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

Birtle, Alison, Johnson, Mark, Chester, John ORCID: https://orcid.org/0000-0002-7830-3840, 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:	19 Apr 2024 18:07
URI:	https://orca.cardiff.ac.uk/id/eprint/129756

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