Abstract
BackgroundPrevious studies comparing primary tumor resection (PTR) to palliative treatment for advanced-stage pancreatic ductal adenocarcinoma (PDA) were limited by strong selection bias. We used multiple methods to control for confounding and selection bias to estimate the effect of PTR on survival for late-stage PDA.MethodsSurveillance, Epidemiology, and End Results (SEER) 18 registry database for 2004 through 2014 was retrieved for the present study. A total of 4322 patients with stage III (AJCC, 6th) PDA were included in this study. Propensity score matching (PSM) was performed to eliminate possible bias. In addition, instrumental variable (IV) analysis was utilized to adjust for both measured and unmeasured confounders.ResultsA total of 4322 patients with stage III PDA including 552 (12.8%) who underwent PTR, 3770 (87.2%) without PTR, were identified. In the multivariable cohort, a clear prognostic advantage of PTR was observed in overall survival (OS) (P < 0.001) and disease-specific survival (DSS) (P < 0.001) compared to patients after non-surgery therapy. In the PSM cohort, patients in PTR group showed a better OS and DSS (both P values < 0.001) compared to patients in non-surgery group. The survival benefit of PTR for stage III PDA was not observed in the two-stage residual inclusion (2SRI) model. Estimates based on this instrument indicated that patients treated with PTR had similar OS (P = 0.448) and DSS (P = 0.719). In IV analyses stratified by chemotherapy and tumor location, patients undergoing PTR had similar OS and DSS compared to patients in non-surgery group across all subgroups.ConclusionsSurvival with PTR did not differ significantly from palliative treatment in marginal patients with stage III pancreatic adenocarcinoma. High-quality randomized trials are needed to validate these results.
Highlights
Previous studies comparing primary tumor resection (PTR) to palliative treatment for advanced-stage pancreatic ductal adenocarcinoma (PDA) were limited by strong selection bias
Subgroup analyses In instrumental variable (IV) analyses stratified by chemotherapy, we found that the similar effects of PTR vs. none on patient survival were consistent across both subgroups (Table 4)
In IV analyses stratified by tumor location, we found that the similar effects of PTR vs. non-PTR on survival were consistent across all subgroups with different tumor location (Table 5)
Summary
Previous studies comparing primary tumor resection (PTR) to palliative treatment for advanced-stage pancreatic ductal adenocarcinoma (PDA) were limited by strong selection bias. We used multiple methods to control for confounding and selection bias to estimate the effect of PTR on survival for late-stage PDA. Primary tumor resection (PTR) is the only curative modality, while more than 80% of tumors were unresectable when present [2]. The 5-year survival of According to American Joint Committee on Cancer (AJCC) classification version 6, patients with stage III PDA (tumors involved celiac axis and/or superior mesenteric artery) can be divided into borderline resectable and unresectable, depending on the extent of the tumor encasement of major vessels [2, 5, 6]. Since the FOLFIRINOX regimen (irinotecan, oxaliplatin, leucovorin, and fluorouracil) was introduced in 2011 by a prospective randomized controlled trial [10], it has been reported to result in objective response rates that were 2–
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