Update on Use of Perioperative Chemotherapy for High-Grade Upper Tract Urothelial Cancer

By: Celeste L. Dixon
Posted: Tuesday, March 21, 2023

Neoadjuvant chemotherapy with gemcitabine and split-dose cisplatin for high-risk upper tract urothelial carcinoma is a well-tolerated, effective therapy that does not seem to significantly delay surgery and has evidence of pathologic response associated with favorable survival outcomes, new study results indicate. Jonathan A. Coleman, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues believe their multicenter phase II trial—which took more than 10 years to complete because of the disease’s rarity—“is the first and only fully accrued prospective study evaluating the role of neoadjuvant chemotherapy followed by effective surgery for [this] high-risk [disease],” they wrote in the Journal of Clinical Oncology.

The study included 57 patients eligible to receive four cycles of gemcitabine and split-dose cisplatin; all proceeded to surgical resection and lymph node dissection. The primary endpoint—rate of pathologic response, defined as <ypT2N0—was reached by 36 patients (63%). Of them, 11 had a complete pathologic response (ypT0N0).

Regarding secondary endpoints, the 2- and 5-year progression-free survival rates were 89% and 72%, respectively, with a median follow-up of 3.1 years; the 2- and 5-year overall survival rates were 93% and 79%, respectively. Additionally, 51 patients (89%) tolerated at least three complete cycles of gemcitabine and split-dose cisplatin; 27 patients (47%) tolerated four cycles. Further, compared with patients who did not respond to the drug regimen, those who had a pathologic complete or partial response had improved progression-free and overall survival.

The authors contend that the data support the use of neoadjuvant chemotherapy as a standard of care for high-risk upper tract urothelial carcinoma—a disease often with a poor prognosis—with gemcitabine and split-dose cisplatin as a viable option. The alternative-dose schedule provides “favorable outcomes, potentially increasing the number of patients eligible for perioperative chemotherapy,” noted Dr. Coleman and co-investigators. “The neoadjuvant setting, during which more patients may be able to tolerate cisplatin-based therapy, [has previously seen] a paucity of prospective data.”

Disclosure: The study authors’ disclosure information can be found at ascopubs.org.

Journal of Clinical Oncology