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Multicenter Study
. 2025 Aug 28;31(32):109383.
doi: 10.3748/wjg.v31.i32.109383.

Role of preoperative circulating tumor DNA in predicting occult metastases in resectable and borderline resectable pancreatic ductal adenocarcinoma

Takeshi Murakami  1 , Masafumi Imamura  2 , Yasutoshi Kimura  1 , Kazunori Watanabe  3   4 , Yoshihito Shinohara  3   4 , Toru Nakamura  3 , Siew-Kee Low  4 , Masayo Motoya  5 , Yujiro Kawakami  6 , Yoshiharu Masaki  6 , Tomohiro Kubo  7 , Makoto Yoshida  7 , Eiji Yoshida  1 , Toru Kato  1 , Kazuharu Kukita  1 , Daisuke Kyuno  1 , Ichiro Takemasa  1
Affiliations
Multicenter Study

Role of preoperative circulating tumor DNA in predicting occult metastases in resectable and borderline resectable pancreatic ductal adenocarcinoma

Takeshi Murakami et al. World J Gastroenterol. .

Abstract

Background: Some patients with resectable or borderline resectable pancreatic ductal adenocarcinoma (PDAC) may have distant metastases, undetected on preoperative imaging or early recurrence, within 6 months after surgery. Occult metastases (OMs) must be accurately predicted to optimize multidisciplinary treatment.

Aim: To investigate the efficacy of circulating tumor DNA (ctDNA) in predicting OM.

Methods: Two Japanese institutions prospectively collected preoperative plasma samples from PDAC patients between July 2019 and September 2021 and evaluated ctDNA using a targeted next-generation sequencing panel covering 52 cancer-related genes.

Results: Among 135 PDAC patients, 38 had OM and 35 were positive for ctDNA. The ctDNA positivity rate was significantly higher in patients with OM than in patients without OM. ctDNA-positive patients had significantly shorter median recurrence-free survival than ctDNA-negative patients. Logistic multivariate regression revealed ctDNA positivity as an independent predictor of OM.

Conclusion: Preoperative ctDNA in resectable PDAC is an independent predictor of OM and indicates poor prognosis following pancreatectomy and may be a useful biomarker in determining multidisciplinary patient care.

Keywords: Circulating tumor DNA; Early recurrence; Multidisciplinary treatment; Occult metastases; Pancreatic ductal adenocarcinoma.

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Conflict of interest statement

Conflict-of-interest statement: The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
Patient enrollment and sample collection. R: Resectable; BR: Borderline resectable; PDAC: Pancreatic ductal adenocarcinoma; NAT: Neoadjuvant therapy; pCR: Pathologiccaly complete response; pTis: Pathological carcinoma in situ.
Figure 2
Figure 2
Association between circulating tumor DNA status and prognosis. A: Kaplan-Meier curve of postoperative recurrence-free survival (RFS) in circulating tumor DNA (ctDNA)-positive and -negative groups of 125 patients who underwent pancreatectomy, excluding 10 patients who underwent laparotomy. During the observation period of 37.1 months, the median RFS in the ctDNA-positive group was 10.2 months, significantly worse than the 258 months in the ctDNA-negative group (P = 0.023); B: Kaplan-Meier curve of postoperative overall survival in ctDNA-positive and -negative groups of 135 patients. The median overall survival in the ctDNA-positive group was 22.9 months, significantly worse than the 411 months in the ctDNA-negative group (P = 0.039). ctDNA: Circulating tumor DNA.
Figure 3
Figure 3
Kaplan-Meier curves of circulating tumor DNA dynamics and postoperative recurrence-free survival in 31 patients sampled before and after neoadjuvant therapy. The median recurrence-free survival (RFS) of 20.2 months for the group whose circulating tumor DNA (ctDNA) changed from positive to negative after neoadjuvant therapy (NAT) was not significantly different from the median RFS of 18 months for the group whose ctDNA remained negative during NAT (P = 0.862). ctDNA: Circulating tumor DNA; RFS: Recurrence-free survival.
See this image and copyright information in PMC

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