Improving long-term outcomes in resectable pancreatic cancer
Letter to the Editor

Improving long-term outcomes in resectable pancreatic cancer

John P. Neoptolemos1 ORCID logo, Christoph Springfeld2 ORCID logo, Thilo Hackert3 ORCID logo, Daniel H. Palmer4 ORCID logo, Daniel Öhlund5 ORCID logo, Teresa Peccerella1 ORCID logo, Jonathan M. Harnoss1 ORCID logo, Thomas Hank1 ORCID logo, Francesco Ladisa1 ORCID logo, Christoph W. Michalski1 ORCID logo

1Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany; 2Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg University Hospital, Heidelberg, Germany; 3Department of General, Visceral and Thoracic Surgery, University Hospital Hamburg-Eppendorf, Hamburg, Germany; 4Cancer Research UK Liverpool Experimental Cancer Medicine Centre, University of Liverpool, Liverpool, UK; 5Department of Diagnostics and Intervention (Oncology), and Wallenberg Centre for Molecular Medicine (WCMM), Umeå University, Umeå, Sweden

Correspondence to: Prof. Dr. med. John P. Neoptolemos, MA, MB, BChir, MD, FRCS, FMedSci, MAE. Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Im Neuenheimer Feld 420, Heidelberg 69120, Baden-Württemberg, Germany. Email: john.neoptolemos@med.uni-heidelberg.de.

Response to: Bertolo A, Hodul P, Kim DW. ESPAC-4 long-term follow-up: shall we choose gemcitabine and capecitabine as adjuvant therapy for elderly and low-risk pancreatic adenocarcinoma following surgical resection? Ann Pancreat Cancer 2026;9:1.

Received: 05 December 2025; Accepted: 15 January 2026; Published online: 27 January 2026.

doi: 10.21037/apc-25-42

The adjuvant chemotherapy paradigm for resectable pancreatic cancer

Bertolo and colleagues in an accompanying commentary highlight the significant therapeutic advances in pancreatic cancer [pancreatic ductal adenocarcinoma (PDAC)] and the evolving landscape for adjuvant treatment which continues to evolve, with the latest trials introducing novel immunologic and targeted strategies (1). Nakasone and Coveler in a further commentary refer to the growing use of neoadjuvant and perioperative chemotherapy largely based on retrospective studies introducing a significant area of controversy (2). The biggest advance in pancreatic cancer surgery since Whipple et al. published the successful two-stage resection of three patients with cancer of the ampulla of Vater in 1935 was the pivotal European Study Group (ESPAC) ESPAC1 and ESPAC1-Plus trials published in the Lancet and New England Journal of Medicine in 2001–2004 (3-5). ESPAC has uniquely and fundamentally changed the treatment of pancreatic cancer. The overall survival (OS) rates improved from <10% to 30–50% with adjuvant chemotherapy, but not chemoradiotherapy for empirically determined resectable (EmR) PDAC (4-16). Empirically (Em) derived stage concepts (presently based on external cross sectional imaging) will continue to evolve with new empirical knowledge (new imaging modalities, circulating tumor sequencing, artificial intelligence, etc.), and so will never reach a steady state but the Em-derived concepts remain sound (14). The Em derived stage concept embraces systems such as the Isaji et al. international ABC consensus, which combines three dimensions, anatomical (A), biological (B) and conditional (C) (17). Even so C is performance status defining fitness for surgery (so not actually tumor staging) and B is not true biology but a carbohydrate antigen 19-9 (CA19-9) somewhat arbitrary cut level of 500 KU/L, so Isaji et al. conclude that it is “controversial and there is the need for further improvements” (17). The ESPAC-based paradigm caused a rapid expansion in the number of pancreatic cancer resections being undertaken, which led to overall 5-year survival rates improving from <5% to 8% for all stages of pancreatic cancer (4-14,16,18-27) (Table 1). Without surgical resection there are no 5-year survivors for any type of chemotherapy with or without the latest targeting agents.

