Long-Term Outcomes of Anatomical and Biological Borderline Resectable Pancreatic Ductal Adenocarcinoma After Gemcitabine/S-1-Based Neoadjuvant Chemoradiotherapy

Background/Objectives: Oncological outcomes in borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) remain unclear. This long-term observational study evaluated these outcomes in patients with BR-PDAC treated with a consistent neoadjuvant chemoradiotherapy (CRT) regimen and explored host-related prognostic markers. Methods: We retrospectively analyzed 206 patients with PDAC who received neoadjuvant gemcitabine plus S-1 with concurrent radiotherapy between 2011 and 2022. Biological BR was defined as anatomically resectable disease with an initial carbohydrate antigen 19-9 (CA19-9) level ≥500 U/mL. Anatomical BR was subdivided into portal venous involvement (BR-PV) and arterial involvement (BR-A). Outcomes were compared according to resectability and surgical resection, with resectable (R) patients as a reference. Prognostic factors among resected BR patients were assessed using multivariable Cox regression analysis. Results: The median follow-up was 62.5 months. Resection rates were 85.7%, 83.3%, 69.8%, and 55.6% for R, biological BR, BR-PV, and BR-A, respectively. Although the resection rate of biological BR was similar to that of R, its survival did not differ significantly from that of anatomical BR. Across all BR subtypes, surgical resection was associated with longer overall survival. Among resected patients, the post-CRT neutrophil-lymphocyte-to-monocyte ratio (NL/M), a peripheral blood cell index, was associated with overall survival (hazard ratio 1.020, p = 0.009). Patients with a high post-CRT NL/M had poorer prognosis than those with a low NL/M (p = 0.001). Conclusions: Biological and anatomical BR-PDAC showed no significant difference in long-term survival after neoadjuvant CRT, and surgical resection was associated with longer survival across BR subtypes. Post-CRT NL/M was associated with overall survival after resection and may serve as a potential host-related prognostic marker, although further validation is needed.