今日の臨床サポート

子宮体がん(初期) :I期

著者: 寺井義人 神戸大学大学院 医学研究科外科系講座産科婦人科分野

監修: 青木大輔 慶應義塾大学医学部産婦人科学教室

著者校正/監修レビュー済:2021/06/30
参考ガイドライン:
  1. 日本婦人科腫瘍学会:子宮体がん治療ガイドライン2018年版
  1. 日本産科婦人科学会日本病理学会:子宮体癌取扱い規約 病理編 第4版
患者向け説明資料

概要・推奨   

  1. 子宮体がんの手術方法は単純子宮全摘術+両側付属器切除+リンパ節の検索(生検または郭清)であり、早期子宮体がんに対しては、腹腔鏡下手術やロボット支援下手術が保険適用となった。
  1. 多囊胞性卵巣症候群(polycystic ovary syndrome、PCOS)は若年性子宮体がんの高リスクである。PCOSは不妊の原因でもあるため、不妊を主訴に来院した場合には内膜の悪性病変の有無を確認することは必要である。
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:
寺井義人 : 特に申告事項無し[2021年]
監修:青木大輔 : 講演料(アストラゼネカ株式会社,武田薬品工業株式会社,中外製薬株式会社),研究費・助成金など(アストラゼネカ株式会社,中外製薬株式会社,インサイト・バイオサイエンシズ・ジャパン合同会社)[2021年]

改訂のポイント:
  1. 改訂された子宮体癌取扱い規約に基づいて用語を変更。
  1. 早期子宮体がん手術療法に腹腔鏡下手術、ロボット支援下手術が保険収載され、その適用を加えた。
  1. 若年者子宮体癌に対する妊孕能温存治療としてホルモン治療を加えた。
  1. 術後補助治療を整理、新たなエビデンスも加えた。

病態・疫学・診察

疾患情報  
  1. 子宮体がんとは、子宮内膜に発生した癌が増殖した疾患で、子宮内膜癌ともいう。
  1. 臨床病理学的特徴から、内膜癌は2種類(Ⅰ型とⅡ型)に分類される。
  1. Ⅰ型は若年から閉経前後に発症するタイプで、エストロゲンの持続的刺激が原因で内膜全体が肥厚し、その一部に癌化が発生するものである。病理組織学的には高分化型類内癌が多く、筋層浸潤も浅く、予後良好とされている。内膜癌はⅠ型が多く、内膜癌の8~9割を占めるとされている。
  1. Ⅱ型はエストロゲンに関係なく発生するものである。内膜癌の1~2割を占める。Ⅱ型に含まれる組織型は、類内膜癌低分化型、非類内膜癌(漿液性癌、明細胞癌、粘液性癌、神経内分泌腫瘍、未分化癌など)がある。特徴として閉経期以降に発症し、エストロゲンに依存しない。発見された時点で子宮筋層深く浸潤していることが多く、予後もⅠ型に比較し不良とされている。
  1. Ⅰ型では肥満、高血圧、糖尿病、未産婦が危険因子とされている一方、Ⅱ型の危険因子は不明である。
問診・診察のポイント  
  1. 子宮体がんの場合は子宮頸がんと異なり、前がん病変である子宮内膜異型増殖症や筋層浸潤のない早期子宮体がんであっても不正性器出血の症状が出やすい。

今なら12か月分の料金で14ヶ月利用できます(個人契約、期間限定キャンペーン)

11月30日(火)までにお申込みいただくと、
通常12ヵ月の使用期間が2ヶ月延長となり、14ヵ月ご利用いただけるようになります。

詳しくはクリック
本サイトの知的財産権は全てエルゼビアまたはコンテンツのライセンサーに帰属します。私的利用及び別途規定されている場合を除き、本サイトの利用はいかなる許諾を与えるものでもありません。 本サイト、そのコンテンツ、製品およびサービスのご利用は、お客様ご自身の責任において行ってください。本サイトの利用に基づくいかなる損害についても、エルゼビアは一切の責任及び賠償義務を負いません。 また、本サイトの利用を以て、本サイト利用者は、本サイトの利用に基づき第三者に生じるいかなる損害についても、エルゼビアを免責することに合意したことになります。  本サイトを利用される医学・医療提供者は、独自の臨床的判断を行使するべきです。本サイト利用者の判断においてリスクを正当なものとして受け入れる用意がない限り、コンテンツにおいて提案されている検査または処置がなされるべきではありません。 医学の急速な進歩に鑑み、エルゼビアは、本サイト利用者が診断方法および投与量について、独自に検証を行うことを推奨いたします。

文献 

著者: Sokbom Kang, Heon Jong Yoo, Jong Ha Hwang, Myong-Cheol Lim, Sang-Soo Seo, Sang-Yoon Park
雑誌名: Gynecol Oncol. 2011 Dec;123(3):522-7. doi: 10.1016/j.ygyno.2011.08.034. Epub 2011 Sep 25.
Abstract/Text OBJECTIVE: The validity of the sentinel lymph node (SLN) procedure for the assessment of nodal status in patients with endometrial cancer is unclear. We aimed to assess the diagnostic performance of this procedure.
METHODS: We searched the PubMed and Embase databases for studies published before June 1, 2011. Eligible studies had a sample size of at least 10 patients, and reported the detection rate and/or sensitivity of the SLN biopsy.
RESULTS: We identified 26 eligible studies, which included 1101 SLN procedures. The overall weighted-mean number of harvested SLNs was 2.6. The detection rate and the sensitivity were 78% (95% confidence interval [CI]=73%-84%) and 93% (95% CI=87%-100%), respectively. Significant between-study heterogeneity was observed in the analysis of the detection rate (I-squared statistic, 80%). The use of pericervical injection was correlated with the increase of the detection rate (P=0.031). The hysteroscopic injection technique was associated with the decrease of the detection rate (P=0.045) and the subserosal injection technique was associated with the decrease of the sensitivity (P=0.049), if they were not combined with other injection techniques. For the detection rate, significant small-study effects were noted (P<0.001).
CONCLUSIONS: Although SLN biopsy has shown good diagnostic performance in endometrial cancer, such performance should be interpreted with caution because of significant small study effects. Current evidence is not yet sufficient to establish the true performance of SLN biopsy in endometrial cancer.

