pT4 and/or pN1-pN3 disease who are suitable to receive CBCC, these proportions were 40% and 24%, respectively (P = .009). Although 50 patients overall received some form of perioperative chemotherapy, only 3 and 11 patients received neoadjuvant and adjuvant CBCC, respectively.
CONCLUSIONS: CKD is prevalent in the UTUC population and a minority of patients has an optimal eGFR to receive neoadjuvant CBCC. Nephrouretectomy may eliminate CBCC as a therapeutic option in 49% of high-risk patients if it is deferred to the adjuvant setting. Multimodal treatment strategies for UTUC should focus on neoadjuvant chemotherapy, as few patients are eligible for adjuvant CBCC because of the substantial decline in eGFR caused by nephroureterectomy.

PMID 20564402  Cancer. 2010 Jun 15;116(12):2967-73. doi: 10.1002/cncr.・・・
著者: François Audenet, David R Yates, Olivier Cussenot, Morgan Rouprêt
雑誌名: Urol Oncol. 2013 May;31(4):407-13. doi: 10.1016/j.urolonc.2010.07.016. Epub 2010 Sep 29.
Abstract/Text OBJECTIVE: Urothelial cell carcinoma of the upper urinary tract (UUT-UCC) is a rare, aggressive urologic cancer with a propensity for multifocality, local recurrence, and metastasis. This review highlights the main chemotherapy regimens available for UUT-UCCs based on the recent literature.
MATERIALS AND METHODS: Data on urothelial malignancies and UUT-UCCs management in the literature were searched using MEDLINE and by matching the following key words: urinary tract cancer; urothelial carcinomas; upper urinary tract; carcinoma; transitional cell; renal pelvis; ureter; bladder cancer; chemotherapy; nephroureterectomy; adjuvant treatment; neoadjuvant treatment; recurrence; risk factors; and survival.
RESULTS: No evidence level 1 information from prospective randomized trials was available. Because of its many similarities with bladder urothelial carcinomas, chemotherapy with a cisplatin-containing regimen is often proposed in patients with metastatic or locally advanced disease. Most teams have proposed a neoadjuvant or an adjuvant treatment based either on the combination of methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) or on gemcitabine/cisplatin (GC). These regimens have been shown to prolong survival moderately. All recent studies have included limited numbers of patients and have reported poor patient outcomes after both neoadjuvant and adjuvant chemotherapy. Regarding metastatic UUT-UCCs, vinflunine has demonstrated moderate activity in these patients with a manageable toxicity. Interestingly, specific molecular markers [microsatellite instability (MSI), E-cadherin, HIF-1α, and RNA levels of the telomerase gene] can provide useful information that can help diagnose and determine patient prognosis in patients with UUT-UCC.
CONCLUSION: Chemotherapy with a cisplatin-containing regimen is often proposed in patients with metastatic or locally advanced disease. However, there is no strong evidence that chemotherapy is effective due to the rarity of the disease and the lack of data in the current literature. Thus, physicians must take into account the specific clinical characteristics of each individual patient with regard to renal function, medical comorbidities, tumor location, grade, and stage, and molecular marker status when determining the optimal treatment regimen for their patients. The ongoing identification of the oncologic mechanisms of this type of cancer might pave the way for the development of specific treatments that are targeted to the characteristics of each patient's tumor in the future.

Copyright © 2013 Elsevier Inc. All rights reserved.
PMID 20884249  Urol Oncol. 2013 May;31(4):407-13. doi: 10.1016/j.urolo・・・
著者: Vitaly Margulis, Shahrokh F Shariat, Surena F Matin, Ashish M Kamat, Richard Zigeuner, Eiji Kikuchi, Yair Lotan, Alon Weizer, Jay D Raman, Christopher G Wood, Upper Tract Urothelial Carcinoma CollaborationThe Upper Tract Urothelial Carcinoma Collaboration
雑誌名: Cancer. 2009 Mar 15;115(6):1224-33. doi: 10.1002/cncr.24135.
Abstract/Text BACKGROUND: The literature on upper tract urothelial carcinoma (UTUC) has been limited to small, single center studies. A large series of patients treated with radical nephroureterectomy for UTUC were studied, and variables associated with poor prognosis were identified.
METHODS: Data on 1363 patients treated with radical nephroureterectomy at 12 academic centers were collected. All pathologic slides were re-reviewed by genitourinary pathologists according to strict criteria.
RESULTS: Pathologic review revealed renal pelvis location (64%), necrosis (21.6%), lymphovascular invasion (LVI) (24.8%), concomitant carcinoma in situ (28.7%), and high-grade disease (63.7%). A total of 590 patients (43.3%) underwent concurrent, lymphadenectomy and 135 (9.9%) were lymph node (LN) -positive. Over a mean follow-up of 51 months, 379 (28%) patients experienced disease recurrence outside of the bladder and 313 (23%) died of UTUC. The 5-year recurrence-free and cancer-specific survival probabilities (+/-SD) were 69%+/-1% and 73%+/-1%, respectively. On multivariate analysis, high tumor grade (hazards ratio [HR]: 2.0, P<.001), advancing pathologic T stage (P-for-trend<.001), LN metastases (HR: 1.8, P<.001), infiltrative growth pattern (HR: 1.5, P<.001), and LVI (HR: 1.2, P=.041) were associated with disease recurrence. Similarly, patient age (HR: 1.1, P=.001), high tumor grade (HR: 1.7, P=.001), increasing pathologic T stage (P-for-trend<.001), LN metastases (HR: 1.7, P<.001), sessile architecture (HR: 1.5, P=.002), and LVI (HR: 1.4, P=.02) were independently associated with cancer-specific survival.
CONCLUSIONS: Radical nephroureterectomy provided durable local control and cancer-specific survival in patients with localized UTUC. Pathologic tumor grade, T stage, LN status, tumor architecture, and LVI were important prognostic variables associated with oncologic outcomes, which could potentially be used to select patients for adjuvant systemic therapy.

