GRANT Score: A simple, accurate algorithm for RCC

A study validating a new scoring algorithm to predict the prognosis in patients with renal cell carcinoma (RCC) showed that the calculations are accurate, fast, and easy to incorporate into clinical practice. The study was published in Annals of Oncology.

Prognostic scores that can estimate the risk of recurrence and the probability of survival after nephrectomy for RCC are helpful in counseling patients, individualizing follow-up, and choosing treatment options, but these tools are currently limited by their complexity and other shortcomings.

Sebastiano Buti, MD, PhD, from the University Hospital of Parma in Parma, Italy, and colleagues, developed a simple score called GRade, Age, Nodes, and Tumor (GRANT) based on four easily obtained parameters: the Fuhrman grade, age of the patient, pathological nodal status, and pathological tumor size. Patients with a score of 0 or 1 are classified as favorable risk, whereas patients with two or more points (risk factors) have an unfavorable risk.

The original version of the score was developed in a prospective, randomized, phase 3 trial of 310 patients with resected RCC that compared the efficacy of five years of adjuvant immunotherapy vs observation. Subgroup analysis showed benefit from adjuvant treatment of patients with tumor Fuhrman grade 1-2, age ≤60 years, pN0, and pT3a stage. Among patients with at least two of these factors, adjuvant immunotherapy had a positive effect on relapse-free survival (hazard ratio [HR]: 0.44), whereas overall survival (OS) in patients with fewer than two factors in the treatment arm was significantly reduced (HR: 2.27).

Based on this evidence, the GRANT score seemed to have predictive value for relapse and a prognostic role in patients treated with adjuvant immunotherapy.

For external validation of the GRANT score, the investigators used the population of RCC patients from the ASSURE trial, a large, multi-center, double-blind, placebo-controlled, randomized, phase 3 trial evaluating adjuvant therapy for high-risk resected kidney cancer. In addition, the authors wanted to determine the prognostic value of the new score in terms of disease-free survival (DFS) and OS, and to evaluate its possible application as predictive tool.

Patients were given one point for each parameter: age > 60 years, Fuhrman grade > 2, pathologic T-stage of T3b, T3c or T4, and pathologic N-stage other than N0 or NX. Patients with a sum of 0 or 1 were classified as favorable risk (GRANT Group 0), whereas patients with two or more points (risk factors) were classified as unfavorable risk (GRANT Group 1).

A secondary analysis in the clear cell subgroup of patients excluded all non-clear cell histologies.

A total of 1,926 cases were included in this analysis. Of these, 639 were randomized to sunitinib, 647 to sorafenib, and 640 to placebo. The Eastern Cooperative Oncology Group (ECOG) performance status (PS) and the University of California Los Angeles Integrated Staging System (UISS) were used for comparison.

Overall, 1,117 patients had a favorable score, and 809 patients had an unfavorable score. Concordance scores for DFS were 0.589, 0.581, and 0.521 according to GRANT score, UISS, and ECOG PS, respectively.

The HRs from proportional hazards models of the risk groups were similar for GRANT score (HR: 2.04, P < 0.001), UISS score (HR: 1.84, P < 0.001) and ECOG PS (HR: 1.29, P = 0.001). For OS, concordance scores were 0.613, 0.590, and 0.536 according to GRANT score, UISS and ECOG PS, respectively.

The HRs from proportional hazards models of the risk groups with OS as the endpoint were similar—HR: 2.49, 2.10, and 1.53, P < 0.001 in all cases—for GRANT score, UISS nomogram, and ECOG PS, respectively. Moreover, the GRANT algorithm carried out similarly to the UISS staging criteria in this population.

Although the main effect of the GRANT group was significant in all models, it did not appear to be predictive of benefit in terms of DFS and OS from adjuvant treatments administered in this study.

Despite a concordance score quite low for both the GRANT score and the UISS, the almost identical results demonstrate that the GRANT algorithm performs similarly to the UISS staging criteria in this population. However, the ease and simplicity could make the GRANT score preferable to others in clinical practice.

It also worked well for the clear-cell RCC subgroup, when compared with the entire population, which confirms its versatility.

However, the GRANT score may have limitations. The Fuhrman nuclear grade, which is not valid for rare histologies, was used instead of the newest grading system indicated by the International Society of Urological Pathology. In addition, the TNM classification for pT3a has been modified over time and the investigation of the predictive value of the score acquired a limited significance in the light of the negative results of the ASSURE trial.

“The GRANT score has been validated as prognostic model in a wide prospective population of patients with resected early stage RCC,” concluded the authors. “It can be useful in clinical practice and for planning future trials with adjuvant immunotherapy.”

To read more about this study, click here.