Copyright © 2011 Elsevier Inc. All rights reserved.
PMID 21945553  Gynecol Oncol. 2011 Dec;123(3):522-7. doi: 10.1016/j.yg・・・
著者: Joan L Walker, Marion R Piedmonte, Nick M Spirtos, Scott M Eisenkop, John B Schlaerth, Robert S Mannel, Gregory Spiegel, Richard Barakat, Michael L Pearl, Sudarshan K Sharma
雑誌名: J Clin Oncol. 2009 Nov 10;27(32):5331-6. doi: 10.1200/JCO.2009.22.3248. Epub 2009 Oct 5.
Abstract/Text PURPOSE: The objective was to compare laparoscopy versus laparotomy for comprehensive surgical staging of uterine cancer.
PATIENTS AND METHODS: Patients with clinical stage I to IIA uterine cancer were randomly assigned to laparoscopy (n = 1,696) or open laparotomy (n = 920), including hysterectomy, salpingo-oophorectomy, pelvic cytology, and pelvic and para-aortic lymphadenectomy. The main study end points were 6-week morbidity and mortality, hospital length of stay, conversion from laparoscopy to laparotomy, recurrence-free survival, site of recurrence, and patient-reported quality-of-life outcomes.
RESULTS: Laparoscopy was initiated in 1,682 patients and completed without conversion in 1,248 patients (74.2%). Conversion from laparoscopy to laparotomy was secondary to poor visibility in 246 patients (14.6%), metastatic cancer in 69 patients (4.1%), bleeding in 49 patients (2.9%), and other cause in 70 patients (4.2%). Laparoscopy had fewer moderate to severe postoperative adverse events than laparotomy (14% v 21%, respectively; P < .0001) but similar rates of intraoperative complications, despite having a significantly longer operative time (median, 204 v 130 minutes, respectively; P < .001). Hospitalization of more than 2 days was significantly lower in laparoscopy versus laparotomy patients (52% v 94%, respectively; P < .0001). Pelvic and para-aortic nodes were not removed in 8% of laparoscopy patients and 4% of laparotomy patients (P < .0001). No difference in overall detection of advanced stage (stage IIIA, IIIC, or IVB) was seen (17% of laparoscopy patients v 17% of laparotomy patients; P = .841).
CONCLUSION: Laparoscopic surgical staging for uterine cancer is feasible and safe in terms of short-term outcomes and results in fewer complications and shorter hospital stay. Follow-up of these patients will determine whether surgical technique impacts pattern of recurrence or disease-free survival.

PMID 19805679  J Clin Oncol. 2009 Nov 10;27(32):5331-6. doi: 10.1200/J・・・
著者: Yoshito Terai, Tomohito Tanaka, Hiroshi Sasaki, Hiroshi Kawaguchi, Satoe Fujiwara, Saha Yoo, Yoshimichi Tanaka, Satoshi Tsunetoh, Masanori Kanemura, Masahide Ohmichi
雑誌名: J Obstet Gynaecol Res. 2014 Feb;40(2):570-5. doi: 10.1111/jog.12194. Epub 2013 Oct 11.
Abstract/Text AIM: This is the first report to determine the feasibility and safety of total laparoscopic modified radical hysterectomy (TLMRH) in the treatment of presumed stage I endometrial cancer.
METHODS: This was a retrospective study of 132 consecutive patients who underwent surgery for early endometrial cancer. Thirty-nine patients underwent TLMRH and bilateral salpingo-oophorectomy (BSO), and 93 had a total abdominal extrafascial hysterectomy and BSO. Lymphadenectomy was performed in 87 patients. The groups were compared for epidemiological and clinical characteristics, surgical outcomes, hospital stay, lymph nodes harvested, and intraoperative and postoperative complications.
RESULTS: The patients in the TLMRH group had less blood loss (42.9 ± 76.3 vs 236.8 ± 186.6 mL, P < 0.0001), a similar number of lymph nodes removed (32.3 ± 13.1 vs 28.0 ± 11.9, P = 0.15), less need for analgesia and a shorter hospital stay (9.3 ± 2.5 vs 14.6 ± 12.6 days, P = 0.009) but longer operations (321.1 ± 65.9 vs 262.6 ± 75.0 min, P < 0.0001) than those treated by laparotomy. In our study, we had no conversions from laparoscopy to laparotomy. No major complications occurred in the TLMRH group. The patients who underwent TLMRH had less intense postoperative pain than patients treated by laparotomy. The median length of vaginal cuff removed was 12.0 ± 4.1 mm in the TLMRH group, and was 5.6 ± 6.6 mm in the laparotomy group (P < 0.0001). No patients demonstrated recurrence in either of the groups after a median follow-up of 48.5 months (range, 1-84).
CONCLUSION: TLMRH is a safe and reliable alternative to open surgery in the management of early endometrial carcinoma, with a significantly reduced hospital stay and complications.

