Oncological Outcomes of Delayed Nephrectomy After Optimal Response to Immune Checkpoint Inhibitors for Metastatic Renal Cell Carcinoma

Background: In the current era of immune checkpoint inhibitors (ICIs), the role and optimal timing of a nephrectomy in patients with metastatic renal cell carcinoma (mRCC) remain unknown.

Objective: To assess the oncological outcomes of patients who responded to ICI-based treatments and were subsequently treated with a delayed nephrectomy.

Design, setting, and participants: This national retrospective evaluation included 30 patients with mRCC who underwent a nephrectomy after a complete response (CR) or a major partial response (>80%) to ICI treatment at metastatic sites.

Intervention: Partial or radical nephrectomy after a favorable response to ICI treatment.

Outcome measurements and statistical analysis: Disease-free survival (DFS), progression-free survival (PFS), overall survival (OS), and potential discontinuation of systemic treatment were assessed.

Results and limitations: ICI-based treatments included ipilimumab-nivolumab (40%), ICI + tyrosine kinase inhibitor (10%), and nivolumab (50%). A delayed nephrectomy was performed after a median ICI treatment duration of 10 mo. In 19 cases (63.3%), surgeons faced difficulties due to adhesions or inflammatory changes. A complete pathological response was observed in 16.7% of patients. After a median follow-up of 19.5 mo after nephrectomy, 76.7% of patients achieved DFS. At 1 yr, 66.7% of patients were free from systemic treatment. The PFS and OS rates were, respectively, 96.7% and 100% at 1 yr, and 78.3% and 86.1% at 2 yr. Patients with a CR at metastatic sites had a better prognosis than those with a major partial response, in terms of DFS (p = 0.022) and PFS (p = 0.014).

Conclusions: Despite potentially challenging surgery, a delayed nephrectomy for patients who responded to ICI treatment provided promising oncological outcomes, and the majority of patients could discontinue systemic treatment.

Patient summary: In this study, we evaluated the clinical outcome in patients who responded well to immunotherapy, and subsequently underwent kidney ablation surgery. Three-quarters of patients experienced no recurrence, and in most cases, medical treatment could be discontinued.