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  • 1. Endometrial, Ovarian, and Cervical Cancer Kristine ZanottiCARCINOMA OF THE ENDOMETRIUM anus, vagina, and cervix is necessary to evaluate for metastatic lesions. A biopsy should be done for any suspicious genital tract lesions S E C T I O N  14 Definition detected on examination. Bimanual and rectovaginal examination to evaluate the uterus, cervix, adnexa, parametria, and rectum is essen-Endometrial cancer arises from the glandular tissue within the tial. Palpation of the inguinal and supraclavicular nodes may revealuterine lining. enlargement in advanced cases with metastatic disease. Histologic evaluation of endometrial tissue is necessary. An endo-Prevalence metrial biopsy can be performed safely and easily in the office setting in most symptomatic patients. The sensitivity for detecting endome-Endometrial cancer is the most common of the gynecologic malig- trial carcinoma approaches that of a dilation and curettage (D&C)   W O M E N ’ S   H E A LT Hnancies. Approximately 2% to 3% of women in the United States will and avoids the expense and morbidity of an operative procedure.develop cancer of the endometrium at some point during their lives. Several biopsy instruments are available for use, including the PipelleWith an estimated 37,000 new cases last year, it is the fourth most sampler and Novak curette.common malignancy among women. It predominantly affects older Occasionally, D&C is necessary to obtain tissue for histologicwomen, with 75% of cases occurring in the postmenopausal years. evaluation. Cervical stenosis and patient discomfort are common indications for D&C. This outpatient surgical procedure may bePathophysiology performed using a paracervical block with sedation; however, in some cases, general or regional anesthesia may be preferred. Hyster-Endometrial cancer is a heterogeneous disease that is believed to have oscopy and saline infusion sonography visualize endometrial lesions,two biologically different subtypes, implying two different mecha- such as polyps, within the uterine cavity and can be useful adjunctsnisms for its origin. to endometrial sampling techniques. If endometrial cancer is confirmed, further studies are needed toLow-Risk Subtype optimize treatment planning, including a chest x-ray to rule out metastatic disease. Other studies may be performed based on aThe most common subtype is a well-differentiated carcinoma (grade patient’s risk factors and symptoms at presentation. These include1 or 2 endometrioid histology) that behaves in an indolent fashion, computed tomography (CT) scans of the abdomen and pelvis withcauses bleeding symptoms in its early stages, and is curable in most oral and intravenous contrast (for preoperative assessment of extra-cases. Risk factors for this low-risk subtype are well known and are uterine tumor spread in high-grade endometrial malignancies); sig-related to an increase in circulating estrogens: obesity, chronic moidoscopy, colonoscopy, or barium enema; intravenous pyelogram;anovulation and nulliparity, estrogen replacement therapy (un- and serum cancer antigen 125 (CA 125) assay for papillary serousopposed by progesterone), and tamoxifen use. carcinoma.High-Risk Subtype TreatmentThe high-risk subtype accounts for a minority of endometrial malig- Treatment is based on the surgically determined disease stage and onnancies. These poorly differentiated tumors (grade 3 endometrioid, assessment of prognostic features.1 Staging of endometrial cancer isclear cell, and papillary serous carcinoma) are not associated with defined by the International Federation of Gynecology and Obstet-increased circulating estrogens. Rather, they appear to occur spon- rics (FIGO) criteria outlined in Table 1. Surgical staging by ex-taneously in postmenopausal women without clearly defined risk ploratory laparotomy requires a peritoneal cytology assessment,factors. These tumors metastasize early and account for a dispropor- intraoperative inspection of the abdominal and pelvic organs (dia-tionate number of mortalities from endometrial malignancy. Modes phragm, liver, omentum, pelvic and aortic lymph nodes, peritonealof spread include local invasion and lymphatic and vascular embo- surfaces) for evaluation of metastatic disease, hysterectomy withlization. The most common metastatic sites include the cervix, bilateral salpingo-oophorectomy, and retroperitoneal lymph nodeadnexa, and retroperitoneal lymph nodes. sampling.2Signs and Symptoms SurgeryEndometrial cancer usually manifests with abnormal uterine bleed- Although endometrial cancer is traditionally managed by laparot-ing. It should be