Cytoreductive nephrectomy in patients with metastatic non-clear-cell renal cell carcinoma (RCC)

Objective To determine whether patients with metastatic non-clear-cell renal cell carcinoma (RCC) benefit from cytoreductive nephrectomy (CN). Patients and Methods We used the Surveillance, Epidemiology, and End Results (SEER) programme to identify a population-based sample of 4914 patients diagnosed with metastatic RCC between 2000 and 2009. Of the 4914 patients, 591 had non-clear-cell histology. The median follow-up was 20 months. The primary outcome measure was RCC-specific mortality. Results Approximately 64% of patients underwent CN. Patients with non-clear-cell histology who underwent CN had lower RCC-specific and all-cause mortality than those who did not (P < 0.001 in both cases). After adjustment for age, gender, race, marital status, year of diagnosis, geographical location and histology, the associations between CN and lower RCC-specific mortality (hazard ratio [HR] 0.62, 95% confidence interval [CI] 0.48–0.80, P < 0.001) and between CN and all-cause mortality (HR 0.45, 95% CI 0.37–0.55, P < 0.001) remained highly significant. Among patients diagnosed between 2006 and 2009 (targeted therapy era), the results remained unchanged (HR 0.50, 95% CI 0.34–0.72, P < 0.001 and HR 0.43, 95% CI 0.31–0.59, P < 0.001, respectively). An interaction model found lower all-cause mortality for all histologies after CN. Conclusions Patients from the SEER programme with metastatic non-clear-cell RCC, including those treated in the targeted therapy era, appear to derive a survival benefit from CN, an association which remained significant regardless of histological subtype. This observation suggests that CN should remain standard in patients with advanced RCC who are deemed to be surgical candidates. Keywords: clear cell, cytoreductive nephrectomy, mortality, non-clear-cell, renal cell carcinoma, survival Introduction It is estimated that 65 000 new cases of kidney cancer were diagnosed in 2012 in the United States, with 13 500 associated deaths [1]. Although the incidence of localized, asymptomatic renal cancers has increased in recent years, largely as a result of the increased use of cross-sectional abdominal imaging, about one third of patients still present with metastatic RCC [2]. An enhanced understanding of the underlying pathogenic mechanism in RCC formation has led to the development of targeted therapies against vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR), which have gained widespread use in recent years [3,4]. In patients with metastatic RCC, the role of cytoreductive nephrectomy (CN) is well established [5–7]; however, it is important to note that RCC is a heterogeneous disease with different histological and genetic subclassifications. While clear cell is the most common subtype, non-clear-cell variants account for ~15% of cases [2]. Notably, the two randomized trials that have shown the benefit of CN in patients with metastatic RCC were conducted in the pre-targeted therapy era and the results were not stratified by histological subtype [5,6]. Retrospective studies investigating CN outcomes in patients with metastatic RCC of non-clear-cell histology have generally been small and underpowered [8,9]. Consequently, the question of whether CN confers a survival benefit among patients with non-clear-cell histology remains unresolved. In addition, the issue of whether a benefit from CN exists among patients treated in the targeted therapy era also remains unclear, despite some positive evidence from retrospective studies and subgroup analysis of large clinical trials [4,8,10]. We used the Surveillance, Epidemiology, and End Results (SEER) database [11] to determine whether CN was associated with improved RCC-specific mortality and overall survival in patients with non-clear-cell, metastatic RCC and also examined this potential association in patients treated in the targeted therapy era.