Long-Term Follow-Up Confirms Benefit of Adjuvant Chemotherapy for High-Risk Upper Tract Urothelial Cancer

New research supports the use of adjuvant platinum chemotherapy after radical nephroureterectomy in patients with upper tract urothelial carcinoma (UTUC) with high-risk features. This research was published in the Journal of Clinical Oncology.

“Despite decades of research, the oncology community has faced significant challenges in establishing robust evidence for the role of perioperative chemotherapy for the treatment of urothelial cancer of the bladder,” wrote Stephanie Berg, DO, Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute, Harvard Medical School in Boston, MA, and coauthors.

The Peri-Operative chemotherapy versus sUrveillance in upper Tract urothelial cancer (POUT) study has provided critical insights into the use of adjuvant platinum-based chemotherapy following nephroureterectomy in patients with high-risk UTUC. After 65 months of follow-up, the study reported a 5-year disease-free survival (DFS) rate of 62% in the chemotherapy group compared with 45% in the surveillance group, showing a significant improvement in outcomes for those receiving adjuvant therapy (hazard ratio [HR] 0.55, 95% CI, 0.38-0.80, P =.049). Additionally, the overall survival (OS) rate observed was 66% in the chemotherapy group vs 57% in the surveillance group (HR 0.68, 95% CI, 0.46-1.00, P =.049). 

Historically, treatment for UTUC has been guided by extrapolations from bladder cancer data due to the rarity of the disease, making randomized trials challenging. The POUT study marked a breakthrough by demonstrating the feasibility of conducting such trials and the safety and efficacy of platinum-based chemotherapy in improving DFS for UTUC patients. However, ongoing questions remain about whether DFS is the optimal endpoint for UTUC and whether carboplatin-based regimens can be substituted for cisplatin-based ones, particularly for patients ineligible for cisplatin.

The study's findings have implications for current treatment practices, especially considering recent trials like Checkmate 274, which evaluated adjuvant nivolumab in patients with urothelial cancer at high risk of recurrence. While cisplatin-based therapy is still supported for eligible patients, the choice between carboplatin-based chemotherapy and immune checkpoint inhibitors like nivolumab for cisplatin-ineligible patients remains a subject of debate.

As UTUC treatment evolves, the role of biomarkers, such as circulating tumor DNA (ctDNA), may offer new ways to guide therapy and improve outcomes. Ongoing clinical trials aim to further refine the use of adjuvant therapies and biomarkers to personalize treatment for UTUC, moving closer to precision medicine for this challenging cancer.

“The POUT study is a major accomplishment proving that adjuvant studies in patients with UTUC can be completed and also meeting the study's primary DFS end point informing clinical practice,” concluded the study authors.

Reference
Berg SA, Galsky MD. Understanding adjuvant therapy for upper tract urothelial carcinoma. J Clin Oncol. 2024;42(13):1459-1461. doi:10.1200/JCO.23.02679