Importance of time to nephrectomy in localized renal cell cancer according to histological subtype

BACKGROUND: The aim of the study was to test the effect of time to nephrectomy (TTN) >3 months on cancer-specific mortality (CSM) in localized renal cell carcinoma (RCC) according to histological subtype (clear-cell, papillary and chromophobe RCC). METHODS: Within the Surveillance, Epidemiology and End Results database (SEER; 2004-2020) we identified 18,056 T1b-2 N0 M0 RCC patients treated with nephrectomy. After propensity score matching (PSM), multivariable competing risks regression (CRR) models addressing CSM were fitted. RESULTS: TTN >3 months was recorded in 2194 (15.8%) of 13,879 clear cell, in 576 (21.7%) of 2656 papillary, and in 217 (14.8%) of 1521 chromophobe RCC patients. The proportion of TTN >3 months increased significantly over time in all three histological subtypes (all P<0.01). After PSM, 60-month CSM rates for TTN >3 vs. ≤3 months were 8.2 vs. 5.9% in clear-cell RCC, which resulted in 1.36-fold higher CSM in multivariable CRR (P<0.001). Conversely, TTN >3 vs. ≤3 months was not related to absolute or relative CSM differences in papillary (5.5 vs. 5.2%, HR: 1.17, P=0.4) and chromophobe RCC (2.3 vs. 2.8%, HR: 0.84, P=0.7). CONCLUSIONS: The proportions of TTN >3 months increased over time across all histological subtypes. However, only in clear-cell RCC, TTN >3 months was associated with higher CSM rates. In consequence, TTN >3 months should be avoided in clear-cell RCC or in all nephrectomy candidates if histological subtype is unknown. Broader use of renal mass biopsy for preoperative distinction of RCC subtypes may help prioritize surgical timing when triage or postponement is necessary.