Chapter 093. Gynecologic Malignancies (Part 6) docx

Chapter 093. Gynecologic Malignancies (Part 6) Uterine Cancer Incidence and Epidemiology Carcinoma of the endometrium is the most common female pelvic malignancy. Approximately 39,080 new cases are diagnosed yearly, although in most (75%), tumor is confined to the uterine corpus at diagnosis, and therefore most can be cured. The 7400 deaths yearly make uterine cancer only the eighth leading cause of cancer death in females. It is primarily a disease of postmenopausal women, although 25% of cases occur in women ages <50 and 5% ages <40. The disease is common in Eastern Europe and the United States and uncommon in Asia. Proliferation of the endometrium is under the control of estrogen, and prolonged exposure to unopposed estrogen from either endogenous or exogenous sources plays a central etiologic role. Risk factors for endometrial cancer include obesity, low fertility index, early menarche, late menopause, and chronic anovulation. Granulosa cell tumors of the ovary that secrete estrogen may present with synchronous endometrial cancers. Chronic unapposed estrogen replacement increases the risk, and women taking tamoxifen for breast cancer treatment or prevention have a twofold increased risk. The Lynch syndrome occurs in families with an autosomal dominant mutation of mismatch repair genes MLH1, MSH2, MSH6, and PMS2, which predispose to nonpolyposis colon cancer as well as endometrial and ovarian cancer. The estimated lifetime risk for endometrial cancer is 40–60%, with a mean age around 50 years. Unlike colorectal cancer, endometrial cancer risk is not lower in MSH6 mutation carriers. Most women present with stage I disease, and the survival rate is generally good (5-year survival 88%). No unique endometrial screening strategies have been established for Lynch family gene carriers. Clinical Presentation Endometrial carcinoma occurs most often in the sixth and seventh decades of life. Symptoms often include abnormal vaginal discharge (90%), abnormal postmenopausal bleeding (80%), and leukorrhea (10%). The risk of endometrial cancer associated with postmenopausal bleeding increases with advancing age (9% at age 50 vs. 60% at age 80). Evaluation of such patients should include a history and physical with pelvic examination followed by an endometrial biopsy or a fractional dilation and curettage. Outpatient procedures such as endometrial biopsy or aspiration curettage can be used but are definitive only when positive. Pathology Between 75 and 80% of all endometrial carcinomas are adenocarcinomas, and the prognosis depends on stage, histologic grade, and extent of myometrial invasion. Grade I tumors are highly differentiated adenocarcinomas, grade II tumors contain some solid areas, and grade III tumors are largely solid or undifferentiated. Adenocarcinoma with squamous differentiation is seen in 10% of patients; the most differentiated form is known as adenoacanthoma, and the poorly differentiated form is called adenosquamous carcinoma. Other less common pathologies include mucinous carcinoma (5%) and papillary serous carcinoma (<10%). This latter type has a natural history similar to ovarian carcinoma and should be managed in the same way. Rarer histologies include secretory (2%), ciliated, clear cell, and undifferentiated carcinomas. Staging The staging of endometrial cancer requires surgery to establish the extent of disease and the depth of myometrial invasion. A total abdominal hysterectomy and bilateral salpingo-oophorectomy should be performed and peritoneal fluid sampled. Frozen sections of the uterine specimen are used to determine the histology and grade and depth of invasion. If indicated, pelvic and para-aortic lymphadenectomy is performed. After evaluation and staging, ~75% of patients are stage I, 13% are stage II, 9% are stage III, and 3% are stage IV. Five-year survival declines with advancing stage: stage I, 89%; stage II, 73%; stage III, 52%; and stage IV, 17% (Table 93-1). Uterine Cancer: Treatment Patients with uncomplicated stage I endometrial carcinoma are effectively managed with total abdominal hysterectomy and bilateral salpingo-oophorectomy. Pre- or postoperative irradiation has been used, and although vaginal cuff recurrence is reduced, survival is not altered. In women with poor histologic grade, deep myometrial invasion, or extensive involvement of the lower uterine segment or cervix, intracavitary or external beam irradiation is warranted. About 15% of women have endometrial carcinoma with extension to the cervix only (stage II), and management depends on the extent of cervical invasion. Superficial cervical invasion can be managed like stage I disease, but extensive cervical invasion requires radical hysterectomy or preoperative radiotherapy followed by extrafascial hysterectomy. Once disease is outside the uterus but still confined to the true pelvis (stage III), management generally includes surgery and irradiation. Patients who have involvement only of the ovary or fallopian tubes generally do well with such therapy (5-year survival of 80%). Other stage III patients with disease extending beyond the adnexa or those with serous carcinomas of the endometrium have a significantly poorer prognosis (5-year survival of 15%). Patients with positive para-aortic nodes (stage IIIC) or those with upper abdominal involvement (stage IV) have shown improved survival with platinum-based chemotherapy compared to whole-abdominal irradiation alone. . Chapter 093. Gynecologic Malignancies (Part 6) Uterine Cancer Incidence and Epidemiology Carcinoma of the endometrium