Copyright (c) 2009 American Cancer Society.
PMID 19156917  Cancer. 2009 Mar 15;115(6):1224-33. doi: 10.1002/cncr.2・・・
著者: H Miyake, I Hara, K Gohji, S Arakawa, S Kamidono
雑誌名: Br J Urol. 1998 Oct;82(4):494-8.
Abstract/Text OBJECTIVE: To determine the efficacy of lymphadenectomy after nephroureterectomy in patients with transitional cell carcinoma (TCC) of the upper urinary tract.
PATIENTS AND METHODS: Between January 1986 and December 1995, 72 patients (mean age 67 years, range 45-82) underwent nephroureterectomy for primary TCC of the upper urinary tract. In 35 patients, a lymphadenectomy was also performed. The clinicopathological data were analysed retrospectively, focusing on the significance of lymphadenectomy.
RESULTS: Lymph vessel invasion was found in 28 patients and its incidence was closely correlated with both tumour grade and pathological stage. Of the 35 patients who underwent lymphadenectomy, lymph node metastases were found in 13 patients, all of whom had lymph vessel invasion. There was no significant difference in the survival rate between patients with and without lymphadenectomy; however, among the 44 patients with no lymph vessel invasion, the survival rate of those with lymphadenectomy was significantly higher than in those without (P<0.05).
CONCLUSION: Lymphadenectomy may provide a therapeutic advantage in patients with upper urinary tract TCC and no lymph vessel invasion. However, patients with lymph vessel invasion seem to have systemic disease; therefore, aggressive systemic adjuvant therapies rather than regional lymphadenectomy should be applied in these patients.

PMID 9806176  Br J Urol. 1998 Oct;82(4):494-8.
著者: Bulent Akdogan, Hasan Serkan Dogan, Saadettin Yilmaz Eskicorapci, Ahmet Sahin, Ilhan Erkan, Haluk Ozen
雑誌名: J Urol. 2006 Jul;176(1):48-52. doi: 10.1016/S0022-5347(06)00511-8.
Abstract/Text PURPOSE: We studied prognostic factors for 5-year disease specific and recurrence-free survival in patients treated for upper urinary tract transitional cell carcinoma.
MATERIALS AND METHODS: Since July 1987, 72 patients with a mean age of 58.9 years have undergone nephroureterectomy with bladder cuff excision. Median followup was 62.2 months (range 6 to 192). Patient age, sex, detection duration and mode, bladder tumor history, smoking habit, stone disease history, and tumor stage, grade and location were evaluated as prognostic factors.
RESULTS: Overall 5-year disease specific and recurrence-free survival rates were 74.9% and 67.8%, respectively. Univariate analysis revealed anemia, positive bladder tumor history, T stage, grade and tumor location in the upper tract as significant prognostic factors. On multivariate analysis T stage, grade and tumor location in the urothelium were the only significant variables for the 5-year disease specific and recurrence-free survival rates.
CONCLUSIONS: High tumor stage and grade, and ureteral location were significantly associated with worse disease specific and recurrence-free survival in patients with upper urinary tract transitional cell carcinoma. Our results may help define the patient groups that need adjuvant therapy and they may form a basis for further controlled studies.

PMID 16753365  J Urol. 2006 Jul;176(1):48-52. doi: 10.1016/S0022-5347(・・・
著者: Sungchan Park, Bumsik Hong, Choung-Soo Kim, Hanjong Ahn
雑誌名: J Urol. 2004 Feb;171(2 Pt 1):621-5. doi: 10.1097/01.ju.0000107767.56680.f7.
Abstract/Text PURPOSE: We assessed the impact of traditional prognostic factors and tumor location on the survival of patients treated for upper tract transitional cell carcinoma (TCC).
MATERIALS AND METHODS: We retrospectively analyzed the data on 86 patients with upper tract TCC who underwent nephroureterectomy with a bladder cuff (95%) or parenchymal sparing surgery (5%). Mean patient age was 59.5 years and median followup was 43.8 months. The influence of traditional prognostic factors such as age, gender, tumor stage, grade and location on 5-year disease specific and recurrence-free (local recurrence or distant metastasis) survival rates was analyzed. The difference in survival rates between renal 45 pelvis and 41 ureteral cases was analyzed according to the respective T stage and grade.
RESULTS: Overall 5-year disease specific and recurrence-free survival rates were 83% and 72%, respectively. The significant prognostic factors for survival rates by univariate analysis were T stage, grade and location. N stage was significant for 5-year recurrence-free survival. On multivariate analysis tumor location was the only independent prognostic factor for the 2 survival rates, while N stage was significant for 5-year recurrence-free survival. Patients with ureteral tumor had a worse prognosis than those with pelvis tumor at the same stage or grade (p = 0.036).
CONCLUSIONS: Pelvis and ureteral TCC are not the same disease in terms of invasion and prognosis. Ureteral TCC is associated with a higher local or distant failure rate than renal pelvis TCC. A radical surgical approach including meticulous lymphadenectomy may be therapeutic in patients with invasive ureteral TCC.

