Prognostic Value of the Vitamin B12/C-Reactive Protein Index in Resected Stage II–III Cutaneous Melanoma: Comparison with Its Individual Components

Background: Recurrence risk in completely resected stage II–III cutaneous melanoma remains incompletely defined by conventional staging alone. This study evaluated whether the baseline vitamin B12 (VB12)/C-reactive protein (CRP) index (BCI), a simple biomarker reflecting metabolic and inflammatory status, is associated with recurrence-free survival (RFS). Methods: This retrospective study included 136 patients. RFS was analyzed using Kaplan–Meier curves and Cox proportional hazards models. Receiver operating characteristic (ROC) analysis was used to determine the optimal BCI cut-off for recurrence, and a median-based cut-off was additionally examined as a sensitivity analysis. The natural logarithms (ln) of CRP, VB12, and BCI were standardized and compared in adjusted Cox models. Results: During a median follow-up of 62.0 months, recurrence occurred in 49 patients (36.0%). ROC analysis yielded an area under the curve of 0.66 (95% confidence interval [CI]: 0.57–0.76; p = 0.002), and the optimal BCI cut-off was 3386, with 65% sensitivity and 67% specificity. Patients with high BCI had significantly shorter median RFS than those with low BCI (63.5 months vs. not reached; p < 0.001). In multivariable analysis using the ROC-derived cut-off, higher Breslow thickness (hazard ratio [HR]: 1.10, 95% CI: 1.03–1.17; p = 0.002), stage III disease (HR: 2.37, 95% CI: 1.06–5.30; p = 0.035), and high BCI (HR: 2.39, 95% CI: 1.30–4.38; p = 0.005) remained independently associated with shorter RFS. The association remained significant using the median BCI cut-off (HR: 2.22, 95% CI: 1.21–4.07; p = 0.010). In head-to-head adjusted models, standardized ln(CRP) (HR per 1-standard-deviation [SD] increase: 1.57, 95% CI: 1.17–2.11; p = 0.002) and ln(BCI) (HR per 1-SD increase: 1.54, 95% CI: 1.16–2.04; p = 0.003) were associated with shorter RFS, whereas ln(VB12) was not (HR per 1-SD increase: 1.01, 95% CI: 0.80–1.28; p = 0.894). The CRP- and BCI-based models showed similar model fit. Conclusions: Higher baseline BCI was associated with shorter RFS after adjustment for clinicopathological factors in patients with resected stage II–III cutaneous melanoma. However, its prognostic performance was comparable to that of CRP alone, and its incremental value over CRP was not established. These findings are exploratory and require external validation before clinical application.