suspected in any postmenopausal woman with omy, increasing evidence supports the safety and efficacy of laparo-bleeding symptoms. Pre- or perimenopausal women might have scopic hysterectomy in appropriately selected patients at low risk forbleeding abnormalities such as menorrhagia or metrorrhagia. extrauterine tumor spread. Less commonly, asymptomatic women can present with anabnormal Papanicolaou (Pap) smear revealing atypical or malignant Adjuvant Treatmentendometrial cells. A normal Pap smear in a symptomatic woman,however, must never be relied on to exclude endometrial pathology. The need for adjuvant therapy is based on disease stage and on risk factors for tumor recurrence.Diagnosis Stage I Disease. For disease confined to the uterus, patients areA complete physical examination is the first step in the evaluation of placed in low-, intermediate-, and high-risk categories, and adjuvanta woman with suspected endometrial cancer. Inspection of the vulva, therapies are based on pathologic features. In general, stage I tumors www.expertconsult.com 1227
  • 2. 1228  Endometrial, Ovarian, and Cervical Cancer Table 1  FIGO Staging for Endometrial Carcinoma Table 2  Endometrial Carcinoma: Stage at Presentation and 5-year  Relative Survival Rate Stage Definition Disease Extent Stage Distribution (%) Survival (%) I Carcinoma confined to the corpus uteri All stages — 84 II Carcinoma that involves the corpus and the cervix but has not extended outside the uterus Localized 73 96 III Carcinoma that extends outside the uterus but is confined Regional 13 66 to the true pelvis and/or retroperitoneal lymph nodes Distant 9 27W O M E N ’ S   H E A LT H IV Carcinoma that involves the bladder or bowel mucosa or that has metastasized to distant sites Unstaged 4 53 FIGO, International Federation of Gynecology and Obstetrics. Adapted from Ries LAG, Kosary CL, Hankey BF, et al (eds): SEER Cancer Statistics  Review, 1973-1995. Bethesda, National Cancer Institute, 1998. that are higher grade and more deeply invasive into the myometrium have a greater risk for recurrence and benefit from adjuvant therapy present with metastatic disease and account for a disproportionate postoperatively. number of endometrial cancer deaths.   Whole-pelvis radiotherapy, with or without vaginal cuffS E C T I O N  14  brachytherapy, is the most commonly used adjuvant postoperative CANCER OF THE OVARY treatment modality. Patients with the histologic variant papillary serous carcinoma, an aggressive endometrial lesion with a high risk Definition for extrapelvic recurrence, are generally offered chemotherapy to reduce postoperative recurrence risk, although this treatment is Ovarian cancer is a heterogeneous group of malignancies that arises controversial. from the various cell types that compose the organ. Stage II Disease. For disease involving the uterine cervix, there Epithelial are several treatment options. When unsuspected cervical stromal involvement is found during surgery, postoperative external-beam Nearly 90% of ovarian malignancies are classified as epithelial radiotherapy with vaginal cuff brachytherapy is indicated. If cervical ovarian carcinomas. These cancers arise from the germinal epithe- involvement is known preoperatively, various combinations of lium lining the ovary. Epithelial ovarian cancer can be further surgery and radiotherapy have been used: subdivided into several histologic cell types: serous, mucinous, endo- metrioid, clear cell, transitional, and undifferentiated carcinomas. ● Hysterectomy, bilateral salpingo-oophorectomy, and node sam- The risk of epithelial ovarian cancer increases with age and is found pling followed by postoperative irradiation predominantly in postmenopausal women. Epithelial tumors of low ● Preoperative intracavitary and external-beam radiation therapy malignant potential (borderline ovarian carcinoma) are a histologic followed by hysterectomy and bilateral salpingo-oophorectomy variant that is less aggressive than their invasive epithelial counter- ● Radical hysterectomy and pelvic lymphadenectomy parts, are found in younger women, and are often confined to the ovary at diagnosis. Unfortunately, there is no standard treatment for stage II endome- trial cancer, and the equivalence of these strategies has not been Germ Cell assessed in comparative randomized trials. Germ cell tumors account for approximately 5% of all ovarian Stage III Disease. In general, postoperative whole-pelvis radio- cancers and recapitulate the developing embryo or placental struc- therapy (vaginal cuff brachytherapy) is indicated when disease tures. Histologic subtypes include dysgerminoma (most common), involves