Staging classification for cancer of the ovary, fallopian tube, and peritoneum

Abstract

Ovarian cancer is the seventh most common cancer diagnosis among women worldwide, and the fifth most common cancer diagnosis among women in higher-resource regions [1]. The world rate is estimated to be 6.3 per 100 000 women, and is highest in high-resource countries (9.3 per 100 000 women) [1]. Primary peritoneal cancer and primary fallopian tube cancer are rare malignancies but share many similarities with ovarian cancer. Clinically, these 3 cancers are managed in a similar manner [2]. The main purpose of staging systems is 2-fold: to provide standard terminology that allows comparison of patients between centers; and to assign patients and their tumors to prognostic groups requiring specific treatments. Ovarian cancer is staged surgically and pathologically, and the last revision of the FIGO staging classification was made in 1988 (Rio de Janeiro). The FIGO Committee on Gynecologic Oncology feels that it is time to revise this classification to improve utility and reproducibility. Cancer staging evolves continuously as scientific developments occur, diagnostic methods improve, and more accurate prognostic information becomes available. Over the past quarter of a century, several scientific developments have challenged traditional concepts in ovarian cancer. Initially, it was recognized that ovarian cancer is not a homogeneous disease, but rather a group of diseases—each with different morphology and biological behavior. Approximately 90% of ovarian cancers are carcinomas (malignant epithelial tumors) and, based on histopathology, immunohistochemistry, and molecular genetic analysis, at least 5 main types are currently distinguished: high-grade serous carcinoma (HGSC [70%]); endometrioid carcinoma (EC [10%]); clear-cell carcinoma (CCC [10%]); mucinous carcinoma (MC [3%]); and low-grade serous carcinoma (LGSC [< 5%]) [3]. These tumor types (which account for 98% of ovarian carcinomas) can be reproducibly diagnosed by light microscopy and are inherently different diseases, as indicated by differences in epidemiologic and genetic risk factors; precursor lesions; patterns of spread; and molecular events during oncogenesis, response to chemotherapy, and prognosis [4,5]. Much less common are malignant germ cell tumors (dysgerminomas, yolk sac tumors, and immature teratomas [3% of ovarian cancers]) and potentially malignant sex cord-stromal tumors (1%–2%, mainly granulosa cell tumors). The biomarker expression profile within a given histotype is consistent across stages. Ovarian cancers differ primarily based on histologic type. In the era of personalized cancer medicine, reproducible histopathologic diagnosis of tumor cell type is a sine qua non for successful treatment. Different tumor histotypes respond differently to chemotherapy. Even if different patterns of dissemination justify the use of separate staging systems for each type of ovarian carcinoma, such a complex classification would not be practical. For the sake of simplicity, the Committee chose a flexible staging system that takes into account the most relevant prognostic parameters shared by all tumor types. It was unanimously agreed that histologic type should be designated at staging (i.e. HGSC, EC, CCC, MC, and LGSC; other or cannot be classified; and malignant germ cell tumors and potentially malignant sex cord-stromal tumors). Another discovery that influenced the new FIGO staging occurred in 2001, when patients with BRCA mutation (breast–ovarian cancer syndrome) undergoing risk-reducing salpingo-oophorectomy were found to have high-grade serous tubal intraepithelial carcinoma (STIC) not in the ovary but in the fallopian tube and, particularly, in the fimbria [6]. Although STIC is capable of metastasizing and, therefore, cannot be considered carcinoma in situ, compelling evidence for a tubal origin of BRCA-positive HGSC (approximately 60% of BRCA cases) has accumulated over the past decade [7,8]. High-grade STIC has also been encountered in an undetermined number of advanced-stage sporadic HGSCs associated with ovarian tumor masses and in rare cases of primary tubal or peritoneal HGSCs without obvious ovarian involvement. The relative proportion of HGSCs of ovarian and tubal derivation is unknown, mainly because tumor growth in advanced-stage cancers conceals the primary site. Even in cases involving BRCA mutation, evidence of a tubal origin of HGSCs is incomplete and a multicentric origin of these tumors (i.e. arising from ovarian surface mesothelial invaginations or inclusion cysts with subsequent müllerian neometaplasia, from implantation of tubal-type epithelium into the ovary [endosalpingiosis], or from the pelvic peritoneum [the so-called secondary müllerian system]) cannot be excluded. As indicated above, HGSCs and LGSCs are fundamentally different tumor types and, consequently, different diseases. High-grade serous carcinomas are the most common ovarian carcinomas and most patients present with advanced-stage disease (approximately 80%)