Trends in Overall Survival With Evolving Systemic Therapies For Metastatic Non-Clear Cell RCC: An Analysis Over Two Decades

Document Type

Conference Proceeding

Publication Date

3-2026

Publication Title

Journal of Clinical Oncology

Abstract

Background: Metastatic non–clear cell renal cell carcinoma (nccRCC) is a rare, heterogeneous disease historically underrepresented in trials. Over the past two decades, systemic therapies including tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (IO), and IO/TKI combinations have expanded, but their impact on survival in nccRCC remains poorly defined. Methods: We included patients diagnosed with metastatic nccRCC between 2004-2020 from National Cancer Database. We stratified patients based on therapy eras: pre-TKI, TKI, IO, and IO–TKI. We utilized Kaplan-Meier analysis and Cox proportional hazard models to study overall survival (OS)in patients with nccRCC. Results: We included 2,753 patients diagnosed with metastatic nccRCC from the NCDB. Among patients with nccRCC, those who did not receive systemic therapy had a median survival of 3.29 months (95% CI: 2.99–3.55 months). In contrast, patients who received systemic therapy had a longer median survival of 7.62 months (95% CI: 7.26–7.98 months). At 6 months, patients who did not receive systemic therapy had a survival probability of 32.9% (95% CI: 29.9–35.9%). By 12 months, survival declined further to 16.9% (95% CI: 14.7–19.5%). In contrast, patients who received systemic therapy demonstrated significantly better outcomes. At 6 months, survival probability was 62.1% (95% CI: 59.5–64.6%), and at 12 months, survival remained 27.6% (95% CI: 25.3–30.0%). Patients who received systemic therapy had 18% less risk of death compared to patients who did not receive systemic therapy. Additionally, each subsequent year of diagnosis had HR of 0.96 (95% CI: 0.95–0.97, p = 0.00) compared to previous year. Conclusions: Patients with metastatic nccRCC who received systemic therapy lived longer than those who did not (median 7.6 vs 3.3 months; ~18% lower mortality risk). Year-over-year survival gains (HR 0.96; p,0.001) align with wider use of TKIs, IO, and IO–TKI regimens. Given persistently modest survival, prioritizing enrollment in subtype-specific trials and ensuring timely access to active combinations should be central to care.

Volume

44

Issue

7 Suppl

First Page

474

Comments

American Society of Clincal Oncology (ASCO) Genitourinary Cancers Symposium, February 26-28, 2026, San Francisco, CA

Last Page

474

DOI

10.1200/JCO.2026.44.7_suppl.474

Link to Full Text

Share

COinS