Pathological Complete Response in Patients With Resected Pancreatic Adenocarcinoma After Preoperative Chemotherapy
Authors: Stoop Thomas F. , Oba Atsushi , Wu Y. H. Andrew , Beaty Laurel E. , Colborn Kathryn L. , Janssen Boris V. , Al-Musawi Mohammed H. , Franco Salvador Rodriguez , Sugawara Toshitaka , Franklin Oskar , Jain Ajay , Saiura Akio , Sauvanet Alain , Coppola Alessandro , Javed Ammar A. , Groot Koerkamp Bas , Miller Braden N. , Mack Claudia E. , Hashimoto Daisuke , Caputo Damiano , Kleive Dyre , Sereni Elisabetta , Belfiori Giulio , Ichida Hirofumi , van Dam Jacob L. , Dembinski Jeanne , Akahoshi Keiichi , Roberts Keith J. , Tanaka Kimitaka , Labori Knut J. , Falconi Massimo , House Michael G. , Sugimoto Motokazu , Tanabe Minoru , Gotohda Naoto , Krohn Paul S. , Burkhart Richard A. , Thakkar Rohan G. , Pande Rupaly , Dokmak Safi , Hirano Satoshi , Burgdorf Stefan K. , Crippa Stefano , van Roessel Stijn , Satoi Sohei , White Steven A. , Hackert Thilo , Nguyen Trang K. , Yamamoto Tomohisa , Nakamura Toru , Bachu Vismaya , Burns William R. , Inoue Yosuke , Takahashi Yu , Ushida Yuta , Aslami Zohra V. , Verbeke Caroline S. , Fariña Arantza , He Jin , Wilmink Johanna W. , Messersmith Wells , Verheij Joanne , Kaplan Jeffrey , Schulick Richard D. , Besselink Marc G. , Del Chiaro Marco 
Published: June 2024

Importance

Preoperative chemo(radio)therapy is increasingly used in patients with localized pancreatic adenocarcinoma, leading to pathological complete response (pCR) in a small subset of patients. However, multicenter studies with in-depth data about pCR are lacking.

Objective

To investigate the incidence, outcome, and risk factors of pCR after preoperative chemo(radio)therapy.

Design, Setting, and Participants

This observational, international, multicenter cohort study assessed all consecutive patients with pathology-proven localized pancreatic adenocarcinoma who underwent resection after 2 or more cycles of chemotherapy (with or without radiotherapy) in 19 centers from 8 countries (January 1, 2010, to December 31, 2018). Data collection was performed from February 1, 2020, to April 30, 2022, and analyses from January 1, 2022, to December 31, 2023. Median follow-up was 19 months.

Exposures

Preoperative chemotherapy (with or without radiotherapy) followed by resection.

Main Outcomes and Measures

The incidence of pCR (defined as absence of vital tumor cells in the sampled pancreas specimen after resection), its association with OS from surgery, and factors associated with pCR. Factors associated with overall survival (OS) and pCR were investigated with Cox proportional hazards and logistic regression models, respectively.

Results

Overall, 1758 patients (mean [SD] age, 64 [9] years; 879 [50.0%] male) were studied. The rate of pCR was 4.8% (n = 85), and pCR was associated with OS (hazard ratio, 0.46; 95% CI, 0.26-0.83). The 1-, 3-, and 5-year OS rates were 95%, 82%, and 63% in patients with pCR vs 80%, 46%, and 30% in patients without pCR, respectively (P &amp;lt; .001). Factors associated with pCR included preoperative multiagent chemotherapy other than (m)FOLFIRINOX ([modified] leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin) (odds ratio [OR], 0.48; 95% CI, 0.26-0.87), preoperative conventional radiotherapy (OR, 2.03; 95% CI, 1.00-4.10), preoperative stereotactic body radiotherapy (OR, 8.91; 95% CI, 4.17-19.05), radiologic response (OR, 13.00; 95% CI, 7.02-24.08), and normal(ized) serum carbohydrate antigen 19-9 after preoperative therapy (OR, 3.76; 95% CI, 1.79-7.89).

Conclusions and Relevance

This international, retrospective cohort study found that pCR occurred in 4.8% of patients with resected localized pancreatic adenocarcinoma after preoperative chemo(radio)therapy. Although pCR does not reflect cure, it is associated with improved OS, with a doubled 5-year OS of 63% compared with 30% in patients without pCR. Factors associated with pCR related to preoperative chemo(radio)therapy regimens and anatomical and biological disease response features may have implications for treatment strategies that require validation in prospective studies because they may not universally apply to all patients with pancreatic adenocarcinoma.