The Relationship between Primary Peritoneal Cancer and Ovarian Cancer

There are many similarities between primary peritoneal cancer and epithelial ovarian cancer, including the most commonly observed symptoms and treatment methods. The peritoneum, which lines the abdomen, and the surface of the ovary both originate from the same tissue during fetal development.

It is believed that the residual ovarian cells left in the abdomen during peritoneal cell development could lead to peritoneal cancer. These similarities between the two cancers are helpful in planning treatment, especially since epithelial ovarian cancer is much more common and has been researched more extensively.

Although primary peritoneal cancer and ovarian cancer are similar, there are significant differences as well. Those diagnosed with peritoneal cancer tend to be older than those with ovarian cancer. Regarding treatments (listed below), the likelihood of successful debulking surgery (a procedure that reduces the tumor burden) is higher in peritoneal cancer, but the overall survival rate is lower. This indicates that there are differences in tumor biology between the two types of cancer.

What are the symptoms of peritoneal cancer?

Similar to ovarian cancer, peritoneal cancer is known as a silent disease in its early stages due to a lack of symptoms. Patients with peritoneal cancer may not exhibit any significant symptoms until the disease has progressed. Symptoms of peritoneal cancer include:

• Abdominal swelling
• Widespread abdominal pain
• Frequent urination
• Feeling full after eating, along with other vague symptoms that are not specific to this type of cancer

Other symptoms include:

• Changes in bowel habits (usually constipation)
• Abnormal vaginal bleeding
• A palpable mass in the abdomen
• Unintentional weight loss

As the disease progresses, fluid buildup (ascites) can occur in the abdominal cavity, leading to abdominal pain, discomfort, nausea, and vomiting, as well as shortness of breath due to pressure on the lungs from the increased abdominal pressure. Fatigue is also common.

Complications of peritoneal cancer can include bowel obstruction (which may require a stoma or a hole between the bowel and the outside of the body), as well as urinary tract obstruction (due to tumor blockage of the ureters) that may require a stent or a nephrostomy tube (a tube from the kidney to the outside of the body).

What are the causes and risk factors of peritoneal cancer?

Although the exact causes of peritoneal cancer are not known, cancer begins when a series of mutations in peritoneal cells result in uncontrolled growth. Peritoneal cancer is much more common in women and has similar risk factors to ovarian cancer.

Most of the risk factors include:

Being over 60 years old History of breast cancer History of endometriosis Obesity

Long-term use of talcum powder below the waist is also thought to be associated with an increased risk.

On the other hand, there are factors associated with a lower than average risk of developing the disease. These include the use of oral contraceptives (birth control pills) (reduced risk can last up to 30 years after discontinuing the medication), tubal ligation, especially giving birth before the age of 35 and breastfeeding. Some studies have not suggested that the use of nonsteroidal anti-inflammatory drugs such as ibuprofen and aspirin can reduce the risk.

As mentioned, some people undergo preventative surgery to remove the fallopian tubes and ovaries (hysterectomy and salpingo-oophorectomy) due to a family history of ovarian cancer or a BRCA gene mutation. This preventative measure can reduce the risk of epithelial ovarian cancer by up to 90%, but the risk of peritoneal cancer persists.

Genetic makeup in peritoneal cancer

Having a family history of ovarian, fallopian tube or peritoneal cancer increases a person’s risk of peritoneal cancer, and approximately 10% of these cancers are considered hereditary. Having certain genetic syndromes such as Lynch syndrome (hereditary non-polyposis colon cancer) or a BRCA gene mutation increases the risk. Women with a BRCA gene mutation have a roughly 5% increased risk of peritoneal cancer even if they have had their ovaries removed.

How is peritoneal cancer diagnosed?

There is no screening test that is effective for the early detection of primary peritoneal cancer, even in those at high risk of developing the disease.

After listening to symptoms and performing a physical examination, there are a number of tests that doctors may consider when making a diagnosis.

Blood tests

A blood test for CA-125 is a tumor marker that may be elevated in people with peritoneal cancer. However, CA-125 levels can be elevated in many conditions, ranging from pelvic infections to pregnancy, and levels may be normal even in the presence of cancer. Another test called the OVA1 test is used to estimate whether there is ovarian or peritoneal cancer before surgery. The test uses a combination of 5 biomarkers to make a probability estimate.

