Long-Term Outcomes of a Multidisciplinary Treatment Strategy Using Neoadjuvant Gemcitabine Plus S-1 Based on Anatomical Resectability Classification and Lymph Node Status in Patients with Perihilar Cholangiocarcinoma

Objectives: The long-term impact of neoadjuvant chemotherapy (NAC) based on anatomical resectability for perihilar cholangiocarcinoma (PHC) remains unclear. We evaluated the mature long-term outcomes of our multidisciplinary treatment strategy based on anatomical resectability classification and regional lymph node (LN) status using gemcitabine plus S-1 (NAC-GS). Methods: Between September 2010 and August 2021, 110 consecutive PHC patients were classified as resectable (R; n = 47), borderline resectable (BR; n = 38), or unresectable locally advanced (UR-LA; n = 25) according to our anatomical resectability classification. NAC-GS was administered to patients with clinically positive LN metastasis and to BR and UR-LA patients. Long-term overall survival (OS), recurrence-free survival (RFS), and prognostic factors were evaluated. Results: NAC-GS was administered to 72 patients (65.5%). Curative-intent resection was achieved in 40 (85.1%), 25 (65.8%), and 6 (24.0%) patients in the R, BR, and UR-LA groups, respectively. In the overall cohort, anatomical resectability significantly stratified OS (p = 0.032). However, among patients who underwent curative-intent resection, OS and RFS were comparable across the three resectability groups. Those receiving NAC-GS showed favorable long-term survival despite having more advanced disease characteristics; however, this comparison was limited to selected patients who ultimately proceeded to surgery. Multivariable analysis identified preoperative serum carcinoembryonic antigen ≥5.5 ng/mL (HR: 3.174, p = 0.003), non-adjuvant therapy (HR: 2.222, p = 0.023) and pathological T4 (HR: 2.397, p = 0.037) as independent predictors of poor survival. Conclusions: Anatomical resectability was associated with long-term prognosis and the likelihood of achieving curative-intent resection. Selected patients who ultimately underwent curative-intent resection after NAC-GS showed favorable long-term outcomes; however, these findings do not establish a survival benefit of NAC-GS over upfront surgery. Prospective multi-institutional validation is warranted.