PMID 14713773  J Urol. 2004 Feb;171(2 Pt 1):621-5. doi: 10.1097/01.ju.・・・
著者: Giovanni Lughezzani, Claudio Jeldres, Hendrik Isbarn, Shahrokh F Shariat, Maxine Sun, Daniel Pharand, Hugues Widmer, Philippe Arjane, Markus Graefen, Francesco Montorsi, Paul Perrotte, Pierre I Karakiewicz
雑誌名: Urology. 2010 Jan;75(1):118-24. doi: 10.1016/j.urology.2009.07.1296. Epub 2009 Oct 28.
Abstract/Text OBJECTIVES: To perform a population-based analysis of the potential staging or prognostic value (or both) of lymph node dissection (LND) in patients without nodal metastases vs no LND. In several previous reports, LND in patients with upper tract urothelial carcinoma (UTUC) treated with nephroureterectomy (NU) was associated with better survival relative to no LND (pN(x)), even in the absence of pathologically confirmed nodal metastases (pN(0)).
METHODS: Within the surveillance, epidemiology, and end results database, we identified 2824 patients treated with NU for UTUC between 1988 and 2004. CSM rates after NU were graphically explored using Kaplan-Meier plots. Univariable and multivariable Cox regression models tested the effect of N(0) vs N(x) stage on CSM, after adjusting for T stage, tumor grade, age, gender, primary tumor location, type, and year of surgery.
RESULTS: The CSM-free survival rate at 5 years after NU was 81.2% and 77.8% respectively for pN(0) and pN(x) patients. In univariable analyses pN(x) vs pN(0) status was not associated with worse survival (HR: 1.19; P = .09). After adjustment for all covariates, pN(x) vs pN(0) status still failed to achieve independent predictor status (HR: 0.99; P = .9).
CONCLUSIONS: We found no survival benefit related to the performance of LND in pN(0) patients, relative to pN(x) patients. Lack of standardized criteria for patients' selection for LND and for pathological lymph node specimen evaluation represents some of the explanation for the observed discrepancy between the current finding and previous findings.

Crown Copyright 2010. Published by Elsevier Inc. All rights reserved.
PMID 19864000  Urology. 2010 Jan;75(1):118-24. doi: 10.1016/j.urology.・・・
著者: Marco Roscigno, Shahrokh F Shariat, Vitaly Margulis, Pierre Karakiewicz, Mesut Remzi, Eiji Kikuchi, Cord Langner, Yair Lotan, Alon Weizer, Karim Bensalah, Jay D Raman, Christian Bolenz, Charles C Guo, Christopher G Wood, Richard Zigeuner, Jeffrey Wheat, Wareef Kabbani, Theresa M Koppie, Casey K Ng, Nazareno Suardi, Roberto Bertini, Mario I Fernández, Shuji Mikami, Masaru Isida, Maurice Stephan Michel, Francesco Montorsi
雑誌名: J Urol. 2009 Jun;181(6):2482-9. doi: 10.1016/j.juro.2009.02.021. Epub 2009 Apr 16.
Abstract/Text PURPOSE: We examined the impact of lymphadenectomy on the clinical outcomes of patients with upper tract urothelial cancer treated with radical nephroureterectomy.
MATERIALS AND METHODS: Data were collected on 1,130 consecutive patients with pT1-4 upper tract urothelial cancer treated with radical nephroureterectomy at 13 centers worldwide. Patients were grouped according to nodal status (pN0 vs pNx vs pN+). The choice to perform lymphadenectomy was determined by the treating surgeon. All pathology slides were reevaluated by dedicated genitourinary pathologists. Univariable and multivariable Cox regression models measured the association of nodal status (pN0 vs pNx vs pN+) with cancer specific survival.
RESULTS: Overall 412 patients (36.5%) had pN0 disease, 578 had pNx disease (51.1%) and 140 had pN+ disease (12.4%). The 5-year cancer specific survival estimate was lower in patients with pN+ compared to those with pNx disease (35% vs 69%, p <0.001), which in turn was lower than that in those with pN0 disease (69% vs 77%, p = 0.024). In the subgroup of patients with pT1 disease (345) cancer specific survival rates were not different in those with pN0 and pNx. In pT2-4 cases (813) cancer specific survival estimates were lowest in pN+, intermediate in pNx and highest in pN0 (33% vs 58% vs 70%, p = 0.017). When adjusted for the effects of standard clinicopathological features pN+ was an independent predictor of cancer specific survival (p <0.001). pNx was significantly associated with worse prognosis than pN0 in pT2-4 upper tract urothelial cancer only.
CONCLUSIONS: Nodal status is a significant predictor of cancer specific survival in upper tract urothelial cancer. pNx is significantly associated with a worse prognosis than pN0 in pT2-4 tumors. Patients expected to have pT2-4 disease should undergo lymphadenectomy to improve staging and thereby help guide decision making regarding adjuvant chemotherapy.

