Survival Analysis of Conversion Surgery in Borderline Resectable and Locally Advanced Unresectable Pancreatic Ductal Adenocarcinoma Addressing Selection and Immortal Time Bias: A Retrospective Single-Center Study.

ABSTRACT

BACKGROUND: The purpose of this study was to provide a detailed evaluation of the oncological advantages of surgery following neoadjuvant chemotherapy (NAC) for patients with borderline resectable (BR) or unresectable (UR) pancreatic ductal adenocarcinoma (PDAC), with a focus on minimizing biases. Recently, NAC has become the standard care for BR or UR locally advanced (UR-LA) PDAC, however, many studies have assessed survival benefits and favorable variables without consideration for biases, particularly immortal time bias. PATIENTS AND METHODS: This study included patients diagnosed with BR or UR-LA PDAC at Juntendo University Hospital from 2019 to 2022. To mitigate bias, we applied methods such as propensity score matching (PSM), time-dependent covariate Cox proportional hazard regression analysis (TDC), landmark analysis, and multivariable Cox proportional hazards regression model. RESULTS: The study analyzed 124 patients, dividing them into a surgery group (n = 57) and a chemotherapy-only group (n = 67). After PSM, there were 21 matched pairs. Survival analysis using TDC analysis showed that the surgery group had significantly better overall survival compared with the chemotherapy-only group in both the entire cohort and the matched pairs. Cox regression analysis of the entire cohort also revealed a similar superiority of surgery, while the landmark analysis showed varying results depending on the landmark setting. CONCLUSIONS: After careful adjustment for selection and immortal time biases, surgery following NAC appears to significantly extend survival in patients with BR or UR PDAC.