New standard for localized UTUC

Upper tract urothelial carcinoma (UTUC) has a worse stage-for-stage prognosis than the related disease urothelial carcinoma of the bladder. UTUC is muscle-invasive or locally advanced at diagnosis in >50% of patients and a similar proportion ultimately die of the disease. Drawing on the clinical benefits achieved with platinum-based chemotherapy for bladder cancer, Birtle et al. initiated the phase III POUT trial of adjuvant chemotherapy for patients with muscle-invasive or lymph-node-positive UTUC. Now, data from this trial support this approach as a new standard of care.

Enrolment for the POUT trial was stopped early after a preplanned interim analysis of data from 261 patients revealed a disease-free survival (DFS) benefit of chemotherapy following nephroureterectomy and resection of any known abnormal lymph nodes. Among 131 patients who received up to four cycles of gemcitabine plus carboplatin or cisplatin, estimated 3-year DFS was 71%, compared with 46% in 129 patients who underwent standard surveillance only (HR 0.45, 95% CI 0.30–0.68; P = 0.0001); 3-year metastasis-free survival was also improved (71% versus 53%; HR 0.48, 95% CI 0.31–0.74; P = 0.0007). These benefits were largely unchanged in multivariate analyses.

Unsurprisingly, chemotherapy significantly increased the risk of toxicities: grade >3 adverse events, mostly decreased neutrophil and/or platelet counts, nausea and vomiting or febrile neutropenia, occurred in 44% of patients, compared with only 4% of the surveillance group (P < 0.0001). Importantly, no treatment-related deaths occurred. Quality of life questionnaires were completed by at least 70% of patients in each group and revealed declines in mean overall global health status scores during and immediately after chemotherapy, which resolved by 12 months.

UTUC is a rare disease affecting ~2 people per 100,000. Thus, Birtle et al. should be commended for performing what is almost certainly the first dedicated phase III study of perioperative therapy for UTUC and the largest-cohort randomized controlled trial in this disease to date. Longer-term results of POUT, including overall survival data, are awaited.

This article is modified from the original in Nat. Rev. Clin. Onc. (https://doi.org/10.1038/s41571-020-0354-6).