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EARLY RECURRENCE PREDICTORS AND PATTERNS AFTER RESECTION FOR PANCREATIC DUCTAL ADENOCARCINOMA: IS THE SURGEON ONLY A BYSTANDER?
Alex M. Roch
*, Alexa J. Hughes, Andrew J. Thyen, Thomas K. Maatman, Ryan J. Ellis, Max Schmidt, Nicholas J. Zyromski, Eugene P. Ceppa, Michael G. House
Surgical Oncology, Indiana University School of Medicine, Indianapolis, IN
Background: Surgical resection stands as the sole potentially curative option for pancreatic ductal adenocarcinoma (PDAC); however, the recurrence rate remains high despite advancements in surgical techniques and perioperative adjuvant therapies. Early recurrence (ER), correlated with a dismal prognosis, represents a distinctive yet inadequately understood challenge. This study seeks to assess the risk factors for ER in PDAC and guide optimal management strategies for high-risk patients following surgical resection.
Methods: All consecutive patients who underwent a pancreatic resection with curative intent for PDAC at our tertiary center (2015-2020) were included. A logistic regression analysis identified predictors of ER, defined as a recurrence within 12 months after surgery. The patterns of ER and their impact on overall survival were also analyzed.
Results: In this study, 348 patients were included with a median follow-up of 1.9 years. Recurrence occurred in 267 patients (76.7%), with 40.2% experiencing ER, 36.5% recurring after 12 months, and 23.3% showing no recurrence at all. Independent risk factors for ER included a higher-grade tumor (p=0.008, OR 2.8), positive lymph nodes (p=0.01, OR 1.4), elevated Carbohydrate Antigen19-9 levels (>37 U/mL) (p=0.014, OR 3.5), or non-production (p=0.049, OR 18.5) at diagnosis, low serum albumin (p=0.007, OR=4.1), and the lack of use of adjuvant chemotherapy (p=0.037, OR 7.5). Analysis of the tumor genomic data revealed that the presence of a CDKNA1/2 mutation increased the risk of ER (p=0.01), whereas a BRCA1/2 mutation demonstrated a protective effect (p=0.016). Notably, the status of resection margins and the occurrence of a clinically-relevant postoperative pancreatic fistula did not correlate with a higher risk of ER (p=0.46 and p=0.23, respectively). The liver was the most frequent site of ER (32.9%). A subset of eleven patients (7.9%) showcased ER with exclusive lung metastasis, which was linked to an extended median post-recurrence survival of 2.2 years compared to 0.48 years for all other sites (p<0.001). ER was associated with poorer overall survival, with rates of 49.3%, 7.9%, and 4.3% at 1, 3, and 5 years for ER patients vs. 100%, 44.9%, and 10.2% for late recurrence patients (p<0.001, p<0.001, and p=0.048, respectively).
Conclusions: Early recurrence stems from a more aggressive tumor biology. Surgical outcomes, particularly margin status and the presence of complications, do not influence the risk of ER significantly. The use of adjuvant chemotherapy and PDAC associated with BRCA mutations are linked to a reduced risk of ER. In a minority of cases, ER manifests as hematogenic dissemination to the lungs only, correlating with a markedly improved prognosis. The identification of risk factors and the pattern of early recurrence can inform personalized management strategies.
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