Predictive value of tumor marker index for pathological complete response following neoadjuvant chemoradiotherapy in locally advanced rectal cancer.

BACKGROUND: Pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC) is associated with favorable outcomes; however, pre-treatment biomarkers that reliably predict pCR remain limited. We evaluated whether the Tumor Marker Index (TMI; geometric mean of normalized CEA and CA19-9) predicts pCR and examined its relationship with recurrence and survival. METHODS: This single-center retrospective study included 123 stage III LARC patients treated with nCRT followed by total mesorectal excision (2015-2022). The primary endpoint was pCR (ypT0N0). Secondary endpoints were progression-free survival (PFS) and overall survival (OS). Receiver operating characteristic (ROC) analysis assessed TMI discrimination and identified a cut-off. Predictors of pCR were evaluated by univariable and multivariable logistic regression. Systemic inflammatory markers (NLR, PLR, SII) were also analyzed. RESULTS: Median age was 67 years; 61.0% were male. pCR occurred in 18.7% (23/123). Patients with pCR had lower baseline CEA and TMI. TMI predicted pCR (AUC 0.633, 95% CI 0.509-0.756; p = 0.036); the Youden cut-off ≤ 0.79 yielded sensitivity 86.96% and NPV 92.31%. In multivariable analysis (outcome coded as non-pCR), comorbidity (aOR 3.871; p = 0.035), cT3 vs. cT2 (aOR 4.447; p = 0.026) and higher TMI (per unit; aOR 3.343; p = 0.036) independently increased the odds of non-pCR, whereas a longer RT-surgery interval (per week) reduced it (aOR 0.940; p = 0.016). NLR/PLR/SII were not independent predictors. Recurrence was lower in low-TMI patients (20.5% vs. 57.5%, p < 0.001). pCR was associated with longer PFS (91.6 vs. 62.2 months; log-rank p = 0.012) but not OS (81.9 vs. 64.2 months; p = 0.165). CONCLUSIONS: Pre-treatment TMI is an independent predictor of pCR and correlates with lower recurrence in LARC after nCRT. Given its high sensitivity/NPV at the identified threshold, TMI may support organ-preservation discussions and guide treatment intensification strategies; prospective validation is warranted.