Invasive Epithelial Ovarian Cancer Survival by Histotype and Disease Stage

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Abstract

The understanding of ovarian cancer pathogenesis has recently shifted to recognize distinct changes in how ovarian cancer histotypes are defined. Using the 2014 World Health Organization (WHO) diagnostic guidelines, we classified ovarian cancer histotypes in Surveillance, Epidemiology, and End Results (SEER) cancer registry data and examined survival patterns by histotype and disease stage.

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Recent progress in the diagnosis and treatment of ovarian cancer.

Danijela Jelovac, Deborah Armstrong (2011)

Epithelial ovarian cancer is the most lethal of the gynecologic malignancies, largely due to the advanced stage at diagnosis in most patients. Screening strategies using ultrasound and the cancer antigen (CA) 125 tumor marker are currently under study and may lower stage at diagnosis but have not yet been shown to improve survival. Women who have inherited a deleterious mutation in the BRCA1 or BRCA2 gene and those with the Lynch syndrome (hereditary nonpolyposis colorectal cancer) have the highest risk of developing ovarian cancer but account for only approximately 10% of those with the disease. Other less common and less well-defined genetic syndromes may increase the risk of ovarian cancer, but their contribution to genetic risk is small. A clear etiology for sporadic ovarian cancer has not been identified, but risk is affected by reproductive and hormonal factors. Surgery has a unique role in ovarian cancer, as it is used not only for diagnosis and staging but also therapeutically, even in patients with widely disseminated, advanced disease. Ovarian cancer is highly sensitive to chemotherapy drugs, particularly the platinum agents, and most patients will attain a remission with initial treatment. Recent advances in the delivery of chemotherapy using the intraperitoneal route have further improved survival after initial therapy. Although the majority of ovarian cancer patients will respond to initial chemotherapy, most will ultimately develop disease recurrence. Chemotherapy for recurrent disease includes platinum-based, multiagent regimens for women whose disease recurs more than 6 to 12 months after the completion of initial therapy and sequential single agents for those whose disease recurs earlier. New targeted biologic agents, particularly those involved with the vascular endothelial growth factor pathway and those targeting the poly (ADP-ribose) polymerase (PARP) enzyme, hold great promise for improving the outcome of ovarian cancer.

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Improved estimates of cancer-specific survival rates from population-based data.

Nadia Howlader, A Mariotto, Marsha Reichman … (2010)

Accurate estimates of cancer survival are important for assessing optimal patient care and prognosis. Evaluation of these estimates via relative survival (a ratio of observed and expected survival rates) requires a population life table that is matched to the cancer population by age, sex, race and/or ethnicity, socioeconomic status, and ideally risk factors for the cancer under examination. Because life tables for all subgroups in a study may be unavailable, we investigated whether cause-specific survival could be used as an alternative for relative survival. We used data from the Surveillance, Epidemiology, and End Results Program for 2,330,905 cancer patients from January 1, 1992, through December 31, 2004. We defined cancer-specific deaths according to the following variables: cause of death, only one tumor or the first of multiple tumors, site of the original cancer diagnosis, and comorbidities. Estimates of relative survival and cause-specific survival that were derived by use of an actuarial method were compared. Among breast cancer patients who were white, black, or of Asian or Pacific Islander descent and who were older than 65 years, estimates of 5-year relative survival (107.5%, 106.6%, and 103.0%, respectively) were higher than estimates of 5-year cause-specific survival (98.6%, 95% confidence interval [CI] = 98.4% to 98.8%; 97.4%, 95% CI = 96.2% to 98.2%; and 99.2%, 95% CI = 98.4%, 99.6%, respectively). Relative survival methods likely underestimated rates for cancers of the oral cavity and pharynx (eg, for white cancer patients aged ≥65 years, relative survival = 54.2%, 95% CI = 53.1% to 55.3%, and cause-specific survival = 60.1%, 95% CI = 59.1% to 60.9%) and the lung and bronchus (eg, for black cancer patients aged ≥65 years, relative survival = 10.5%, 95% CI = 9.9% to 11.2%, and cause-specific survival = 11.9%, 95% CI = 11.2 % to 12.6%), largely because of mismatches between the population with these diseases and the population used to derive the life table. Socioeconomic differences between groups with low and high status in relative survival estimates appeared to be inflated (eg, corpus and uterus socioeconomic status gradient was 13.3% by relative survival methods and 8.8% by cause-specific survival methods). Although accuracy of the cause of death on a death certificate can be problematic for cause-specific survival estimates, cause-specific survival methods may be an alternative to relative survival methods when suitable life tables are not available.

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Morphological subtypes of ovarian carcinoma: a review with emphasis on new developments and pathogenesis.

W. McCluggage (2011)

Ovarian carcinomas comprise a heterogeneous group of neoplasms, the four most common subtypes being serous, endometrioid, clear cell and mucinous. In recent years, our understanding of the underlying pathogenesis and initiating molecular events in the different tumour subtypes has greatly increased, and although ovarian carcinoma is often considered clinically as one disease, there is now a much greater realisation that the various subtypes have a different natural behaviour and prognosis. At present, adjuvant therapy is mainly dependent upon tumour stage and grade rather than type; however, this is likely to change in the future with the development of new chemotherapeutic agents and targeted therapies and clinical trials are necessary to evaluate the efficacy of different agents in clear cell, mucinous and low grade serous carcinomas, neoplasms which are considered relatively resistant to traditional chemotherapeutic regimes. In this review, the major subtypes of ovarian carcinoma are discussed. It is now firmly established that there are two distinct types of ovarian serous carcinoma, low grade and high grade, the former being much less common and arising in many cases from a serous borderline tumour. Low grade and high grade serous carcinoma represent two distinct tumour types with a different underlying pathogenesis rather than low grade and high grade variants of the same neoplasm. Both are usually advanced stage (stage III or IV) at diagnosis. B-raf and k-ras mutations are important molecular events in low grade serous carcinomas while high grade serous carcinomas are almost always associated with TP53 mutation. There is now emerging and compelling evidence that many high grade serous carcinomas (by far the most common subtype of ovarian carcinoma) actually arise from the epithelium of the distal fallopian tube. Future studies regarding the initiating molecular events in the development of this aggressive neoplasm should concentrate on this site. Primary ovarian mucinous carcinomas are uncommon, almost always unilateral and stage I, and largely of so-called intestinal or enteric type. Most arise in a stepwise manner from a pre-existing mucinous cystadenoma and mucinous borderline tumour. Endometrioid and clear cell carcinomas typically present as low stage neoplasms and in many, or most, cases arise from endometriosis; the former are usually well differentiated and there is now evidence that the majority of neoplasms reported in the past as high grade endometrioid carcinoma are of serous type. WT1 is useful in this regard since it is a relatively specific marker of a serous phenotype. It is recommended that different subtypes of ovarian carcinoma are graded using different systems rather than employing a universal grading system.