What is Pancreatic Cancer?
Pancreatic cancer is a rare but aggressive disease that is often diagnosed at an advanced stage due to vague early symptoms, with up to 80% of cases identified too late for curative surgery. Peritoneal metastases are present in up to 14% of patients at diagnosis and occur in 40–50% of recurrences, contributing to severe symptoms and limited treatment options.
While there is abundant information on more conventional treatments for Pancreatic Cancer, our focus here will be on the rationale and available data supporting the use of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) in these specific cases. It is important to emphasize that evidence regarding the benefit of CRS/HIPEC for Pancreatic Cancer remains limited. Nevertheless, reports suggest potential benefits for certain patients facing Pancreatic Cancer with rare indications for CRS/HIPEC.
Pancreatic cancer is a rare and highly aggressive cancer that originates in the tissues of the pancreas. It often presents with vague symptoms, making it challenging to diagnose early. As a result, up to 80% of cases are diagnosed at advanced stages, which significantly complicates treatment. [see References: 1] Peritoneal metastases, which commonly cause severe symptoms, are present in up to 14% of cases at diagnosis. [2] Furthermore, the peritoneum is one of the most frequent sites of recurrence, occurring in 40-50% of cases.[3]
Pancreatic cancer treatment typically involves a combination of systemic chemotherapy, surgery, and radiation therapy. Surgery is generally reserved for early-stage cases where the tumor can be entirely removed, offering the only chance at a cure.[4] However, only a small percentage (10-15%) of patients are eligible for surgery as the tumor has typically spread by the time of diagnosis.[5, 6] For recurrent or metastatic pancreatic cancer, current treatments are mainly palliative and consist of systemic chemotherapy or participation in clinical trials. In some cases, minor surgeries may be performed to help alleviate symptoms, such as bile duct or stomach blockages. Given the poor survival rates of 2-6 months and the limited treatment options, there is a need for alternative therapies.[4] While cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is not a standard treatment for pancreatic cancer, there is some interest in exploring this approach due to its success in treating other abdominal cancers.[7-9]
The current evidence for CRS/HIPEC in pancreatic cancer is extremely scarce, but initial findings suggest that this approach may offer prolonged survival in carefully selected patients. In one study, 23 patients treated with CRS/HIPEC were compared to 38 patients who received standard systemic chemotherapy. The CRS/HIPEC group demonstrated a significantly longer overall survival, with a median of 41 months vs 19 months for the chemotherapy group. Additionally, patients who underwent complete CRS/HIPEC had a median progression-free survival of 17 months, indicating that surgery may provide a substantial survival benefit.[10] Other studies have reported similar findings, with median survival ranging from 12-36 months, and most studies showing progression-free survival exceeding 12 months, potentially offering patients more time off treatment compared to standard therapies.[11-13]
While the variability in results highlights the importance of careful patient selection, most studies have not been able to identify specific prognostic factors due to small sample sizes.[14] Key factors that appear to influence outcomes include performance status, the ability to tolerate extensive surgery, the feasibility of achieving a complete cytoreduction, and the response to previous treatments. These factors, among others, should be carefully evaluated by a team of peritoneal surface malignancy specialists on a case-by-case basis.
Some studies have also suggested that HIPEC could benefit patients at high risk for recurrence following local tumor resection. Early results indicate that HIPEC may help reduce the risk of peritoneal recurrence, a condition associated with poor prognosis.[15, 16] One study also investigated the potential role of laparoscopic CRS/HIPEC in patients with limited peritoneal disease. It reported promising overall and progression free survival of 26 and 20 months, respectively, supporting its potential in locally advanced or borderline resectable cases.[17] A systematic review of the available literature concluded that HIPEC, both as a prophylactic measure and for the treatment of peritoneal metastases, was associated with improved survival rates. Additionally, the use of PIPAC and intraperitoneal chemotherapy for palliative treatment of unresectable disease are emerging as promising approaches.[18] Despite these promising findings, the data remains early, and these approaches warrant further investigation to better understand their potential benefits and optimize patient selection.
Finding Specialized Care
Finding a care provider who is knowledgeable with colorectal cancer and how to treat it is critically important. To search for providers who specialize in performing CRS/HIPEC and providers who specialize in colorectal cancer, navigate to our Find a Specialist page.​​
please note: Our goal is to provide information to help you find a doctor closest to your home that can provide the best quality of care for your diagnosis or your anticipated CRS/HIPEC procedure. The Abdominal Cancers Alliance does not endorse any care provider or medical center over another.
Clinical Trials
There are many actively recruiting clinical trials for pancreatic cancer registered online. Below is a sample of a few of the clinical trials for HIPEC listed on www.ClinicalTrials.gov. Your oncologists (medical, surgical, and radiation) can also help you review clinical trial options and recommendations.
Hyperthermic Intraperitoneal Chemotherapy for the Treatment of Pancreatic Cancer Metastasis (NCT04858009)
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Status: Recruiting
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This phase II trial aims to study to the effect of CRS/HIPEC as treatment for pancreatic cancer with peritoneal metastases by evaluating survival and toxicity.
- Inclusion criteria: Age ≥18 and ≤80, pancreatic cancer with metastases to the peritoneum, no extraperitoneal disease, responded to preoperative chemotherapy, high likelihood of complete cytoreduction with low tumor burden, able to undergo treatment
Intra-abdominal Hyperthermic Chemotherapy and Pancreatic Cancer (NCT03251365)
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Status: Recruiting
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This is a randomized phase II-III clinical trial comparing CRS and CRS/HIPEC for the treatment of pancreatic cancer with peritoneal metastases. Both groups also receive adjuvant systemic chemotherapy.
