Neoadjuvant Chemotherapy Resulting in Suboptimal CA19-9 Response is Associated with No Survival Benefit Compared to Surgery First Approach in Resectable or Borderline Resectable Pancreatic Cancer

Abstract

Introduction: Neoadjuvant chemotherapy (NAC) is gaining popularity over surgery-first (SF) approach in treating resectable and borderline resectable pancreatic ductal adenocarcinoma (PDAC). Although CA19-9 change during NAC predicts oncological outcomes among NAC patients, how patients with suboptimal CA19-9 response compare to SF patients is unknown. Methods: We retrospectively analyzed resectable and borderline resectable PDAC patients who underwent pancreaticoduodenectomy (2010-2019) at a single institution. Optimal CA19-9 response was defined as normalization and >50% reduction. We utilized Kaplan-Meier and multivariate-adjusted Cox models for statistical analysis. Overall survival (OS) was calculated from both diagnosis and surgery to account for the immortal time bias of receiving NAC. Results: 488 patients were included in this study. The multivariate-adjusted analysis demonstrated OS benefit in the NAC group only when OS was calculated from diagnosis (HR=0.77, p=0.034), but not from surgery (HR=0.89, p=0.369). However, in 57 patients who achieved optimal CA19-9 response, OS is significantly longer than the 106 patients with suboptimal CA19-9 response (39.5m vs 21.3m, p=0.004) or the 110 SF patients (39.5m vs 20.1m, p=0.001). Importantly, a suboptimal CA19-9 response conferred no OS advantage compared to SF patients in both unadjusted and multivariate-adjusted models, even when calculating OS from diagnosis (HR=0.91, p=0.601). Conclusions: Suboptimal CA19-9 NAC responses correlated with no survival benefit when compared to SF approach, even when accounting for the NAC immortal-time. This result should be verified in a multi-institutional study. Nevertheless, we underlined a possible threshold of NAC response to achieve superior survival and highlighted the necessity of efficacy assessment during NAC.