How is Peritoneal Cancer Treated?

The peritoneum lines the inside of the abdomen in a manner analogous to the lining of the purse. The abdominal organs, including the stomach, intestine, spleen etc. are covered by the peritoneum. Although only a couple of millimeters thick, the peritoneum is comprised of three discrete layers: mesothelium, basement membrane and sub-mesothelium [1]. Cancer (i.e. invasive cells) can arise from these layers primarily or spread to the peritoneum from a secondary organ. Primary peritoneal cancer originates from the cells lining the peritoneum such as the mesothelium. Secondary peritoneal cancers usually metastasize or spread to the peritoneum from remote or adjacent gastrointestinal or gynecological organs such as the stomach, small intestine, appendix, colon, rectum or ovaries. Cancer that spreads to the peritoneal cavity from another site, such as the colon, are considered Stage IV as the peritoneum represents a distant site of spread. Peritoneal carcinomatosis (PC) generally refers to cancer from a gastrointestinal or genitourinary site that has metastasized to the peritoneum and historically was associated with a very poor prognosis. In the European multicenter EVOCAPE I study, median survival was just 5.2 months for colorectal cancer and 3.1 months for advanced gastric cancer with peritoneal carcinomatosis without any treatment [2].  

 

Peritoneal mesothelioma (PM) is a particularly rare malignancy involving the peritoneal lining. Four principal malignant pathologic variants of PM have been described, namely well-differentiated papillary, epithelioid, sarcomatoid and biphasic [3, 4]. For appropriately selected patients with primary (e.g. peritoneal mesothelioma) and secondary peritoneal cancer, aggressive cytoreductive surgery (CRS) +/- the use hyperthermic intraperitoneal chemotherapy (HIPEC) has emerged as the standard of care and can offer long-term survival. A multi-institutional review of 401 patients with advanced mesothelioma showed an overall median survival of 53 months and 5-year overall survival of 47% after CRS/HIPEC +/- EPIC [5]. A benign variant, multi-cystic mesothelioma, is predominantly found in females of reproductive age and can disseminate locally [6]. Use of CRS/HIPEC has also been reported in this subtype, with recurrence rates of 21% at 69 months and mean recurrence-free survival of 159 months [7].

​

The most common application of CRS +/- HIPEC is in colorectal cancer that has metastasized to the peritoneum (i.e. colorectal carcinomatosis). A meta-analysis by Franko et al. demonstrated that patients with colorectal peritoneal carcinomatosis without extra-peritoneal metastases can expect a median survival of 16-17 months with modern systemic therapy alone, including targeted agents [8]. The combination of systemic therapy (e.g. chemotherapy) with aggressive surgery to remove all known remaining visible disease has be shown to produce prolonged survival [9]. In the latest randomized control trial evaluating the role of HIPEC in addition to aggressive cytoreductive surgery, median survival was ≥40 months regardless of the use of HIPEC[10]. These represent some of the best longterm results we have seen for this disease and indicate that with appropriate patient selection and multi-disciplinary care, longterm survival is possible. Large, multi-institutional datasets continue to confirm that the combination of modern systemic therapy with complete cytoreduction (i.e. removal of primary and visible peritoneal cancer) +/- the use of intra-operative intraperitoneal chemotherapy, such as HIPEC, can produce long-term survivors[11]. Factors such as the molecular profile of the primary cancer (e.g. mutation status), the presence of absence of extra-peritoneal metastases (e.g. liver metastases), the burden of lymph node involvement, the grade and histology of the tumor and the age of the patient are all important prognostic factors. One of the most important factors in patient selection for surgery in addition to systemic therapy is the burden of peritoneal disease as defined by the peritoneal carcinomatosis index (PCI). This is a method of reproducibly quantifying the burden of peritoneal disease (i.e. score of 0-39) and is directly correlated with outcome. Data from the United States and Europe suggests that for patients with colorectal peritoneal carcinomatosis, a PCI score of ≥20 is a contra-indication to aggressive cytoreductive surgery. Patients with such a high burden of disease may do equally well if not better with systemic therapy alone and long-term cure is not possible with surgery [11]. 