- Inclusion criteria: Age ≥18, histologically confirmed cholangiocarcinoma or gallbladder cancer with peritoneal metastases, able to undergo treatment
Combined Nabpaclitaxel Pressurized Aerosol Chemotherapy with Systemic Nabpaclitaxel-Gemcitabine Chemotherapy for Pancreatic Cancer with Peritoneal Metastases (Nab-PIPAC) (NCT05371223)
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Status: Recruiting
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This phase II study is investigating the anti-tumor activity of combined systemic chemotherapy and PIPAC for pancreatic cancer with peritoneal metastases.
- Inclusion criteria: Age ≥18, pancreatic cancer with peritoneal disease, no extra-abdominal disease, able to undergo treatment
1. Park W, Chawla A, O'Reilly EM. Pancreatic Cancer: A Review. JAMA. 2021 Sep 7;326(9):851-862. doi: 10.1001/jama.2021.13027. Erratum in: JAMA. 2021 Nov 23;326(20):2081. doi: 10.1001/jama.2021.19984. PMID: 34547082; PMCID: PMC9363152. 2. Rijken A, Bakkers C, van Erning FN, van der Geest LG, de Vos-Geelen J, Besselink MG, Lemmens VE, de Hingh IHJT; Dutch Pancreatic Cancer Group. Incidence, Treatment, and Survival of Synchronous Peritoneal Metastases in Pancreatic Cancer: Update of a Nationwide Cohort. Pancreas. 2021 Jul 1;50(6):827-833. doi: 10.1097/MPA.0000000000001857. PMID: 34347730. 3. Warshaw AL, Fernández-del Castillo C. Pancreatic carcinoma. N Engl J Med. 1992 Feb 13;326(7):455-65. doi: 10.1056/NEJM199202133260706. PMID: 1732772. 4. McGuigan A, Kelly P, Turkington RC, Jones C, Coleman HG, McCain RS. Pancreatic cancer: A review of clinical diagnosis, epidemiology, treatment and outcomes. World J Gastroenterol. 2018 Nov 21;24(43):4846-4861. doi: 10.3748/wjg.v24.i43.4846. 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Hoefer RA, Obiora C, Azab B, Harden EA, Kessler JF. Combined modality therapy including cytoreductive surgery and heated intraperitoneal chemotherapy for synchronous low volume peritoneal carcinomatosis from adenocarcinoma of the tail of pancreas in a BRCA-2 carrier resulting in long-term disease-free survival: A case report. Int J Surg Case Rep. 2021 Jun;83:106047. doi: 10.1016/j.ijscr.2021.106047. Epub 2021 May 29. PMID: 34091215; PMCID: PMC8188393. 12. Tentes AA, Pallas N, Karamveri C, Kyziridis D, Hristakis C. Cytoreduction and HIPEC for peritoneal carcinomatosis of pancreatic cancer. J BUON. 2018 Mar-Apr;23(2):482-487. PMID: 29745096. 13. Tentes AK. Hyperthermic intra-operative intraperitoneal chemotherapy as an adjuvant to pancreatic cancer resection. J Gastrointest Oncol. 2021 Apr;12(Suppl 1):S91-S98. doi: 10.21037/jgo-20-46. PMID: 33968429; PMCID: PMC8100705. 14. Yan G, Zhang K, Yan L, Zhang Y. Efficacy and safety of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy in patients with pancreatic cancer peritoneal metastasis. World J Surg Oncol. 2024 Sep 2;22(1):212. doi: 10.1186/s12957-024-03464-9. PMID: 39218891; PMCID: PMC11367765. 15. Tentes AA, Kyziridis D, Kakolyris S, Pallas N, Zorbas G, Korakianitis O, Mavroudis C, Courcoutsakis N, Prasopoulos P. Preliminary results of hyperthermic intraperitoneal intraoperative chemotherapy as an adjuvant in resectable pancreatic cancer. Gastroenterol Res Pract. 2012;2012:506571. doi: 10.1155/2012/506571. Epub 2012 May 27. PMID: 22693491; PMCID: PMC3368190. 16. Tentes AA, Stamou K, Pallas N, Karamveri C, Kyziridis D, Hristakis C. The effect of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) as an adjuvant in patients with resectable pancreatic cancer. Int J Hyperthermia. 2016 Dec;32(8):895-899. doi: 10.1080/02656736.2016.1227094. Epub 2016 Sep 4. PMID: 27545750. 17. Grotz TE, Yonkus JA, Thiels CA, Warner SG, McWilliams RR, Mahipal A, Bekaii-Saab TS, Cleary SP, Kendrick ML, Truty MJ. Cytoreduction with Hyperthermic Intraperitoneal Chemoperfusion for Pancreatic Cancer with Low-Volume Peritoneal Metastasis: Results from a Prospective Pilot Study. Ann Surg Oncol. 2023 Jan;30(1):395-403. doi: 10.1245/s10434-022-12328-z. Epub 2022 Aug 16. PMID: 35972667. 18. Frassini S, Calabretto F, Granieri S, Fugazzola P, Viganò J, Fazzini N, Ansaloni L, Cobianchi L. Intraperitoneal chemotherapy in the management of pancreatic adenocarcinoma: A systematic review and meta-analysis. Eur J Surg Oncol. 2022 Sep;48(9):1911-1921. doi: 10.1016/j.ejso.2022.05.030. Epub 2022 Jun 2. PMID: 35688711.