Effect of stage and grade migration on cancer specific mortality in renal cell carcinoma patients, according to clear cell vs. non-clear cell histology: A contemporary population-based analysis

Objectives: To test the effect of stage and grade migration on cancer specific mortality (CSM) in renal cell carcinoma (RCC) patients, according to clear cell (ccRCC) vs. non-ccRCC histology. Methods and Materials: Within the Surveillance, Epidemiology, and End Results registry (2004–2015), we identified patients with ccRCC and non-ccRCC (papillary [papRCC], chromophobe [chRCC], sarcomatoid [sarcRCC], and collecting duct [cdRCC]). Two consecutive time groups were considered – historical (2004–2009) and contemporary era (2010–2015). Temporal trends of tumor characteristics were evaluated. Cumulative incidence plots and multivariable competing risks regression models tested the effect of year groups on CSM. Results: Overall, 24,746 and 73,228 patients with non-ccRCC and ccRCC were evaluated. Of those, 42% and 58% were recorded in historical and contemporary era. Time trend analyses showed (1) tumor size decreased for non-ccRCC (estimated annual percent changes [EAPC]: −1.1%; P <0.01) and for ccRCC (EAPC: −1.0%; P <0.01), (2) rates of G3/G4 decreased for non-ccRCC (EAPC: −0.7%; P = 0.03), but increased for ccRCC (EAPC: +1.1; P <0.01), 3) rates of node positive disease decreased for non-ccRCC (EAPC:−3.1%; P = 0.02), but were stable for ccRCC (EAPC: +0.4; P =0.5), (4) rates of metastatic disease at diagnosis decreased for non-ccRCC (EAPC: −3.2%; P <0.01), but were stable for ccRCC (EAPC: −0.6%; P = 0.1), (5) among non-ccRCC, the percentage of papRCC increased (EAPC:+1%; P <0.01), while the percentage of sarcRCC (EAPC: −7%; P <0.01) and cdRCC (EAPC: −11.2%; P <0.01) decreased. Finally, in multivariable CRR models, lower CSM was recorded for contemporary non-ccRCC (HR: 0.7; P <0.001) and ccRCC (HR: 0.8; P <0.001) patients. Conclusion: Our findings illustrate a favorable stage and grade migration and improved cancer-specific mortality in contemporary non-ccRCC. Additionally, despite absence of meaningful stage migration in ccRCC, improved cancer-specific mortality in contemporary patients was also recorded. In consequence, a 2-tiered process appears to be operational in non-ccRCC vs. a 1-tiered phenomenon in ccRCC.