© 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.
PMID 24118459  J Obstet Gynaecol Res. 2014 Feb;40(2):570-5. doi: 10.11・・・
著者: Nobuo Yaegashi, Kiyoshi Ito, Hitoshi Niikura
雑誌名: Int J Clin Oncol. 2007 Jun;12(3):176-80. doi: 10.1007/s10147-006-0621-2. Epub 2007 Jun 27.
Abstract/Text Total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO) have been performed as a standard surgical treatment for endometrial cancer. Many studies have reported on issues such as whether retroperitoneal lymphadenectomy should also be performed with TAH+BSO, to what extent lymphadenectomy should be performed when TAH+BSO is performed, and in what type of patients should lymphadenectomy be performed. These issues have been actively discussed, but there has not been any consensus. In this review article, the benefits of retroperitoneal lymphadenectomy in the initial surgical treatment for endometrial cancer will be discussed in terms of patients with pelvic lymphadenectomy and those with paraaortic (PA) lymphadenectomy. From the previous data, the establishment of TAH+BSO plus pelvic lymphadenectomy as the standard surgical treatment for endometrial cancer is thought to be reasonable. In this situation, is there benefit in performing PA lymphadenectomy? A discussion will be provided by separating the diagnostic significance from the therapeutic significance of this treatment. At present, there are no established treatments for PA-lymph node-positive patients that can be recommended more than the adjuvant therapies that are already performed at various institutions. A scientific basis that clearly indicates the therapeutic effect of PA lymphadenectomy does not exist at the present time. Despite performing thorough PA lymphadenectomy, the route of progression to extrauterine sites cannot be completely controlled. The standard surgical procedure for endometrial cancer is TAH+BSO+pelvic lymphadenectomy, which is considered necessary and sufficient. At present, the addition of PA lymphadenectomy for endometrial cancer can be regarded as only an investigated protocol.

PMID 17566839  Int J Clin Oncol. 2007 Jun;12(3):176-80. doi: 10.1007/s・・・
著者: Nadeem R Abu-Rustum, Jacob D Gomez, Kaled M Alektiar, Robert A Soslow, Martee L Hensley, Mario M Leitao, Ginger J Gardner, Yukio Sonoda, Dennis S Chi, Richard R Barakat
雑誌名: Gynecol Oncol. 2009 Nov;115(2):236-8. doi: 10.1016/j.ygyno.2009.07.016. Epub 2009 Aug 9.
Abstract/Text OBJECTIVE: To describe the incidence of isolated paraaortic nodal metastasis in surgically staged endometrial cancer patients with negative pelvic lymph nodes.
METHODS: Using a prospectively maintained database we identified all cases of endometrial cancer that had both pelvic and aortic nodal dissection and determined the rate of isolated paraaortic nodal metastasis in the setting of negative pelvic nodes. For this report a satisfactory pelvic node dissection meant the identification of 8 or more pelvic nodes on final pathology.
RESULTS: 1942 endometrial cancer patients were surgically treated at our institution from 1/93 to 1/08. 847 had both pelvic and paraaortic nodes removed during surgery and identified by pathology. 734 had negative pelvic nodes with at least one paraaortic node identified. Only 12 (1.6%) had positive paraaortic nodes with negative pelvic nodes. Seven (1%) of 640 cases with 8 or more negative pelvic nodes had positive paraaortic nodes. Final grade for these cases included: G1 (2), G2 (2), G3 (1), papillary serous (1), and undifferentiated (1). Of the 570 cases with a final diagnosis of grade 1 endometrial cancer, 187 had both pelvic and aortic node dissection during the same operation, and 2/187 (1%) had a positive paraaortic node with negative pelvic nodes.
CONCLUSIONS: Isolated paraaortic nodal metastasis in the setting of negative pelvic nodes occurs in approximately 1% of surgically staged endometrial cancer cases. This low rate seems consistent for low- and high-grade lesions. Future studies looking at the incidence of isolated paraaortic nodal metastasis in the setting of negative sentinel pelvic nodes are warranted.

PMID 19666190  Gynecol Oncol. 2009 Nov;115(2):236-8. doi: 10.1016/j.yg・・・
著者: Yukiharu Todo, Hidenori Kato, Masanori Kaneuchi, Hidemichi Watari, Mahito Takeda, Noriaki Sakuragi
雑誌名: Lancet. 2010 Apr 3;375(9721):1165-72. doi: 10.1016/S0140-6736(09)62002-X. Epub 2010 Feb 24.
Abstract/Text BACKGROUND: In response to findings that pelvic lymphadenectomy does not have any therapeutic benefit for endometrial cancer, we aimed to establish whether complete, systematic lymphadenectomy, including the para-aortic lymph nodes, should be part of surgical therapy for patients at intermediate and high risk of recurrence.
METHODS: We selected 671 patients with endometrial carcinoma who had been treated with complete, systematic pelvic lymphadenectomy (n=325 patients) or combined pelvic and para-aortic lymphadenectomy (n=346) at two tertiary centres in Japan (January, 1986-June, 2004). Patients at intermediate or high risk of recurrence were offered adjuvant radiotherapy or chemotherapy. The primary outcome measure was overall survival.
FINDINGS: Overall survival was significantly longer in the pelvic and para-aortic lymphadenectomy group than in the pelvic lymphadenectomy group (HR 0.53, 95% CI 0.38-0.76; p=0.0005). This association was also recorded in 407 patients at intermediate or high risk (p=0.0009), but overall survival was not related to lymphadenectomy type in low-risk patients. Multivariate analysis of prognostic factors showed that in patients with intermediate or high risk of recurrence, pelvic and para-aortic lymphadenectomy reduced the risk of death compared with pelvic lymphadenectomy (0.44, 0.30-0.64; p<0.0001). Analysis of 328 patients with intermediate or high risk who were treated with adjuvant radiotherapy or chemotherapy showed that patient survival improved with pelvic and para-aortic lymphadenectomy (0.48, 0.29-0.83; p=0.0049) and with adjuvant chemotherapy (0.59, 0.37-1.00; p=0.0465) independently of one another.
INTERPRETATION: Combined pelvic and para-aortic lymphadenectomy is recommended as treatment for patients with endometrial carcinoma of intermediate or high risk of recurrence. If a prospective randomised or comparative cohort study is planned to validate the therapeutic effect of lymphadenectomy, it should include both pelvic and para-aortic lymphadenectomy in patients of intermediate or high risk of recurrence.
FUNDING: Japanese Foundation for Multidisciplinary Treatment of Cancer, and the Japan Society for the Promotion of Science.

