Redefining operability after neoadjuvant therapy in pancreatic ductal adenocarcinoma: a biology-driven surgical framework

Supreet Kumar

doi:10.18203/2349-2902.isj20263882

Authors

Supreet Kumar Department of Surgical Gastroenterology and GI Oncosurgery, Krishna Vikash Hospital, Sambalpur, Odisha, India https://orcid.org/0000-0003-4798-9293

DOI:

https://doi.org/10.18203/2349-2902.isj20263882

Keywords:

Pancreatic ductal adenocarcinoma, Neoadjuvant therapy, Surgical decision making, Tumor regression grading, Vascular resection, Circulating tumor DNA

Abstract

Neoadjuvant therapy (NAT) has reshaped the management of pancreatic ductal adenocarcinoma (PDAC), improving systemic control and increasing margin-negative resection rates. However, it has also introduced complexity into surgical decision making. Post-treatment imaging, tumor markers, and pathologic findings frequently diverge, creating uncertainty regarding operability. Traditional anatomy-based frameworks are increasingly insufficient in the era of biologically driven therapy. The objective was to synthesize contemporary evidence and propose a practical, multidisciplinary framework for post-neoadjuvant surgical decision making in PDAC, particularly in the setting of discordant radiologic and biologic signals. A focused narrative review of PubMed-indexed literature (2015-2025) was conducted, emphasizing systematic reviews, prospective studies, and contemporary cohort analyses addressing response assessment, vascular resection, tumor regression grading, nodal downstaging, biomarker kinetics, and emerging technologies. Evidence was integrated into a structured tumor board–oriented decision framework. Post-NAT radiologic stability does not reliably indicate treatment failure, as therapy-induced fibrosis may mimic persistent vascular invasion. CA19-9 kinetics, staging laparoscopy, and patient physiologic reserve provide critical complementary information. Venous resection following NAT is oncologically justified in selected patients with favourable biology, whereas arterial resection requires stricter selection. Standardized pathology reporting, including tumor regression grading and nodal assessment, refines prognostication. Emerging tools such as circulating tumor DNA and radiomics show promise but require prospective validation. Post-neoadjuvant operability in PDAC demands integration of anatomy, biology, and patient resilience rather than reliance on a single modality. A structured, multidisciplinary framework enables biologically informed restraint or resection, ensuring that surgery is not merely technically feasible but oncologically justified.

Author Biography

Supreet Kumar, Department of Surgical Gastroenterology and GI Oncosurgery, Krishna Vikash Hospital, Sambalpur, Odisha, India

CONSULTANT

SURGICAL GASTROENTEROLOGY AND GI ONCOLOGY

INDRAPRASTHA APOLLO HOSPITALS

NEW DELHI

References

Conroy T, Hammel P, Hebbar M, Ben Abdelghani M, Wei AC, Raoul JL, et al. Canadian Cancer Trials Group and the Unicancer-GI–PRODIGE Group. FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer. N J Med. 2018;379(25):2395-406.

Tempero MA, Malafa MP, Al-Hawary M. Pancreatic adenocarcinoma, version 2.2021, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2021;19(4):439-57.

Suker M, Beumer BR, Sadot E. FOLFIRINOX for locally advanced pancreatic cancer: a systematic review and patient-level meta-analysis. Lancet Oncol. 2016;17(6):801-10.

Katz MH, Marsh R, Herman JM, Shi Q, Collison E, Venook AP, et al. Borderline resectable pancreatic cancer: need for standardization and methods for optimal clinical trial design. Ann Surgic Oncol. 2013;20(8):2787-95.

Ferrone CR, Marchegiani G, Hong TS, Ryan DP, Deshpande V, McDonnell EI, et al. Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer. Ann Surg. 2015;261(1):12-7.

Cassinotto C, Sa-Cunha A, Trillaud H. Radiological evaluation of response to neoadjuvant treatment in pancreatic cancer. Diagnost Interv Imag. 2016;97(12):1225-32.

Jenvrin A, Sartoris R, Dokmak S. Comparison of radiological and pathological tools to assess response to neoadjuvant treatment in resected pancreatic ductal adenocarcinoma patients. Ther Adv Med Oncol. 2025;17:17588359251403909.

Tang K, Lu W, Qin W, Wu Y. Neoadjuvant therapy for patients with borderline resectable pancreatic cancer: A systematic review and meta-analysis of response and resection percentages. Pancreatology. 2016;16(1):28-37.

College of American Pathologists. Protocol for the examination of specimens from patients with carcinoma of the pancreas (latest update). CAP Cancer Protocols. 2025.

Lee SM, Katz MH, Liu L, Sundar M, Wang H, Varadhachary GR, et al. Validation of a Proposed Tumor Regression Grading Scheme for Pancreatic Ductal Adenocarcinoma After Neoadjuvant Therapy as a Prognostic Indicator for Survival. Am J Surgic Pathol. 2016;40(12):1653-60.

Hank T, Hinz U, Tarantino I, Kaiser J, Niesen W, Bergmann F, et al. Validation of at least 1 mm as cut-off for resection margins for pancreatic adenocarcinoma of the body and tail. Br J Surg. 2018;105(9):1171-81.

Okada K, Uemura K, Kondo N, Sumiyoshi T, Seo S, Otsuka H, et al. Neoadjuvant therapy contributes to nodal downstaging of pancreatic cancer. Langenb Arch Surg. 2022;407(2):623-32.