adnexal structures or retroperitoneal nodes. Patients endodermal sinus tumor, immature teratoma, choriocarcinoma, and with para-aortic involvement might benefit from extended-field embryonal carcinoma. Germ cell ovarian cancer can occur in women radiotherapy. of any age, but approximately 80% of these are diagnosed in women younger than 30 years. Stage IV Disease. The site of metastatic disease and associated symptoms dictate the appropriate treatment of stage IV endometrial Sex Cord–Stromal cancer. For bulky pelvic disease, radiation therapy consisting of a combination of intracavitary and external beam irradiation is used. Sex cord–stromal tumors, which account for approximately 5% of When distant metastases are present, systemic therapy is indicated. all ovarian cancers, develop in the connective tissue and supporting Satisfactory tumor responses to hormonal treatment with progesta- ovarian stroma. These tumors are generally less aggressive and often tional agents can often be achieved in well-differentiated (grades 1 produce steroid hormones, including estrogen, progesterone, and and 2) tumors. Useful chemotherapeutic agents include doxorubicin testosterone. Some patients with hormone-producing tumors and paclitaxel. present with signs and symptoms of steroid excess, such as vaginal bleeding or hyperandrogenism. Outcomes Prevalence Endometrial cancer is one of the most curable of the gynecologic cancers because most patients have well-differentiated tumors and According to the American Cancer Society, there were more present with symptoms early in the disease process (Table 2). Five- than 23,000 new cases of ovarian cancer and 14,000 deaths from year survival rates are much poorer in patients with the less common the disease in the United States in 2001. It is estimated that a and poorly differentiated tumor histologies. These patients often woman has a 1% to 2% lifetime risk for developing ovarian cancer. www.expertconsult.com
  • 3.   Endometrial, Ovarian, and Cervical Cancer  1229Ovarian carcinoma is the fifth most frequent cause of cancer death another common finding. The distended abdomen is dull to percus-in women, and one half of all cases occur in women older than 65 sion and an omental cake may be palpated in the upper abdomen.years. Further diagnostic workup is necessary to establish extent of disease and exclude other causes of an adnexal mass, carcinomatosis, orPathophysiology ascites.The cause of ovarian cancer is poorly understood; however, risk Imaging Studiesfactors and mode of spread have been well described. Transvaginal ultrasound uses higher-frequency sound waves toRisk Factors image the ovaries, allowing improved morphologic characterization. S E C T I O N  14  The addition of color flow Doppler can further characterize the mass.The most significant risk factor for ovarian cancer is a positive family A vascular mass with low resistive indices supports a diagnosis ofhistory. When two or more first-degree relatives have or have had malignancy. Chest x-ray might indicate pleural effusion, which isovarian cancer, a woman’s lifetime risk for developing this cancer is common in patients with ovarian carcinomatosis. CT scans of the7%. If a heritable cancer syndrome is identified, this lifetime risk can abdomen and pelvis with intravenous and oral contrast characterizeincrease 17- to 50-fold. Three dominantly inherited mutations are tumor burden and assist in evaluating other causes of adnexal mass,known to be associated with the development of approximately 10% carcinomatosis, or ascites. Other studies may be performed based onof all ovarian carcinomas: breast-ovarian cancer syndrome, which is a patient’s risk factors and symptoms at presentation. These include   W O M E N ’ S   H E A LT Hassociated with mutations in BRCA-1 and BRCA-2 genes; site- sigmoidoscopy, colonoscopy, or barium enema; upper gastrointesti-specific ovarian carcinoma; and hereditary nonpolyposis colorectal nal endoscopy; and intravenous pyelogram.cancer (Lynch syndrome II), which is associated with mutations inmismatch repair genes. Advanced age is also associated with increased Serum Tumor Markersrisk, whereas high parity, oral contraceptive use, tubal ligation, andhysterectomy decrease one’s risk. Serum tumor markers can assist in preoperative evaluation; however, their limitations must be understood so they are not misinterpretedMode of Spread or obtained inappropriately. Serum testing is essential to monitoring treatment response for ovarian cancer, but its usefulness as a diag-Ovarian cancer usually spreads via cellular shedding into the perito- nostic tool is hindered by poor sensitivity and specificity. CA 125 isneal cavity followed by implantation on the peritoneal surface. Local a high-molecular-weight glycoprotein that is expressed by more thaninvasion of the bowel and bladder is common in advanced cases. 