Introduction The role of consolidative nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) patients treated with immune checkpoint inhibitors (ICIs) remains unknown. As patients derive variable benefit from immunotherapy (IO), understanding how treatment response correlates with long-term outcomes could inform patient surgical selection. We thus conducted a retrospective study to evaluate whether radiographic and pathologic tumor responses after immunotherapy are associated with survival in patients undergoing CN at a high-volume academic center.

Methods We identified mRCC patients treated with at least one IO-containing regimen followed by CN between 2015 and 2024. Radiographic response was assessed using RECIST. Pathologic response was measured using percent residual viable tumor (RVT), with major pathologic response (MPR) defined as RVT <10%. Outcomes included progression-free (PFS) and overall survival (OS), analyzed using Cox proportional hazards models.

Results Sixty patients underwent CN after immunotherapy. Median time to nephrectomy was 9 months (IQR: 7, 14) and 2-year OS was 75% (95% CI: 60-85). Fifteen patients (26%) had an MPR and 21 patients (35%) had a radiographic response of the primary tumor. Radiographic response was moderately correlated with RVT (Spearman correlation 0.51, p <0.001) and was protective but not significantly associated with PFS or OS. MPR was significantly associated with PFS (HR: 0.05, 95% CI: 0.01-0.41; p=0.005) and OS (HR: 0.07, 95% CI: 0.01-0.88; p=0.04).

Conclusion Patients with MPR at nephrectomy had longer PFS and OS. Pathologic response may help guide post-nephrectomy treatment timing and sequencing, though future efforts should further validate the utility of post-IO pathologic endpoints.

The authors have declared no competing interest.

Research support: This work was supported in part by a National Institutes of Health (NIH) / National Cancer Institute cancer center support grant (P30 CA008748) and by the Mazumdar-Shaw Translational Research Initiative in Kidney Cancer. YK is supported by a National Cancer Institute T32 grant (5T32CA082088-25). RRK is supported, in part, by a Department of Defense Early Career Investigator Grant Award (KCRP-AKCI, W81XWH-21-1-0942).

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