​

For less common cancers of the peritoneum, such as cancers arising from the appendix or the mesothelium, less is known about the upper limit of utility for aggressive surgical management. However, the best available data suggests that appendiceal cancers from low-grade mucinous appendiceal neoplasms to infiltrative adenocarcinomas can be safely and effectively managed with curative intent with aggressive cytoreductive surgery and intraperitoneal chemotherapy [12]. Carcinomatosis secondary to appendiceal adenocarcinoma is treated very similarly to colorectal carcinomatosis. For low-grade appendiceal neoplasms, such as those that produce pseudomyxoma peritonei, which is informally known as 'Jelly Belly', cytoreductive surgery followed by HIPEC is the only known effective treatment and produces 10-year overall survival of ≥60%. The multidisciplinary management of invasive epithelioid peritoneal mesothelium, including the use of cytoreductive surgery and intraperitoneal chemotherapy can produce 5-year survival of 40-50% [5]. 

​

Regardless of the indication the standard of care for peritoneal cancer is management within an established, high-volume, multi-disciplinary team.

​

​

 

1.    Lemoine, L., P. Sugarbaker, and K. Van der Speeten, Pathophysiology of colorectal peritoneal carcinomatosis: Role of the peritoneum. World J Gastroenterol, 2016. 22(34): p. 7692-707.
2.    Sadeghi, B., et al., Peritoneal carcinomatosis from non-gynecologic malignancies: results of the EVOCAPE 1 multicentric prospective study. (0008-543X (Print)).
3.    Greenbaum, A. and H.R. Alexander, Peritoneal mesothelioma. Transl Lung Cancer Res, 2020. 9(Suppl 1): p. S120-S132.
4.    Turaga, K.K., M. Deraco, and H.R. Alexander, Current management strategies for peritoneal mesothelioma. Int J Hyperthermia, 2017. 33(5): p. 579-581.
5.    Yan, T.D., et al., Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for malignant peritoneal mesothelioma: multi-institutional experience. J Clin Oncol, 2009. 27(36): p. 6237-42.
6.    Noiret, B., et al., Multicystic peritoneal mesothelioma: a systematic review of the literature. Pleura Peritoneum, 2019. 4(3): p. 20190024.
7.    Nizri, E., et al., Multicystic mesothelioma: Operative and long-term outcomes with cytoreductive surgery and hyperthermic intra peritoneal chemotherapy. Eur J Surg Oncol, 2018. 44(7): p. 1100-1104.
8.    Franko, J., et al., Prognosis of patients with peritoneal metastatic colorectal cancer given systemic therapy: an analysis of individual patient data from prospective randomised trials from the Analysis and Research in Cancers of the Digestive System (ARCAD) database. The Lancet Oncology, 2016. 17(12): p. 1709-1719.
9.    Tournigand, C., et al., FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol, 2004. 22(2): p. 229-37.
10.    Quenet, F., et al., A UNICANCER phase III trial of hyperthermic intra-peritoneal chemotherapy (HIPEC) for colorectal peritoneal carcinomatosis (PC): PRODIGE 7. Journal of Clinical Oncology, 2018. 36(18_suppl): p. LBA3503-LBA3503.
11.    Elias, D., et al., Peritoneal colorectal carcinomatosis treated with surgery and perioperative intraperitoneal chemotherapy: retrospective analysis of 523 patients from a multicentric French study. J Clin Oncol, 2010. 28(1): p. 63-8.
12.    Chua, T.C., et al., Early- and long-term outcome data of patients with pseudomyxoma peritonei from appendiceal origin treated by a strategy of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. J Clin Oncol, 2012. 30(20): p. 2449-56.