Imaging tests

Oncological radiological exams can help evaluate symptoms of peritoneal cancer. An ultrasound (transvaginal ultrasound) is often the first test performed. Magnetic resonance imaging (MRI) or computed tomography (CT) scans of the abdomen and pelvis can also be useful. PET-CT is quite useful in evaluating treatment response after a person has been diagnosed.

Biopsy and Laparoscopy

Often, a biopsy is required to confirm or rule out a diagnosis. During laparoscopy, several small incisions are made in the abdominal skin to take a biopsy from the peritoneum and instruments are inserted to remove tissue samples from the abdomen or pelvis.

Laparoscopy can also provide important information about treatment. A 2018 study found laparoscopy to be highly accurate in determining who would respond well to optimal cytoreductive surgery. Since cytoreductive surgery, meaning “to remove all visible tumor”, is critical, laparoscopy can be very helpful in deciding which patients should undergo the surgery and when the risks may outweigh the benefits.

When fluid is present, a procedure called paracentesis may be performed to remove some of the fluid and help with breathing (see detailed explanation below). The fluid can also be examined under a microscope for the presence of cancer cells.

Other diagnoses that can mimic a diagnosis of primary peritoneal cancer

There are several conditions that can mimic primary peritoneal cancer. These include different types of ovarian cancer, intra-abdominal abscesses, cystic collections of fluid such as bile or lymph fluid, and other cancers that metastasize to the peritoneum.

What are the stages of peritoneal cancer?

Unlike many cancers that are divided into stages 1-4 (I-IV), primary peritoneal cancer does not have an early stage. Regardless of symptoms and findings, this cancer is always diagnosed at stage 3 or stage 4. In stage 3, the cancer may have spread outside the pelvis or to nearby lymph nodes (retroperitoneal lymph nodes). With stage 4 peritoneal cancer, the tumor has usually metastasized to abdominal organs like the liver or to other parts of the body like the lungs.

What is the treatment for peritoneal cancer?

The treatment for peritoneal cancer will depend on a number of factors, including the location of the cancer, the stage of the cancer, and a person’s overall health. Treatment options include:

Surgery

It is recommended that the procedure be performed by a specialist known as a gynecologic oncologist for those who will undergo surgery. Studies have shown that when these specialists perform surgery, the outcomes are better than when the surgery is performed by a general surgeon or gynecologist. It is also important to find a gynecologic oncologist who has experience in treating women with ovarian and peritoneal cancer.

The most commonly performed surgery is an oncologic surgery known as cytoreduction or debulking surgery. The goal is to remove the cancer in an optimal/ideal amount, but removing all of the cancer is often impossible.

In this surgery, a surgeon removes both the uterus (hysterectomy), fallopian tubes, and ovaries (bilateral salpingo-oophorectomy) as well as the main site of the cancer in the peritoneum. Sometimes, the omentum, which is a layer of fatty tissue that surrounds the intestines, is also removed (omentectomy). Depending on the area and size of the cancer, nearby lymph nodes and the appendix may also be removed (the peritoneum itself cannot be removed). Peritoneal cancer can spread extensively throughout the abdominal cavity, and often most of the tumor is removed.

Cytoreductive surgery may seem confusing to those familiar with other types of cancer. For example, if lung cancer or breast cancer cannot be completely removed with surgery, performing surgery does not improve survival (although it may reduce pain and complications). In contrast, it is known that removing as much of the tumor as possible in peritoneal and ovarian cancer contributes to increased survival. Chemotherapy can be given during or after surgery.

The goal of cytoreductive surgery is usually not complete removal of the cancer, but rather the “optimal” removal of the tumor. With optimal cytoreductive surgery, there should be no cancer area larger than 1 centimeter (about half an inch) in the abdominal area. After reducing the amount of existing tumor, chemotherapy works better.

