Advertisement

A dynamic analysis of empirical survival outcomes after pancreatectomy for pancreatic ductal adenocarcinoma

Published:December 28, 2022DOI:https://doi.org/10.1016/j.surg.2022.11.015

      Abstract

      Background

      Survival outcomes after pancreatectomy for pancreatic ductal adenocarcinoma may be biased by right-censoring. We herein analyzed a large dataset with no censored events for up to 5 years and dynamically investigated the impact of known prognostic factors, accounting for unobserved tumor characteristics.

      Methods

      Consecutive patients undergoing pancreatectomy from 2000 to July 2015 were included. The 1- to 5-year empirical survival rates were calculated, and factors associated with long-term survival (≥5 years) were analyzed using multivariable models. Dynamic analyses of survival and recurrence were conducted through landmarking, and the contribution of unobserved heterogeneity was estimated using frailty models.

      Results

      The study population included 1,048 patients. The median follow-up was 30.4 months in the whole cohort and 97.2 months in survivors. The median survival was 30.4 months, with empirical 1- to 5-year rates of 85.5%, 59.6%, 43.2%, 32.1%, and 27.5%. A favorable pathological profile was associated with 5-year survival, albeit 25.7% of long-survivors received an R1 resection, and 28.8% had N2 disease. The median recurrence-free survival was 17.2 months. At landmark analyses, baseline prognostic lost strength over time, with no independent predictors of survival being identified in the sets of patients alive at 4 and 5 years. There was a significant amount of unobserved heterogeneity in the early postoperative period.

      Conclusion

      The 5-year post-pancreatectomy empirical survival was 27.5%. Dynamic analyses showed a time-varying structure of prognostic variables and a substantial impact of unobserved tumor characteristics that may drive the disease course under the selective pressure of surgical resection and adjuvant chemotherapy.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Surgery
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Strobel O.
        • Lorenz P.
        • Hinz U.
        • et al.
        Actual five-year survival after upfront resection for pancreatic ductal adenocarcinoma: who beats the odds?.
        Ann Surg. 2022; 275: 962-971
        • Ferrone C.R.
        • Pieretti-Vanmarcke R.
        • Bloom J.P.
        • et al.
        Pancreatic ductal adenocarcinoma: long-term survival does not equal cure.
        Surgery. 2012; 152: S43-S49
        • Mehtsun W.T.
        • Hashimoto D.A.
        • Ferrone C.R.
        Status of 5-year survivors of the Whipple procedure for pancreatic adenocarcinoma.
        Adv Surg. 2019; 53: 253-269
        • Bengtsson A.
        • Andersson R.
        • Ansari D.
        The actual 5-year survivors of pancreatic ductal adenocarcinoma based on real-world data.
        Sci Rep. 2020; 1016425
        • Neoptolemos J.P.
        • Stocken D.D.
        • Friess H.
        • et al.
        A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer.
        N Eng J Med. 2004; 350: 1200-1210
        • Neoptolemos J.P.
        • Stocken D.D.
        • Bassi C.
        • et al.
        Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial.
        JAMA. 2010; 304: 1073-1081
        • Neoptolemos J.P.
        • Palmer D.H.
        • Ghaneh P.
        • et al.
        Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial.
        Lancet. 2017; 389: 1011-1024
        • Sinn M.
        • Striefler J.K.
        • Sinn B.V.
        • et al.
        Does long-term survival in patients with pancreatic cancer really exist? Results from the CONKO-001 study.
        J Surg Oncol. 2013; 108: 398-402
        • Berger A.C.
        • Winter K.
        • Hoffman J.P.
        • et al.
        Five year results of US intergroup/RTOG 9704 with postoperative CA 19-9 90 U/mL and comparison to the CONKO-001 trial.
        Int J Radiat Oncol Biol Phys. 2012; 84: e291-e297
        • Conroy T.
        • Castan F.
        • Lopez A.
        • et al.
        Five-year outcomes of FOLFIRINOX vs gemcitabine as adjuvant therapy for pancreatic cancer. A randomized clinical trial.
        JAMA Oncol. 2022; 8: 1571-1578
        • Datta J.
        • Wilson G.C.
        • D’Angelica M.I.
        • et al.
        A call for caution in overinterpreting exceptional outcomes following radical surgery for pancreatic cancer: let the data speak.
        Ann Surg. 2021; 274: e82-e84
        • Leung K.M.
        • Elashoff R.M.
        • Afifi A.A.
        Censoring issues in survival analysis.
        Annu Rev Public Health. 1997; 18: 83-104
        • Schemper M.
        • Stare J.
        Explained Variation in survival analysis.
        Stat Med. 1996; 15: 1999-2012
        • Hieke S.
        • Kleber M.
        • Konig C.
        • et al.
        Conditional survival: a useful concept to provide information on how prognosis evolves over time.
        Clin Cancer Res. 2015; 21: 1530-1536
        • Latenstein A.E.J.
        • van Roessel S.
        • van der Geest L.G.M.
        • et al.
        Conditional survival after resection for pancreatic cancer: a population-based study and prediction model.
        Ann Surg Oncol. 2020; 27: 2516-2524
        • Malleo G.
        • Maggino L.
        • Ferrone C.R.
        • et al.
        Reappraising the concept of conditional survival after pancreatectomy for ductal adenocarcinoma: a bi-institutional analysis.
        Ann Surg. 2020; 27: 1148-1155
        • Malleo G.
        • Maggino L.
        • Qadan M.
        • et al.
        Reassessment of the optimal number of examined lymph nodes in pancreatoduodenectomy for pancreatic ductal adenocarcinoma.
        Ann Surg. 2022; 276: e518-e526
        • Malleo G.
        • Maggino L.
        • Ferrone C.R.
        • et al.
        Number of examined lymph nodes and nodal status assessment in distal pancreatectomy for body/tail ductal adenocarcinoma.
        Ann Surg. 2019; 270: 1138-1146
        • Zhang B.
        • Lee G.C.
        • Qadan M.
        • et al.
        Revision of pancreatic neck margin based on intraoperative frozen section analysis is associated with improved survival in patients undergoing pancreatectomy for ductal adenocarcinoma.
        Ann Surg. 2021; 274: e134-e142
      1. National Comprehensive Cancer Network. Clinical practice guidelines in oncology. Pancreatic adenocarcinoma, version 1; 2022. Accessed July 1, 2022. https://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf.

