What Is Primary Peritoneal Cancer

Overview

What is the peritoneum?

The peritoneum is a serous membrane organ, which acts as a protective internal lining of the abdominal cavity. The peritoneum is thin, consisting of two layers with interlayer space that consists of serous fluid which lubricates the layers, reducing friction to allow organs to move freely. the outer of the two layers is called the parietal peritoneum which is fixed to the walls of the abdomen and pelvis, while the second, inner layer is called the the visceral layer that lines internal organs located within the intraperitoneal space. The peritoneum comprises of mesenchymal cells which are derived from the mesoderm, a germ layer which forms during early embryonic development. 

The peritoneum has key functions to support the abdomen by monitoring the movement of intraabdominal organs and maintaining homeostasis in the abdomen. This includes involvement in the regulation of inflammatory responses, exchange of peritoneal fluid and working to prevent the formation of fibrosis in the abdomen. Dysfunction to mechanisms that mediate functions of the peritoneum are thought to be implicated in the pathogenesis of peritoneal malignancy (cancer of peritoneum).¹

What is peritoneal cancer?

Peritoneal cancer, also known as peritoneal surface malignancy, is characterised by the invasion of malignant cells which targets and consequently affects the serous membrane that lines the abdominal cavity.

Peritoneal cancer is classified according to two types:

1. Primary Peritoneal cancer

2. Secondary Peritoneal cancer²

What is primary peritoneal cancer?

Peritoneal tumours are rare malignancies with an incidence rate of 6.78 per million. Primary peritoneal cancer is considered a terminal illness independent of its origin, with a survival rate of 11 to 17 months. The occurence of primary peritoneal cancer is greatest in white people and lowest in black people. Primary peritoneal cancer is characterised by the origin of tumour cells in the mesothelium of the abdomen. This is distinctively different from secondary peritoneal cancer, where tumour cells originate in other sites and migrate to the peritoneal cavity.²

Primary peritoneal cancer subtypes and risk factors

Primary Peritoneal cancer is further classified into numerous subtypes according to histological examination. A summary of the most well studied histological subtypes of primary peritoneal cancer and their risk factors are outlined below.

Extraovarian primary peritoneal carcinoma (EOPCC)

EOPPC is a subtype of primary peritoneal cancer that occurs exclusively in individuals assigned female at birth (AFAB) who are most commonly between the ages of 56 and 62 years of age. The pathogenesis of EOPPC is attributed to germline mutations in the BRCA 1 gene, which has been found responsible in 17.6% of reported cases. The most common growth pattern of this cancer is serous carcinoma of the peritoneum, accounting for 10% of pelvic malignancies.²

Malignant peritoneal mesothelioma (MPM)

MPM is an aggressive form of primary peritoneal cancer most commonly associated with people assigned male at birth (AMAB) above the age of 60 years old. The occurrence of MPM has been associated with increased asbestos exposure, implicated in 33% to 50% of reported cases. Exposure to talc, volcanic ashes or radiation, and having chronic peritonitis have also been implicated in increased risk of MPM. MPM is the second most common type of pelvic malignancy, having one of the poorest prognoses.²

Disseminated peritoneal leiomyomatosis

Disseminated peritoneal leiomyomatosis is attributed to increased levels of oestogen in postmenopausal AFABs. It is the most common subtype of peritoneal cancer that forms within the peritoneal cavity itself.²

Desmoplastic small round cells tumour (DSRCT)

DSRCT is a small cell tumour commonly found in adolescents, with a median age of 19 years old, and implicated in 85% of cases in Caucasians. Translocations to [t(11;22)(p13;q12)] has been implicated in the pathogenesis of DSRCT.²

Symptoms of primary peritoneal cancer

The symptoms of peritoneal cancers are usually non-specific and can include:

• Abdominal bloating
• Distension
• Abdominal pain
• Back pain
• Nausea
• Indigestion
• Anorexia
• Weight loss
• Fatigue
• Constipation²

Staging of primary peritoneal cancer

The primary peritoneal cancer is only diagnosed as either stage III or stage IV. Stage III is defined as the localisation of the tumour in the peritoneal cavity, while stage IV is defined as the metastatis of the tumour to other organs outside of the peritoneal cavity.² 

Stage III is further divided into three sections:

• A - tumour has metastised to the retroperitoneal lymph nodes (RLN) only or the tumour has metastised (microscopically) to just above the pelvic inlet with/without retroperitoneal lymph nodes affected
• B - tumour has metastised outside of the pelvis under 2cm with/without RLN affected
• C - tumour has metastised outside of the pelvis greater than 2cm with/without RLN or other tissue around the organs affected (e.g. spleen).⁴

Berichard, CC BY-SA 3.0 <https://creativecommons.org/licenses/by-sa/3.0>, via Wikimedia Commons

Human pelvis. Red line refers to the pelvic inlet region.

Diagnosis of primary peritoneal cancer:

Physical examination

Your GP may take a physical exam and note down your medical history. A physical examination allows the clinician to check for signs of primary peritoneal cancers including any abnormalities. A pelvic exam assesses the vagina, cervix, uterus, fallopian tubes, ovaries and rectum through insertion of a speculum into the vagina. ^2,3

Medical imaging

Computed tomography (CT) scan

A CT scan is used in the primary investigation for primary peritoneal cancer in patients who present with abdominal pain and distention. CT scans are useful at detecting masses as small as 5mm in size, however the findings identified from a CT scan are often non-specific for malignant and non-malignant conditions.²

Magnetic resonance imaging (MRI) scan

MRI scans are advantageous over CT scans to visualise peritoneal tumours thanks to increased detection sensitivity, which is 84% for MRI scans compared to 54% for CT scans. This correlates with increased contrast resolution, benefitting the diagnosis and staging of lesions less than a centimetre in size.