Table 1

Randomized adjuvant trials in resectable pancreatic cancer since publication of the ESPAC1 and ESPAC1-Plus studies

Trial Recruitment period Treatment arms Number of patients mOS (months) P for mOS 5-year overall survival (%) Comments
ESPAC1Plus (4)† 1994–2000 No CRT; CRT 178; 175 16.1; 15.5 0.24 19.5; 10.3 ECOG 0, 1, 2; R0/R1. Significant for chemotherapy overall but not in the 2×2 factorial. Not significant for CRT overall or in 2×2 factorial
No chemotherapy; 5FU/FA 235; 238 14.0; 19.7 <0.001 9.9; 23.3
ESPAC1 (5)‡ 1994–2000 No CRT; CRT 144; 145 17.9; 15.9 0.05 19.6; 10.8 ECOG 0, 1, 2. R0/R1
No chemotherapy; 5FU/FA 142; 147 15.5; 20.1 0.009 8.4; 21.1
Observation; CRT; 5FU/FA; CRT + 5FU/FA 69; 73; 75; 72 16.9; 13.9; 21.6; 19.9 – 10.7; 7.3; 29.0; 13.2
CONKO-001 (6,9) 1998–2004 GEM 179 22.8 0.01 20.7 Post-op CA19-9>92.5 KU/L=0.0%
Observation 175 20.2 10.4
EORTC40891 (18) 1987–1995 CRT 60 24.5 0.099 20 T1–2, N0–1a, M0 pancreatic head cancer
Observation 54 19 10
RTOG 9704 (19,20) 1998–2002 5FU/FA, 5FU+RT, 5FU/FA 230 – 0.34 – Median survival only reported in 388 with pancreatic head tumors=20.5 (GEM) vs. 16.9 (5FU) months, P=0.09
GEM, 5FU-RT, GEM 221
ESPAC3 (8) 2000–2007 5FU/FA 551 23.0 0.39 15.9 ECOG 0, 1, 2; R0/R1
GEM 537 23.6 17.5
JSAP-02 (21) 2002–2005 GEM + IORT in 27 58 22.3 0.19 23.9 Karnofsky >50
IORT in 47 then observation 60 18.4 10.6
CapRI (22) 2004–2007 5FU, cisplatin, IFNα2b + RT, CI 5FU 64 32.1 0.49 25 ECOG 0,1,2; R0/R1
5FU/FA 68 25.5 25
JASPAC-01 (10) 2007–2010 GEM 190 25.2 <0.0001 24.4 ECOG 0=68.7%; post-op CA19-9 >37 KU/L =21%; R1 pos. =31%; LN pos. =62.9%
S-1 187 46.5 44.1
CONKO-005 (23) 2008–2013 GEM 217 26.2 0.06 20.0 Karnofsky PS ≥60%. Only R0 resected patients
GEM-erlotinib 219 24.5 25.0
CONKO-006 (24) 2008–2013 GEM 65 17.1 0.94 – Karnofsky PS ≥60%. Only R1 patients
GEM-sorafenib 57 18.2
ESPAC4 (11,16) 2008–2014 GEM 366 28.4 0.03 25.0 R0 and R1 patients
GEMCAP 365 31.6 32.0
NRG Oncology/ RTOG 0848 (25,26)§ 2009–2014 GEM 163 29.9 0.62 – Post-op. CA 19-9 <180 KU/L. Step 1: 5 cycles GEM +/−erlotinib. Step 2: 6th cycle GEM +/−CRT. 1-sided test
GEM + erlotinib 159 28.1 –
Chemotherapy 174 31.0 0.38 23.0
Chemotherapy +CRT 180 27.0 28.0
PRODIGE-24 (12,14) 2012–2016 GEM 246 35.5 0.001 31.4 ECOG 0, 1. Post-op CA 19-9 <180 KU/L. <80 years
mFOLFIRINOX 247 53.5 43.2
APACT (27) 2014–2018 GEM 434 37.7 0.009, not primary end point 31.0 ECOG 0, 1; post-op CA 19-9<100 KU/L; primary endpoint DFS, not met. 18.0 (GEM) vs. 19.4 (GEM + NabP) months, P=0.18
GEM-NabP 432 41.8 38.0