PMID 19371878  J Urol. 2009 Jun;181(6):2482-9. doi: 10.1016/j.juro.200・・・
著者: Marco Roscigno, Shahrokh F Shariat, Vitaly Margulis, Pierre Karakiewicz, Mesut Remzi, Eiji Kikuchi, Richard Zigeuner, Alon Weizer, Arthur Sagalowsky, Karim Bensalah, Jay D Raman, Christian Bolenz, Wassim Kassou, Theresa M Koppie, Christopher G Wood, Jeffrey Wheat, Cord Langner, Casey K Ng, Umberto Capitanio, Roberto Bertini, Mario I Fernández, Shuji Mikami, Masaru Isida, Philipp Ströbel, Francesco Montorsi
雑誌名: Eur Urol. 2009 Sep;56(3):512-8. doi: 10.1016/j.eururo.2009.06.004. Epub 2009 Jun 18.
Abstract/Text BACKGROUND: The role and extent of lymphadenectomy in patients with upper-tract urothelial carcinoma (UTUC) is debated.
OBJECTIVE: To establish whether the number of lymph nodes (LNs) removed might be associated with better cause-specific survival in patients with UTUC.
DESIGN, SETTING, AND PARTICIPANTS: The study included 552 consecutive patients who underwent radical nephroureterectomy (RNU) and lymphadenectomy between 1992 and 2006.
INTERVENTION: Patients were treated with RNU and lymphadenectomy.
MEASUREMENTS: Univariable and multivariable Cox proportional hazards regression models addressed the association between the number of LNs removed and cause-specific mortality (CSM). The number of LNs removed was coded as a cubic spline to allow for nonlinear effects. Finally, the most informative cut-off for the number of removed LNs was identified.
RESULTS AND LIMITATIONS: In the entire population, the number of LNs removed was not associated with CSM in univariable (hazard ratio [HR]: 0.99; p=0.16) or in multivariable (HR: 0.97; p=0.12) analyses. In contrast, in the subgroup of pN0 patients (n=412), the number of LNs removed achieved the independent predictor status of CSM (HR: 0.93; p=0.02). Eight LNs removed was the most informative cut-off in predicting CSM (HR: 0.42; p=0.004). The inclusion of the variable defining dichotomously the number of removed LNs (< 8 vs > or = 8) in the base model (age, Eastern Cooperative Oncology Group performance status, pathologic stage, grade, architecture, and lymphovascular invasion) significantly increased the accuracy in predicting CSM (+1.7%; p<0.001).
CONCLUSIONS: The extension of the lymphadenectomy in pN0 UTUC patients seems to be associated with CSM. Longer survival was observed in patients in whom at least eight LNs had been removed.

PMID 19559518  Eur Urol. 2009 Sep;56(3):512-8. doi: 10.1016/j.eururo.2・・・
著者: Demetrius H Bagley, Michael Grasso
雑誌名: World J Urol. 2010 Apr;28(2):143-9. doi: 10.1007/s00345-010-0525-7. Epub 2010 Mar 14.
Abstract/Text BACKGROUND: Endoscopic management of upper urinary tract transitional cell carcinoma has assumed an important role in diagnosis and treatment. The introduction of small diameter rigid and flexible ureteroscopes has permitted access to the upper tract. Biopsy techniques have been developed for accurate diagnosis, and the addition of lasers has given the urologists an excellent tool for treatment.
METHODS: Medical literature available relative to the endoscopic laser treatment of upper tract neoplasms has been reviewed.
RESULTS: Ureteroscopic treatment has been characterized by good success with high recurrence rates, both in the upper tract and in the bladder. Bladder recurrence rates are similar to those seen after surgical treatment of upper tract tumors. Surveillance has been ureteroscopic since the other diagnostic options are inadequate. The holmium and neodymium:YAG lasers are the devices most commonly used now for the endoscopic treatment of upper tract tumors.
CONCLUSION: Ureteroscopic treatment of upper tract neoplasms usually with ablation and resection using the neodymium and holmium:YAG lasers is a current acceptable procedure. This should be considered as one of the options in tumor treatment.

