Pathologic Response to Immunotherapy Is Associated with Survival in Patients Undergoing Delayed Nephrectomy for...

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

We identified mRCC patients treated with at least one IO-containing regimen followed by CN between 2015 and 2024. A radiographic response was assessed using the Response Evaluation Criteria in Solid Tumors. A pathologic response was measured using the percentage of residual viable tumor (RVT), with a major pathologic response (MPR) defined as RVT <10%. Outcomes included progression-free (PFS) and overall (OS) survival, analyzed using Cox proportional hazards models.

Sixty patients underwent CN after IO. The median time to nephrectomy was 9 mo (interquartile range: 7, 14), and the 2-yr OS rate was 75% (95% confidence interval [CI]: 60-85%). Fifteen patients (26%) had an MPR and 21 patients (35%) had a radiographic response of the primary tumor. The radiographic response was protective but not significantly associated with PFS or OS. The MPR was significantly associated with PFS (hazard ratio [HR]: 0.05, 95% CI: 0.01-0.41; p = 0.005) and OS (HR: 0.07, 95% CI: 0.01-0.88; p = 0.039).

Patients with an MPR at nephrectomy had longer PFS and OS. A pathologic response helps guide postnephrectomy treatment timing and sequencing, although future efforts should further validate the utility of post-IO pathologic endpoints.