Do patients with intermediate-risk renal carcinoma who receive adjuvant pembrolizumab really benefit in recurrence-free survival? Analysis of a cohort of nephrectomies over 10 years.

Purpose: Pembrolizumab has shown benefits as adjuvant therapy in the Keynote-564 trial, improving disease-free survival (DFS) across broad patient subgroups. However, it remains unclear if all patients, including those potentially cured by surgery alone, derive real benefits or are unnecessarily exposed to adverse effects and costs. This study aimed to evaluate DFS in Keynote-564-like patients who underwent nephrectomy without adjuvant pembrolizumab.

Methods: We included nephrectomy patients meeting Keynote-564 criteria. Clinical and pathological features were analyzed, and Cox regression was used to identify predictors. DFS and overall survival (OS) were assessed.

Results: Forty-three patients met Keynote-564 criteria (100% intermediate risk). Among them, 12 patients (28%) experienced recurrence. Significant differences between recurrent (Re+) and non-recurrent (Re-) patients were observed in ECOG ≥ 1 frequency (25% vs. 0%; p < 0.05), tumour size (9.4 vs. 6.9 cm; p = 0.02), and renal pelvis invasion (50% vs. 19%; p = 0.04). Cox regression identified ECOG ≥ 1 as a predictor of recurrence (HR = 17.97, 95% CI 1.76-187.16; p = 0.016). After a median follow-up of 59.5 months, 2-year DFS and OS were 86% and 93%, respectively. Treating only relapsed patients with pembrolizumab would have saved €1,254,167.

Conclusion: Our recurrence rate was lower than Keynote-564, whereby no strong predictors of recurrence were identified. Although ECOG ≥ 1 was statistically significant, its clinical utility remains limited. Further research is needed to determine if adjuvant pembrolizumab provides a true benefit in intermediate-risk patients.