80% of nonmucinous epithelial ovarian cancers. Although elevatedTumor cells also may block diaphragmatic lymphatics. The resulting in most women with advanced ovarian cancer, only 50% of patientsimpairment of lymphatic drainage of the peritoneum is believed to with early-stage disease have an elevated CA 125, and mucinousplay a role in development of ascites in ovarian cancer. Transdia- epithelial ovarian cancers express this antigen poorly. Furthermore,phragmatic spread and seeding of the pleura with pleural effusion an elevated CA 125 is not specific for ovarian cancer. Many nongy-are also common in advanced cases. necologic and benign gynecologic conditions also are associated with elevations in this serum antigen.Signs and Symptoms If nonepithelial ovarian cancer is suspected, other tumor markers may be useful to assist in diagnosis. Alpha fetoprotein, human cho-Unfortunately, most patients with epithelial ovarian cancer experi- rionic gonadotropin, and lactic dehydrogenase may be expressed byence few or no symptoms until the disease has widely metastatasized. germ cell malignancies. If metastatic colon or pancreatic carcinomaManifesting symptoms usually relate to an increasing intra- is suspected, serum carcinoembryonic antigen and CA 19-9 mightabdominal tumor burden and ascites and are often vague, mimicking also be elevated. Limitations in the sensitivity and specificity of theseother more common diseases. Symptoms include fatigue; bloating or tests must be understood so they can be interpreted appropriatelya feeling of fullness; abdominal swelling or pain; early satiety; vague for each patient.but persistent gastrointestinal complaints, such as gas, nausea, andindigestion; frequency or urgency of urination; change in bowel Paracentesishabits; unexplained weight loss or gain; shortness of breath; andobstructive symptoms, such as nausea, vomiting, and constipation Malignant ascites is common in patients with metastatic epithelialor obstipation. ovarian carcinoma. However, ascites due to other conditions such as On the other hand, borderline, germ cell, and sex cord–stromal congestive heart failure and cirrhosis must be ruled out by carefultumors are often confined to the ovary at the time of diagnosis. They history and, if necessary, diagnostic testing.may be quite large at presentation, and associated symptoms may be Although paracentesis may be performed for cytologic examina-related to their large size. These masses are occasionally detected tion, diagnostic paracentesis is not necessary for most patients if theyduring the screening pelvic examination. More commonly, patients have already been deemed appropriate for exploratory surgery andfeel the mass themselves or present with symptoms of acute abdomen operative management. Furthermore, a negative cytology from pre-due to torsion of the adnexa or rupture of the tumor. operative paracentesis does not exclude the possibility of malignancy, and differentiating the site of tumor origin is rarely possible onDiagnosis cytologic examination. Large-volume therapeutic paracentesis, however, may be useful for palliation of symptoms of abdominalA complete physical examination is the first step in the diagnosis distention and associated respiratory compromise due to diaphrag-of ovarian cancer. Although pelvic examination is notoriously inef- matic elevation.ficient at detecting presymptomatic early ovarian cancer, a pelvicmass can often be palpated on examination in symptomatic patients. ConsultationThe finding of a unilateral or bilateral nonmobile (fixed) mass ischaracteristic of epithelial ovarian carcinoma. Cul-de-sac masses If a reasonably high probability for ovarian malignancy exists,may also be palpated with rectovaginal examination. Impingement consultation with a gynecologic oncologist is essential to ensureof the rectum and compromise of lumen diameter can also be appre- appropriate preoperative counseling and preparation, operativeciated on this examination. Abdominal distention due to ascites is management, and postoperative care. www.expertconsult.com
