The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study

Rangelova E, Stoop TF, van Ramshorst TM, Ali M, van Bodegraven EA, Javed AA, Hashimoto D, Steyerberg E, Banerjee A, Jain A, Sauvanet A, Serrablo A, Giani A, Giardino A, Zerbi A, Arshad A, Wijma AG, Coratti A, Zironda A, Socratous A, Rojas A, Halimi A, Ejaz A, Oba A, Patel BY, Björnsson B, Reames BN, Tingstedt B, Goh BK, Payá-Llorente C, Del Pozo CD, González-Abós C, Medin C, van Eijck CH, de Ponthaud C, Takishita C, Schwabl C, Månsson C, Ricci C, Thiels CA, Douchi D, Hughes DL, Kilburn D, Flanking D, Kleive D, Silva DS, Edil BH, Pando E, Moltzer E, Kauffman EF, Warren E, Bozkurt E, Sparrelid E, Thoma E, Verkolf E, Ausania F, Giannone F, Hüttner FJ, Burdio F, Souche FR, Berrevoet F, Daams F, Motoi F, Saliba G, Kazemier G, Roeyen G, Nappo G, Butturini G, Ferrari G, Kito Fusai G, Honda G, Sergeant G, Karteszi H, Takami H, Suto H, Matsumoto I, Mora-Oliver I, Frigerio I, Fabre JM, Chen J, Sham JG, Davide J, Urdzik J, de Martino J, Nielsen K, Okano K, Kamei K, Okada K, Tanaka K, Labori KJ, Goodsell KE, Alberici L, Webber L, Kirkov L, de Franco L, Miyashita M, Maglione M, Gramellini M, Ramera M, Amaral MJ, Ramaekers M, Truty MJ, van Dam MA, Stommel MW, Petrikowski M, Imamura M, Hayashi M, D'Hondt M, Brunner M, Hogg ME, Zhang C, Suárez-Muñoz M, Luyer MD, Unno M, Mizuma M, Janot M, Sahakyan MA, Jamieson NB, Busch OR, Bilge O, Belyaev O, Franklin O, Sánchez-Velázquez P, Pessaux P, Holka PS, Ghorbani P, Casadei R, Sartoris R, Schulick RD, Grützmann R, Sutcliffe R, Mata R, Patel RB, Takahashi R, Rodriguez Franco S, Cabús SS, Hirano S, Gaujoux S, Festen S, Kozono S, Maithel SK, Chai SM, Yamaki S, van Laarhoven S, Mieog JS, Murakami T, Codjia T, Sumiyoshi T, Karsten TM, Nakamura T, Sugawara T, Boggi U, Hartman V, de Meijer VE, Bartholomä W, Kwon W, Koh YX, Cho Y, Takeyama Y, Inoue Y, Nagakawa Y, Kawamoto Y, Ome Y, Soonawalla Z, Uemura K, Wolfgang CL, Jang JY, Padbury R, Satoi S, Messersmith W, Wilmink JW, Abu Hilal M, Besselink MG, Del Chiaro M, Ishida H, Dennahy IS, Carter JA, Olapo JS, Caldera M, Mazzola M, Oshima M, Tanaka N, Choi SH, Sato S, Sugawara S, Abadia-Forcen T, Pawlik TM, Kimura Y (2025)

Publication Type: Journal article

Publication year: 2025

Journal

DOI: 10.1016/j.annonc.2024.12.015

Abstract

Background: Left-sided pancreatic cancer is associated with worse overall survival (OS) compared with right-sided pancreatic cancer. Although neoadjuvant therapy is currently seen as not effective in patients with resectable pancreatic cancer (RPC), current randomized trials included mostly patients with right-sided RPC. The purpose of this study was to assess the association between neoadjuvant therapy and OS in patients with left-sided RPC compared with upfront surgery. Patients and methods: This was an international multicenter retrospective study including consecutive patients after left-sided pancreatic resection for pathology-proven RPC, either after neoadjuvant therapy or upfront surgery in 76 centers from 18 countries on 4 continents (2013-2019). The primary endpoint was OS from diagnosis. Time-dependent Cox regression analysis was carried out to investigate the association of neoadjuvant therapy with OS, adjusting for confounders at the time of diagnosis. Adjusted OS probabilities were calculated. Results: Overall, 2282 patients after left-sided pancreatic resection for RPC were included of whom 290 patients (13%) received neoadjuvant therapy. The most common neoadjuvant regimens were (m)FOLFIRINOX (38%) and gemcitabine-nab-paclitaxel (22%). After upfront surgery, 72% of patients received adjuvant chemotherapy, mostly a single-agent regimen (74%). Neoadjuvant therapy was associated with prolonged OS compared with upfront surgery (adjusted hazard ratio 0.69, 95% confidence interval 0.58-0.83) with an adjusted median OS of 53 versus 37 months (P = 0.0003) and adjusted 5-year OS rates of 47% versus 35% (P = 0.0001) compared with upfront surgery. Interaction analysis demonstrated a stronger effect of neoadjuvant therapy in patients with a larger tumor (Pinteraction = 0.003) and higher serum carbohydrate antigen 19-9 (CA19-9; Pinteraction = 0.005). In contrast, the effect of neoadjuvant therapy was not enhanced for splenic artery (Pinteraction = 0.43), splenic vein (Pinteraction = 0.30), retroperitoneal (Pinteraction = 0.84), and multivisceral (Pinteraction = 0.96) involvement. Conclusions: Neoadjuvant therapy in patients with left-sided RPC was associated with improved OS compared with upfront surgery. The impact of neoadjuvant therapy increased with larger tumor size and higher serum CA19-9 at diagnosis. Randomized controlled trials on neoadjuvant therapy specifically in patients with left-sided RPC are needed.