Copyright 2010 Elsevier Ltd. All rights reserved.
PMID 20188410  Lancet. 2010 Apr 3;375(9721):1165-72. doi: 10.1016/S014・・・
著者: Camille C Gunderson, Amanda Nickles Fader, Kathryn A Carson, Robert E Bristow
雑誌名: Gynecol Oncol. 2012 May;125(2):477-82. doi: 10.1016/j.ygyno.2012.01.003. Epub 2012 Jan 11.
Abstract/Text OBJECTIVE: The objective of this review was to analyze published contemporary oncologic and reproductive outcomes in women with endometrial hyperplasia or cancer undergoing medical management with progestin therapy.
METHODS: A systematic review of oncologic and pregnancy outcomes in women with complex atypical hyperplasia or grade 1 adenocarcinoma was performed using a comprehensive search of the MEDLINE literature. English language studies published from 2004 to 2011 which utilized hormonal therapy were identified using key words endometrial hyperplasia, endometrial cancer, fertility preservation, hormone and progestin therapy. Fisher's exact test was used to calculate statistical differences.
RESULTS: Forty-five studies with 391 study subjects were identified. The median age was 31.7 years. Therapies included medroxyprogesterone (49%), megestrol acetate (25%), levonorgestrel intrauterine device (19%), hydroxyprogesterone caproate (0.8%), and unspecified/miscellaneous progestins (13.5%). Overall, 344 women (77.7%) demonstrated a response to hormonal therapy. After a median follow up period of 39 months, a durable complete response was noted in 53.2%. The complete response rate was significantly higher for those with hyperplasia than for women with carcinoma (65.8% vs. 48.2%, p=.002). The median time to complete response was 6 months (range, 1-18 months). Recurrence after an initial response was noted in 23.2% with hyperplasia and 35.4% with carcinoma during the study periods (p=.03). Persistent disease was observed in 14.4% of women with hyperplasia and 25.4% of women with carcinoma (p=.02). During the respective study periods, 41.2% of those with hyperplasia and 34.8% with a history of carcinoma became pregnant (p=.39), with 117 live births reported.
CONCLUSION: Based on this systematic review of the contemporary literature, endometrial hyperplasia has a significantly higher likelihood of response (66%) to hormonal therapy than grade 1 endometrial carcinoma (48%). Disease persistence is more common in women with carcinoma (25%) compared to hyperplasia (14%). Reproductive outcomes do not seem to differ between the cohorts.

Copyright © 2012 Elsevier Inc. All rights reserved.
PMID 22245711  Gynecol Oncol. 2012 May;125(2):477-82. doi: 10.1016/j.y・・・
著者: Nobuyuki Susumu, Satoru Sagae, Yasuhiro Udagawa, Kenji Niwa, Hiroyuki Kuramoto, Shinji Satoh, Ryuichi Kudo, Japanese Gynecologic Oncology Group
雑誌名: Gynecol Oncol. 2008 Jan;108(1):226-33. doi: 10.1016/j.ygyno.2007.09.029. Epub 2007 Nov 9.
Abstract/Text OBJECTIVE: To establish an optimal adjuvant therapy for intermediate- and high-risk endometrial cancer patients, we conducted a multi-center randomized phase III trial of adjuvant pelvic radiation therapy (PRT) versus cyclophosphamide-doxorubicin-cisplatin (CAP) chemotherapy in women with endometrioid adenocarcinoma with deeper than 50% myometrial invasion.
METHODS: Among 385 evaluated patients, 193 patients received PRT and 192 received CAP. The PRT group received at least 40 Gy. The CAP group received cyclophosphamide (333 mg/m2), doxorubicin (40 mg/m2) and cisplatin (50 mg/m2) every 4 weeks for 3 or more courses.
RESULTS: No statistically significant differences in progression-free survival (PFS) and overall survival (OS) were observed. The 5-year PFS rates in the PRT and CAP groups were 83.5% and 81.8% respectively, while the 5-year OS rates were 85.3% and 86.7% respectively. These rates were also not significantly different in a low- to intermediate-risk group defined as stage IC patients under 70 years old with G1/2 endometrioid adenocarcinoma. However, among 120 patients in a high- to intermediate-risk group defined as (1) stage IC in patients over 70 years old or with G3 endometrioid adenocarcinoma or (2) stage II or IIIA (positive cytology), the CAP group had a significantly higher PFS rate (83.8% vs. 66.2%, log-rank test P=0.024, hazard ratio 0.44) and higher OS rate (89.7% vs. 73.6%, log-rank test P=0.006, hazard ratio 0.24). Adverse effects were not significantly increased in the CAP group versus the PRT group.
CONCLUSION: Adjuvant chemotherapy may be a useful alternative to radiotherapy for intermediate-risk endometrial cancer.

