Safety and efficacy of neoadjuvant chemotherapy based on our resectability criteria for locally advanced perihilar cholangiocarcinoma

Purpose Neoadjuvant chemotherapy (NAC) is not commonly used for perihilar cholangiocarcinoma (PHC). This study evaluated the safety and efficacy of NAC for PHC. Methods Ninety-one PHC patients without metastases were treated at our department. Patients were classified as resectable (R), borderline resectable (BR), or locally advanced unresectable (LA). Upfront surgery (US) was performed for R-PHC patients without regional lymph node metastases (LNM) or those unable to tolerate NAC. The NAC regimen comprised two courses of gemcitabine-based chemotherapy for advanced PHC: R-PHC with LNM, BR, and LA. Results US and NAC were performed on 32 and 59 patients, respectively. For US, 31 patients underwent curative intent surgery (upfront-CIS). NAC caused adverse effects in 10/59 (17%), allowed 36/59 (61%) to undergo curative intent surgery (NAC-CIS) without impairing liver function, and spared 23/59 (39%) from undergoing resection (NAC-UR). Overall survival was better in the upfront-CIS and NAC-CIS groups than in the NAC-UR group (MST: 74 vs 57 vs 17 months, p < 0.001). In 59 NAC patients, tumour size response occurred in 11/11 (100%) of R, 22/33 (66.7%) of BR, and 9/15 (60.0%) of LA patients. The un-resection rate was the highest in the LA group (27% [3/11] than in R, 30% [10/33] in BR, and 67% [10/15] in LA, p = 0.039). Multivariate analyses revealed that LA and age were independent risk factors for non-resection after NAC. Conclusion was safe and contributed to improving survival in advanced PHC patients. R-PHC was responsive to NAC, but LA remains a risk factor for non-resection through NAC.