ORIGINAL ARTICLES

Defining and Predicting Early Recurrence in 957 Patients With Resected Pancreatic Ductal Adenocarcinoma

Groot, Vincent P. MD^∗,†; Gemenetzis, Georgios MD^∗; Blair, Alex B. MD^∗; Rivero-Soto, Roberto J. MD^∗; Yu, Jun MD, PhD^∗; Javed, Ammar A. MD^∗; Burkhart, Richard A. MD^∗; Rinkes, Inne H. M. Borel MD, PhD^†; Molenaar, I. Quintus MD, PhD^†; Cameron, John L. MD, FACS^∗; Weiss, Matthew J. MD, FACS^∗; Wolfgang, Christopher L. MD, PhD, FACS^∗; He, Jin MD, PhD, FACS^∗

Author Information

^∗Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

^†Department of Surgery, UMC Utrecht Cancer Center, University Medical Center Utrecht, Utrecht, The Netherlands.

Reprints: Jin He, MD, PhD, FACS, Assistant Professor of Surgery and Oncology, Department of Surgery, The Johns Hopkins University School of Medicine, Halsted 614, 600 North Wolfe Street, Baltimore, MD 21287. E-mail: [email protected].

This study was supported in the form of grants for a research fellowship by VPG by Foundation De Drie Lichten (The Netherlands), Prins Bernhard Cultuurfonds (The Netherlands), VSBfonds (The Netherlands), Prof. Michaël-van Vloten Fonds (The Netherlands), and the Living With Hope Foundation (The Netherlands).

The authors report no conflicts of interest.

Annals of Surgery 269(6):p 1154-1162, June 2019. | DOI: 10.1097/SLA.0000000000002734

Abstract

Objectives:

To establish an evidence-based cut-off to differentiate between early and late recurrence and to compare clinicopathologic risk factors between the two groups.

Summary Background Data:

A clear definition of “early recurrence” after pancreatic ductal adenocarcinoma resection is currently lacking.

Methods:

Patients undergoing pancreatectomy for pancreatic ductal adenocarcinoma between 2000 and 2013 were included. Exclusion criteria were neoadjuvant therapy and incomplete follow-up. A minimum P-value approach was used to evaluate the optimal cut-off value of recurrence-free survival to divide the patients into early and late recurrence cohorts based on subsequent prognosis. Potential risk factors for early recurrence were assessed with logistic regression models.

Results:

Of 957 included patients, 204 (21.3%) were recurrence-free at last follow-up. The optimal length of recurrence-free survival to distinguish between early (n = 388, 51.5%) and late recurrence (n = 365, 48.5%) was 12 months (P < 0.001). Patients with early recurrence had 1-, and 2-year post-recurrence survival rates of 20 and 6% compared with 45 and 22% for the late recurrence group (both P < 0.001). Preoperative risk factors for early recurrence included a Charlson age-comorbidity index ≥4 (OR 1.65), tumor size > 3.0 cm on computed tomography (OR 1.53) and CA 19-9 > 210 U/mL (OR 2.30). Postoperative risk factors consisted of poor tumor differentiation grade (OR 1.66), microscopic lymphovascular invasion (OR 1.70), a lymph node ratio > 0.2 (OR 2.49), and CA 19-9 > 37 U/mL (OR 3.38). Adjuvant chemotherapy (OR 0.28) and chemoradiotherapy (OR 0.29) were associated with a reduced likelihood of early recurrence.

Conclusion:

A recurrence-free interval of 12 months is the optimal threshold for differentiating between early and late recurrence, based on subsequent prognosis.

Article Keywords

Keywords
carbohydrate antigen 19-9, early recurrence, pancreatectomy, pancreatic ductal adenocarcinoma, post-recurrence survival, recurrence-free survival

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Defining and Predicting Early Recurrence in 957 Patients With Resected Pancreatic Ductal Adenocarcinoma