Adjuvant Therapy in Pancreas Cancer: Does It Influence Patterns of Recurrence?

• Published in: Journal of the American College of Surgeons Vol. 222; no. 4; pp. 448 - 456
• Main Authors: Parikh, Alexander A., MD, MPH, FACS, Maiga, Amelia, MD, MPH, Bentrem, David, MD, FACS, Squires, Malcolm H., MD, Kooby, David A., MD, FACS, Maithel, Shishir K., MD, FACS, Weber, Sharon M., MD, FACS, Cho, Clifford S., MD, FACS, Katz, Matthew, MD, FACS, Martin, Robert C., MD, PhD, FACS, Scoggins, Charles R., MD, MBA, FACS, Sutton, Jeff, MD, Ahmad, Syed A., MD, FACS, Abbott, Daniel E., MD, FACS, Carr, Jacquelyn, MD, Kim, Hong Jin, MD, FACS, Yakoub, Danny, MD, FACS, Idrees, Kamran, MD, FACS, Merchant, Nipun, MD, FACS
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2016
• Subjects: Aged; Carcinoma, Pancreatic Ductal - mortality; Carcinoma, Pancreatic Ductal - pathology; Carcinoma, Pancreatic Ductal - therapy; Chemoradiotherapy, Adjuvant; Chemotherapy, Adjuvant; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local - diagnosis; Neoplasm Recurrence, Local - epidemiology; Pancreatectomy; Pancreatic Neoplasms - mortality; Pancreatic Neoplasms - pathology; Pancreatic Neoplasms - therapy; Pancreaticoduodenectomy; Proportional Hazards Models; Retrospective Studies; Surgery; adjuvant chemotherapy; LN; OS; local recurrence-free survival; adjuvant chemoradiation; HR; IQR; interquartile range; pancreatic ductal adenocarcinoma; distant recurrence-free survival; LRFS; ACT; CONKO; PDAC; European Study Group for Pancreatic Cancer; lymph node; ESPAC; hazard ratio; overall survival; ACRT; DRFS; Charité Onkologie
• ISSN: 1072-7515; 1879-1190
• DOI: 10.1016/j.jamcollsurg.2015.12.031

Background Level 1 data demonstrate that adjuvant chemotherapy (ACT) improves survival after surgical resection of pancreatic ductal adenocarcinoma (PDAC), (adjuvant gemcitabine, CONKO-001 study; adjuvant 5-FU, ESPAC3 study). The role of adjuvant chemoradiation therapy (ACRT) remains controversial. What is less clear is whether adjuvant therapy influences patterns of recurrence. The purpose of this study was to perform the first multicenter study analyzing patterns of recurrence after adjuvant therapy for PDAC. Study Design Patients undergoing resection for PDAC from 8 medical centers over a 10-year period were analyzed. Demographics, tumor characteristics, operative treatment, type of adjuvant therapy, recurrence pattern, and survival were reviewed. Using Cox-proportional hazards multivariate (MV) regression, the impact of ACT and ACRT on overall survival (OS), local recurrence (LR), and distant recurrence (DR) was investigated. Results There were 1,130 patients who were divided into those having surgery alone (n = 392), ACT (n = 291), or ACRT (n = 447). Median follow-up was 18 months. Compared with patients undergoing surgery alone, ACT, but not ACRT, demonstrated a significant OS advantage on MV analysis. Patients receiving ACT had significantly fewer recurrences (LR and DR); those receiving ACRT had significantly less LR but not DR. On subset MV analysis, ACT and ACRT resulted in less LR in patients with lymph node (LN) positive and margin negative disease. No improvements in LR, DR, or OS were seen in margin positive patients with either ACT or ACRT. Conclusions This is the first analysis demonstrating differences in recurrence patterns in PDAC patients based on type of adjuvant therapy. Adjuvant chemotherapy provided an OS advantage likely related to its effect on reducing both LR and DR. Adjuvant chemoradiation therapy appears to decrease LR, but not DR, and therefore has less impact on OS. Future investigations and treatment protocols should consider additional ACT rather than ACRT in the treatment of PDAC.