Predictive value of tumor marker index for pathological complete response following neoadjuvant chemoradiotherapy in...

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.

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.

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).

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.