†, all patients and early follow-up of 2×2 factorial patients. ‡, 2×2 factorial, final follow-up. §, 2-step trial. 5FU, 5-fluorouracil; CA19-9, carbohydrate antigen 19-9; CAP, capecitabine; CI, continuous infusion; CRT, chemoradiotherapy; CTX, chemotherapy; DFS, disease-free survival; DOX, doxorubicin; ECOG, Eastern Cooperative Oncology Group; FA, folinic acid; GEM, gemcitabine; IORT, intra-operative radiotherapy; LN, lymph node; mFOLFIRINOX, modified FA, 5FU, irinotecan and oxaliplatin; mOS, median overall survival; NabP, nab-paclitaxel; pos., positive; post-op, post-operative; PS, performance status; RT, radiotherapy.

ESPAC1 and ESPAC1-Plus showed that post-operative adjuvant chemotherapy based on using only 5-fluorouracil (5FU) monotherapy (with the 5FU enhancer leucovorin) but not radiochemotherapy substantially improved overall and 5-year survival rates compared to surgical removal alone (4,5). Further randomized trials adopting the evolving the contemporary standard of care (SOC) as the control arm in each case came from the ESPAC, Charité Onkologie (CONKO) and the Japan Adjuvant Study Group of Pancreatic Cancer (JASPAC) teams have confirmed the survival advantage of adjuvant monochemotherapy not only with 5FU but also with gemcitabine, and the oral agent S1 actually comprising tegafur (a 5FU prodrug), plus the enhancers and toxicity modifiers gimeracil, and oteracil potassium (6,9,10). The ESPAC3 trial definitively showed that gemcitabine did not have longer survival than 5FU, but was preferred because of the lower toxicity (8). These trials then evolved into adjuvant combination chemotherapy regimens providing even greater overall and 3–5-year survival rates. The ESPAC4 study showed improved OS with the GemCap combination of gemcitabine with the oral 5FU prodrug capecitabine in patients with relatively unrestricted eligibility criteria with no upper age limit and no constraints on serum CA19-9 levels (11,16). The France-Canada PRODIGE24-CCTG PA.6 trial demonstrated even better overall survival using modified (m) FOLFIRINOX [comprising 5FU, folinic acid (FA), irinotecan, and oxaliplatin] but with greater toxicity necessitating more stringent selection criteria, requiring patients aged <79 years, with a World Health Organisation (WHO) performance status of 0–1, no significant cardiovascular disease, and a postoperative serum tumor marker CA19-9 level <180 KU/L (12,14). This additional toxicity may result in <50% of patients receiving adjuvant mFOLFIRINOX, falling to less than 10% of those aged >70 years (12,14). The long-term follow-up study of ESPAC4 showed that 26% of patients not conforming to the eligibility criteria for mFOLFIRINOX, benefited from GemCap with improved survival and should be used in preference to gemcitabine monotherapy in this setting (16). The APACT study comparing gemcitabine plus nab-paclitaxel (Gem-NabP) against gemcitabine did not meet its primary end point of independently assessed median disease-free survival (DFS) and OS was not significantly different initially but was on further follow-up (27). This emphasizes that surrogate endpoints such as DFS and local investigator versus independent review may be unreliable requiring the use of OS as the hard primary end-point. Gem-NabP is not approved by the Food and Drug Administration (FDA) as adjuvant therapy for pancreatic cancer. Current guidelines emphasize that mFOLFIRINOX is the established reference standard for fit patients, with GemCap as an option typically for patients not eligible for, or choosing not to have, mFOLFIRINOX (28,29).

