Advancing Prognostic Accuracy Beyond Classical N Staging in Colorectal Cancer: An Observational Cohort Study to Define a Lymph Node Ratio Based Risk Score

Purpose: Lymph node involvement is critical for colorectal cancer (CRC) staging and prognosis. The lymph node ratio (LNR), defined as the ratio of metastatic to total examined lymph nodes, has shown promise as a superior prognostic metric compared to traditional TNM staging and total lymph node yield (LNY). This study compared the prognostic value of LNR, N staging, and LNY and developed an LNR-based survival risk score (LNR-SRSCRC). Secondary objectives included evaluating the impact of multidisciplinary team (MDT) care and molecular markers (KRAS, NRAS, BRAF) on survival. Patients and Methods: A population-based cohort of 2013 CRC cases (2013–2018) from the Reggio Emilia Cancer Registry was analyzed. Prognostic models, including T-LNR-M, TNM, and T-LNY-M, were compared using Harrell’s C-index, Akaike Information Criterion (AIC), and net reclassification improvement (NRI). Patients were randomly assigned to training (1026) and validation (987) cohorts. Multivariable analysis identified significant predictors, and a survival risk score (SRSCRC) was validated. The study also assessed the independent prognostic role of MDT care and molecular markers. Results: The T-LNR-M model outperformed TNM (C-index 71% vs 70%; NRI 4.7%, P = 0.002) and T-LNY-M (C-index 71% vs 70%) with the lowest AIC (8356). Predictors of mortality included T4 stage, LNR, metastasis, and age >78.6 years. LNR-SRSCRC stratified patients into low, intermediate, intermediate-high, and high-risk groups with distinct survival probabilities. Validation confirmed its prognostic accuracy (C-index 71.4%). MDT care was associated with significantly improved survival (HR = 1.63; P = 0.047), while molecular markers (KRAS, NRAS, BRAF) were not significant. Conclusion: LNR provides superior prognostic value compared to N staging or LNY. The LNR-SRSCRC enhances risk stratification and, together with MDT care, may enhance personalized CRC management. Prospective validation is warranted.