  • 4. 1230  Endometrial, Ovarian, and Cervical Cancer Table 3  FIGO Staging for Ovarian Cancer although some regimens are given over a period of several days, requiring hospitalization. Stage Definition For epithelial ovarian cancer, platinum-based therapy-either cis- I Growth limited to the ovaries platin or carboplatin-in combination with paclitaxel has demon- strated the highest activity of all agents studied.4 These agents are II Growth involves one or both ovaries with pelvic extension generally given intravenously every 3 weeks for a total of six courses. One study, however, suggests that continuation of single-agent pacl- III Tumor with peritoneal implants outside the pelvis, or itaxel for 12 courses is associated with an improved disease-free positive retroperitoneal or inguinal nodes, or both survival. Although its impact on overall survival is uncertain, these IV Tumor involves one or both ovaries with distant metastasis findings have the potential to significantly affect recommended adju-W O M E N ’ S   H E A LT H vant therapy for this disease. FIGO, International Federation of Gynecology and Obstetrics. Stage I Disease. Patients with stage Ia or Ib tumors that are well-differentiated (grade 1) have an excellent prognosis, and the addition of adjuvant chemotherapy has not been demonstrated to Treatment improve survival in these patients. However, caution must be exer- cised when considering withholding adjuvant therapy in patients Ovarian cancer is initially managed with exploratory laparotomy to with presumed stage I disease who have not had the benefit of confirm the diagnosis and determine the extent of disease (surgical adequate surgical staging. Reoperation for staging purposes is an staging) and for tumor cytoreduction. option in these patients. Patients with grades 2 and 3 tumors are at   increased risk for recurrence and appear to benefit from adjuvantS E C T I O N  14  Histologic Identification chemotherapy. The availability of reliable intraoperative frozen section is essential Stages II to IV Disease. The use of adjuvant chemotherapy has for optimal surgical decision making and management. For survival and palliative benefits in patients with metastatic ovarian example, fertility-sparing surgery may be an option in select carcinoma and a larger tumor burden. Adjuvant therapy for tumors ovarian malignancies, such as germ cell tumors. In addition, of borderline histology is generally not indicated. Little evidence although tumor debulking appears to have survival benefit in exists that postoperative chemotherapy or radiation therapy alters patients with ovarian malignancies, carcinomatosis related to an the course of these tumors in any beneficial way. extraovarian primary tumor does not necessarily benefit from such All patients with germ cell tumors, except those with stage I, grade measures. 1 immature teratoma and stage IA dysgerminoma, require postop- erative chemotherapy.5 With platinum-based combination chemo- Surgical Staging therapy, the prognosis for patients with endodermal sinus tumors, immature teratomas, embryonal carcinomas, choriocarcinomas, and Accurate staging determines both treatment and prognosis. Inade- mixed tumors containing one or more of these elements has improved quate surgical staging is a common problem in patients with pre- dramatically. sumed early-stage disease when the operating surgeon does not Most patients with advanced ovarian cancer ultimately develop perform the necessary procedures for adequate staging. Therefore, it progressive or recurrent disease after initial surgery and adjuvant is imperative that the operating surgeon is familiar with staging cri- chemotherapy and require some form of palliative therapy. teria and has the surgical skills necessary to perform all the necessary Patients with recurrent ovarian carcinoma are considered either steps of the staging procedure. FIGO staging criteria are described in platinum sensitive or platinum resistant, depending on whether Table 3. the response duration was less than or longer than 6 months from prior therapy with a platinum-based agent. Potentially Cytoreduction platinum-sensitive patients often benefit from re-treatment with a platinum-based agent. Owing to its favorable toxicity profile, carbo- Metastatic implants of ovarian cancer typically involve the peritoneal platin is ideally suited for palliative therapy in the appropriate surfaces and are often amenable to resection along with the primary patient. tumor mass. Although not documented by any randomized clinical Platinum-resistant patients, on the other hand, generally have trial, optimal tumor cytoreduction (defined as removal of the more limited responses to alternative chemotherapeutic agents. A primary tumor and all gross metastatic implants to less than 1 cm number of second-line chemotherapeutic agents might have pallia- residual in largest diameter) is believed to improve chemotherapy tive benefit, including paclitaxel, liposomal doxorubicin, topotecan, response