Management of Peritoneal Metastasis in Patients with Pancreatic Ductal Adenocarcinoma

Our plain-English summary of Management of Peritoneal Metastasis in Patients with Pancreatic Ductal Adenocarcinoma, by G. Wu, O.J. Standring, D.A. King, et al (Current Oncology, 2025).

The study

• Authors: G. Wu, O.J. Standring, D.A. King, S. Gholami, C.E. Devoe, C.A. Thiels, T.E. Grotz, M.J. Weiss, R.L. Whelan, M. Raoof, D.K. DePeralta
• Journal: Current Oncology
• Published: 2025;32(2)
• Type of article: Review
• Cited by: 11 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The peritoneum is the second most common site of metastasis in patients with pancreatic ductal adenocarcinoma (PDAC). Up to half of all patients that undergo curative-intent resection eventually develop peritoneal metastasis (PM), which accounts for significant morbidity and drives mortality. Despite recent advances in management, PM is associated with very poor prognosis, which is often measured in weeks to months. Clinical manifestations including bowel obstruction, ascites, and urinary obstruction have profound impact on quality of life. Even with relatively advanced disease, PM often remains occult on imaging and thus tend to be underdiagnosed and understudied. Many patients with peritoneal-only PM are excluded from clinical trials because response cannot be measured by standard radiographic criteria. Furthermore, as patients with PM are not eligible for surgical resection and low-volume peritoneal disease is often not amenable to percutaneous biopsy, tissue samples for peritoneal-specific translational studies are limited. Intraperitoneal therapeutics have been proposed as an attractive option for PM, as better penetration of tumor tissue can be achieved with less systemic toxicity compared with intravenous chemotherapy. Heated intraperitoneal chemotherapy (HIPEC), typically combined with cytoreductive surgery (CRS), is an option for select patients with PM from gynecologic or gastrointestinal primary, and for patients with primary peritoneal mesothelioma. However, the incorporation of locoregional therapy for PM in patients with PDAC has been poorly studied given the aggressive nature of pancreatic cancer and overall poor prognosis. With recent advances in existing treatment options, there may be a subset of patients who may derive benefits from locoregional control with cytoreduction and/or intraperitoneal chemotherapy. Critically, additional work is needed to determine PM-favorable clinical and tumoral predictive biomarkers to identify patients who may benefit from a more aggressive approach. We describe the current state of management of patients with peritoneal metastasis from PDAC and review the available data exploring peritoneal-directed therapy with cytoreductive surgery and/or intraperitoneal chemotherapy.