MRI scans are useful to identify:

• The primary site of metastasis
• Tumour morphology characterised as solid, cystic or mixed
• The quantity of ascites
• The presence or absence of tumour outside of the peritoneum
• The pattern of the tumour growth such as swelling of the tissue or formation of lumps
• Involvement of lymph nodes
• Whether the cancer has spread or if it spread to distant tissues/organs²

Invasive techniques:

Abdominal percutaneous paracentesis 

Ascitic fluid analysis

Ascites are identified in 10% of peritoneal malignancies and are characterised by high protein levels, elevated lactate dehydrogenase (LDH) and low glucose levels. Ascitic fluid analysis is also used to detect increased levels of vascular endothelial growth factor (VEGF) which is a tumour marker associated with peritoneal cancer.² 

Cytology

Cytology is a sensitive technique used to detect 50-70% of malignancy. Cytology is positive in 83% of peritoneal cancers, and often needs to be accompanied by immunohistochemical staining for peritoneal tumour marker proteins such as calretinin, cytokeratin and BerEP4.²

Diagnostic laparoscopy

Laparoscopy is a minimally invasive procedure with 100% sensitivity which allows a clinician to fully visualise the peritoneal lavage to identify the tumour. Laparoscopic procedures enables a biopsy to be taken for histological diagnosis and cancer staging.²

Treatment and management of primary peritoneal cancer

Cytoreductive surgery

One way to manage peritoneal malignancies is by considering surgery. Surgical procedures will initially be carried out to resect the area of the peritoneum affected by tumour cells. For example, for EOPPC, a hysterectomy with bilateral salpingo-oophorectomy and omentectomy is done in most cases, supplemented with chemotherapy and targeted therapy. 

First-line treatment for MPM involves cytoreductive surgery, followed by intraperitoneal chemotherapy. However, surgery poses risk of adhesions, which are injuries which result in scar tissue and may manifest following surgical treatment for primary peritoneal cancer. The formation of adhesions needs to be monitored for as they have negative implications which can result in bowel obstructions.^2,3

Hyperthermic intraperitoneal chemotherapy (HIPEC)

In cases where full resection is not possible, the clinician may suggest further administration of additional rounds of chemotherapy. This may involve the use HIPEC in patients with a poor prognosis. Patients can expect a clinician to administer HIPEC directly to the peritoneal surface in aim to reduce the size of the tumour. 

HIPEC involves administration of drugs including cisplatin with mitomycin C, melphalan, ifosfamide, at a temperature higher than body temperature, at 41-43°C into the peritoneal cavity over a period of 2 hours immediately after surgery is performed. This results in hyperthermia that causes DNA damage to cancer cells, resulting in their cell death while healthy cells are able to survive.^2,3

Early postoperative intraperitoneal chemotherapy (EPIC)

Another type of interaperitoneal chemotherapy is EPIC, which is administered the day after surgery over a period of 5 to 7 days. The most common drugs used during EPIC include 5-fluorouracil, taxanes and leucoverin. Patients can expect EPIC to be delivered by catheter while the building-up fluids are drained using suction tubes.²

Targeted therapies

With increased understanding of the physiology of the peritoneum and cancer signalling pathways, emerging research has led to advancements in effective targeted therapies.

Targeted therapies include ADP-ribose polymerase inhibitors which block DNA repair, including olaparib, rucaparib, niraparib or veliparib.²

FAQ

How agressive is peritoneal cancer?

Peritoneal cancer is often diagnosed late due to the non-specific symptoms. It is considered agressive and patients are given poor prognosis with severity dependent on the subtype. However, emerging new approaches and therapies offer hope for longer patient survival or even cure in the future.⁵

Where does peritoneal cancer spread to first?

This depends on the cancerous tissue origin. Primary peritoneal cancer originates from the peritoneal mesothelium hence cancerous cells can seperate from it and travel anywhere within the peritoneal cavity to organs such as spleen or liver but also outside through vascular and lymphatic systems.²

Summary

The peritoneum is a serous organ which lines the abdominal cavity and functions to protect the abdomen. Peritoneal cancer is a rare malignancy which affects the peritoneal cavity and is categorised into primary and secondary peritoneal cancers. Tumour cells of primary peritoneal cancer originates in the mesothelium of the abdomen, being categorised as a terminal illness with a survival rate being between 11 to 17 months from diagnosis. 

Common subtypes of primary peritoneal cancer include EOPCC, MPM, disseminated peritoneal leiomyomatosis and DSRCT. Primary peritoneal cancer is identified in patients presenting with abdominal distention and discomfort, weight loss, fatigue, nausea, indigestion and constipation. Common risk factors and causes include genetic mutations such as for BRCA1, increased exposure to asbestos or radiation and occurs following events of chronic peritonitis. 

Primary peritoneal cancer is staged at either stage III, being localised to the peritoneal cavity, or at stage IV when the tumour has metastasised to other organs. It is diagnosed using a range of imaging and invasive techniques, and treated using cytoreductive surgery, chemotherapy and targeted therapies.