Authors with CRIS profile

Involved external institutions

Misericordia Hospital - Grosseto / Ospedale Della Misericordia Grosseto Italy (IT) Mayo Clinic United States (USA) (US) Ospedale P. Pederzoli Italy (IT) Humanitas University Italy (IT) Hospital Universitario Dr. Peset Aleixandre Spain (ES) University of Oklahoma United States (USA) (US) Autonomous University of Barcelona (UAB) / Universitat Autònoma de Barcelona Spain (ES) Sahlgrenska University Hospital / Sahlgrenska Universitetssjukhuset Sweden (SE) University of Amsterdam Netherlands (NL) Karolinska University Hospital / Karolinska Universitetssjukhuset Sweden (SE) University of Montpellier / Université Montpellier France (FR) Amsterdam University Medical Centers (Amsterdam UMC) / Amsterdam Universitair Medische Centra Netherlands (NL) Flinders Medical Centre Australia (AU) University of Washington United States (USA) (US) Hospital Geral de Santo António Portugal (PT) Kansai Medical University Japan (JP) Leiden University Medical Center Netherlands (NL) Royal Free Hospital United Kingdom (GB) Uppsala University Sweden (SE) Pitié-Salpêtrière University Hospital / Hôpital universitaire Pitié-Salpêtrière France (FR) University Hospitals Birmingham NHS Foundation Trust United Kingdom (GB) Beaujon Hospital / Hôpital Beaujon France (FR) Hospital Universitario Miguel Servet Spain (ES) Kagawa University Japan (JP) Kindai University / 近畿大学 Japan (JP) Ospedale Niguarda Ca' Granda / ASST Grande Ospedale Metropolitano Niguarda Italy (IT) University Hospital Southampton NHS United Kingdom (GB) Hiroshima University / 広島大学 Japan (JP) University Medical Center Groningen (UMCG) / Universitair Medisch Centrum Groningen Netherlands (NL) Oslo University Hospital / Oslo Universitetssykehus Rikshospitalet Norway (NO) Fiona Stanley Hospital Australia (AU) Radboud University Nijmegen Medical Centre / Radboudumc of voluit Radboud Universitair Medisch Centrum (UMC) Netherlands (NL) The Cancer Institute Hospital / がん研有明病院 Japan (JP) University of Pisa / Università di Pisa (UniPi) Italy (IT) Emory University United States (USA) (US) Hospital Universitario Virgen de la Victoria Spain (ES) Catharina Hospital / Catharina Ziekenhuis Netherlands (NL) Koç-Universität (KU) Turkey (TR) Tohoku University Japan (JP) Universitätsklinikum Ulm Germany (DE) Erasmus University Medical Center (MC) Netherlands (NL) Katholisches Klinikum Bochum (St. Josef- und St. Elisabeth-Hospital gGmbH) Germany (DE) University of Glasgow United Kingdom (GB) Hospital Clínic de Barcelona Spain (ES) Hôpitaux universitaires de Strasbourg (HUS) / University Hospital Strasbourg France (FR) Hospital del Mar Spain (ES) University of Colorado Anschutz Medical Campus United States (USA) (US) NorthShore University HealthSystem United States (USA) (US) Umeå University Sweden (SE) Ohio State University United States (USA) (US) Universitetssjukhuset i Linköping Sweden (SE) Lund University / Lunds universitet Sweden (SE) University Hospital Ghent Belgium (BE) Yamagata University (YU) Japan (JP) Hospital Network Antwerp / Ziekenhuis Netwerk Antwerpen (ZNA) Belgium (BE) National Cancer Centre Singapore (NCCS) Singapore (SG) Tokyo Women's Medical University Japan (JP) Hasselt University / Universiteit Hasselt Belgium (BE) University Hospitals Bristol NHS Foundation Trust United Kingdom (GB) Tokyo Medical University (TMU) / 東京医科大学 Japan (JP) Nagoya University / 名古屋大学 Japan (JP) Medizinische Universität Innsbruck Austria (AT) University of Bologna / Università di Bologna Italy (IT) Hospital Clínico Universitario de Valencia Spain (ES) Centro Hospitalar e Universitário de Coimbra (CHUC) Portugal (PT) Oxford University Hospitals NHS Foundation Trust United Kingdom (GB) Sapporo Medical University / 札幌医科大学 Japan (JP) az groeninge Belgium (BE) Hospital de la Santa Creu i Sant Pau Spain (ES) Onze Lieve Vrouwe Gasthuis Netherlands (NL) PathWest Laboratory Medicine WA Australia (AU) Hospital Center University Rouen / Centre hospitalier universitaire de Rouen (CHU) France (FR) New York University (NYU) United States (USA) (US) Seoul National University (SNU) / 서울대학교 Korea, Republic of (KR) Linköpings universitet / Linköping University Sweden (SE)

How to cite

APA:

Rangelova, E., Stoop, T.F., van Ramshorst, T.M., Ali, M., van Bodegraven, E.A., Javed, A.A.,... Kimura, Y. (2025). The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study. Annals of Oncology. https://doi.org/10.1016/j.annonc.2024.12.015

MLA:

Rangelova, E., et al. "The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study." Annals of Oncology (2025).

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