PMID 20229233  World J Urol. 2010 Apr;28(2):143-9. doi: 10.1007/s00345・・・
著者: Morgan Rouprêt, Vincent Hupertan, Olivier Traxer, Guillaume Loison, Emmanuel Chartier-Kastler, Pierre Conort, Marc-Olivier Bitker, Bernard Gattegno, François Richard, Olivier Cussenot
雑誌名: Urology. 2006 Jun;67(6):1181-7. doi: 10.1016/j.urology.2005.12.034.
Abstract/Text OBJECTIVES: To compare the outcomes in patients who had undergone either open nephroureterectomy or conservative endoscopic surgery (ureteroscopic or percutaneous management) for upper urinary tract transitional cell carcinoma.
METHODS: We performed a retrospective review of the data for patients treated surgically for upper urinary tract transitional cell carcinoma from 1990 to 2004. The data included patient sex, age at diagnosis, mode of diagnosis, smoking history, history of bladder cancer, type of surgery, complications, and tumor site, size, stage, grade, recurrence, and progression. We also evaluated the recurrence and survival rates.
RESULTS: Data were analyzed for 97 patients. The median patient age was 68 years. Sixteen patients had a history of bladder tumor. The surgical procedure was open nephroureterectomy in 54 patients, ureteroscopy in 27, and percutaneous endoscopic ablation in 16. The tumor stage, grade, and site were independent prognostic factors for survival in a multivariate analysis (P <0.05). The 5-year disease-specific survival rate was 81.9% for low-grade tumors and 47.3% for high-grade tumors (P = 0.0001). A correlation (P = 0.002) was found between low-grade tumors and superficial tumors. In patients with low-grade tumors (n = 46), the 5-year disease-specific survival rate after nephroureterectomy, ureteroscopy, and percutaneous endoscopy was 84%, 80.7%, and 80%, respectively (P = 0.89); the corresponding 5-year tumor-free survival rates were 75.3%, 71.5%, and 72% (P = 0.78).
CONCLUSIONS: Conservative surgery can be recommended as an alternative to nephroureterectomy for low-grade or superficial upper urinary tract transitional cell carcinoma. For patients with high-grade or invasive tumors to be candidates for conservative surgery will require the development of additional prognostic factors (eg, molecular markers). These patients require long-term postoperative surveillance.

PMID 16765178  Urology. 2006 Jun;67(6):1181-7. doi: 10.1016/j.urology.・・・
著者: Hans von der Maase, Lisa Sengelov, James T Roberts, Sergio Ricci, Luigi Dogliotti, T Oliver, Malcolm J Moore, Annamaria Zimmermann, Michael Arning
雑誌名: J Clin Oncol. 2005 Jul 20;23(21):4602-8. doi: 10.1200/JCO.2005.07.757.
Abstract/Text PURPOSE: To compare long-term survival in patients with locally advanced or metastatic transitional cell carcinoma (TCC) of the urothelium treated with gemcitabine/cisplatin (GC) or methotrexate/vinblastine/doxorubicin/cisplatin (MVAC).
PATIENTS AND METHODS: Efficacy data from a large randomized phase III study of GC versus MVAC were updated. Time-to-event analyses were performed on the observed distributions of overall and progression-free survival.
RESULTS: A total of 405 patients were randomly assigned: 203 to the GC arm and 202 to the MVAC arm. At the time of analysis, 347 patients had died (GC arm, 176 patients; MVAC arm, 171 patients). Overall survival was similar in both arms (hazard ratio [HR], 1.09; 95% CI, 0.88 to 1.34; P = .66) with a median survival of 14.0 months for GC and 15.2 months for MVAC. The 5-year overall survival rates were 13.0% and 15.3%, respectively (P = .53). The median progression-free survival was 7.7 months for GC and 8.3 months for MVAC, with an HR of 1.09. The 5-year progression-free survival rates were 9.8% and 11.3%, respectively (P = .63). Significant prognostic factors favoring overall survival included performance score (> 70), TNM staging (M0 v M1), low/normal alkaline phosphatase level, number of disease sites (CONCLUSION: Long-term overall and progression-free survival after treatment with GC or MVAC are similar. These results strengthen the role of GC as a standard of care in patients with locally advanced or metastatic TCC.

