S-GRAS score and the complementary prognostic value of neutrophil-to-lymphocyte ratio in adrenocortical carcinoma: evidence for a synergistic interaction

Introduction This study aimed to assess the prognostic values of the S-GRAS model and two of the most frequently used inflammation-based scores – neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) – and to characterise the potential interaction between the two measures. Patients and methods In this single-centre, retrospective, observational cohort analysis, 67 adult patients with histologically confirmed adrenocortical carcinoma (ACC) were analysed. The S-GRAS score and the inflammation-based markers were evaluated using Kaplan-Meier survival analysis with log-rank tests, univariate and multivariate Cox proportional hazards regressions. Discriminative ability was assessed using Harrell’s C-index, later compared with likelihood ratio tests. An interaction analysis was conducted by constructing a multivariate regression with mean-centred variables and their interaction term. Results External validation on the S-GRAS scoring system demonstrated the superior discriminative ability of the model (C-index=0.765) compared to its constituents. Our sub-analysis on 42 patients identified NLR as a significant predictor of mortality (HR = 3.1; p=0.008), whilst PLR failed to reach statistical significance. Our interaction analysis revealed a significant synergistic interaction between S-GRAS and NLR (HR = 1.177, p=0.009). While both S-GRAS (C-index=0.803) and NLR (C-index=0.722) was found to be a significant predictor of survival, their joint application demonstrated superior prognostic discrimination (C-index=0.822) over their individual use (p=0.006 and p<0.001). Conclusions NLR provides independent and complementary predictive value to the well-established S-GRAS score, and their combination offers superior discrimination over each marker alone. A synergistic interaction between the two metrics is the most prominent in high-risk patient groups. External validation confirms the prognostic robustness of the S-GRAS score.