PMID 17996926  Gynecol Oncol. 2008 Jan;108(1):226-33. doi: 10.1016/j.y・・・
著者: Khadra Galaal, Mansour Al Moundhri, Andrew Bryant, Alberto D Lopes, Theresa A Lawrie
雑誌名: Cochrane Database Syst Rev. 2014 May 15;(5):CD010681. doi: 10.1002/14651858.CD010681.pub2. Epub 2014 May 15.
Abstract/Text BACKGROUND: Approximately 13% of women diagnosed with endometrial cancer present with advanced stage disease (International Federation of Gynecology and Obstetrics (FIGO) stage III/IV). The standard treatment of advanced endometrial cancer consists of cytoreductive surgery followed by radiation therapy, or chemotherapy, or both. There is currently little agreement about which adjuvant treatment is the safest and most effective.
OBJECTIVES: To evaluate the effectiveness and safety of adjuvant chemotherapy compared with radiotherapy or chemoradiation, and to determine which chemotherapy agents are most effective in women presenting with advanced endometrial cancer (FIGO stage III/IV).
SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Collaborative Review Group's Trial Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 10 2013), MEDLINE and EMBASE up to November 2013. Also we searched electronic clinical trial registries for ongoing trials.
SELECTION CRITERIA: Randomised controlled trials (RCTs) of adjuvant chemotherapy compared with radiotherapy or chemoradiation in women with FIGO stage III and IV endometrial cancer.
DATA COLLECTION AND ANALYSIS: Two review authors selected trials, extracted data, and assessed trials for risk of bias. Where necessary, we contacted trial investigators for relevant, unpublished data. We pooled data using the random-effects model in Review Manager (RevMan) software.
MAIN RESULTS: We included four multicentre RCTs involving 1269 women with primary FIGO stage III/IV endometrial cancer. We considered the trials to be at low to moderate risk of bias. All participants received primary cytoreductive surgery. Two trials, evaluating 620 women (83% stage III, 17% stage IV), compared adjuvant chemotherapy with adjuvant radiotherapy; one trial evaluating 552 women (88% stage III, 12% stage IV) compared two chemotherapy regimens (cisplatin/doxorubicin/paclitaxel (CDP) versus cisplatin/doxorubicin (CD) treatment) in women who had all undergone adjuvant radiotherapy; and one trial contributed no data.Overall survival (OS) and progression-free survival (PFS) was longer with adjuvant chemotherapy compared with adjuvant radiotherapy (OS: hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.57 to 0.99, I² = 22%; and PFS: HR 0.74, 95% CI 0.59 to 0.92, I² = 0%). Sensitivity analysis using adjusted and unadjusted OS data, gave similar results. In subgroup analyses, the effects on survival in favour of chemotherapy were not different for stage III and IV, or stage IIIA and IIIC (tests for subgroup differences were not significant and I² = 0%). This evidence was of moderate quality. Data from one trial showed that women receiving adjuvant chemotherapy were more likely to experience haematological and neurological adverse events and alopecia, and more likely to discontinue treatment (33/194 versus 6/202; RR 5.73, 95% CI 2.45 to 13.36), than those receiving adjuvant radiotherapy. There was no statistically significant difference in treatment-related deaths between the chemotherapy and radiotherapy treatment arms (8/309 versus 5/311; Risk Ratio (RR) 1.67, 95% CI 0.55 to 5.00).There was no clear difference in PFS between intervention groups in the one trial that compared CDP versus CD (552 women; HR 0.90, 95% CI 0.69 to 1.17). We considered this evidence to be of moderate quality. Mature OS data from this trial were not yet available. Severe haematological and neurological adverse events occurred more frequently with CDP than CD.We found no trials to include of adjuvant chemotherapy versus chemoradiation in advanced endometrial cancer; however we identified one ongoing trial of this comparison.
AUTHORS' CONCLUSIONS: There is moderate quality evidence that chemotherapy increases survival time after primary surgery by approximately 25% relative to radiotherapy in stage III and IV endometrial cancer. There is limited evidence that it is associated with more adverse effects. There is some uncertainty as to whether triplet regimens offer similar survival benefits over doublet regimens in the long-term. Further research is needed to determine which chemotherapy regimen(s) are the most effective and least toxic, and whether the addition of radiotherapy further improves outcomes. A large trial evaluating the benefits and risks of adjuvant chemoradiation versus chemotherapy in advanced endometrial cancer is ongoing.

