A prospective external validation of the GRade, Age, Nodes and Tumor score in the ECOG-ACRIN EA8143 PROSPER trial

TL;DR

The GRANT score, a tool for predicting cancer recurrence risk in kidney cancer patients, was successfully validated in a large clinical trial, showing better outcomes for patients with favorable scores.

Contribution

The GRANT score was prospectively validated in a phase III clinical trial for surgically treated renal cell carcinoma patients.

Findings

Patients with favorable GRANT scores had significantly longer relapse-free and overall survival compared to those with unfavorable scores.

The GRANT score showed better prognostic performance in nonclear cell renal cell carcinoma subtypes.

The model's discrimination was moderate with c-indices of 0.63 for relapse-free survival and 0.66 for overall survival.

Abstract

The GRade, Age, Nodes and Tumor (GRANT) score is one of the prognostic models recommended by international guidelines to refine recurrence risk stratification in patients with surgically treated renal cell carcinoma (RCC) and integrates age, tumor size, grade, and nodal status. In this study, we aimed to validate the GRANT score within the ECOG-ACRIN EA8143 PROSPER prospective trial.

We conducted a validation analysis of the GRANT score within the phase III randomized EA8143 PROSPER study of perioperative nivolumab in surgically treated RCC. Patients were classified into 2 risk groups, favorable (0-1 risk factors) versus unfavorable (2-4 risk factors). Relapse-free survival (RFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Model discrimination were evaluated using Harrell’s C-index.

Among 714 patients included, 58.3% were favorable and 41.7% unfavorable based on the GRANT score. Patients in the favorable group had a significantly longer median RFS (61.1 vs. 36.9 months; hazard ratio [HR]: 0.36, 95% confidence interval [CI]: 0.27-0.48, P < .001) and OS (median not reached, HR: 0.25, 95% CI: 0.15-0.42, P < .001) compared to patients in the unfavorable group. The c-index was 0.63 and 0.66 for RFS and OS, respectively. A better prognostic performance was observed among nonclear cell RCC for both RFS (HR: 0.13, 95% CI: 0.05-0.33, P < .001; c-index: 0.74) and OS (HR: 0.14, 95% CI: 0.04-0.50, P < .001; c-index 0.74).

The GRANT score was prospectively validated in the PROSPER study, demonstrating prognostic value for both RFS and OS, especially in nonclear RCC, further supporting its use in clinical practice. Clinical trial registration number: ClinicalTrials.gov, NCT03055013.

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