Emerging role for neoadjuvant therapy in borderline resectable but not for resectable pancreatic cancer

There is emerging evidence to support the use of short course neoadjuvant therapy in patients with Em determined borderline resectable (EmBR), notably PREOPANC1 and ESPAC5 (Table 2) (30-40). There is however no robust evidence to support the use of neoadjuvant therapy for EmR pancreatic cancer (Table 3) (41-44). Clonal evolutionary biology demonstrates that patients with EmBR are distinct from EmR pancreatic cancers with differential responses to therapeutic intervention (45-50). Before ESPAC1 and the subsequent evolutionary trials, chemoradiotherapy was a “popular” treatment of pancreatic cancer being promoted in all kinds of clinical scenarios and in various ways. Whilst there may be a role for chemoradiotherapy in PDAC it has yet to be demonstrated to improve survival in any randomized trial compared to the respective SOC and has been largely abandoned for this purpose in patients with either EmR or EmBR tumors (4,5,18,25,26,31,32,37,41,42,44). The latest “popular” treatment is the use of neoadjuvant therapy, not only in the EmBR population in which we can see a survival benefit but also in the EmR population where its role remains unproven (Tables 2,3) (30-44).

Table 2

Randomized trials of neoadjuvant treatment for resectable pancreatic cancer recruiting from 2010

Trial Recruitment period Treatment arms Number of patients mOS (months) P for mOS Comments
PACT-15 (30) 2010–2015 PEXG + surgery + PEXG 26 – – <75 years, stage I–II, protocol event-free at 1-year: 6 (23%, 95% CI: 7–39%) of 30; 15 (50%, 95% CI: 32–68%) of 30; 19 (66%, 95% CI: 49–83%) of 29
Surgery + GEM 30
Surgery + PEXG 32
PREOPANC1 (31,32) 2013–2017 CRT + GEM + Surgery + GEM 65 14.6 0.83 Longterm follow-up mOS HR =0.79 (95% CI: 0.54–1.16)
Surgery + GEM 68 15.6
SWOG S1505 (33) 2015–2018 mFOLFIRINOX + surgery + mFOLFIRINOX 55 23.2 Not significant Primary end point >2-year OS of 40%: 47% (95% CI: 31–61%) for arm 1 and 48% (95% CI: 31–63%) for arm 2
GEM-NabP + surgery + GEM-NabP 47 23.6
NEONAX-AIO-PAK-0313 (34) 2015–2021 GEM-NabP + surgery + GEM-NabP Resected 48/63 25.2 Not significant Planned 166 patients. Primary endpoint median DFS rate of 55% at 18 months double negative result: neoadjuvant 32.2%; adjuvant 41.4%
Surgery + GEM Resected 51/64 16.7
PANACHE01-PRODIGE48 (35) 2017–2020 mFOLFIRINOX+ surgery + CTX 72 31.3 (90% CI: 21.5–NR) Not significant CTX = initially GEM, 5FU, and GEM CAP, but latterly and mostly mFOLFIRINOX
FOLFOX + surgery + CTX 48 31.8 (90% CI: 23.8–NR)
Surgery + CTX 28 NR (90% CI: 18.5–NR)
NORPACT-1 (36) 2017–2021 mFOLFIRINOX + surgery + mFOLFIRINOX 77 25.1 0.05 Primary endpoint was patients alive at 18 months: 60% in the neoadjuvant group versus 73% in the upfront surgery group (P=0.03); upfront surgery had longer survival
Surgery + mFOLFIRINOX 63 38.5
PREOPANC2 (37) 2018–2021 FOLFIRINOX + surgery Resected 99/120 – – For all cases mixed resectable and borderline median survival =21.9 months chemo vs. 21.3 months CRT, P=0.32
GEM + CRT + surgery+ GEM Resected
95/121
NEPAFOX (38) 2015–2018 Surgery + GEM mFOLFIRINOX + 21 25.7 – Mixed resectable (76%) and borderline resectable (79%); trial closed due to slow accrual target =126 patients
Surgery + mFOLFIRINOX 19 10.0
Prep-02/JSAP-05 (39) 2013–2016 GEM + S1 + surgery+ S1 131 HR =0.73 (95% CI: 0.56–0.95) 0.02 Adjuvant CTX “advised”—not required. ECOG =0/1, <80 years. The study includes both resectable (n=163) and borderline (n=68), results are not cleanly separated
Surgery + S1 132
Zhejiang (40) 2018–2024 GEM-NabP+ mFOLFIRINOX+ Surgery+ Gem-CAP or mFOLFIRINOX Resected 135/162 35.4 (95% CI: 27.9–5.1) 0.048 Left pancreatectomies in 147 (52%); CA19-9>500 KU/L in 138 (43%); R0 in 237 (83%). CTX “recommended” not required; 169 (52%) “completed” CTX. Short follow-up median =18.7 months
Surgery+ Gem-CAP or mFOLFIRINOX Resected 149/162 27.2 (95% CI: 19.8–33.5)

