ASCO GU 2018: Survival Following Upfront Cytoreductive Nephrectomy Versus Targeted Therapy for Metastatic Renal Cell Carcinoma

San Francisco, CA ( Dr. Bimal Bhindi and coauthors from the Mayo Clinic presented their population level analysis assessing survival following upfront cytoreductive nephrectomy versus targeted therapy for patients with metastatic RCC at this morning’s GU ASCO 2018 RCC poster session. The optimal sequence of cytoreductive nephrectomy and targeted therapy for patients with mRCC remains to be established. As such, the objective of this study was to compare overall survival (OS) between patients with mRCC receiving initial cytoreductive nephrectomy with or without subsequent targeted therapy versus initial targeted therapy with or without subsequent cytoreductive nephrectomy.

For this study, the authors used the National Cancer Database (NCDB) to identify 15,068 patients diagnosed between 2006-2013 with RCC that was metastatic at diagnosis who received cytoreductive nephrectomy, targeted therapy, or both. Those with other prior cancer history were excluded. The cumulative incidence of receiving targeted therapy after cytoreductive nephrectomy and cytoreductive nephrectomy after targeted therapy were evaluated, with death prior to second treatment as a competing risk. To account for treatment selection bias, inverse probability of treatment weighting (IPTW) was performed based on the propensity to receive initial cytoreductive nephrectomy or targeted therapy. OS from diagnosis was compared using Cox regression.

The cohort included 15,068 patients, of whom 6,731 (44.7%) underwent initial cytoreductive nephrectomy and 8,337 (55.3%) underwent initial targeted therapy. At 6 months from diagnosis, the probability of receiving targeted therapy after cytoreductive nephrectomy was 46.2%, with 13.6% of patients having died after initial cytoreductive nephrectomy prior to receiving targeted therapy. The probability at 6 months of undergoing cytoreductive nephrectomy after initial targeted therapy was 4.4%, with 38.3% of this group having died prior to undergoing cytoreductive nephrectomy. In the IPTW analysis, baseline characteristics were balanced (standardized difference < 0.1). Initial cytoreductive nephrectomy was associated with improved OS compared to initial targeted therapy (median 16.5 vs 9.2 months; HR 0.62, 95%CI 0.61-0.64). Findings were similar in all sensitivity analyses, including: (i) propensity score matching and adjustment, (ii) regression adjustment, (iii) 6-month landmark analysis, (iv) clear cell mRCC subset, and (v) exclusion of patients who had metastasectomy.

Although initial cytoreductive nephrectomy was associated improved OS versus initial targeted therapy in this national dataset, initial cytoreductive nephrectomy was associated with delays in, and even death prior to, receipt of targeted therapy. As such, while the survival data here support initial cytoreductive nephrectomy in appropriate surgical candidates, continued efforts to develop the optimal multimodal approach to these patients are warranted.

Speaker: Bimal Bhindi, Mayo Clinic, Rochester, MN

Co-Authors: Elizabeth Butzer Habermann, Ross Mason, Brian Addis Costello, Lance C. Pagliaro, Robert Houston Thompson, Bradley C. Leibovich, Stephen A. Boorjian

Written by: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md, at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA