Endometrial, Ovarian, and Cervical Cancer

Endometrial, Ovarian, and Cervical Cancer



Kristine Zanotti



CARCINOMA OF THE ENDOMETRIUM



Definition


Endometrial cancer arises from the glandular tissue within the uterine lining.



Prevalence


Endometrial cancer is the most common of the gynecologic malignancies. Approximately 2% to 3% of women in the United States will develop cancer of the endometrium at some point during their lives. With an estimated 37,000 new cases last year, it is the fourth most common malignancy among women. It predominantly affects older women, with 75% of cases occurring in the postmenopausal years.



Pathophysiology


Endometrial cancer is a heterogeneous disease that is believed to have two biologically different subtypes, implying two different mechanisms for its origin.



Low-Risk Subtype


The most common subtype is a well-differentiated carcinoma (grade 1 or 2 endometrioid histology) that behaves in an indolent fashion, causes bleeding symptoms in its early stages, and is curable in most cases. Risk factors for this low-risk subtype are well known and are related to an increase in circulating estrogens: obesity, chronic anovulation and nulliparity, estrogen replacement therapy (unopposed by progesterone), and tamoxifen use.



High-Risk Subtype


The high-risk subtype accounts for a minority of endometrial malignancies. These poorly differentiated tumors (grade 3 endometrioid, clear cell, and papillary serous carcinoma) are not associated with increased circulating estrogens. Rather, they appear to occur spontaneously in postmenopausal women without clearly defined risk factors. These tumors metastasize early and account for a disproportionate number of mortalities from endometrial malignancy. Modes of spread include local invasion and lymphatic and vascular embolization. The most common metastatic sites include the cervix, adnexa, and retroperitoneal lymph nodes.



Signs and Symptoms


Endometrial cancer usually manifests with abnormal uterine bleeding. It should be suspected in any postmenopausal woman with bleeding symptoms. Pre- or perimenopausal women might have bleeding abnormalities such as menorrhagia or metrorrhagia.


Less commonly, asymptomatic women can present with an abnormal Papanicolaou (Pap) smear revealing atypical or malignant endometrial cells. A normal Pap smear in a symptomatic woman, however, must never be relied on to exclude endometrial pathology.



Diagnosis


A complete physical examination is the first step in the evaluation of a woman with suspected endometrial cancer. Inspection of the vulva, anus, vagina, and cervix is necessary to evaluate for metastatic lesions. A biopsy should be done for any suspicious genital tract lesions detected on examination. Bimanual and rectovaginal examination to evaluate the uterus, cervix, adnexa, parametria, and rectum is essential. Palpation of the inguinal and supraclavicular nodes may reveal enlargement in advanced cases with metastatic disease.


Histologic evaluation of endometrial tissue is necessary. An endometrial biopsy can be performed safely and easily in the office setting in most symptomatic patients. The sensitivity for detecting endometrial carcinoma approaches that of a dilation and curettage (D&C) and avoids the expense and morbidity of an operative procedure. Several biopsy instruments are available for use, including the Pipelle sampler and Novak curette.


Occasionally, D&C is necessary to obtain tissue for histologic evaluation. Cervical stenosis and patient discomfort are common indications for D&C. This outpatient surgical procedure may be performed using a paracervical block with sedation; however, in some cases, general or regional anesthesia may be preferred. Hysteroscopy and saline infusion sonography visualize endometrial lesions, such as polyps, within the uterine cavity and can be useful adjuncts to endometrial sampling techniques.


If endometrial cancer is confirmed, further studies are needed to optimize treatment planning, including a chest x-ray to rule out metastatic disease. Other studies may be performed based on a patient’s risk factors and symptoms at presentation. These include computed tomography (CT) scans of the abdomen and pelvis with oral and intravenous contrast (for preoperative assessment of extrauterine tumor spread in high-grade endometrial malignancies); sigmoidoscopy, colonoscopy, or barium enema; intravenous pyelogram; and serum cancer antigen 125 (CA 125) assay for papillary serous carcinoma.



