Epithelial Ovarian, Fallopian Tube, and Peritoneal Cancer

Abstract

Overview Ovarian cancer is one of the most treatable solid tumors, as the majority will respond temporarily to surgery and cytotoxic agents. The disease, however, frequently persists and recurs in 70% of cases, having the highest fatality‐to‐case ratio of all the gynecologic cancers. Ovarian cancer is neither a common nor a rare disease, with a lifetime risk of 1 in 70 and a prevalence in the postmenopausal population in the United States of 1 in 2500, which impact strategies for early detection and prevention. Germ line mutations of BRCA1 and BRCA2 are associated with 10–15% of ovarian cancers and increase the risk of ovarian cancer dramatically. Factors that contribute to persistent ovulation increase the risk in women with sporadic disease, whereas use of oral contraceptives decreases the risk of disease post menopause. While epithelial ovarian cancers have been thought to arise from the ovarian surface epithelium or in the lining of inclusion cysts beneath the ovarian surface, many high‐grade serous “ovarian” carcinomas as well as peritoneal cancers are now believed to arise in the fimbriae of fallopian tube, rather than the ovary or peritoneum. Epithelial ovarian cancers can exhibit serous, endometrioid, mucinous, or clear cell histotypes. Low‐grade type I ovarian cancers grow slowly, can evolve from tumors of low malignant potential, bear Ras mutations in a majority of cases, express wild type TP53, often are detected in early stage (I–II), and respond less frequently to platinum‐ and taxane‐based therapy. High‐grade type II ovarian cancers grow rapidly, arise from precursors with TP53 mutations, are driven by DNA copy number changes, are diagnosed in late stage (III–IV), and frequently respond to combination chemotherapy. Owing to a lack of specific symptoms or an effective screening strategy, more than 70% of ovarian cancers are diagnosed in an advanced stage (III–IV). Primary treatment of epithelial ovarian cancer involves cytoreductive surgery and 6–8 cycles of carboplatin and paclitaxel. For those women with small volumes of disease after surgery, intraperitoneal administration of chemotherapy improves survival. Recurrent disease cannot be cured with currently available agents, but survival can be prolonged with combinations of cytotoxic agents including retreatment with paclitaxel and carboplatin. Palliative agents include liposomal doxorubicin, gemcitabine, topotecan, bevacizumab, pemetrexed, and etoposide. Experimental therapy for low‐grade cancers involves MEK inhibitors, whereas trials of PI3K pathway inhibitors and PARP inhibitors are underway in patients with high‐grade epithelial ovarian cancers. Combinations of targeted agents will be required.