Extraovarian Primary Peritoneal Carcinoma

Drs. Eltabbakh and Piver present a comprehensive review of the management and prognosis of patients with extraovarian primary peritoneal carcinoma (EOPPC). Increased recognition and more precise definition have led many physicians and scientists to recognize EOPPC as a distinct clinical entity with a unique etiology. However, staging and treatment criteria for EOPPC have been modeled after criteria for papillary serous ovarian cancer, which is clinically and histologically similar. The Gynecologic Oncology Group (GOG) has allowed the inclusion of patients with EOPPC into clinical trials designed for patients with epithelial ovarian cancer.

Treatment Approach

It has been our practice at the University of California, Irvine, to treat patients with EOPPC and advanced epithelial ovarian cancer with the same approach; namely, maximal surgical debulking followed by platinum-based chemotherapy. In the case-control study by Bloss et al, patients with EOPPC were selected based on a standardized definition from the GOG and were compared to matched ovarian cancer controls. [1] In addition, all patients without clinical recurrence underwent second-look laparotomies so that the responses could be surgically documented. The patients with EOPPC and those with ovarian cancer had a similar response to primary chemotherapy, disease-free interval, salvage chemotherapy, and median survival. The numbers in this study were too small to examine the effectiveness of cytoreductive surgery, and disease was optimally debulked to less than 2 cm in only one-third of patients.

In the more recent study by Piver et al, patients with EOPPC were also included based on the GOG definition, and optimal debulking to less than 1 cm was achieved in 70%.[2] A statistically significant improvement in survival was noted in patients in whom optimal cytoreduction was accomplished.

Molecular Studies

Even though EOPPC is treated in the same manner as ovarian cancer, molecular studies suggest that it is a distinct disease entity. The clinical and histologic similarities may be explained by the fact that the peritoneal mesothelium and the müllerian duct epithelium have a common celomic origin. It is generally believed that cells within a tumor are derived from a single transformed cell. Genetic studies of ovarian cancer have supported this unifocal-origin theory by demonstrating identical p53 mutations and loss of heterozygosity at primary and metastatic sites.

The leading hypothesis of the etiology of EOPPC suggests that field carcinogenesis induces multifocal malignant transformation of the abdominal and pelvic peritoneum. The study by Muto et al supports the multifocal origin of EOPPC by demonstrating different p53 mutations and allelic loss at varied tumor sites in the same patient.[3]

The distinct nature of this disease is also supported by the occasional development of diffuse carcinomatosis that is histologically indistinguishable from epithelial ovarian cancer many years after prophylactic oophorectomy performed because of familial ovarian cancer. A review of the Gilda Radner Familial Ovarian Cancer Registry identified 324 women who had a prophylactic oophorectomy.[4] In this group of patients, six cases of EOPPC were diagnosed, indicating that prophylactic oophorectomy does not fully prevent familial ovarian cancer.

Summary

Extraovarian primary peritoneal carcinoma exemplifies the problems associated with the management of ovarian cancer. Since no identifiable precursor lesions exist, there is no adequate screening test, and the majority of patients present with widespread intraperitoneal tumor. Since drug resistance develops in most patients, the survival rate is poor.

It is clear that alternative treatments are needed. Perhaps future studies of EOPPC will elucidate the molecular events that lead to the development of these aggressive malignancies and, thus, improve treatment and outcome.