Research Article|Articles in Press

Regret affects the choice between neoadjuvant therapy and upfront surgery for potentially resectable pancreatic cancer

Published:March 15, 2023DOI:



      When treating potentially resectable pancreatic adenocarcinoma, therapeutic decisions are left to the sensibility of treating clinicians who, faced with a decision that post hoc can be proven wrong, may feel a sense of regret that they want to avoid. A regret-based decision model was applied to evaluate attitudes toward neoadjuvant therapy versus upfront surgery for potentially resectable pancreatic adenocarcinoma.


      Three clinical scenarios describing high-, intermediate-, and low-risk disease-specific mortality after upfront surgery were presented to 60 respondents (20 oncologists, 20 gastroenterologists, and 20 surgeons). Respondents were asked to report their regret of omission and commission regarding neoadjuvant chemotherapy on a scale between 0 (no regret) and 100 (maximum regret). The threshold model and a multilevel mixed regression were applied to analyze respondents’ attitudes toward neoadjuvant therapy.


      The lowest regret of omission was elicited in the low-risk scenario, and the highest regret in the high-risk scenario (P < .001). The regret of the commission was diametrically opposite to the regret of omission (P ≤ .001). The disease-specific threshold mortality at which upfront surgery is favored over the neoadjuvant therapy progressively decreased from the low-risk to the high-risk scenarios (P ≤ .001). The nonsurgeons working in or with lower surgical volume centers (P = .010) and surgeons (P = .018) accepted higher disease-specific mortality after upfront surgery, which resulted in the lower likelihood of adopting neoadjuvant therapy.


      Regret drives decision making in the management of pancreatic adenocarcinoma. Being a surgeon or a specialist working in surgical centers with lower patient volumes reduces the likelihood of recommending neoadjuvant therapy.

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        • Mokdad A.A.
        • Minter R.M.
        • Zhu H.
        • et al.
        Neoadjuvant therapy followed by resection versus upfront resection for resectable pancreatic cancer: a propensity score matched analysis.
        J Clin Oncol. 2017; 35: 515-522
        • da Costa Jr., W.L.
        • Tran Cao H.S.
        • Sheetz K.H.
        • Gu X.
        • Norton E.C.
        • Massarweh N.N.
        Comparative effectiveness of neoadjuvant therapy and upfront resection for patients with resectable pancreatic adenocarcinoma: an instrumental variable analysis.
        Ann Surg Oncol. 2021; 28: 3186-3195
        • Reni M.
        • Balzano G.
        • Zanon S.
        • et al.
        Safety and efficacy of pre-operative or postoperative chemotherapy for resectable pancreatic adenocarcinoma (PACT-15): a randomised, open-label, phase 2-3 trial.
        Lancet Gastroenterol Hepatol. 2018; 3: 413-423
        • Cucchetti A.
        • Crippa S.
        • Dajti E.
        • et al.
        Trial sequential analysis of randomized controlled trials on neoadjuvant therapy for resectable pancreatic cancer.
        Eur J Surg Oncol. 2022; 48: 1994-2001
        • Djulbegovic B.
        • Tsalatsanis A.
        • Mhaskar R.
        • Hozo I.
        • Miladinovic B.
        • Tuch H.
        Eliciting regret improves decision making at the end of life.
        Eur J Cancer. 2016; 68: 27-37
        • Tsalatsanis A.
        • Hozo I.
        • Djulbegovic B.
        Acceptable regret model in the end-of-life setting: patients require high level of certainty before forgoing management recommendations.
        Eur J Cancer. 2017; 75: 159-166
        • Cucchetti A.
        • Djulbegovic B.
        • Tsalatsanis A.
        • et al.
        When to perform hepatic resection for intermediate-stage hepatocellular carcinoma.
        Hepatology. 2015; 61: 905-914
        • Hernandez J.M.
        • Tsalatsanis A.
        • Humphries L.A.
        • Miladinovic B.
        • Djulbegovic B.
        • Velanovich V.
        Defining optimum treatment of patients with pancreatic adenocarcinoma using regret-based decision curve analysis.
        Ann Surg. 2014; 259: 1208-1214
        • Djulbegovic M.
        • Beckstead J.
        • Elqayam S.
        • et al.
        Thinking styles and regret in physicians.
        PLoS One. 2015; 10e0134038
        • Djulbegovic B.
        • Elqayam S.
        • Reljic T.
        • et al.
        How do physicians decide to treat: an empirical evaluation of the threshold model.
        BMC Med Inform Decis Mak. 2014; 14: 47
        • Tong A.
        • Sainsbury P.
        • Craig J.
        Consolidated criteria for reporting qualitative research (COREQ): a 32-item checklist for interviews and focus groups.
        Int J Qual Health Care. 2007; 19: 349-357
        • Tsalatsanis A.
        • Hozo I.
        • Vickers A.
        • Djulbegovic B.
        A regret theory approach to decision curve analysis: a novel method for eliciting decision makers’ preferences and decision-making.
        BMC Med Inform Decis Mak. 2010; 10: 51
        • Pauker S.G.
        • Kassirer J.P.
        The threshold approach to clinical decision making.
        N Engl J Med. 1980; 302: 1109-1117
        • Levy A.G.
        • Hershey J.C.
        Value-induced bias in medical decision making.
        Med Decis Making. 2008; 28: 269-276
        • Katz M.H.
        • Hu C.Y.
        • Fleming J.B.
        • Pisters P.W.
        • Lee J.E.
        • Chang G.J.
        Clinical calculator of conditional survival estimates for resected and unresected survivors of pancreatic cancer.
        Arch Surg. 2012; 147: 513-519
        • Strijker M.
        • Chen J.W.
        • Mungroop T.H.
        • et al.
        Systematic review of clinical prediction models for survival after surgery for resectable pancreatic cancer.
        Br J Surg. 2019; 106: 342-354
        • Djulbegovic B.
        • Elqayam S.
        Many faces of rationality: implications of the great rationality debate for clinical decision-making.
        J Eval Clin Pract. 2017; 23: 915-922
        • Djulbegovic B.
        • Elqayam S.
        • Dale W.
        Rational decision making in medicine: implications for overuse and underuse.
        J Eval Clin Pract. 2018; 24: 655-665
        • National Comprehensive Cancer Network
        NCCN guidelines for patients: pancreatic cancer; 2021.
        • Ducreux M.
        • Cuhna A.S.
        • Caramella C.
        • et al.
        ESMO Guidelines Committee. Cancer of the pancreas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.
        Ann Oncol. 2015; 26: v56-v68
        • Brennan M.F.
        • Kattan M.W.
        • Klimstra D.
        • Conlon K.
        Prognostic nomogram for patients undergoing resection for adenocarcinoma of the pancreas.
        Ann Surg. 2004; 240: 293-298
        • Gooiker G.A.
        • Lemmens V.E.
        • Besselink M.G.
        • et al.
        Impact of centralization of pancreatic cancer surgery on resection rates and survival.
        Br J Surg. 2014; 101: 1000-1005
        • Hsu D.S.
        • Kumar N.S.
        • Le S.T.
        • et al.
        Centralization of pancreatic cancer treatment within an integrated healthcare system improves overall survival.
        Am J Surg. 2022; 223: 1035-1039
        • Cucchetti A.
        • Evans D.
        • Casadei-Gardini A.
        • et al.
        The perceived ability of gastroenterologists, hepatologists and surgeons can bias medical decision making.
        Int J Environ Res Public Health. 2020; 17: 1058