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Adjuvant chemotherapy in upper tract urothelial carcinoma: results of the POUT phase III randomised controlled trial

Birtle, Alison, Johnson, Mark, Chester, John, Jones, Robert, Dolling, David, Bryan, Richard, Harris, Christopher, Winterbottom, Andrew, Blacker, Anthony, Catto, James, Chakraborti, Prabir, Donovan, Jenny, Elliott, Paul, French, Ann, Jagdev, Satinder, Jenkins, Benjamin, Keeley, Francis, Kockelbergh, Roger, Powles, Thomas, Wagstaff, John, Wilson, Caroline, Todd, Rachel, Lewis, Rebecca and Hall, Emma 2020. Adjuvant chemotherapy in upper tract urothelial carcinoma: results of the POUT phase III randomised controlled trial. The Lancet 395 (10232) , pp. 1268-1277. 10.1016/S0140-6736(20)30415-3

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Abstract

Background Urothelial carcinomas of the upper urinary tract (UTUC) are rare, with poorer stage-forstage prognosis than urothelial carcinoma of the urinary bladder. No international consensus exists on the benefit of adjuvant chemotherapy for UTUC patients following nephro-ureterectomy with curative intent; the POUT trial (NCT01993979) aimed to assess the efficacy of systemic platinum-based chemotherapy Methods This phase III randomised controlled open-label trial recruited UTUC patients following nephro-ureterectomy staged as pT2-pT4 pN0-3 M0, or pTany N1-3 M0 at 71 UK hospitals. Participants were centrally assigned (1:1) to surveillance or to four 21-day cycles of intravenous chemotherapy using a minimisation algorithm with a random element. Chemotherapy was either cisplatin (70mg/m 2 ) or carboplatin (AUC4.5/AUC5, for reduced GFR (<50mL/min) only) given on day 1 and gemcitabine (1000mg/m 2 ) on days 1 and 8 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. Findings A pre-planned interim analysis met the efficacy criterion for early closure, after recruitment of 261 participants (132 chemotherapy, 129 surveillance). Participants were enrolled between 19/06/2012 and 08/11/2017 from 56/71 opened sites. One participant withdrew consent for data usage and is excluded from analyses. Chemotherapy significantly improved disease-free survival (hazard ratio 0.45; 95% CI: 0.30-0.68; p=0 . 00017) at a median follow up of 30.3 months (IQR: 18.0-47.5). Three-year event-free estimates were 71% (95% CI: 61-78) and 46% (95% CI: 36-56) for chemotherapy and surveillance respectively. Acute grade≥3 emergent adverse events were experienced by 44% (55/126) participants who started chemotherapy and 4% (5/129) managed by surveillance. There were no treatment related deaths. Interpretation Adjuvant platinum-based chemotherapy should be considered a new standard of care following nephro-ureterectomy for patients with locally advanced UTUC. Funding POUT was funded by Cancer Research UK (CRUK/11/027).

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Elsevier
ISSN: 0140-6736
Date of First Compliant Deposit: 24 February 2020
Date of Acceptance: 12 February 2020
Last Modified: 24 Nov 2020 19:12
URI: http://orca.cf.ac.uk/id/eprint/129756

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