CUA 2018: Comparative Survival Following Initial Cytoreductive Nephrectomy versus Initial Targeted Therapy for Metastatic Renal Cell Carcinoma

Halifax, Nova Scotia ( Bimal Bhindi, MD presented a population level analysis assessing survival following upfront cytoreductive nephrectomy (CN) versus targeted therapy (TT) for patients with metastatic RCC. The optimal sequence of CN and TT for patients with mRCC remains to be established. The CARMENA study demonstrated that sunitinib was non-inferior to CN followed by sunitinib.1. Therefore, the authors aimed to compare overall survival (OS) between patients with mRCC receiving initial CN with or without subsequent TT versus initial TT with or without subsequent CN.

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 CN, TT, or both. Those with other prior cancer history were excluded. The cumulative incidence of receiving TT after CN and CR after TT 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 CN or TT. OS from diagnosis was compared using Cox regression analyses.

The cohort included 15,068 patients, of whom 6,731 (44.7%) underwent initial CN and 8,337 (55.3%) underwent initial TT. At 6 months from diagnosis, the probability of receiving TT after CN was 46.2%, with 13.6% of patients having died after initial CN prior to receiving TT. The probability at 6 months of undergoing CN after initial TT was 4.4%, with 38.3% of this group having died prior to undergoing CN. In the IPTW analysis, baseline characteristics were balanced (standardized difference < 0.1). Initial CN was associated with improved OS compared to initial TT (median 16.5 vs 9.2 months; HR 0.62, 95%CI 0.61-0.64), as shown in Figure 1. 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.

Figure 1 – Kaplan Meyer results comparing overall survival:
UroToday CUA 2018 Kaplan Meyer results comparing overall survival

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

The limitations of this study include its observational retrospective nature, unmeasured differences between groups, and incomplete capture of subsequent therapies beyond 6 months.

1. Ravaud et al. NEJM 2018

Presented by: Bimal Bhindi, Mayo Clinic, US

Written By: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto   Twitter: @tchandra_uromd at the 73rd Canadian Urological Association Annual Meeting - June 23 - 26, 2018 - Halifax, Nova Scotia