Molecular Peritoneal Staging for Pancreatic Ductal Adenocarcinoma Using Mutant KRAS Droplet-Digital Polymerase Chain Reaction: Results of a Prospective Clinical Trial - 23/06/21

Doi : 10.1016/j.jamcollsurg.2021.05.009

Jennifer A. Yonkus, MD ^a, Roberto Alva-Ruiz, MD ^a, Amro M. Abdelrahman, MBBS ^a, Jennifer L. Leiting, MD ^a, Amber R. Schneider, BS ^b, Travis E. Grotz, MD ^a, Sean P. Cleary, MD, FACS ^a, Rory L. Smoot, MD, FACS ^a, David M. Nagorney, MD, FACS ^a, Michael L. Kendrick, MD, FACS ^a, Benjamin R. Kipp, PhD ^b, Mark J. Truty, MS, MD, FACS ^a,^⁎
^a Section of Hepatobiliary and Pancreatic Surgery, Division of Subspecialty General Surgery, Department of Surgery
^b Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN

^∗Correspondence address: Mark J Truty, MS, MD, FACS, Mayo Clinic, 200 First St Southwest, Rochester, MN 55905.Mayo Clinic200 First St SouthwestRochesterMN55905

Abstract

Background

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with predilection for peritoneal dissemination. Accurate peritoneal staging is imperative for treatment recommendations, as one-third of patients develop peritoneal recurrence after resection. Because >90% of PDAC tumors harbor mutant KRAS (mKRAS), we sought to determine feasibility of mKRAS DNA detection in peritoneal lavage (PL) fluid using droplet-digital polymerase chain reaction (ddPCR) via a prospective trial.

Study design

Patients with nonmetastatic PDAC undergoing staging laparoscopy with PL were included. PL fluid was sent for cytologic examination, CA19-9/CEA levels, and mKRAS ddPCR assay. Clinically positive laparoscopy was defined as gross metastases or positive cytology. PL mKRAS status was compared with gross findings, cytology, and CA19-9/CEA levels.

Results

There were 136 patients enrolled; 70 of 136 (51%) patients received neoadjuvant therapy before PL, and 32 of 136 (24%) patients had clinically positive laparoscopy. Cytology was positive in 17 of 136 (13%) patients, and 22 of 136 (16%) patients had gross metastases. Of patients with gross metastases, only 8 of 22 (36%) had positive cytology; 97 of 136 (71%) patients had mKRAS in PL. PL mKRAS was present in 27 of 32 (84%) clinically positive laparoscopies, with higher mean copy number in clinically positive patients (643 vs 10, p = 0.02). Peritoneal mKRAS was positive in an additional 70 clinically negative patients.

Conclusions

This prospective study establishes the feasibility of PL mKRAS detection. Clinically positive disease was identified in 1 in 4 staging laparoscopies. Although PL mKRAS was highly associated with clinically positive findings, many clinically negative laparoscopies had detectable PL mKRAS, suggesting that standard staging may be inadequate. Longer follow-up will elucidate utility of this promising molecular assay.

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