5FU, 5-fluorouracil; CA19-9, carbohydrate antigen 19-9; CAP, capecitabine; CI, confidence interval; CRT, chemoradiotherapy; CTX, chemotherapy; DFS, disease-free survival; ECOG, Eastern Cooperative Oncology Group; GEM, gemcitabine; GEM-NabP, gemcitabine-nab-paclitaxel; HR, hazard ratio; mFOLFIRINOX, modified folinic acid, 5FU, irinotecan and oxaliplatin; mOS, median overall survival; NR, not reached; PEXG, cisplatin, epirubicin, gemcitabine, and capecitabine.

Table 3

Randomized trials of neoadjuvant treatment for borderline resectable pancreatic cancer

Trial Recruitment period Treatment arms Number of patients mOS (months) P for mOS Comments
Korea multi-center (41) 2012–2014 CRT + GEM + surgery + GEM + CRT 27 [8] 21 0.03 (one-sided) Target =110 patients; only 8 and 6 patients, respectively, had per-protocol treatment; pre-planned P value not valid
Surgery + GEM + CRT 23 [6] 12
PREOPANC1 (31,32) 2013–2017 CRT + GEM + surgery + GEM 54 17.6 0.03 HR =0.62 (95% CI: 0.40–0.95)
Upfront resection + GEM 59 13.2
ESPAC5 (42) 2014–2018 Surgery + adjuvant 32 – <0.001 Primary end point, 1-year OS: immediate surgery =40% (95% CI: 26–62%) and 77% (95% CI: 66–89%) for neoadjuvant therapy
GEM + CAP + surgery + adjuvant 20
FOLFIRINOX + surgery + adjuvant 20
CAP + CRT + surgery + adjuvant 16
NUPAT-01 (43) 2015–2020 FOLFIRINOX + surgery + CTX 26 – – Primary end point R0 resection rate: 73.1% for FOLFIRINOX, 56.0%%, for Gem-NabP; 3-year OS =55.3% for FOLFIRINOX and 54.4% for Gem-NabP
GEM-NabP + surgery + CTX 25
Alliance A021501 (44) 2016–2019 mFOLFIRINOX + surgery + adjuvant 54 31.0 Not significant Primary endpoint, 18 months OS: 93.1% (95% CI: 84.3–100%) and 78.9% (95% CI: 62.6–99.6%), respectively
mFOLFIRINOX + SBRT + surgery + adjuvant 56 17.1

CAP, capecitabine; CI, confidence interval; CRT, chemoradiotherapy; CTX, chemotherapy; GEM, gemcitabine; Gem-NabP, gemcitabine-nab-paclitaxel; HR, hazard ratio; mFOLFIRINOX, modified folinic acid, 5-fluorouracil, irinotecan and oxaliplatin; mOS, median overall survival; SBRT, stereotactic body radiotherapy.

