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Importance: International guidelines lack consistency in their recommendations regarding routine imaging in the follow-up after pancreatic resection for pancreatic ductal adenocarcinoma (PDAC). Consequently, follow-up strategies differ between centers worldwide., Objective: To compare clinical outcomes, including recurrence-focused treatment and survival, in patients with PDAC recurrence who received symptomatic follow-up or routine imaging after pancreatic resection in international centers affiliated with the European-African Hepato-Pancreato-Biliary Association (E-AHPBA)., Design, Setting, and Participants: This was a prospective, international, cross-sectional study. Patients from a total of 33 E-AHPBA centers from 13 countries were included between 2020 and 2021. According to the predefined study protocol, patients who underwent PDAC resection and were diagnosed with disease recurrence were prospectively included. Patients were stratified according to postoperative follow-up strategy: symptomatic follow-up (ie, without routine imaging) or routine imaging., Exposures: Symptomatic follow-up or routine imaging in patients who underwent PDAC resection., Main Outcomes and Measures: Overall survival (OS) was estimated with Kaplan-Meier curves and compared using the log-rank test. To adjust for potential confounders, multivariable logistic regression was used to evaluate the association between follow-up strategy and recurrence-focused treatment. Multivariable Cox proportional hazard analysis was used to study the independent association between follow-up strategy and OS., Results: Overall, 333 patients (mean [SD] age, 65 [11] years; 184 male [55%]) with PDAC recurrence were included. Median (IQR) follow-up at time of analysis 2 years after inclusion of the last patient was 40 (30-58) months. Of the total cohort, 98 patients (29%) received symptomatic follow-up, and 235 patients (71%) received routine imaging. OS was 23 months (95% CI, 19-29 months) vs 28 months (95% CI, 24-30 months) in the groups who received symptomatic follow-up vs routine imaging, respectively (P = .01). Routine imaging was associated with receiving recurrence-focused treatment (adjusted odds ratio, 2.57; 95% CI, 1.22-5.41; P = .01) and prolonged OS (adjusted hazard ratio, 0.75; 95% CI, 0.56-.99; P = .04)., Conclusion and Relevance: In this international, prospective, cross-sectional study, routine follow-up imaging after pancreatic resection for PDAC was independently associated with receiving recurrence-focused treatment and prolonged OS.

Background: Distinguishing postoperative fibrosis from isolated local recurrence (ILR) after resection of pancreatic ductal adenocarcinoma (PDAC) is challenging. A prognostic model that helps to identify patients at risk of ILR can assist clinicians when evaluating patients' postoperative imaging. This nationwide study aimed to develop a clinically applicable prognostic model for ILR after PDAC resection., Patients and Methods: An observational cohort study was performed, including all patients who underwent PDAC resection in the Netherlands (2014-2019; NCT04605237). On the basis of recurrence location (ILR, systemic, or both), multivariable cause-specific Cox-proportional hazard analysis was conducted to identify predictors for ILR and presented as hazard ratios (HRs) with 95% confidence intervals (CIs). A predictive model was developed using Akaike's Information Criterion, and bootstrapped discrimination and calibration indices were assessed., Results: Among 1194/1693 patients (71%) with recurrence, 252 patients (21%) developed ILR. Independent predictors for ILR were resectability status (borderline versus resectable, HR 1.42; 95% CI 1.03-1.96; P = 0.03, and locally advanced versus resectable, HR 1.11; 95% CI 0.68-1.82; P = 0.66), tumor location (head versus body/tail, HR 1.50; 95% CI 1.00-2.25; P = 0.05), vascular resection (HR 1.86; 95% CI 1.41-2.45; P < 0.001), perineural invasion (HR 1.47; 95% CI 1.01-2.13; P = 0.02), number of positive lymph nodes (HR 1.04; 95% CI 1.01-1.08; P = 0.02), and resection margin status (R1 < 1 mm versus R0 ≥ 1 mm, HR 1.64; 95% CI 1.25-2.14; P < 0.001). Moderate performance (concordance index 0.66) with adequate calibration (slope 0.99) was achieved., Conclusions: This nationwide study identified factors predictive of ILR after PDAC resection. Our prognostic model, available through www.pancreascalculator.com , can be utilized to identify patients with a higher a priori risk of developing ILR, providing important information in patient evaluation and prognostication., (© 2024. The Author(s).)