and disease-free survival.3 To achieve these goals, surgical and gemcitabine. Because of poorer response rates in most patients techniques such as en bloc hysterectomy with resection of the recto- with platinum-resistant disease, participation in clinical trials evalu- sigmoid, small bowel, total omentum, spleen, and possibly more may ating new therapies is also appropriate. be necessary. When disease-related symptoms can be palliated, such as the Aggressive resection of tumor does not appear to have any clini- reversal of intestinal obstruction, surgical intervention might cal advantage unless all metastatic implants also can be optimally improve the quality of life. However, palliation is rarely achieved in reduced. The operating surgeon must exercise judgment as to advanced disease when there are multiple areas of partial or complete whether optimal tumor reduction is possible and can be safely obstruction or when the transit time is prolonged due to diffuse achieved without incurring significant complications that would peritoneal carcinomatosis. delay chemotherapy. Adjuvant Treatment Outcomes Most, but not all, ovarian cancer patients require adjuvant chemo- Survival in ovarian cancer is related to surgical stage and tumor therapy after surgery. The importance of adequate surgical staging is histology (Table 4). Patients with borderline tumors, germ cell evident when making decisions regarding adjuvant therapy in stage malignancies, and sex cord–stromal tumors often present with ear- I disease. Most chemotherapy can be given on an outpatient basis, lier-stage disease and generally have improved prognoses. www.expertconsult.com
  • 5.   Endometrial, Ovarian, and Cervical Cancer  1231Table 4  Ovarian Carcinoma: Stage at Presentation and 5-Year  Table 5  FIGO Staging for Cervical CancerRelative Survival Rate Stage Definition Disease Extent Stage Distribution (%) Survival (%) 0 Preinvasive disease (carcinoma in situ) All stages — 50 I Carcinoma strictly confined to the cervix Localized 25 95 II Carcinoma that extends into the parametrium (but not onto Regional 9 79 the pelvic sidewall) or the upper two thirds of the vagina Distant 61 28 III Carcinoma that has extended onto the pelvic sidewall or S E C T I O N  14  involves the lower one third of the vagina. All cases with Unstaged 6 29 a hydronephrosis or nonfunctioning kidney should be included, unless they are known to be due to other causes.Adapted from Ries LAG, Kosary CL, Hankey BF, et al (eds): SEER Cancer Statistics  Review, 1973-1995. Bethesda: National Cancer Institute, 1998. IV Carcinoma that has extended beyond the true pelvis to distant organs or has clinically involved the mucosa of the bladder, rectum, or bothCANCER OF THE CERVIX   FIGO, International Federation of Gynecology and Obstetrics. W O M E N ’ S   H E A LT HDefinitionCervical carcinoma has its origins at the squamocolumnar junction Colposcopy is a technique of visually evaluating the cervix foror the cervix. The precursor lesion is dysplasia or carcinoma in situ abnormalities. The colposcope is a magnifying device that aids the(cervical intraepithelial neoplasia III). Squamous cell carcinoma examination of the cervix. Light filters and staining solutions areaccounts for 90% and adenocarcinoma accounts for 10% of cervical used in combination to identify cervical dysplasia. If an abnormalitycancers. is identified, a biopsy may be recommended. Treatment is usually based on the results of the biopsy. Referral to an expert familiar withPrevalence the colposcopy technique and the treatment of cervical dysplasia is recommended.Last year, cervical cancer was diagnosed in approximately 14,000 When a colposcopic abnormality or a grossly visible cervicalwomen in the United States, and there were 4,700 deaths from the lesion is identified, a biopsy is necessary for histologic evaluation.disease. Peak incidence of cervical carcinoma is at 51 years of age, Pap smear cytology is not adequate for diagnosis. Cervical biopsywhereas that for carcinoma in situ is approximately 10 years younger. may be accomplished in an office setting using any number of instru- ments, such as the Tischler-Morgan, Kevorkian, and mini-TownsendPathophysiology biopsy instruments or even a loop electrode. With documented invasive cervical carcinoma, further diagnosticEpidemiologic studies convincingly demonstrate that the major risk workup is necessary to establish the extent of disease. Cervical cancerfactor for preinvasive or invasive cervical carcinoma is infection with staging is defined clinically by FIGO criteria using physical examina-the human papillomavirus (HPV). HPV DNA is detected in