      2. Amin M.B. Edge S.B. Greene F.L. AJCC Cancer Staging Manual. 8th ed. Springer, New York, NY2017
        • Clark T.G.
        • Bradburn M.J.
        • Love S.B.
        • Altman D.G.
        Survival analysis part I: basic concepts and first analyses.
        Br J Cancer. 2003; 89: 232-238
        • Peterson A.V.
        Expressing the Kaplan-Meier estimator as a function of empirical subsurvival functions.
        J Am Stat Assoc. 1977; 72: 845-858
        • Moore D.F.
        Applied Survival Analysis Using R.
        Springer International Publishing, Cham, Switzerland2016
        • van Houwelingen H.C.
        • Putter H.
        Dynamic Predictions in Clinical Survival Analysis.
        CRC Press, Inc, Boca Raton, FL2012
        • Putter H.
        • van Houwelingen H.C.
        Understanding landmarking and its relation with time-dependent cox regression.
        Stat Biosci. 2017; 9: 489-503
        • Wienke A.
        Frailty Models in Survival Analysis.
        CRC Press, Inc., Boca Raton, FL2011
        • Ma S.J.
        • Oladeru O.T.
        • Miccio J.A.
        • et al.
        Association of timing of adjuvant therapy with survival in patients with resected stage I to II pancreatic cancer.
        JAMA Netw Open. 2019; 2e199126
        • Maggino L.
        • Malleo G.
        • Marchegiani G.
        • et al.
        Outcomes of primary chemotherapy for borderline resectable and locally advanced pancreatic ductal adenocarcinoma.
        JAMA Surg. 2019; 154: 932-942
        • van Roessel S.
        • Kasumova G.G.
        • Verheij J.
        • et al.
        International validation of the eighth edition of the American Joint Committee on Cancer (AJCC) TNM staging system in patients with resected pancreatic cancer.
        JAMA Surg. 2018 1; 153e183617
        • Paniccia A.
        • Hosokawa P.
        • Henderson W.
        • et al.
        Characteristics of 10-year survivors of pancreatic ductal adenocarcinoma.
        JAMA Surg. 2015; 150: 701-710
        • Weniger M.
        • Miksch R.C.
        • Maisonneuve P.
        • et al.
        Improvement of survival after surgical resection of pancreatic cancer independent of adjuvant chemotherapy in the past two decades - a meta-regression.
        Eur J Surg Oncol. 2020; 46: 1516-1523
        • Groot V.P.
        • Rezaee N.
        • Wu W.
        • et al.
        Patterns, timing, and predictors of recurrence following pancreatectomy for pancreatic ductal adenocarcinoma.
        Ann Surg. 2017; 267: 936-945
        • Daamen L.A.
        • Groot V.P.
        • Besselink M.G.
        • et al.
        Detection, treatment, and survival of pancreatic cancer recurrence in the Netherlands: a nationwide analysis.
        Ann Surg. 2022; 275: 769-775
        • Daamen L.A.
        • Groot V.P.
        • Intven M.P.W.
        • et al.
        Postoperative surveillance of pancreatic cancer patients.
        Eur J Surg Oncol. 2019; 45: 1770-1777