A number of studies have caused considerable confusion in interpretation by combining recruitment of patients with both EmR and EmBR tumors and/or failing to include the contemporary SOC as the control arm from which inappropriate conclusions are drawn. These studies include PREOPANC1, PREOPANC2, Prep-02/JSAP05 and most recently PACT21-CASSANDRA. In PREOPANC1 the results are sufficiently discriminatory so it can be seen that a neoadjuvant therapy survival benefit is seen in the patients with EmBR tumors but not those with EmR (31,32,37,39,51). The PREOPANC2 trial compared neoadjuvant full-dose FOLFIRINOX but with no scheduled adjuvant chemotherapy versus neoadjuvant chemoradiotherapy and gemcitabine plus adjuvant gemcitabine in both EmR and EmBR patients with no significant differences in OS (37). Again there was no proper control group for the EmR patients which is resection followed by 6 months adjuvant mFOLFIRINOX and survival estimates separated for resected EmR, EmBR, FOLFIRINOX, and chemoradiotherapy groups were not provided inhibiting inter-trial comparisons (37).

In the neoadjuvant Prep-02/JSAP05 trial patients were only “strongly advised” to take adjuvant therapy but were not required to do so, thus lacking a SOC control arm with a vague distinction between EmR and EmBR and an absence of does intensities (39). Remarkably the protocol is not available and there is no mention of the statistical analysis plan. The CASSANDRA “2×2 factorial” superiority trial was conducted in 260 patients with EmR/EmBR PDAC tumors aged <75 years, but lacking a SOC control (51). In the first randomization patients were enrolled to either four months induction PAXG (capecitabine, cisplatin, nab-paclitaxel, and gemcitabine) or to four months induction mFOLFIRINOX. Then in the second randomization they were allocated to either two more months of chemotherapy before surgery and no further chemotherapy or surgery followed by two months adjuvant chemotherapy. The primary endpoint was event-free survival (EFS) using methodology that has not been previously validated. The preliminary findings of the first randomization were presented at ASCO 2025 (LBA4004), and were not significantly different for OS, even though interim analyses were not allowed for. This is not a “2×2 factorial” design, rather it is two staggered randomizations. OS will be reported (again) after 173 deaths but this is not specified in the sample size calculation, and with no alpha adjustment for multiplicity (51). The second randomization is on a different population due to the dropouts, which makes interpretation muddled. Remarkably CASSANDRA had exactly 63 resectable cases in each of the two arms even though this was not a stratification factor (screening numbers are missing). This is a phase II not III study, and without independent data and safety monitoring (51).

The recent single center study from Zhejiang University Hospital, Hangzhou, randomized 324 patients with EmR PDAC to neoadjuvant Gem-NabP plus mFOLFIRINOX or upfront surgery (40). Adjuvant GemCap was only “recommended” for both groups but not required (40). Only 169 (52%) patients randomized “completed” chemotherapy: 89 patients (55%) in the neoadjuvant group and 80 patients (49%) in the upfront surgery group and most importantly no total dose intensities for either group were provided. The median OS was 35.4 months in the neoadjuvant therapy group versus 27.2 months in the upfront surgery group (P=0.048) (40). The conclusions of this trial are further questionable, being potentially biased as an open labelled single center trial, unspecified adjuvant therapy, by the short median follow-up (18.7 months), a high proportion of patients with a CA19-9>500 KU/L (in 138, 43%), an unusually high R0 rate (in 237, 83%), and a very high proportion of left pancreatectomies (in 147, 52%) (40). The NORPACT-1 multicenter trial from hospitals in Denmark, Finland, Norway, and Sweden, that randomized patients with EmR PDAC to receive either neoadjuvant mFOLFIRINOX or upfront surgery group followed by adjuvant chemotherapy found that the upfront surgery group had longer survival (36).