Treatment


Treatment is based on the surgically determined disease stage and on assessment of prognostic features.1 Staging of endometrial cancer is defined by the International Federation of Gynecology and Obstetrics (FIGO) criteria outlined in Table 1. Surgical staging by exploratory laparotomy requires a peritoneal cytology assessment, intraoperative inspection of the abdominal and pelvic organs (diaphragm, liver, omentum, pelvic and aortic lymph nodes, peritoneal surfaces) for evaluation of metastatic disease, hysterectomy with bilateral salpingo-oophorectomy, and retroperitoneal lymph node sampling.2


Table 1 FIGO Staging for Endometrial Carcinoma


















Stage Definition
I Carcinoma confined to the corpus uteri
II Carcinoma that involves the corpus and the cervix but has not extended outside the uterus
III Carcinoma that extends outside the uterus but is confined to the true pelvis and/or retroperitoneal lymph nodes
IV Carcinoma that involves the bladder or bowel mucosa or that has metastasized to distant sites

FIGO, International Federation of Gynecology and Obstetrics.



Surgery


Although endometrial cancer is traditionally managed by laparotomy, increasing evidence supports the safety and efficacy of laparoscopic hysterectomy in appropriately selected patients at low risk for extrauterine tumor spread.



Adjuvant Treatment


The need for adjuvant therapy is based on disease stage and on risk factors for tumor recurrence.



Stage I Disease


For disease confined to the uterus, patients are placed in low-, intermediate-, and high-risk categories, and adjuvant therapies are based on pathologic features. In general, stage I tumors that are higher grade and more deeply invasive into the myometrium have a greater risk for recurrence and benefit from adjuvant therapy postoperatively.


Whole-pelvis radiotherapy, with or without vaginal cuff brachytherapy, is the most commonly used adjuvant postoperative treatment modality. Patients with the histologic variant papillary serous carcinoma, an aggressive endometrial lesion with a high risk for extrapelvic recurrence, are generally offered chemotherapy to reduce postoperative recurrence risk, although this treatment is controversial.



Stage II Disease


For disease involving the uterine cervix, there are several treatment options. When unsuspected cervical stromal involvement is found during surgery, postoperative external-beam radiotherapy with vaginal cuff brachytherapy is indicated. If cervical involvement is known preoperatively, various combinations of surgery and radiotherapy have been used:


• Hysterectomy, bilateral salpingo-oophorectomy, and node sampling followed by postoperative irradiation

• Preoperative intracavitary and external-beam radiation therapy followed by hysterectomy and bilateral salpingo-oophorectomy

• Radical hysterectomy and pelvic lymphadenectomy

Unfortunately, there is no standard treatment for stage II endometrial cancer, and the equivalence of these strategies has not been assessed in comparative randomized trials.



Stage III Disease


In general, postoperative whole-pelvis radiotherapy (vaginal cuff brachytherapy) is indicated when disease involves adnexal structures or retroperitoneal nodes. Patients with para-aortic involvement might benefit from extended-field radiotherapy.



Stage IV Disease


The site of metastatic disease and associated symptoms dictate the appropriate treatment of stage IV endometrial cancer. For bulky pelvic disease, radiation therapy consisting of a combination of intracavitary and external beam irradiation is used. When distant metastases are present, systemic therapy is indicated. Satisfactory tumor responses to hormonal treatment with progestational agents can often be achieved in well-differentiated (grades 1 and 2) tumors. Useful chemotherapeutic agents include doxorubicin and paclitaxel.



Outcomes


Endometrial cancer is one of the most curable of the gynecologic cancers because most patients have well-differentiated tumors and present with symptoms early in the disease process (Table 2). Five-year survival rates are much poorer in patients with the less common and poorly differentiated tumor histologies. These patients often present with metastatic disease and account for a disproportionate number of endometrial cancer deaths.


