Continuing Education
for Urology & GU Oncology Clinicians

Washington, DC ( The SUO-CTC session included a sub-session highlighting upcoming surgically relevant clinical trials, including SWOG 1931, the next cytoreductive trial presented by Dr. Hyung Kim. SWOG 1931 will be a phase III trial of immunotherapy-based combination therapy with or without cytoreductive nephrectomy for patients with metastatic renal cell carcinoma (RCC).  

Two prior New England Journal of Medicine papers have been paramount in the field of cytoreductive nephrectomy. The first, published in 2001, SWOG 8949, randomly assigned patients with metastatic RCC who were acceptable candidates for nephrectomy to undergo radical nephrectomy followed by therapy with interferon alfa-2b or to receive interferon alfa-2b therapy alone.1 The median survival of 120 eligible patients assigned to surgery followed by interferon was 11.1 months, and among the 121 eligible patients assigned to interferon alone, it was 8.1 months (p = 0.05). The difference in median survival between the two groups was independent of performance status, metastatic site, and the presence or absence of a measurable metastatic lesion. The second study, published last year, was CARMENA, where patients were randomly assigned 1:1 to undergo nephrectomy and then receive sunitinib or to receive sunitinib alone. The primary endpoint was overall survival. A total of 450 patients were enrolled and at the planned interim analysis, the median follow-up was 50.9 months, with 326 deaths observed. The results in the sunitinib-alone group were noninferior to those in the nephrectomy-sunitinib group with regard to OS (stratified HR 0.89, 95% CI 0.71-1.10; the upper boundary of the 95% CI for noninferiority, ≤1.20). The median overall survival was 18.4 months in the sunitinib-alone group and 13.9 months in the nephrectomy-sunitinib group.

Dr. Kim notes that there are several explanations for CARMENA, including that patients were higher risk than SWOG 8949, they had a greater metastatic burden, they received more effective therapy, and they received a TKI and not immunotherapy. In CARMENA, patients had immediate nephrectomy or no nephrectomy, whereas in SurTime patients had deferred nephrectomy vs immediate nephrectomy, with a better OS for the patients undergoing deferred nephrectomy.3 

The current design for SWOG 1931 is as follows:

Importantly, radical nephrectomy will be within 8 weeks of randomization and the recommendation is for systemic treatment to be held for 12 weeks during the perioperative period. Using a median OS time of 25 months for control and median OS of 37 months for intervention (HR 0.68), for 85% power, a sample size of 302 (364 assuming 20% of patients will not be randomized and 10% will be ineligible) will be required.

In summary, this trial builds on SWOG 8949, EORTC 30947, CARMENA and SurTime. Furthermore, the time is right in the setting of powerful immunotherapy combinations.

Presented by: Hyung L. Kim, MD, Director of the Cedars-Sinai Academic Urology Program, Associate Director of Surgical Research in the Samuel Oschin Comprehensive Cancer Center, Cedars Sinai Medical Center, Los Angeles, California 

Written by: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md, at the 20th Annual Meeting of the Society of Urologic Oncology (SUO), December 4 - 6, 2019,  Washington, DC