Abstract
INTRODUCTION: Despite widespread adoption of neoadjuvant chemoradiotherapy (nCRT), locally advanced rectal cancer (LARC) shows highly heterogeneous treatment responses and survival outcomes. Pretreatment biopsy-derived Immunoscore (IS(B)) and the pan-immune-inflammation value (PIV) reflect local and systemic inflammation, respectively, and each has demonstrated prognostic value in LARC. However, the prognostic impact of integrating IS(B) with PIV has not been evaluated. This study aimed to determine whether combining IS(B) and PIV to jointly assess local and systemic inflammatory profiles improves risk stratification in LARC. MATERIALS AND METHODS: We retrospectively analyzed 65 patients with LARC who underwent nCRT and surgery. IS(B) was assessed using pretreatment endoscopic biopsy specimens immunohistochemically stained for CD3 and CD8. RESULTS: Patients were stratified into three groups according to their combined PIV-IS(B) profiles: Group 1 (PIV-High and IS(B)-Low), Group 2 (mixed-risk patterns), and Group 3 (PIV-Low and IS(B)-Intermediate/High). Group 1 exhibited higher C-reactive protein levels than those of Group 3 (p = 0.043). Five-year overall survival (OS) rates were 44.4%, 78.1%, and 82.7% in Groups 1, 2, and 3, respectively (p = 0.007), whereas disease-free survival (DFS) did not differ significantly (p = 0.186). In multivariate analysis, Group 2 independently predicted OS (vs. Group 1; hazard ratio [HR] 0.190, 95% confidence interval [CI] 0.043-0.831, p = 0.027), while lymphovascular invasion predicted OS (HR 6.386, 95% CI 1.412-28.882, p = 0.016) and DFS (HR 3.683, 95% CI 1.272-10.664, p = 0.016). CONCLUSION: Integrating IS(B) and PIV provides improved prognostic stratification in patients with LARC treated with nCRT, identifying a high-risk subgroup with markedly inferior OS.