An increase in splenic volume after first-line immunotherapy is associated with worse PFS in patients with metastatic renal cell carcinoma.

IMPORTANCE: Reliable prognostic markers for immune checkpoint inhibitor (ICI) response in metastatic renal cell carcinoma (mRCC) remain limited. OBJECTIVE: To examine the impact of splenic volume change after ICI initiation on progression-free survival (PFS) and overall survival (OS) in patients with mRCC. DESIGN: A retrospective cohort study reviewing data from 2015 to 2023. SETTING: The Emory Kidney Cancer database (single-center academic instution). PARTICIPANTS: Patients with mRCC who underwent first-line ICI treatment and had available abdominal imaging 30 days before and 60-120 days after ICI initiation. A total of 109 patients met inclusion criteria. EXPOSURE: Splenic volume change calculated as a percentage difference between baseline and follow-up imaging (median 2.8 months post-initiation) using a standardized formula, grouped into ≥10% increase and <10% increase. MAIN OUTCOMES AND MEASURES: Differences in OS and PFS assessed using Kaplan-Meier curves and multivariable Cox hazards regression models. RESULTS: A total of 109 patients met inclusion criteria. Median follow-up time was 25.2 months (IQR 11.2-41.5), during which there were 47 mortality events. Patients with a splenic volume increase ≥ 10% at a median 2.8 months after ICI initiation had worse 2-year PFS (28.5% vs 50.4%, P = .022) but not OS (69.4% vs 77.8%, P = .853) compared to patients with a < 10% increase in splenic volume. On multivariable analysis, a splenic volume increase ≥ 10% was independently associated with worse PFS (2.33 [95% CI 1.37-3.96], P = .002). CONCLUSIONS AND RELEVANCE: In patients with mRCC, a splenic volume increase ≥ 10% at a median of 2.8 months following ICI initiation is independently associated with worse survival compared to an < 10% increase. Monitoring splenic volume changes may serve as a cost-effective radiographic prognostic marker to guide treatment sequencing.