What matters for patients with pancreatic cancer is OS, and in its absence great caution needs to be taken in interpreting surrogate markers, especially in the neoadjuvant setting which do not have the same reliability as in the adjuvant setting (50). Retrospective studies based on registries and single center studies are invariably circumspect because of the considerable bias involved in patient selection and investigator interpretation, for example in the criteria selection bias employed in multivariate models.

The PANACHE01-PRODIGE48 trial is cited by Nakasone and Coveler in support of neoadjuvant therapy in EmR patients with an improved EFS in both of the neoadjuvant mFOLFIRINOX and FOLFOX groups compared to the upfront surgery-adjuvant group (2,35). Importantly however there was no significant difference in median OS 31.3 months [95% confidence interval (CI): 21.5–not reached], 31.8 months (95% CI: 23.8–not reached), and not reached (95% CI: 18.5–not reached) in the three arms respectively, and if anything, the upfront surgery group having the longer survival (35).

State of the art

Clearly further trials such as Alliance A021806 phase III trial (NCT04340141) and PREOPANC3 (NCT04927780) trials will add to the body of knowledge but as the evidence stands the SOC is adjuvant chemotherapy for EmR and short course neoadjuvant therapy for EmBR. We fully concur with Nakasone and Coveler on the importance of the application of (genuine) tumor biology to treatment selection for chemotherapy as investigated in the COPMPASS and NeoPancOne studies as well refining the role of circulating CA19-9 (2,52,53). The ESPAC6 randomized adjuvant trial in EmR (NCT05314998) will investigate a transcriptomic signature in the experimental arm to allocate patients to either mFOLFIRINOX or GemCap against the mFOLFIRINOX control arm. These are also exciting times in terms of the latest developments of drugs targeting major tumor drivers such as KRAS and c-MYC or vulnerabilities like homologous recombination deficiency and methylthioadenosine phosphorylase (MTAP) deletions as well as a variety of immunotherapies (54-57). Each must be objectively evaluated in randomized trials drawing on the lessons of the many false dawns of the past 30 years following the breakthrough of whole genome sequencing (58,59). For now only the correct sequential use of surgery and systemic chemotherapy provides the best probability towards the prime objective of long-term cure albeit with only 30–50% long term survivors (60).

Acknowledgments

None

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Annals of Pancreatic Cancer. The article did not undergo external peer review.

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://apc.amegroups.com/article/view/10.21037/apc-25-42/coif). J.P.N. receives grants from Heidelberger Stiftung Chirurgie, Stiftung Deutsche Krebshilfe, Dietmar Hopp Stiftung GmbH, and the Bundesministerium für Bildung und Forschung; patent for: Metavert, APO-01; and served on advisory board for BioNTech Advisory Board on BNT321. D.H.P. receives grants from BMS, Medannex and Nucana; consulting fees from Servier, AZ, Pfizer, Viatris, Jazz, Ono, and BMS; support for attending meetings and travel from Medannex; participation on a Data Safety Monitoring Board/Advisory Board for Boehringer Ingelheim; receipt for other services from Revolution Medicine, Medannex, and Redx. J.M.H. received a grant by the German Cancer Aid. C.S. has received honoraria for lectures from Roche, support for attending meetings and travel by Servier, and served on Advisory Boards for Astra Zeneca, Bayer, BMS, Incyte, Servier, Taiho and Revolution Medicines. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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doi: 10.21037/apc-25-42
Cite this article as: Neoptolemos JP, Springfeld C, Hackert T, Palmer DH, Öhlund D, Peccerella T, Harnoss JM, Hank T, Ladisa F, Michalski CW. Improving long-term outcomes in resectable pancreatic cancer. Ann Pancreat Cancer 2026;9:6.

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