In plain English

This article was a review, not a new study. It concerned peritoneal metastasis (cancer spread to the abdominal lining) from pancreatic ductal adenocarcinoma, not asbestos; peritoneal mesothelioma was mentioned only in passing. The authors reviewed studies and ongoing trials of heated intraperitoneal chemotherapy (HIPEC), with or without cytoreductive surgery, aerosolized chemotherapy (PIPAC) and normothermic intraperitoneal chemotherapy. One reviewed randomized trial, by Padilla-Valverde and colleagues, treated localized pancreatic cancer without peritoneal spread, and both groups could also receive chemotherapy after surgery. Cancer recurred near the original site in 11 of 21 patients (52%) without HIPEC and 2 (10%) with HIPEC, but median overall survival did not differ statistically. A Mayo Clinic retrospective study of highly selected patients reported 3-year survival, counted from diagnosis of peritoneal metastasis, of 8% with systemic therapy alone and 59% with systemic chemotherapy plus cytoreductive surgery and HIPEC; the authors said a select group may benefit. In one PIPAC study, 7 of 20 patients (35%) showed tumor regression under the microscope. The authors concluded these approaches are controversial and unproven in this cancer, though they may have a role.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of published studies and ongoing clinical trials on peritoneal-directed therapy for peritoneal metastasis from pancreatic ductal adenocarcinoma
• Who was studied: Patients with pancreatic ductal adenocarcinoma in the reviewed studies. These included four adjuvant HIPEC studies totalling 88 patients and six PIPAC studies of approximately 77 patients, plus CRS/HIPEC and NIPEC studies.
• Exposure: No asbestos or other environmental exposure was studied. The review covered treatments: HIPEC (mainly gemcitabine, or cisplatin with mitomycin C or paclitaxel), cytoreductive surgery, PIPAC (cisplatin with doxorubicin, or oxaliplatin) and normothermic intraperitoneal paclitaxel.
• Main results:
  • The Padilla-Valverde trial was one of four reviewed adjuvant HIPEC studies. These studies selected patients with localized PDAC and no evidence of peritoneal metastasis, with the goal of reducing the risk of peritoneal relapse.
  • In the reviewed randomized trial by Padilla-Valverde et al., there were 21 patients per arm, and patients in both arms could receive adjuvant systemic chemotherapy (16 of 21 without HIPEC and 12 of 21 with HIPEC). Locoregional recurrence was 11 (52%) in the arm given resection without HIPEC, which the article labels 'resection only', and 2 (10%) with resection plus HIPEC (p = 0.004). There was no statistical difference in median overall survival: 18 months without HIPEC versus 17.1 months with HIPEC.
  • In the reviewed Tentes et al. study of 39 patients given resection plus HIPEC, 23 (59%) developed recurrence: 19 (48.7%) distant and 4 (10.3%) locoregional.
  • The reviewed Mayo Clinic retrospective study compared 38 patients given systemic chemotherapy alone with 23 given CRS/HIPEC. The Mayo studies were of a highly select group with low-volume peritoneal metastasis and a response to systemic chemotherapy. At 3 years after diagnosis of peritoneal metastasis, 8% of the systemic-chemotherapy-alone group were alive, compared with 59% of those treated with both systemic chemotherapy and HIPEC/CRS.
  • The review said the Mayo results suggest that a select group of patients with PDAC and isolated peritoneal metastases may benefit from locoregional treatment with CRS/HIPEC.
  • In the reviewed Khosrawipour et al. PIPAC study, 7 of 20 patients (35%) had objective histological tumor regression.
  • In a reviewed phase I/II study of added intraperitoneal paclitaxel, peritoneal cytology converted to negative in 18 of 46 patients (39%), and median overall survival was 14.5 months.
• The authors' conclusion: The authors concluded that cytoreductive surgery and intraperitoneal chemotherapy are controversial and unproven in pancreatic ductal adenocarcinoma, but that these regional approaches may have a role in palliative and curative-intent or adjuvant settings. They called for standardized treatments and response measures.
• Limitations the authors state:
  • Early PIPAC studies included mixed groups of patients with different tumor types, extents of disease and systemic regimens, so conclusions about efficacy could not be drawn.
  • Any long-term survival benefit of HIPEC awaits randomized clinical trials.

Topics

Medical terms in this study, explained in our Lexicon: Metastasis, Adenocarcinoma, Peritoneum, Prognosis, Ascites, Quality of Life, Clinical Trial, Surgical Resection.

Related studies

• Expression of Calretinin, Marker of Mesothelial Differentiation, in Pancreatic Ductal Adenocarcinoma: A Potential Diagnostic Pitfall — G. Askan, O. Basturk (2021)
• Efficacy and immunogenic effects of Tumor Treating Fields (TTFields) in preclinical models of pancreatic ductal adenocarcinoma, with and without gemcitabine/nab-paclitaxel — T. Kan, T. Haj Khalil, et al. (2026)
• Focal adhesion kinase a potential therapeutic target for pancreatic cancer and malignant pleural mesothelioma — R. Kanteti, T. Mirzapoiazova, et al. (2018)
• Exposure to environmental chemicals and heavy metals, and risk of pancreatic cancer — S.O. Antwi, E.C. Eckert, et al. (2015)
• Isolated pancreatic metastasis from a malignant pleural mesothelioma diagnosed using endoscopic ultrasonography-guided fine needle aspiration biopsy — Y. Ishikawa-Kakiya, H. Maruyama, et al. (2022)
• Itraconazole therapy in a pancreatic adenocarcinoma patient: A case report — N.R. Lockhart, J.A. Waddell, et al. (2016)

Browse more research in Current Oncology, or return to medical research.