virtually tion and a limited number of diagnostic studies (Table 5).all cervical cancers, with HPV subtypes 16, 18, and 31 identified most A pelvic examination is necessary to assess tumor size and con-commonly. Other known risk factors include early age at first inter- figuration and to identify possible vaginal metastasis and parametrialcourse, number of sexual partners, and a positive smoking history. or pelvic sidewall involvement. Additionally, lymphatic metastasis is Cervical carcinoma spreads predominantly by local invasion and common in advanced cervical cancer. Assessment of groin andlymphatic metastasis. The most common metastatic sites include the supraclavicular lymph nodes might reveal enlargement. Lowervagina, parametrium, and pelvic lymph nodes. extremity edema might also be present with an expanded tumor diameter, significant pelvic lymphadenopathy, or both. Homans’Signs and Symptoms sign or a palpable cord may be identified if there is an associated deep venous thrombosis.Precancerous changes of the cervix rarely cause symptoms and are Chest x-ray can identify pulmonary metastasis. Computed tomog-generally detected by pelvic examination and Pap smear screening. raphy of the abdomen and pelvis (with oral, rectal, and intravenousSymptoms usually do not appear until lesions become cancerous and contrast) allows for more complete assessment of tumor extent withininvade underlying cervical stroma. Postcoital vaginal spotting may the abdomen and pelvis. Although not part of FIGO clinical stagebe one of the first symptoms of the disease. Ultimately, an enlarging criteria, it is useful for treatment planning. An intravenous pyelogramand vascular tumor mass can become ulcerated, leading to frank may be obtained if ureteral obstruction or bladder involvement isvaginal bleeding, heavy vaginal discharge, or both. As the tumor suspected. Cystoscopy or sigmoidoscopy may be obtained if bladderinvades locally or spreads into the regional lymphatics, patients involvement, rectal involvement, or both are suspected.develop pain, lower extremity edema, and lower extremity deepvenous thrombosis. TreatmentDiagnosis Treatment and prognosis of cervical cancer are greatly affected by the extent of disease at the time of diagnosis.Cervical cancer may be detected in its early stages by the screeningPap smear or by identification of larger lesions in the symptomatic Stage 0 Disease (Carcinoma in Situ)patient. The Pap smear is a screening test only. Patients whose Papsmears indicate cytologic abnormalities suggestive of high-grade Invasive cervical carcinoma must be excluded with confidence beforelesions are at risk for invasive cancer and warrant further diagnostic therapy for preinvasive disease is undertaken. Standard treatmenttesting with colposcopy. Ablative procedures should not be per- options include excisional and ablative therapy. In general, excisionalformed without a thorough colposcopic examination. therapies are preferred because they are associated with a lower www.expertconsult.com
  • 6. 1232  Endometrial, Ovarian, and Cervical Cancer failure rate and provide tissue for histologic evaluation to assess Table 6  Cervical Carcinoma: 5-Year Relative Survival Rate margins and exclude invasion. Excisional therapies include the loop Disease Extent Survival (%) electrosurgical excision procedure (LEEP), laser conization, cold knife conization, and extrafascial hysterectomy. Ablative therapies All stages 84 include cryotherapy and laser ablation therapy. In most cases, outpatient LEEP is preferred.6 LEEP uses a fine wire Localized 96 loop with electrical energy flowing through it to remove the trans- formation zone of the cervix or focal areas of dysplasia. It can quickly Regional 66 and easily be performed in an office setting and generally requires Distant 27 only local anesthesia, thus avoiding the risks associated withW O M E N ’ S   H E A LT H general anesthesia. Cold knife or laser conization require general Adapted from Ries LAG, Kosary CL, Hankey BF, et al (eds): SEER Cancer Statistics  anesthesia. Review, 1973-1995. Bethesda, National Cancer Institute, 1998. Stage Ia1 (Microinvasive Cervical Cancer) Outcomes Cervical cancer in its earliest stages of invasion is termed microinva- sive carcinoma. It is defined as invasion of the stroma no greater than If not diagnosed in its early stages, cervical cancer carries high mor- 3 mm deep and no wider than 7 mm in diameter with no lymph- tality (Table 6). Properly diagnosed and managed, tumor control of vascular space involvement. in situ cervical carcinoma should be nearly 100%. Disease meeting this strictly defined criteria has a very limited