PMID 24832785  Cochrane Database Syst Rev. 2014 May 15;(5):CD010681. d・・・
著者: Hiroyuki Nomura, Daisuke Aoki, Hirofumi Michimae, Mika Mizuno, Hidekatsu Nakai, Masahide Arai, Motoi Sasagawa, Kimio Ushijima, Toru Sugiyama, Motoaki Saito, Hideki Tokunaga, Maki Matoda, Toru Nakanishi, Yoh Watanabe, Fumiaki Takahashi, Toshiaki Saito, Nobuo Yaegashi, Japanese Gynecologic Oncology Group
雑誌名: JAMA Oncol. 2019 Jun 1;5(6):833-840. doi: 10.1001/jamaoncol.2019.0001.
Abstract/Text Importance: The efficacy of taxane plus platinum regimens has been demonstrated for advanced or recurrent endometrial cancer; however, it has not been assessed in postoperative adjuvant chemotherapy for endometrial cancer.
Objective: To evaluate the clinical benefit of taxane plus platinum compared with standard doxorubicin plus cisplatin as postoperative adjuvant chemotherapy in endometrial cancer.
Design, Setting, and Participants: In this multicenter, open-label, phase 3 randomized clinical trial, patients with endometrial cancer at high-risk stage I or II or stage III or IV that did not extend beyond the abdominal cavity and had 2 cm or greater residual tumor were included from 118 institutions in Japan from November 24, 2006, to January 7, 2011. Data was analyzed from March 15, 2017, to June 30, 2017.
Interventions: Eligible patients were randomly assigned (1:1:1) to receive 6 cycles of doxorubicin, 60 mg/m2, plus cisplatin, 50 mg/m2, on day 1; docetaxel, 70 mg/m2, plus cisplatin, 60 mg/m2, on day 1; or paclitaxel, 180 mg/m2, plus carboplatin (area under the curve, 6.0 mg/mL × min) on day 1 every 3 weeks.
Main Outcomes and Measures: The primary end point was progression-free survival. Secondary end points were overall survival, occurrence of adverse events, tolerability, and status of lymph node dissection.
Results: Among 788 eligible patients, the median (SD) age was 59 (22-74) years; 263 patients were assigned to doxorubicin plus cisplatin treatment, 263 patients to docetaxel plus cisplatin treatment, and 262 patients to paclitaxel plus carboplatin treatment. The number of patients who did not complete 6 cycles was 53 (20.1%) for the doxorubicin plus cisplatin group, 45 (17.1%) for the docetaxel plus cisplatin group, and 63 (24.0%) for the paclitaxel plus carboplatin group. Tolerability of these regimens were not statistically different. After a median follow-up period of 7 years, there was no statistical difference of progression-free survival (doxorubicin plus cisplatin, 191; docetaxel plus cisplatin, 208; paclitaxel plus carboplatin, 187; P = .12) or overall survival (doxorubicin plus cisplatin, 217; docetaxel plus cisplatin, 223; paclitaxel plus carboplatin, 215; P = .67) among the 3 groups. The 5-year progression-free survival rate was 73.3% for the doxorubicin plus cisplatin group, 79.0% for the docetaxel plus cisplatin group, and 73.9% for the paclitaxel plus carboplatin group, while the 5-year overall survival rates were 82.7%, 88.1%, and 86.1%, respectively.
Conclusions and Relevance: There was no significant difference of survival among patients receiving doxorubicin plus cisplatin, docetaxel plus cisplatin, or paclitaxel plus carboplatin as postoperative adjuvant chemotherapy for endometrial cancer. Because each regimen showed adequate tolerability but different toxic effects, taxane plus platinum regimens may be a reasonable alternative to treatment with doxorubicin plus cisplatin.
Trial Registration: UMIN-CTR identifier: UMIN000000522.

PMID 30896757  JAMA Oncol. 2019 Jun 1;5(6):833-840. doi: 10.1001/jamao・・・
著者: Carien L Creutzberg, Remi A Nout, Marnix L M Lybeert, Carla C Wárlám-Rodenhuis, Jan J Jobsen, Jan-Willem M Mens, Ludy C H W Lutgens, Elisabeth Pras, Lonneke V van de Poll-Franse, Wim L J van Putten, PORTEC Study Group
雑誌名: Int J Radiat Oncol Biol Phys. 2011 Nov 15;81(4):e631-8. doi: 10.1016/j.ijrobp.2011.04.013. Epub 2011 Jun 2.
Abstract/Text PURPOSE: To evaluate the very long-term results of the randomized Post Operative Radiation Therapy in Endometrial Carcinoma (PORTEC)-1 trial for patients with Stage I endometrial carcinoma (EC), focusing on the role of prognostic factors for treatment selection and the long-term risk of second cancers.
PATIENTS AND METHODS: The PORTEC trial (1990-1997) included 714 patients with Stage IC Grade 1-2 or Stage IB Grade 2-3 EC. After surgery, patients were randomly allocated to external-beam pelvic radiotherapy (EBRT) or no additional treatment (NAT). Analysis was by intention to treat.
RESULTS: 426 patients were alive at the date of analysis. The median follow-up time was 13.3 years. The 15-year actuarial locoregional recurrence (LRR) rates were 6% for EBRT vs. 15.5% for NAT (p < 0.0001). The 15-year overall survival was 52% vs. 60% (p = 0.14), and the failure-free survival was 50% vs. 54% (p = 0.94). For patients with high-intermediate risk criteria, the 15-year overall survival was 41% vs. 48% (p = 0.51), and the 15-year EC-related death was 14% vs. 13%. Most LRR in the NAT group were vaginal recurrences (11.0% of 15.5%). The 15-year rates of distant metastases were 9% vs. 7% (p = 0.25). Second primary cancers had been diagnosed over 15 years in 19% of all patients, 22% vs. 16% for EBRT vs. NAT (p = 0.10), with observed vs. expected ratios of 1.6 (EBRT) and 1.2 (NAT) compared with a matched population (p = NS). Multivariate analysis confirmed the prognostic significance of Grade 3 for LRR (hazard ratio [HR] 3.4, p = 0.0003) and for EC death (HR 7.3, p < 0.0001), of age >60 (HR 3.9, p = 0.002 for LRR and 2.7, p = 0.01 for EC death) and myometrial invasion >50% (HR 1.9, p = 0.03 and HR 1.9, p = 0.02).
CONCLUSIONS: The 15-year outcomes of PORTEC-1 confirm the relevance of HIR criteria for treatment selection, and a trend for long-term risk of second cancers. EBRT should be avoided in patients with low- and intermediate-risk EC.

