Further Support for Adjuvant Chemotherapy for Upper Tract Urothelial Cancer

Final Results From the Phase 3 POUT Trial

According to updated results from the phase 3 POUT trial, the use of adjuvant chemotherapy among patients with upper tract urothelial carcinoma has been further validated, with the potential for long-term benefits.

In this randomized, open-label trial, 261 patients with muscle-invasive or lymph node-positive, nonmetastatic upper tract urothelial cancer undergoing radical nephroureterectomy were randomly assigned on a 1-to-1 basis to receive either platinum-based chemotherapy (n = 132) or surveillance (n = 129). Results of the primary outcome analysis were practice-changing, “demonstrating improved disease-free survival (DFS) [and] support[ing] the use of adjuvant gemcitabine-platinum chemotherapy” in this patient population, Alison J Birtle, MD, MBBS, MRCP, Lancashire Teaching Hospitals NHS Foundation Trust, Preston, UK, and coauthors wrote. These results report on updated DFS data and a prespecified final analysis of overall survival (OS), as well as other secondary end points including metastasis-free survival (MFS), disease-specific survival (DSS), and quality of life (QoL).

The risk of recurrence or death was reduced among those patients who received chemotherapy, with a 5-year DFS of 62% vs 45% in the surveillance arm (univariable hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.38 to 0.80; P = .001). The restricted mean survival time (RMST) for DFS was 72 months in the chemotherapy arm and 54 months in the surveillance arm, an 18-month improvement with chemotherapy (P = .003). The 5-year OS was 66% vs 57% in the chemotherapy and surveillance arms respectively (univariable HR, 0.68; 95% CI, 0.46 to 1.00; P = 0.49). The RMST for OS was 78 months vs 67 months, respectively, for a difference of 11 months (P = .036).

Dr Birtle et al, concluded, “a statistically significant OS advantage was seen in univariable analysis (P = .049) and, although nonsignificant, multivariable modeling showed a consistent positive trend.” They added that these results “add further support to the value of adjuvant systemic gemcitabine-platinum combination chemotherapy after nephroureterectomy” among patients with upper tract urothelial cancer.

Source:

Birtle AJ, Jones R, Chester J, et al. Improved disease-free survival with adjuvant chemotherapy after nephroureterectomy for upper tract urothelial cancer: Final results of the POUT trial. J Clin Oncol. Published online February 13, 2024. doi:10.1200/JCO.23.01659