Primary peritoneal cancer

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]

Pathophysiology

• Primary peritoneal cancer is a cancer of the cells lining the peritoneum, or abdominal cavity. Some studies indicate that between 7 and 20 percent of initially diagnosed epithelial ovarian cancers could be properly reclassified as primary peritoneal cancers. Primary peritoneal cancer or carcinoma is also known as serous surface papillary carcinoma, primary peritoneal carcinoma, extra-ovarian serous carcinoma, primary serous papillary carcinoma, psammomacarcinoma.
• Primary peritoneal neoplasms comprise of an uncommon group of heterogenous entities.
• The list includes
• Mesothelial derivatives

• Primary (malignant) peritoneal mesothelioma
• Primary perioneal multicystic mesothelioma
• Primary peritoneal well differentiated papillary mesothelioma
• Primary peritoneal adenomatoid tumour

• Epithelial derivatives

• Primary peritoneal serous carcinoma / primary peritoneal papillary serous carcinoma
• Primary peritoneal serous borderline tumour
• Smooth muscle cell derivatives
• Diffuse peritoneal leiomyomatosis (leiomyomatosis peritonialis disseminata)

• Others

• Desmoplastic small round cell tumour arising from the peritoneum
• Solitary fibrous tumour arising the abdomen / peritoneum
• Peritoneal lymphangioma : sometimes considered as a benign neoplasm 2

Theory

Ovarian and peritoneal epithelium share common embryonal origin, the coelomic epithelium (mesodermal origin). Coelomic epithelium is thought to be of mesonephric origin. With the overall point being that normal ovarian and peritoneal tissue is derived from the mesonephros. On the contrary, fallopian tube epithelium, endometrium and endocervix are related to paramesonephros (Müllerian duct). Surprisingly, epithelial ovarian cancer and primary peritoneal cancer are histologically similar to the Mullerian epithelium; not their embryonal origin, the mesonephros. Either a metaplasia has occurred or Mullerian remnants have been left behind in coelemic epithelium, which have turned oncogenic.

Genetics

Although the precise causes are not known, a link with certain variants of BRCA1/2 has been described. Furthermore, women with BRCA1/2 mutation have a 5% risk of developing primary peritoneal cancer even after prophylactic oophorectomy. Primary peritoneal carcinoma shows similar rates of tumor suppressor gene dysfunction (p53, BRCA, WT1) as ovarian cancer and can also show an increased expression of HER-2/neu. An association with vascular endothelial growth factor has been observed.

Causes

• The cause of primary peritoneal cancer has not been identified.

Differentiating Primary peritoneal cancer from other Diseases

Primary peritoneal cancer must be differentiated from asbestos, fibroids, pregnancy, pelvic inflammatory diseases, and ovarian cysts.

Demographics

Age

• Primary peritoneal cancer commonly affects individuals older than 30 years of age.

Gender

• Females are more commonly affected with primary peritoneal cancer than males.

Natural History, Complications and Prognosis

• Primary peritoneal cancer is associated with a particularly poor prognosis. Median survival period is 12-25 months.

Diagnosis

Staging

• Primary peritoneal cancer may be classified into 2 subtypes based on extend of spread, stage 3, and stage 4.

Diagnostic Criteria

• If available, the diagnostic criteria are provided here.

History

• A directed history should be obtained to ascertain

Symptoms

• Ascitis
• Weight loss
• Abdominal mass
• Abdominal pain
• Indigestion
• Nausea
• Shortness of breath

Physical Examination

Appearance of the Patient

• Patients with primary peritoneal cancer usually appear cachetic.

Abdomen

• The presence of a large ill defined anterior abdominal mass on physical examination is diagnostic of primary peritoneal cancer.

Treatment

• Prognosis and treatment is the same as for the most common type of ovarian cancer, which is epithelial ovarian cancer.
• The median survival of primary peritoneal carcinomas is usually shorter by 2–6 months time when compared with serous ovarian cancer. Studies show median survival varies between 11.3–17.8 months. One study reported 19-40 month median survival (95% CI) with a 5 year survival of 26.5%.
• Elevated albumin levels have been associated with a more favorable prognosis.
• Optimal tumor debulking followed by chemotherapy is the mode of treatment of primary peritoneal cancer.

Pharmacotherapy

• Preferred regimen(1): Paclitaxel 135 mg/m2 IV over 24 h on day 1 AND cisplatin 100 mg/m2 IP on day 2 AND paclitaxel 60 mg/m 2 IP on day 8 for 21 days for 6 cycles.
• Preferred regimen (2): [Paclitaxel 135-175 mg/m2 IV infused over 3 hours AND carboplatin AUC 5-7.5 IV infused over 30-60 min every 21 d for three to six cycles] OR [Docetaxel 60-75 mg/m 2 IV infused over 1 h AND carboplatin AUC 5-6 IV infused over 1 h every 21 d for three to six cycles]

Platinum-sensitive disease

• Preferred regimen(1): Paclitaxel 135-175 mg/m 2 IV infused over 3 h plus carboplatin AUC 5-6 IV infused over 1 h every 21 d for six cycles

• Preferred regimen(2): Docetaxel 60-75 mg/m 2 IV infused over 1 h plus carboplatin AUC 5 IV infused over 1 h every 21 d for three to six cycles
• Preferred regimen(3): Pegylated liposomal doxorubicin 30 mg/m 2 IV infused over 30 min plus carboplatin AUC 5 IV every 21 d for six cycles
• Preferred regimen(4): Gemcitabine 1000 mg/m 2 IV on days 1 and 8 plus carboplatin AUC 4 on day 1 every 21 d for six cycles

Note: Bevacizumab (15 mg/kg every 3 wk) may be added to the regimen

• Preferred regimen(5): Carboplatin AUC 2 IV push with paclitaxel 80 mg/m 2 IV infused over 3 h on days 1, 8, and 15

Platinum-resistant disease

• Preferred regimen(1): Pegylated liposomal doxorubicin 50 mg/m 2 IV infused over 30 min every 21 d
• Preferred regimen(2): Topotecan 1.25 mg/m 2 IV infused over 30 min on days 1-5 every 21 d
• Preferred regimen(3): Gemcitabine 1000 mg/m 2 IV infused over 30 min on days 1 and 8 every 21 d

Combination Regimen

• Bevacizumab 10 mg/kg IV every 14 d in combination with one of the following IV chemotherapy regimens: paclitaxel, pegylated liposomal doxorubicin, or topotecan (topotecan is given weekly)
• Bevacizumab 15 mg/kg IV every 21 d in combination with topotecan (every 21 d)

Surgery and Device Based Therapy

• Surgery is the primary treatment for extra-ovarian primary peritoneal carcinoma. The type of surgery done is surgical debulking. Surgical staging is done at the same time as debulking.