PMID 16034041  J Clin Oncol. 2005 Jul 20;23(21):4602-8. doi: 10.1200/J・・・
著者: Alison Birtle, Mark Johnson, John Chester, Robert Jones, David Dolling, Richard T Bryan, Christopher Harris, Andrew Winterbottom, Anthony Blacker, James W F Catto, Prabir Chakraborti, Jenny L Donovan, Paul Anthony Elliott, Ann French, Satinder Jagdev, Benjamin Jenkins, Francis Xavier Keeley, Roger Kockelbergh, Thomas Powles, John Wagstaff, Caroline Wilson, Rachel Todd, Rebecca Lewis, Emma Hall
雑誌名: Lancet. 2020 Apr 18;395(10232):1268-1277. doi: 10.1016/S0140-6736(20)30415-3. Epub 2020 Mar 5.
Abstract/Text BACKGROUND: Urothelial carcinomas of the upper urinary tract (UTUCs) are rare, with poorer stage-for-stage prognosis than urothelial carcinomas of the urinary bladder. No international consensus exists on the benefit of adjuvant chemotherapy for patients with UTUCs after nephroureterectomy with curative intent. The POUT (Peri-Operative chemotherapy versus sUrveillance in upper Tract urothelial cancer) trial aimed to assess the efficacy of systemic platinum-based chemotherapy in patients with UTUCs.
METHODS: We did a phase 3, open-label, randomised controlled trial at 71 hospitals in the UK. We recruited patients with UTUC after nephroureterectomy staged as either pT2-T4 pN0-N3 M0 or pTany N1-3 M0. We randomly allocated participants centrally (1:1) to either surveillance or four 21-day cycles of chemotherapy, using a minimisation algorithm with a random element. Chemotherapy was either cisplatin (70 mg/m2) or carboplatin (area under the curve [AUC]4·5/AUC5, for glomerular filtration rate <50 mL/min only) administered intravenously on day 1 and gemcitabine (1000 mg/m2) administered intravenously on days 1 and 8; chemotherapy was initiated within 90 days of surgery. Follow-up included standard cystoscopic, radiological, and clinical assessments. The primary endpoint was disease-free survival analysed by intention to treat with a Peto-Haybittle stopping rule for (in)efficacy. The trial is registered with ClinicalTrials.gov, NCT01993979. A preplanned interim analysis met the efficacy criterion for early closure after recruitment of 261 participants.
FINDINGS: Between June 19, 2012, and Nov 8, 2017, we enrolled 261 participants from 57 of 71 open study sites. 132 patients were assigned chemotherapy and 129 surveillance. One participant allocated chemotherapy withdrew consent for data use after randomisation and was excluded from analyses. Adjuvant chemotherapy significantly improved disease-free survival (hazard ratio 0·45, 95% CI 0·30-0·68; p=0·0001) at a median follow-up of 30·3 months (IQR 18·0-47·5). 3-year event-free estimates were 71% (95% CI 61-78) and 46% (36-56) for chemotherapy and surveillance, respectively. 55 (44%) of 126 participants who started chemotherapy had acute grade 3 or worse treatment-emergent adverse events, which accorded with frequently reported events for the chemotherapy regimen. Five (4%) of 129 patients managed by surveillance had acute grade 3 or worse emergent adverse events. No treatment-related deaths were reported.
INTERPRETATION: Gemcitabine-platinum combination chemotherapy initiated within 90 days after nephroureterectomy significantly improved disease-free survival in patients with locally advanced UTUC. Adjuvant platinum-based chemotherapy should be considered a new standard of care after nephroureterectomy for this patient population.
FUNDING: Cancer Research UK.

Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.
PMID 32145825  Lancet. 2020 Apr 18;395(10232):1268-1277. doi: 10.1016/・・・
著者: Ricardo L Favaretto, Shahrokh F Shariat, Daher C Chade, Guilherme Godoy, Matthew Kaag, Angel M Cronin, Bernard H Bochner, Jonathan Coleman, Guido Dalbagni
雑誌名: Eur Urol. 2010 Nov;58(5):645-51. doi: 10.1016/j.eururo.2010.08.005. Epub 2010 Aug 11.
Abstract/Text BACKGROUND: Open radical nephroureterectomy (ORN) is the current standard of care for upper tract urothelial carcinoma (UTUC), but laparoscopic radical nephroureterectomy (LRN) is emerging as a minimally invasive alternative. Questions remain regarding the oncologic safety of LRN and its relative equivalence to ORN.
OBJECTIVE: Our aim was to compare recurrence-free and disease-specific survival between ORN and LRN.
DESIGN, SETTING, AND PARTICIPANTS: We retrospectively analyzed data from 324 consecutive patients treated with radical nephroureterectomy (RN) between 1995 and 2008 at a major cancer center. Patients with previous invasive bladder cancer or contralateral UTUC were excluded. Descriptive data are provided for 112 patients who underwent ORN from 1995 to 2001 (pre-LRN era). Comparative analyses were restricted to patients who underwent ORN (n=109) or LRN (n=53) from 2002 to 2008. Median follow-up for patients without disease recurrence was 23 mo.
INTERVENTION: All patients underwent RN.
MEASUREMENTS: Recurrence was categorized as bladder-only recurrence or any recurrence (bladder, contralateral kidney, operative site, regional lymph nodes, or distant metastasis). Recurrence-free probabilities were estimated using Kaplan-Meier methods. A multivariable Cox model was used to evaluate the association between surgical approach and disease recurrence. The probability of disease-specific death was estimated using the cumulative incidence function.
RESULTS AND LIMITATIONS: Clinical and pathologic characteristics were similar for all patients. The recurrence-free probabilities were similar between ORN and LRN (2-yr estimates: 38% and 42%, respectively; p=0.9 by log-rank test). On multivariable analysis, the surgical approach was not significantly associated with disease recurrence (hazard ratio [HR]: 0.88 for LRN vs ORN; 95% confidence interval [CI], 0.57-1.38; p=0.6). There was no significant difference in bladder-only recurrence (HR: 0.78 for LRN vs ORN; 95% CI, 0.46-1.34; p=0.4) or disease-specific mortality (p=0.9). This study is limited by its retrospective nature.
CONCLUSIONS: Based on the results of this retrospective study, no evidence indicates that oncologic control is compromised for patients treated with LRN in comparison with ORN.

