Adjuvant pembrolizumab, approved based on the KEYNOTE-564 trial, is the standard of care for high-risk renal cell carcinoma (RCC). However, this “high-risk” eligible population is heterogeneous, and improved tools are needed to quantify individual risk and guide shared decision-making regarding the benefit of systemic therapy. We aimed to develop and validate a simple, integer-based prognostic score within a real-world cohort of KEYNOTE-564 eligible patients.
Whitin a retrospective analysis of a large institutional registry, we identified KEYNOTE-564 eligible patients. A novel prognostic scoring system predicting risk of recurrence and/or death was developed based on backward stepwise Cox regression (at 48 months, using AIC criteria). The model’s performance were assessed using a bootstrapping concordance index (C-index). Regression tree analysis identified informative cut-offs. Kaplan-Meier survival analysis was used to evaluate the score’s ability to stratify patients. The clinical utility of the score was evaluated using Decision Curve Analysis (DCA).
Starting from on the overall cohort (Table 1) we developed a model (Table 2) yealding moderate discrimination ability, with a corrected C-index of 67.6%. From this model, the following integer-based prognostic score was derived: Necrosis (1 point), M1 NED (2 points), IVC (Inferior Vena Cava) tumor thrombus (2 points), WHO tumor grade 3 (2 points), grade 4 and/or sarcomatoid features (3 points), and pT4 and/or pN+ (3 points). Four risk-sugroups with significantly different DFS outcomes at 48 months were identified (p<0.0001, Figure 1). Particularly, a risk score < 2 exhibited negligible risk of disease recurrence and or death. DCA indicated that using the risk score (cut-off of 2) to determine the administration of adjuvant therapy provides a superior net benefit compared to alternative strategies (treat all or treat none) across a wide range of clinically relevant threshold probabilities between 25-50% (Figure 2).
This novel integer-based scoring system is a simple and valid tool for DFS prognosis. It effectively stratifies recurrence risk and demonstrates clinical utility in supporting shared decision-making, helping to quantify risk within the broad KEYNOTE-564 eligible population to better select candidates for adjuvant therapy.
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