Gynecologic malignancies

Incidence

Approximately 63,230 new cases of cancer of the uterus (commonly of the endometrium, excluding cancers of the cervix) were reported in 2018. Endometrial cancer incidence is rising, and mortality rates have not decreased. It is most common in postmenopausal women, and the incidence increases with age, reaching 1 in 75 women by the eighth decade.

Risk factors

The incidence of endometrial cancer increases with age and is uncommon in women under age 40. In general, factors that increase exposure of estrogen, including obesity, younger age at menarche, late menopause, and nulliparity will increase the risk of developing endometrial cancer. ^, Additional risk factors include prior tamoxifen use (usually in the adjuvant setting for breast cancer), hypertension, diabetes mellitus, and Lynch syndrome (also known as hereditary nonpolyposis colorectal cancer).

Prognosis

Patients with localized uterine cancer have a 94.9% 5-year survival. For those with regional spread to lymph nodes at the time of diagnosis, 5-year survival is estimated to be 68.6%. Unfortunately, the survival drops off dramatically for those with metastatic disease to 16.3% at 5 years.

Treatment overview

The treatment for endometrial cancer varies based on the stage at presentation. The endometrioid histology is the most common type of endometrial cancer, and its treatment is discussed below. Of note, rarer histologic subtypes of endometrial cancer can require alternative treatment strategies. Patients with stage IA disease (invasion to <50% of the myometrium) without other risk factors are often treated with surgery alone, and most patients will be cured without additional treatment. Patients with more locally advanced disease that has not extended outside of the uterus (i.e., stages IB-II) are often treated with adjuvant radiation following surgery to decrease their risk of recurrent disease. Patients with stage III disease often receive postoperative adjuvant radiation and chemotherapy, such as external beam radiation therapy with concurrent cisplatin as a radiation sensitizer, followed by carboplatin and paclitaxel.

Patients presenting with metastatic disease are often treated with chemotherapy, typically carboplatin and paclitaxel, based on its efficacy and tolerability. Carboplatin alternatively can be combined with liposomal doxorubicin. Topotecan and the antiangiogenic drug bevacizumab, which is a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), also have activity as single agents. Recent studies support the use of immune checkpoint inhibitors in tumors with high microsatellite instability (MSI-H), including endometrial cancers. ^, In this regard, the US Food and Drug Administration (FDA) has granted accelerated approval to the immune checkpoint inhibitor pembrolizumab for treatment of MSI high tumors of any histologic type that has progressed after standard therapy.

Cardiovascular risk

Systemic treatments for endometrial cancer are typically well tolerated from a cardiovascular perspective. The drug-specific toxicities for the most commonly used antineoplastic agents (carboplatin, paclitaxel, liposomal doxorubicin, and pembrolizumab) are discussed below.

Incidence

Ovarian cancer most often presents at an advanced stage with widespread disease within the peritoneum and/or distant metastases. High-grade serous carcinoma is the most common histology. The staging is determined surgically. In the United States in 2018, there were approximately 22,240 new cases of ovarian cancer diagnosed and 14,070 ovarian cancer deaths. After endometrial cancer, it is the second most common gynecologic malignancy, but also the most lethal, owing to the fact that it presents at an advanced stage in the majority of patients. The median age at diagnosis is 63 years; it is most often diagnosed in women between 55 and 64 years.

Risk factors

The strongest clinical risk factor is a family history of ovarian or breast cancer, which may be a surrogate for germline mutation in high-risk genes such as BRCA1 or BRCA2 . In particular, women with a genetic predisposition, such as known carriers of BRCA1 /2 mutation or mutations in mismatch repair genes (Lynch syndrome) have the highest risk of developing this disease. The US Preventive Services Task Forces currently recommends against routine screening for ovarian cancer, although the role of screening continues to be evaluated, especially in women with a genetic predisposition. In that regard, for women with a known germline mutation that predisposes to a high risk of developing ovarian cancer (e.g., mutation in either BRCA1 or BRCA2 ), a prophylactic bilateral oophorectomy is recommended once childbearing is complete. Other risk factors include increasing age, polycystic ovarian syndrome, infertility, and endometriosis (specifically for clear cell, endometrioid and low grade histology).