Copyright © 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.
PMID 20724065  Eur Urol. 2010 Nov;58(5):645-51. doi: 10.1016/j.eururo.・・・
著者: Morgan Rouprêt, Richard Zigeuner, Juan Palou, Andreas Boehle, Eero Kaasinen, Richard Sylvester, Marko Babjuk, Willem Oosterlinck
雑誌名: Eur Urol. 2011 Apr;59(4):584-94. doi: 10.1016/j.eururo.2010.12.042. Epub 2011 Jan 14.
Abstract/Text CONTEXT: The European Association of Urology (EAU) Guideline Group for urothelial cell carcinoma of the upper urinary tract (UUT-UCC) has prepared new guidelines to aid clinicians in assessing the current evidence-based management of UUT-UCC and to incorporate present recommendations into daily clinical practice.
OBJECTIVE: This paper provides a brief overview of the EAU guidelines on UUT-UCC as an aid to clinicians in their daily practice.
EVIDENCE ACQUISITION: The recommendations provided in the current guidelines are based on a thorough review of available UUT-UCC guidelines and papers identified using a systematic search of Medline. Data on urothelial malignancies and UUT-UCCs in the literature were searched using Medline with the following keywords: urinary tract cancer, urothelial carcinomas, upper urinary tract, carcinoma, transitional cell, renal pelvis, ureter, bladder cancer, chemotherapy, nephroureterectomy, adjuvant treatment, neoadjuvant treatment, recurrence, risk factors, and survival. A panel of experts weighted the references.
EVIDENCE SYNTHESIS: There is a lack of data in the current literature to provide strong recommendations due to the rarity of the disease. A number of recent multicentre studies are now available, whereas earlier publications were based only on limited populations. However, most of these studies have been retrospective analyses. The TNM classification 2009 is recommended. Recommendations are given for diagnosis as well as for radical and conservative treatment; prognostic factors are also discussed. Recommendations are provided for patient follow-up after different therapeutic options.
CONCLUSIONS: These guidelines contain information for the diagnosis and treatment of individual patients according to a current standardised approach. When determining the optimal treatment regimen, physicians must take into account each individual patient's specific clinical characteristics with regard to renal function including medical comorbidities; tumour location, grade and stage; and molecular marker status.

Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.
PMID 21269756  Eur Urol. 2011 Apr;59(4):584-94. doi: 10.1016/j.eururo.・・・
著者: Richard Zigeuner, Karl Pummer
雑誌名: Eur Urol. 2008 Apr;53(4):720-31. doi: 10.1016/j.eururo.2008.01.006. Epub 2008 Jan 14.
Abstract/Text OBJECTIVES: Open radical nephroureterectomy (O-RNU) has been the gold standard for the treatment of upper urinary tract urothelial carcinoma (UUT-UC) for decades. With the advances in laparoscopic techniques and endourologic procedures, this concept has been increasingly challenged. Oncologic outcome prediction is mainly based on stage and grade. With progress in medical treatment, adjuvant therapies may gain importance in the future. This review assesses the values of the variety of available treatments as well as prognostic factors that may become relevant regarding patient selection for future adjuvant treatment trials.
METHODS: We performed a systematic literature research using MEDLINE with emphasis on open surgical, laparoscopic, and endourologic (ureteroscopic or percutaneous) techniques and prognostic contents.
RESULTS: Overall, no evidence level 1 information from prospective randomised trials is available for treatment of UUT-UC. Laparoscopic radical nephroureterectomy (L-RNU) is increasingly challenging open surgery. Currently, L-RNU should be reserved for low-stage, low-grade tumours. Ureteroscopy and percutaneous nephron-sparing techniques show favourable survival data but high local recurrence rates. Regarding prognosis, estimation of outcome still relies mainly on stage and grade because no additional parameters have been introduced in a routine clinical setting.
CONCLUSIONS: O-RNU still represents the gold standard for the treatment of UUT-UC. The laparoscopic approach is not yet standard of care and should be reserved for low-stage, low-grade tumours. Endourologic nephron-sparing treatments are still experimental in elective indications due to high local recurrence rates. For prognosis, no parameters in addition to stage and grade have been standardised.