Table 2 Endometrial Carcinoma: Stage at Presentation and 5-year Relative Survival Rate



























Disease Extent Stage Distribution (%) Survival (%)
All stages — 84
Localized 73 96
Regional 13 66
Distant 9 27
Unstaged 4 53

Adapted from Ries LAG, Kosary CL, Hankey BF, et al (eds): SEER Cancer Statistics Review, 1973-1995. Bethesda, National Cancer Institute, 1998.



CANCER OF THE OVARY



Definition


Ovarian cancer is a heterogeneous group of malignancies that arises from the various cell types that compose the organ.



Epithelial


Nearly 90% of ovarian malignancies are classified as epithelial ovarian carcinomas. These cancers arise from the germinal epithelium lining the ovary. Epithelial ovarian cancer can be further subdivided into several histologic cell types: serous, mucinous, endometrioid, clear cell, transitional, and undifferentiated carcinomas. The risk of epithelial ovarian cancer increases with age and is found predominantly in postmenopausal women. Epithelial tumors of low malignant potential (borderline ovarian carcinoma) are a histologic variant that is less aggressive than their invasive epithelial counterparts, are found in younger women, and are often confined to the ovary at diagnosis.



Germ Cell


Germ cell tumors account for approximately 5% of all ovarian cancers and recapitulate the developing embryo or placental structures. Histologic subtypes include dysgerminoma (most common), endodermal sinus tumor, immature teratoma, choriocarcinoma, and embryonal carcinoma. Germ cell ovarian cancer can occur in women of any age, but approximately 80% of these are diagnosed in women younger than 30 years.



Sex Cord–Stromal


Sex cord–stromal tumors, which account for approximately 5% of all ovarian cancers, develop in the connective tissue and supporting ovarian stroma. These tumors are generally less aggressive and often produce steroid hormones, including estrogen, progesterone, and testosterone. Some patients with hormone-producing tumors present with signs and symptoms of steroid excess, such as vaginal bleeding or hyperandrogenism.



Prevalence


According to the American Cancer Society, there were more than 23,000 new cases of ovarian cancer and 14,000 deaths from the disease in the United States in 2001. It is estimated that a woman has a 1% to 2% lifetime risk for developing ovarian cancer. Ovarian carcinoma is the fifth most frequent cause of cancer death in women, and one half of all cases occur in women older than 65 years.



Pathophysiology


The cause of ovarian cancer is poorly understood; however, risk factors and mode of spread have been well described.



Risk Factors


The most significant risk factor for ovarian cancer is a positive family history. When two or more first-degree relatives have or have had ovarian cancer, a woman’s lifetime risk for developing this cancer is 7%. If a heritable cancer syndrome is identified, this lifetime risk can increase 17- to 50-fold. Three dominantly inherited mutations are known to be associated with the development of approximately 10% of all ovarian carcinomas: breast-ovarian cancer syndrome, which is associated with mutations in BRCA-1 and BRCA-2 genes; site-specific ovarian carcinoma; and hereditary nonpolyposis colorectal cancer (Lynch syndrome II), which is associated with mutations in mismatch repair genes. Advanced age is also associated with increased risk, whereas high parity, oral contraceptive use, tubal ligation, and hysterectomy decrease one’s risk.



Mode of Spread


Ovarian cancer usually spreads via cellular shedding into the peritoneal cavity followed by implantation on the peritoneal surface. Local invasion of the bowel and bladder is common in advanced cases. Tumor cells also may block diaphragmatic lymphatics. The resulting impairment of lymphatic drainage of the peritoneum is believed to play a role in development of ascites in ovarian cancer. Transdiaphragmatic spread and seeding of the pleura with pleural effusion are also common in advanced cases.

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Jul 18, 2017 | Posted by in GENERAL SURGERY | Comments Off on Endometrial, Ovarian, and Cervical Cancer

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