Truty MJ, Kendrick ML, Nagorney DM, Smoot RL, Cleary SP, Graham RP, et al. Factors Predicting Response, Perioperative Outcomes, and Survival Following Total Neoadjuvant Therapy for Borderline/Locally Advanced Pancreatic Cancer. Ann Surg. 2021;273(2):341-9.

Cloyd JM, Ejaz A, Shen C, Dillhoff M, Williams TM, Noonan A, et al. Pathologic complete response following neoadjuvant therapy for pancreatic ductal adenocarcinoma: defining the incidence, predictors. and outcomes. Int Hepato Pancreato Biliary Assoc. 2020;22(11):1569-76.

Gudmundsdottir H, Yonkus JA, Alva-Ruiz R, Kendrick M, Smoot R, Warner S, et al. Yield of Staging Laparoscopy for Pancreatic Cancer in the Modern Era: Analysis of More than 1,000 Consecutive Patients. J Am Coll Surg. 2023;237(1):49-57.

De Rosa A, Cameron IC, Gomez D. Indications for staging laparoscopy in pancreatic cancer. HPB (Oxford). 2016;18(1):13-20.

Ballehaninna UK, Chamberlain RS. The clinical utility of serum CA19-9 in the diagnosis, prognosis and management of pancreatic adenocarcinoma. J Gastrointest Oncol. 2012;3(2):105-19.

Versteijne E, de Hingh IHJT, Homs MYV, Intven MPW, Klaase JM, van Santvoort HC, et al. Neoadjuvant Treatment for Resectable and Borderline Resectable Pancreatic Cancer: Chemotherapy or Chemoradiotherapy? Front Oncol. 2022;11:744161.

Xue K, Huang X, Zhao P, Zhang Y, Tian B. Perioperative and long-term survival outcomes of pancreatectomy with arterial resection in borderline resectable or locally advanced pancreatic cancer following neoadjuvant therapy: a systematic review and meta-analysis. Int J Surg (London, England). 2023;109(12):4309-21.

Abdelrahman AM, Goenka AH, Alva-Ruiz R. FDG-PET Predicts Neoadjuvant Therapy Response and Survival in Borderline Resectable/Locally Advanced Pancreatic Adenocarcinoma. J Natl Compr Canc Netw. 2022;20(9):1023-32.

Lee W, Oh M, Kim JS, Park Y, Kwon JW, Jun E, et al. Metabolic activity by FDG-PET/CT after neoadjuvant chemotherapy in borderline resectable and locally advanced pancreatic cancer and association with survival. Br J Surg. 2021;109(1):61-70.

Hammad AY, Hodges JC, AlMasri S, Paniccia A, Lee KK, Bahary N, et al. Evaluation of Adjuvant Chemotherapy Survival Outcomes Among Patients With Surgically Resected Pancreatic Carcinoma With Node-Negative Disease After Neoadjuvant Therapy. JAMA Surg. 2023;158(1):55-62.

Marti-Bonmati L, Cerdá-Alberich L, Pérez-Girbés A. Pancreatic cancer, radiomics and artificial intelligence. Br J Radiol. 2022;95(1137):20220072.

Yeung KTD, Kumar S, Cunningham D, Jiao LR, Bhogal RH. Surgical Outcomes Following Neoadjuvant Treatment for Locally Advanced and Borderline Resectable Pancreatic Ductal Adenocarcinoma. Ann Surg. 2024;5(3):e486.

Wittmann D, Hall WA, Christians KK, et al. Impact of Neoadjuvant Chemoradiation on Pathologic Response in Patients With Localized Pancreatic Cancer. Front Oncol. 2020;10:460.

Choi GW, Seo Y, Lee I. Evaluating Tumor Regression and Survival Outcomes in Pancreatic Ductal Adenocarcinoma After Neoadjuvant Treatment according to CAP Grading System: Clinical Usefulness and Limitations. Ann Surg Oncol. 2025;32:9956-65.

Leonhardt CS, Niesen W, Kalkum E. Prognostic relevance of the revised R status definition in pancreatic cancer: meta-analysis. BJS Open. 2022;6(2):10.

Jin WH, Mellon EA, Frakes JM, Murimwa GZ, Hodul PJ, Pimiento JM, et al. Impact of sarcopenia in borderline resectable and locally advanced pancreatic cancer patients receiving stereotactic body radiation therapy. Journal of gastrointestinal oncology, 2018;9(1):24-34.

van Dongen JC, Versteijne E, Bonsing BA, Mieog JSD, de Hingh IHJT, Festen S, et al. The yield of staging laparoscopy for resectable and borderline resectable pancreatic cancer in the PREOPANC randomized controlled trial. Eur J Surg Oncol. 2023;49(4):811-7.

Tinguely P, Hidalgo Salinas C, Staubli SM, Raptis DA, Fusai GK. . Analysis of Short-Term Outcomes in Pancreatic Surgery with Vascular Resection from a Prospective Multicenter Global Study. Ann Surg Oncol. 2025;32(12):8870-80.

Leonhardt CS, Niesen W, Kalkum E, Klotz R, Hank T, Büchler W, et al. Prognostic relevance of the revised R status definition in pancreatic cancer: meta-analysis. BJS Open. 2022;6(2):10.

Walma M, Maggino L, Smits FJ, Borggreve AS, Daamen LA, Groot VP, et al. The Difficulty of Detecting Occult Metastases in Patients with Potentially Resectable Pancreatic Cancer: Development and External Validation of a Preoperative Prediction Model. J Clin Med. 2024;13(6):1679.