PMID 18207315  Eur Urol. 2008 Apr;53(4):720-31. doi: 10.1016/j.eururo.・・・
著者: Joaquim Bellmunt, Ronald de Wit, David J Vaughn, Yves Fradet, Jae-Lyun Lee, Lawrence Fong, Nicholas J Vogelzang, Miguel A Climent, Daniel P Petrylak, Toni K Choueiri, Andrea Necchi, Winald Gerritsen, Howard Gurney, David I Quinn, Stéphane Culine, Cora N Sternberg, Yabing Mai, Christian H Poehlein, Rodolfo F Perini, Dean F Bajorin, KEYNOTE-045 Investigators
雑誌名: N Engl J Med. 2017 Mar 16;376(11):1015-1026. doi: 10.1056/NEJMoa1613683. Epub 2017 Feb 17.
Abstract/Text BACKGROUND: Patients with advanced urothelial carcinoma that progresses after platinum-based chemotherapy have a poor prognosis and limited treatment options.
METHODS: In this open-label, international, phase 3 trial, we randomly assigned 542 patients with advanced urothelial cancer that recurred or progressed after platinum-based chemotherapy to receive pembrolizumab (a highly selective, humanized monoclonal IgG4κ isotype antibody against programmed death 1 [PD-1]) at a dose of 200 mg every 3 weeks or the investigator's choice of chemotherapy with paclitaxel, docetaxel, or vinflunine. The coprimary end points were overall survival and progression-free survival, which were assessed among all patients and among patients who had a tumor PD-1 ligand (PD-L1) combined positive score (the percentage of PD-L1-expressing tumor and infiltrating immune cells relative to the total number of tumor cells) of 10% or more.
RESULTS: The median overall survival in the total population was 10.3 months (95% confidence interval [CI], 8.0 to 11.8) in the pembrolizumab group, as compared with 7.4 months (95% CI, 6.1 to 8.3) in the chemotherapy group (hazard ratio for death, 0.73; 95% CI, 0.59 to 0.91; P=0.002). The median overall survival among patients who had a tumor PD-L1 combined positive score of 10% or more was 8.0 months (95% CI, 5.0 to 12.3) in the pembrolizumab group, as compared with 5.2 months (95% CI, 4.0 to 7.4) in the chemotherapy group (hazard ratio, 0.57; 95% CI, 0.37 to 0.88; P=0.005). There was no significant between-group difference in the duration of progression-free survival in the total population (hazard ratio for death or disease progression, 0.98; 95% CI, 0.81 to 1.19; P=0.42) or among patients who had a tumor PD-L1 combined positive score of 10% or more (hazard ratio, 0.89; 95% CI, 0.61 to 1.28; P=0.24). Fewer treatment-related adverse events of any grade were reported in the pembrolizumab group than in the chemotherapy group (60.9% vs. 90.2%); there were also fewer events of grade 3, 4, or 5 severity reported in the pembrolizumab group than in the chemotherapy group (15.0% vs. 49.4%).
CONCLUSIONS: Pembrolizumab was associated with significantly longer overall survival (by approximately 3 months) and with a lower rate of treatment-related adverse events than chemotherapy as second-line therapy for platinum-refractory advanced urothelial carcinoma. (Funded by Merck; KEYNOTE-045 ClinicalTrials.gov number, NCT02256436 .).

PMID 28212060  N Engl J Med. 2017 Mar 16;376(11):1015-1026. doi: 10.10・・・
著者: Y Fradet, J Bellmunt, D J Vaughn, J L Lee, L Fong, N J Vogelzang, M A Climent, D P Petrylak, T K Choueiri, A Necchi, W Gerritsen, H Gurney, D I Quinn, S Culine, C N Sternberg, K Nam, T L Frenkl, R F Perini, R de Wit, D F Bajorin
雑誌名: Ann Oncol. 2019 Jun 1;30(6):970-976. doi: 10.1093/annonc/mdz127.
Abstract/Text BACKGROUND: Novel second-line treatments are needed for patients with advanced urothelial cancer (UC). Interim analysis of the phase III KEYNOTE-045 study showed a superior overall survival (OS) benefit of pembrolizumab, a programmed death 1 inhibitor, versus chemotherapy in patients with advanced UC that progressed on platinum-based chemotherapy. Here we report the long-term safety and efficacy outcomes of KEYNOTE-045.
PATIENTS AND METHODS: Adult patients with histologically/cytologically confirmed UC whose disease progressed after first-line, platinum-containing chemotherapy were enrolled. Patients were randomly assigned 1 : 1 to receive pembrolizumab [200 mg every 3 weeks (Q3W)] or investigator's choice of paclitaxel (175 mg/m2 Q3W), docetaxel (75 mg/m2 Q3W), or vinflunine (320 mg/m2 Q3W). Primary end points were OS and progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) by blinded independent central radiology review (BICR). A key secondary end point was objective response rate per RECIST v1.1 by BICR.
RESULTS: A total of 542 patients were enrolled (pembrolizumab, n = 270; chemotherapy, n = 272). Median follow-up as of 26 October 2017 was 27.7 months. Median 1- and 2-year OS rates were higher with pembrolizumab (44.2% and 26.9%, respectively) than chemotherapy (29.8% and 14.3%, respectively). PFS rates did not differ between treatment arms; however, 1- and 2-year PFS rates were higher with pembrolizumab. The objective response rate was also higher with pembrolizumab (21.1% versus 11.0%). Median duration of response to pembrolizumab was not reached (range 1.6+ to 30.0+ months) versus chemotherapy (4.4 months; range 1.4+ to 29.9+ months). Pembrolizumab had lower rates of any grade (62.0% versus 90.6%) and grade ≥3 (16.5% versus 50.2%) treatment-related adverse events than chemotherapy.
CONCLUSIONS: Long-term results (>2 years' follow-up) were consistent with those of previously reported analyses, demonstrating continued clinical benefit of pembrolizumab over chemotherapy for efficacy and safety for treatment of locally advanced/metastatic, platinum-refractory UC.
TRIAL REGISTRATION: ClinicalTrials.gov: NCT02256436.

© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
PMID 31050707  Ann Oncol. 2019 Jun 1;30(6):970-976. doi: 10.1093/annon・・・

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