英国皇家普雷斯顿医院Alison Birtle课题组探索了辅助化疗治疗上尿路尿路上皮癌的疗效。该项研究成果发表在2020年3月5日出版的《柳叶刀》杂志上。

上尿路尿路上皮癌（UTUC）很少见，与膀胱尿路上皮癌相比预后较差。对于有根治性目的的肾癌切除术后UTUC患者，辅助化疗是否有益尚无国际共识。

为了评估系统铂类化疗对UTUC患者的疗效，2012年6月19日至2017年11月8日，研究组在英国的71家医院进行了一项临床3期、开放标签、随机对照试验。招募了261例在肾结直肠切除术后分期为pT2-T4 pN0-N3 M0或pTany N1-3 M0的UTUC患者，将其按1：1随机分组，其中132例在术后90天接受吉西他滨-铂类联合化疗，129例接受监测。

接受化疗的1名患者撤回了同意书，将其排除。中位随访30.3个月后，辅助化疗显著改善了无病生存率，风险比为0.45。化疗组和监测组的3年无事件生存率分别为71%和46%。化疗组中有44%发生3级及以上紧急不良事件，与报道相符；监测组中有4%。两组均没有与治疗相关的死亡事件。

总之，肾结直肠切除术后90天内开始吉西他滨-铂类联合化疗，可显著改善局部晚期UTUC患者的无病生存期。

附：英文原文

Title: Adjuvant chemotherapy in upper tract urothelial carcinoma (the POUT trial): a phase 3, open-label, randomised controlled trial

Author: 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

Issue&Volume: 2020-03-05

Abstract: BackgroundUrothelial 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.MethodsWe 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.FindingsBetween 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.InterpretationGemcitabine–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.

DOI: 10.1016/S0140-6736(20)30415-3

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30415-3/fulltext