Transforming renal cell carcinoma outcomes: The paradigm shift influenced by immune checkpoint inhibitors.

Abstract

e16559 Background: Renal Cell Carcinoma (RCC) is a malignancy that arises from the renal tubular epithelial cells. It has distinct sub-types with clear cell carcinoma accounting for 75%-85% of tumors. The use of immune checkpoint inhibitors (ICI) since 2015 has revolutionized the treatment of RCC. The purpose of this study is to determine the survival trends in patients with RCC before and after the introduction of ICI. Methods: 78998 cases of RCC were collected from SEER Plus Database, 17 Registries, Nov 2024 Sub (2000-2022), using the ICD Code 8312/3. A multivariate Cox regression model was used to examine the effects of independent variables including age [continuous variable], sex [reference = males], race [ref = Caucasians], stage [ref = locoregional], median household income inflation adjusted to 2023 [ref = < 100K], and treatment including surgery, chemotherapy (CTX), XRT [ref = no Tx utilized, respectively] on the survival. Dependent variables were survival (months) and an event (1 = death, 0 = censored). All analysis was conducted using GraphPad Prism 10.6.1. Results: From 2000 to 2014, with every 1-year increase in age, the hazard of death increased by 3.6% whereas in the ICI (2015 and onwards) era it was 2.5% (p < 0.0001). Females had 13% lower risk of death compared to males pre-ICI (p < 0.0001) whereas the risk was 6% less post-ICI (p 0.0027). Distant staging had 3-fold higher risk of death compared to locoregional stage pre-ICI, while it was 4.16-fold higher risk in the post ICI (2015+) (p < 0.0001). For people with income > 100K, the risk of death was 12% lower compared to income < 100K in both time periods (p < 0.0001). Risk reduction with surgery was 65% up to 2014, but it was 72% after 2015 (p < 0.0001). HR with the use of XRT was 1.5 pre-2015 (p < 0.0001) while 0.89 from 2015 onwards (p 0.0005). Chemotherapy use had no statistical significance in the pre-ICI duration but was significant with 26% lower risk in the ICI duration (p < 0.0001). Race had no significant association with survival in both eras. Conclusions: In this large population-based retrospective analysis, survival outcomes for RCC improved consistently in the ICI era, with greater relative benefits observed across age, and treatment-related variables. The seemingly reduced benefit observed in female gender with the advent of ICI is attributable to the overall improvement male mortality during the same time period. Higher hazard risk with distant stage post-2014 highlights the possibility of either worse outcomes with newer modalities or aggressive genetic mutations. Persistent socioeconomic hazard disparities highlight the need for equitable access to evolving oncologic treatments for better outcomes. These findings suggest that advances in systemic therapy have translated into a measurable population-level survival benefit and underscore the importance of continued efforts to optimize care and address disparities in the modern era.