Copyright © 2011 Elsevier Inc. All rights reserved.
PMID 21640520  Int J Radiat Oncol Biol Phys. 2011 Nov 15;81(4):e631-8.・・・
著者: Henry M Keys, James A Roberts, Virginia L Brunetto, Richard J Zaino, Nick M Spirtos, Jeffrey D Bloss, Andrew Pearlman, Mitchell A Maiman, Jeffrey G Bell, Gynecologic Oncology Group
雑誌名: Gynecol Oncol. 2004 Mar;92(3):744-51. doi: 10.1016/j.ygyno.2003.11.048.
Abstract/Text BACKGROUND: Despite their low risk for recurrence, many women with endometrial adenocarcinoma receive postoperative radiation therapy (RT). This study was developed to determine if adjunctive external beam irradiation lowers the risk of recurrence and death in women with endometrial cancer International Federation of Gynaecology and Obstetrics (FIGO) stages IB, IC, and II (occult disease).
METHODS: Four hundred forty-eight consenting patients with "intermediate risk" endometrial adenocarcinoma were randomized after surgery to either no additional therapy (NAT) or whole pelvic radiation therapy (RT). They were followed to determine toxicity, date and location of recurrence, and overall survival. A high intermediate risk (HIR) subgroup of patients was defined as those with (1) moderate to poorly differentiated tumor, presence of lymphovascular invasion, and outer third myometrial invasion; (2) age 50 or greater with any two risk factors listed above; or (3) age of at least 70 with any risk factor listed above. All other eligible participants were considered to be in a low intermediate risk (LIR) subgroup.
RESULTS: Three hundred ninety-two women met all eligibility requirements (202 NAT, 190 RT). Median follow-up was 69 months. In the entire study population, there were 44 recurrences and 66 deaths (32 disease or treatment-related deaths), and the estimated 2-year cumulative incidence of recurrence (CIR) was 12% in the NAT arm and 3% in the RT arm (relative hazard (RH): 0.42; P=0.007). The treatment difference was particularly evident among the HIR subgroup (2-year CIR in NAT versus RT: 26% versus 6%; RH=0.42). Overall, radiation had a substantial impact on pelvic and vaginal recurrences (18 in NAT and 3 in RT). The estimated 4-year survival was 86% in the NAT arm and 92% for the RT arm, not significantly different (RH: 0.86; P=0.557).
CONCLUSIONS: Adjunctive RT in early stage intermediate risk endometrial carcinoma decreases the risk of recurrence, but should be limited to patients whose risk factors fit a high intermediate risk definition.

PMID 14984936  Gynecol Oncol. 2004 Mar;92(3):744-51. doi: 10.1016/j.yg・・・
著者: ASTEC/EN.5 Study Group, P Blake, Ann Marie Swart, J Orton, H Kitchener, T Whelan, H Lukka, E Eisenhauer, M Bacon, D Tu, M K B Parmar, C Amos, C Murray, W Qian
雑誌名: Lancet. 2009 Jan 10;373(9658):137-46. doi: 10.1016/S0140-6736(08)61767-5. Epub 2008 Dec 16.
Abstract/Text BACKGROUND: Early endometrial cancer with low-risk pathological features can be successfully treated by surgery alone. External beam radiotherapy added to surgery has been investigated in several small trials, which have mainly included women at intermediate risk of recurrence. In these trials, postoperative radiotherapy has been shown to reduce the risk of isolated local recurrence but there is no evidence that it improves recurrence-free or overall survival. We report the findings from the ASTEC and EN.5 trials, which investigated adjuvant external beam radiotherapy in women with early-stage disease and pathological features suggestive of intermediate or high risk of recurrence and death from endometrial cancer.
METHODS: Between July, 1996, and March, 2005, 905 (789 ASTEC, 116 EN.5) women with intermediate-risk or high-risk early-stage disease from 112 centres in seven countries (UK, Canada, Poland, Norway, New Zealand, Australia, USA) were randomly assigned after surgery to observation (453) or to external beam radiotherapy (452). A target dose of 40-46 Gy in 20-25 daily fractions to the pelvis, treating five times a week, was specified. Primary outcome measure was overall survival, and all analyses were by intention to treat. These trials were registered ISRCTN 16571884 (ASTEC) and NCT 00002807 (EN.5).
FINDINGS: After a median follow-up of 58 months, 135 women (68 observation, 67 external beam radiotherapy) had died. There was no evidence that overall survival with external beam radiotherapy was better than observation, hazard ratio 1.05 (95% CI 0.75-1.48; p=0.77). 5-year overall survival was 84% in both groups. Combining data from ASTEC and EN.5 in a meta-analysis of trials confirmed that there was no benefit in terms of overall survival (hazard ratio 1.04; 95% CI 0.84-1.29) and can reliably exclude an absolute benefit of external beam radiotherapy at 5 years of more than 3%. With brachytherapy used in 53% of women in ASTEC/EN.5, the local recurrence rate in the observation group at 5 years was 6.1%.
INTERPRETATION: Adjuvant external beam radiotherapy cannot be recommended as part of routine treatment for women with intermediate-risk or high-risk early-stage endometrial cancer with the aim of improving survival. The absolute benefit of external beam radiotherapy in preventing isolated local recurrence is small and is not without toxicity.

