The optimal sequence of cytoreductive nephrectomy and targeted therapy of metastatic renal cell carcinoma is unclear. We compared overall survival between patients with metastatic renal cell carcinoma treated with initial cytoreductive nephrectomy with or without subsequent targeted therapy vs initial targeted therapy with or without subsequent cytoreductive nephrectomy.
We evaluated the records of patients in the NCDB (National Cancer Database) diagnosed with metastatic renal cell carcinoma between 2006 and 2013 who were treated with cytoreductive nephrectomy and/or targeted therapy. Receipt of targeted therapy after initial cytoreductive nephrectomy and cytoreductive nephrectomy after initial targeted therapy were evaluated on competing risks analyses. To account for treatment selection bias the inverse probability of treatment weighting was determined based on the propensity of initial cytoreductive nephrectomy or initial targeted therapy. Overall survival was compared between the groups by Kaplan-Meier analysis and Cox proportional hazards regression.
Of the 15,068 patients included in study 6,731 underwent initial cytoreductive nephrectomy and 8,337 received initial targeted therapy. Six months after initial cytoreductive nephrectomy 48.0% of patients received targeted therapy, of whom 15.3% died after initial cytoreductive nephrectomy prior to targeted therapy. Six months after initial targeted therapy 4.7% of patients underwent cytoreductive nephrectomy, of whom 44.9% died after initial targeted therapy prior to cytoreductive nephrectomy. Initial cytoreductive nephrectomy was more likely to be performed at academic vs community institutions (OR 2.02, 95% CI 1.69-2.43, p <0.001) while cytoreductive nephrectomy was more likely to be performed after initial targeted therapy (HR 2.60, 95% CI 1.69-4.01, p <0.001). On inverse probability of treatment weighting analysis initial cytoreductive nephrectomy was associated with improved overall survival compared to initial targeted therapy (median 16.5 vs 9.2 months, HR 0.61, 95% CI 0.59-0.64, p <0.001).
Given the greater likelihood of receiving multimodal therapy and the associated overall survival benefit, these data support cytoreductive nephrectomy as the initial approach to metastatic renal cell carcinoma in appropriate surgical candidates. Continued efforts are warranted to establish the optimal multimodal approach in these patients.
The Journal of urology. 2018 Mar 21 [Epub ahead of print]
Bimal Bhindi, Elizabeth B Habermann, Ross J Mason, Brian A Costello, Lance C Pagliaro, R Houston Thompson, Bradley C Leibovich, Stephen A Boorjian
Department of Urology, Mayo Clinic, Rochester, Minnesota., Department of Health Services Research, Mayo Clinic, Rochester, Minnesota., Department of Medical Oncology, Mayo Clinic, Rochester, Minnesota., Department of Urology, Mayo Clinic, Rochester, Minnesota. Electronic address: .