Gemcitabine-platinum combination chemotherapy initiated within 90 days after nephroureterectomy should be the new standard of care for locally advanced urothelial carcinomas of the upper urinary tract (UTUCs), findings in the Lancet show.
The Peri-Operative chemotherapy versus sUrveillance in upper Tract urothelial cancer (POUT) trial aimed to assess the efficacy of systemic platinum-based chemotherapy in patients with UTUCs. The phase 3, open-label, randomised controlled trial was carried out at 71 hospitals in the UK and included patients with UTUC after nephroureterectomy staged as either pT2-T4 pN0-N3 M0 or pTany N1-3 M0.
Participants were randomised to either surveillance or four 21-day cycles of chemotherapy. Chemotherapy was either cisplatin (70 mg/m2) or carboplatin (area under the curve [AUC] 4.5/AUC5, for glomerular filtration rate
Between 19 June 2012 and 8 November 2017, 261 participants were recruited from 57 of 71 open study sites.
Adjuvant chemotherapy significantly improved disease-free survival (hazard ratio [HR] 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).
Three-year event-free estimates were 71% (95% CI 61-78) and 46% (95% CI 36-56) for chemotherapy and surveillance, respectively.
A total of 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.
The authors concluded that gemcitabine-platinum combination chemotherapy initiated within 90 days after nephroureterectomy significantly improves disease-free survival in patients with locally advanced UTUC.
They said adjuvant platinum-based chemotherapy should be considered a new standard of care after nephroureterectomy for this patient population.