Background: Novel definitions suggest that resectability status for pancreatic ductal adenocarcinoma (PDAC) should be assessed beyond anatomical criteria, considering both biological and conditional factors. This has, however, yet to be validated on a nationwide scale. This study evaluated the prognostic value of biological and conditional factors for staging of patients with resectable PDAC., Patients and Methods: A nationwide observational cohort study was performed, including all consecutive patients who underwent upfront resection of National Comprehensive Cancer Network resectable PDAC in the Netherlands (2014-2019) with complete information on preoperative carbohydrate antigen (CA) 19-9 and Eastern Cooperative Oncology Group (ECOG) performance status. PDAC was considered biologically unfavorable (R B+ ) if CA19-9 ≥ 500 U/mL and favorable (R B- ) otherwise. ECOG ≥ 2 was considered conditionally unfavorable (R C+ ) and favorable otherwise (R C- ). Overall survival (OS) was assessed using Kaplan-Meier and Cox-proportional hazard analysis, presented as hazard ratios (HRs) with 95% confidence interval (CI)., Results: Overall, 688 patients were analyzed with a median overall survival (OS) of 20 months (95% CI 19-23). OS was 14 months (95% CI 10 months-median not reached) in 20 R B+C+ patients (3%; HR 1.61, 95% CI 0.86-2.70), 13 months (95% CI 11-15) in 156 R B+C- patients (23%; HR 1.86, 95% CI 1.50-2.31), and 21 months (95% CI 12-41) in 47 R B-C+ patients (7%; HR 1.14, 95% CI 0.80-1.62) compared with 24 months (95% CI 22-27) in 465 patients with R B-C- PDAC (68%; reference)., Conclusions: Survival after upfront resection of anatomically resectable PDAC is worse in patients with CA19-9 ≥ 500 U/mL, while performance status had no impact. This supports consideration of CA19-9 in preoperative staging of resectable PDAC., (© 2024. The Author(s).)

Background: Disease recurrence remains one of the biggest concerns in patients after resection of pancreatic ductal adenocarcinoma (PDAC). Despite (neo)adjuvant systemic therapy, most patients experience local and/or distant PDAC recurrence within 2 years. High-level evidence regarding the benefits of recurrence-focused surveillance after PDAC resection is missing, and the impact of early detection and treatment of recurrence on survival and quality of life is unknown. In most European countries, recurrence-focused follow-up after surgery for PDAC is currently lacking. Consequently, guidelines regarding postoperative surveillance are based on expert opinion and other low-level evidence. The recent emergence of more potent local and systemic treatment options for PDAC recurrence has increased interest in early diagnosis. To determine whether early detection and treatment of recurrence can lead to improved survival and quality of life, we designed an international randomized trial., Methods: This randomized controlled trial is nested within an existing prospective cohort in pancreatic cancer centers in the Netherlands (Dutch Pancreatic Cancer Project; PACAP) and the United Kingdom (UK) (Pancreas Cancer: Observations of Practice and survival; PACOPS) according to the "Trials within Cohorts" (TwiCs) design. All PACAP/PACOPS participants with a macroscopically radical resection (R0-R1) of histologically confirmed PDAC, who provided informed consent for TwiCs and participation in quality of life questionnaires, are included. Participants randomized to the intervention arm are offered recurrence-focused surveillance, existing of clinical evaluation, serum cancer antigen (CA) 19-9 testing, and contrast-enhanced computed tomography (CT) of chest and abdomen every three months during the first 2 years after surgery. Participants in the control arm of the study will undergo non-standardized clinical follow-up, generally consisting of clinical follow-up with imaging and serum tumor marker testing only in case of onset of symptoms, according to local practice in the participating hospital. The primary endpoint is overall survival. Secondary endpoints include quality of life, patterns of recurrence, compliance to and costs of recurrence-focused follow-up, and the impact on recurrence-focused treatment., Discussion: The RADAR-PANC trial will be the first randomized controlled trial to generate high level evidence for the current clinical equipoise regarding the value of recurrence-focused postoperative surveillance with serial tumor marker testing and routine imaging in patients after PDAC resection. The Trials within Cohort design allows us to study the acceptability of recurrence-focused surveillance among cohort participants and increases the generalizability of findings to the general population. While it is strongly encouraged to offer all trial participants treatment at time of recurrence diagnosis, type and timing of treatment will be determined through shared decision-making. This might reduce the potential survival benefits of recurrence-focused surveillance, although insights into the impact on patients' quality of life will be obtained., Trial Registration: Clinicaltrials.gov, NCT04875325 . Registered on May 6, 2021., (© 2024. The Author(s).)