To evaluate stage at presentation and cancer specific mortality (CSM) according to variant histology (VH) relative to clear cell renal cell carcinoma (ccRCC).
Within Surveillance, Epidemiology and End Results registry (SEER, 2001-2016), we identified VH and ccRCC patients. Cumulative incidence-plots, multivariate Cox regression models matched for stage, grade and other patient characteristics addressed CSM. Subgroup analyses relied on inverse probability treatment weighting (IPTW) according to nephrectomy (NT) type.
Of all 69,785 RCC patients, 2495 harbored VH (3.6%). Of VH patients, 70.1% (1748) harboured sarcomatoid vs. 11.2% (280) collecting duct, vs. 7.6% (190) mesenchymal, vs. 3.8% (94) neuroendocrine, vs. 2.9% (72) renal medullary, vs. 2.5% (62) mucinous tubular and spindle cell (MTSCT) and 2.0% (49) rhabdoid tumors. All VH patients exhibited more advanced TNM-stage at diagnosis than ccRCC, except for MTSCT. After matching with G4 ccRCC, collecting duct (multivariate hazard ratio (HR):1.6, p<0.01), sarcomatoid (HR:1.8, p<0.01), renal medullary (HR:1.7, p=0.1) and rhabdoid VH (HR:1.5, p=0.1) showed higher CSM than ccRCC. No CSM differences were recorded for mesenchymal, neuroendocrine and MTSCT VH. In nephrectomy-subgroup, higher CSM was recorded after partial nephrectomy (PN) than radical nephrectomy in sarcomatoid VH after IPTW and multivariate adjustment (HR=1.2, p=0.02).
TNM-stage at diagnosis is universally more advanced in VH patients, except for MTSCT. CSM is higher in collecting duct, sarcomatoid, rhabdoid and renal medullary VH, but not in other VH. PN is associated with worse survival in sarcomatoid VH, but could not be assessed in other VH due to small sample size.