risk   for lymphatic metastasis, and outcome is excellent with less-radical SummaryS E C T I O N  14  therapies. Expert pathology review is essential when considering less radical therapies for disease qualifying as microinvasive. Equivalent ● Endometrial cancer is one of the most curable of the treatment options include extrafascial hysterectomy, cervical coniza- gynecologic cancers because most patients have well- tion, and intracavitary radiation alone (without external beam differentiated tumors and present with symptoms early in radiotherapy). the disease process. ● A woman’s lifetime risk for developing ovarian cancer is All Other Stage I and Stage IIa Disease 7% when two or more first-degree relatives have this cancer. This lifetime risk can increase 17- to 50-fold if a Risk for lymphatic metastasis is increased with larger and more heritable cancer syndrome is identified. deeply invasive lesions. For this reason, radical therapies are neces- ● Unfortunately, most patients with epithelial ovarian cancer sary, and referral to a qualified gynecologic oncologist is appropriate experience few or no symptoms until the occurrence of and recommended. widespread metastatic disease. Therapy selection depends on patient factors, tumor factors, and ● Serum tumor markers can assist in the preoperative surgical expertise. Radical hysterectomy with bilateral pelvic lymph- evaluation of ovarian cancer; however, their limitations adenectomy is one option; combined external beam radiotherapy must be understood so they are not misinterpreted or and brachytherapy with concurrent chemotherapy is an equivalent obtained inappropriately. option. ● Epidemiologic studies convincingly demonstrate that the Several randomized phase III trials have shown an overall survival major risk factor for preinvasive or invasive cervical advantage for cisplatin-based therapy given concurrently with radia- carcinoma is infection with the human papillomavirus tion therapy. As a result of these findings, the National Cancer Insti- (HPV). tute issued a clinical announcement suggesting that “strong consideration should be given to the incorporation of concurrent cisplatin-based chemotherapy with radiation therapy in women who Suggested Readings require radiation therapy for treatment of cervical cancer.”7 Creasman WT, Morrow CP, Bundy BN, et al: Surgical pathologic spread patterns of endometrial cancer. A Gynecologic Oncology Group Study. Cancer 1987;60(Suppl Stages IIb to IVa Disease 8):2035-2041. Ferenczy A, Choukroun D, Arseneau J: Loop electrosurgical excision procedure for squamous intraepithelial lesions of the cervix: Advantages and potential pitfalls. With tumor spread beyond the cervix and upper vagina, cure rates Obstet Gynecol 1996;87:332-337. for radical surgery decline. Stages IIb to IVa cervical cancer are best Gershenson DM, Morris M, Cangir A, et al: Treatment of malignant germ cell tumors treated by radiation therapy using combined external beam pelvic of the ovary with bleomycin, etoposide, and cisplatin. J Clin Oncol 1990;8:715-720. radiation and concurrent cisplatin-based chemotherapy with intra- Hoskins WJ, Bundy BN, Thigpen JT, Omura GA: The influence of cytoreductive surgery on recurrence-free interval and survival in small-volume stage III epithelial ovarian cavitary brachytherapy or interstitial therapy. cancer: A Gynecologic Oncology Group study. Gynecol Oncol 1992;47:159-166. McGuire WP, Hoskins WJ, Brady MF, et al: Cyclophosphamide and cisplatin compared Stage IVb Disease with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. N Engl J Med 1996;334:1-6. National Cancer Institute: Long-term data support cisplatin-based chemoradiation for Patients with distant metastasis are no longer amenable to cure by cervical cancer. Available at http://www.cancer.gov/clinicaltrials/results/cisplatin- radiation therapy. Unfortunately, response rates to standard chemo- cervical0507 (accessed March 20, 2009). therapy are generally less than 20% and are typically brief. All patients Omura GA: Chemotherapy for cervix cancer. Semin Oncol 1994;21:54-62. with distant metastasis or recurrent disease should be considered Ries LAG, Kosary CL, Hankey BF, et al (eds): SEER Cancer Statistics Review, 1973-1995. Bethesda: National Cancer Institute, 1998. appropriate candidates for phases I and II clinical trials investigating new treatments. Palliative treatment options include radiation therapy to relieve References pelvic disease and chemotherapy with agents such as cisplatin, ifos- famide, paclitaxel, gemcitabine, and irinotecan.8 For a complete list of references, log onto www.expertconsult.com. www.expertconsult.com