Peritoneal Cancer Index and Its Importance

Peritoneal Cancer Index (PCI) is used to assess the rate of peritoneal cancer throughout the peritoneal cavity. For this purpose, the peritoneal cavity is divided into 13 well-defined regions (see the figure below). In each of the 13 regions, the size of the largest tumor nodule is measured. If no tumor is visualized, the region is assigned a score of “0”. If the largest tumor nodule is smaller than 0.5 cm, the score is “1”. The score is “2” for tumors measured between 0.5 cm and 5 cm. The score is “3” for lesions larger than 5 cm or for the merging of multiple small tumor nodules. The Peritoneal Cancer Index is calculated by adding the scores for all 13 regions, with a maximum score of 39 (13 × 3).

As the Peritoneal Cancer Index decreases, disease-free survival and overall survival increase. Generally, patients with a high PCI score are not recommended aggressive treatments.

Chemotherapy

Chemotherapy is typically used in peritoneal cancer during or after surgery. Chemotherapy can be given intravenously (through the veins) or injected directly into the abdominal cavity (intraperitoneal chemotherapy). Clinical studies suggest that a quite different treatment could be beneficial for peritoneal cancer. In this practice, heated chemotherapy drugs are injected into the abdomen during surgery (intraoperative) or after surgery; this is called hyperthermic intraperitoneal chemotherapy (HIPEC). In heated intraperitoneal chemotherapy, chemotherapy drugs are heated up to 42 degrees before being injected into the abdomen. Heat makes cancer cells more susceptible to chemotherapy.

Targeted Cancer Drugs

Targeted drugs are drugs that target specific intracellular pathways that play a role in the growth of cancer cells.

In 2016, the drug bevacizumab, which is effective on angiogenesis, was approved by the FDA for use in combination with chemotherapy for peritoneal cancer. Lynparza (olaparib) can be used for women with BRCA gene mutations. An anti-EGFR drug called Tarceva (erlotinib) may be effective for some peritoneal cancer patients. In addition, some primary peritoneal cancers overexpress HER2, similar to some breast cancers, and may respond to HER2-targeted therapies. In 2018, Rubraca (rucaparib) received FDA approval for the treatment of primary peritoneal cancer due to a treatment resulting in significantly longer progression-free survival than placebo.

Radiotherapy

Radiation is rarely used for peritoneal cancer, but it can be useful for isolated cancer areas.

Clinical Trials

There are currently several clinical trials evaluating new ways to treat peritoneal cancer, including other targeted therapies and immunotherapy drugs.

Supportive/Palliative Care

Unfortunately, most people are diagnosed with peritoneal cancer in advanced stages and when complete treatment is not possible. However, there are many things that can be done to prolong life and improve quality of life.

Paracentesis (insertion of a needle through the skin into the abdominal cavity to drain fluid) can reduce shortness of breath. Nutritional consultation (dietitian support) can help with cancer-related loss of appetite and may reduce the risk of cancer cachexia.

Pain control is important because this cancer can be very uncomfortable and nausea management can also improve quality of life. Complementary and alternative therapies are not effective in shrinking the tumor, but some complementary practices can help manage symptoms related to cancer and cancer treatments. Integrative therapies such as yoga, meditation, massage, acupuncture, and more are offered in many larger cancer centers.

Prognosis (disease outlook)

The prognosis of peritoneal cancer is generally poor, but in a small percentage of patients, the cancer can be completely eradicated. There are few studies evaluating survival rates, but there are some factors associated with better survival rates. These include the absence of cancer in lymph nodes, optimal or complete cytoreductive surgery, and use of hyperthermic intraperitoneal chemotherapy.

Dealing with Peritoneal (Abdominal) Cancer

Dealing with any type of cancer is difficult, and many people may have never heard of peritoneal cancer. This can be especially isolating when compared to the support offered to individuals with other cancer types, such as breast cancer. However, although finding a support group for peritoneal cancer may be challenging due to its relative rarity in communities, there are online peritoneal cancer communities where people can connect day and night when needed.

Receiving any cancer diagnosis can be scary, but considering that peritoneal cancer is rare and often diagnosed in advanced stages, it can be particularly daunting. When learning about your cancer, you may feel discouraged.

However, it can be helpful to keep in mind that treatment options for advanced cancers have significantly improved in recent years. While the possibility of completely curing peritoneal cancer is very low, symptoms and signs related to cancer can be significantly controlled with many appropriate approaches, allowing patients to live comfortable and satisfying lives.