PMID 19070891  Lancet. 2009 Jan 10;373(9658):137-46. doi: 10.1016/S014・・・
著者: J Tate Thigpen, Mark F Brady, Howard D Homesley, John Malfetano, Brent DuBeshter, Robert A Burger, Shu Liao
雑誌名: J Clin Oncol. 2004 Oct 1;22(19):3902-8. doi: 10.1200/JCO.2004.02.088.
Abstract/Text PURPOSE: Doxorubicin and cisplatin have activity in endometrial carcinoma and at initiation of this study ranked as the most active agents. This trial of stage III, IV, or recurrent disease evaluated whether combining these agents increases response rate (RR) and prolongs progression-free survival (PFS) and overall survival (OS) over doxorubicin alone.
PATIENTS AND METHODS: Of 299 patients registered, 281 (94%) were eligible. Regimens were doxorubicin 60 mg/m(2) intravenously or doxorubicin 60 mg/m(2) plus cisplatin 50 mg/m(2) every 3 weeks until disease progression, unacceptable toxicity, or a total of 500 mg/m(2) doxorubicin.
RESULTS: There were 12 (8%) complete (CR) and 26 (17%) partial responses (PR) among 150 patients receiving doxorubicin versus 25 (19%) CRs and 30 (23%) PRs among patients receiving the combination. The overall response rate was higher among patients receiving the combination (42%) compared with patients receiving doxorubicin (25%; P =.004). Median PFS was 5.7 and 3.8 months, respectively, for the combination and single agent. The PFS hazard ratio was 0.736 (95% CI, 0.577 to 0.939; P =.014). Median OS was 9.0 and 9.2 months, respectively, for the combination and single agent. Overall death rates were similar in the two groups (hazard ratio, 0.928; 95% CI, 0.727 to 1.185). Nausea, vomiting, and hematologic toxicities were common. The combination produced more grade 3 to 4 leukopenia (62% v 40%), thrombocytopenia (14% v 2%), anemia (22% v 4%), and nausea/vomiting (13% v 3%).
CONCLUSION: Adding cisplatin to doxorubicin in advanced endometrial carcinoma improves RR and PFS with a negligible impact on OS and produces increased toxicity. These results have served as a building block for subsequent phase III trials in patients with disseminated and high-risk limited endometrial carcinoma.

PMID 15459211  J Clin Oncol. 2004 Oct 1;22(19):3902-8. doi: 10.1200/JC・・・
著者: Gini F Fleming, Virginia L Brunetto, David Cella, Katherine Y Look, Gary C Reid, Adnan R Munkarah, Richard Kline, Robert A Burger, Annekathryn Goodman, R Tucker Burks
雑誌名: J Clin Oncol. 2004 Jun 1;22(11):2159-66. doi: 10.1200/JCO.2004.07.184.
Abstract/Text PURPOSE: To determine whether the addition of paclitaxel to doxorubicin plus cisplatin improves overall survival (OS) in women with advanced or recurrent endometrial carcinoma. Secondary comparisons included progression-free survival (PFS), response rate (RR), and toxicities.
PATIENTS AND METHODS: Eligible, consenting patients received doxorubicin 60 mg/m(2) and cisplatin 50 mg/m(2) (AP), or doxorubicin 45 mg/m(2) and cisplatin 50 mg/m(2) (day 1), followed by paclitaxel 160 mg/m(2) (day 2) with filgrastim support (TAP). The initial doxorubicin dose in the AP arm was reduced to 45 mg/m(2) in patients with prior pelvic radiotherapy and those older than 65 years. Both regimens were repeated every 3 weeks to a maximum of seven cycles. Patients completed a neurotoxicity questionnaire before each cycle.
RESULTS: Two hundred seventy-three women (10 ineligible) were registered. Objective response (57% v 34%; P <.01), PFS (median, 8.3 v 5.3 months; P <.01), and OS (median, 15.3 v 12.3 months; P =.037) were improved with TAP. Treatment was hematologically well tolerated, with only 2% of patients receiving AP, and 3% of patients receiving TAP experiencing neutropenic fever. Neurologic toxicity was worse for those receiving TAP, with 12% grade 3, and 27% grade 2 peripheral neuropathy, compared with 1% and 4%, respectively, in those receiving AP. Patient-reported neurotoxicity was significantly higher in the TAP arm following two cycles of therapy.
CONCLUSION: TAP significantly improves RR, PFS, and OS compared with AP. Evaluation of this regimen in the high-risk adjuvant setting is warranted, but close attention should be paid to the increased risk of peripheral neuropathy.

PMID 15169803  J Clin Oncol. 2004 Jun 1;22(11):2159-66. doi: 10.1200/J・・・

ページ上部に戻る

戻る

さらなるご利用にはご登録が必要です。

こちらよりご契約または優待日間無料トライアルお申込みをお願いします。

(※トライアルご登録は1名様につき、一度となります)


ご契約の場合はご招待された方だけのご優待特典があります。

以下の優待コードを入力いただくと、

契約期間が通常12ヵ月のところ、14ヵ月ご利用いただけます。

優待コード: (利用期限:まで)

ご契約はこちらから