Gynecologic Cancer
Thomas McNally
Richard T. Penson
Chau Tran
Michael J. Birrer
I. CERVICAL CANCER
In 2009, the American Cancer Society (ACS) reported an estimated 11,270 new cases of cervical cancer in the United States, with 4,070 deaths attributable to the disease. Historically a common disease, cervical cancer has become relatively rare in the developed world, thanks to successful screening with the Papanicolaou (Pap) test, which has allowed for early detection and therefore drastically reduced mortality rates. In developing countries, however, where access to effective and regular screening is not always available, the incidence of disease is much higher. As many as 300,000 women die globally each year as a result of cervical cancer.
The vast majority of cervical cancers are caused by human papillomavirus (HPV) infection. The development of an effective HPV vaccine has made the disease all the more preventable, and the mortality associated with cervical cancer in developed countries should decrease further in the coming decades. Still, global rates will remain high until both the vaccine and Pap test are readily and consistently available in both poor and developed countries.
A. Histology
Cervical cancer is classified as squamous cell carcinoma (keratinizing, nonkeratinizing, verrucous: 80% to 85%; endometrioid and adenocarcinoma,15%; and adenosquamous: 3% to 5%).
B. Screening
Early-stage disease is asymptomatic, and preinvasive lesions are found only after abnormal routine screening Pap smear of the ecto-/endocervix (transformation zone) junction. Cervical cancer mortality has decreased in the United States by over 70% since the Pap test was introduced in 1941.
Cervical cancer in the absence of demonstrable HPV infection is extremely rare, and HPV testing appears to be more sensitive and superior to standard Pap screening. Conventional cytology screening is reported to be 60% (30% to 87%) sensitive for dysplasia. Newer techniques using an ethanol medium (Sure-Path, BD Diagnostics, Franklin Lakes, NJ; Thin-Prep, Hologic, Bedford, MA; MonoPrep, MonoGen, Lincolnshire, IL) are as effective as conventional methods, are easier to read, and allow for sexually transmitted infection and HPV testing.
The Pap test is simple, safe, inexpensive, and well validated. Screening should start within 3 years of initiating sexual intercourse, or from age 21, and be repeated every 1 to 3 years. Approximately 3.5 million women have an abnormal Pap smear every year in the United States. The American Congress of Obstetricians and Gynecologists (ACOG) and ACS recommend that if a patient is exposed to diethylstilbestrol or is immunosuppressed (e.g., due to human immunodeficiency virus [HIV] infection), screening should be indefinite. HPV-negative women over the age of 30 years with normal Pap tests can decrease their screening interval to every 3 years and stop at the age of 70, at which point the risk of having significant dysplasia is about 1 in 1000.
The older terminology (mild, moderate, severe dysplasia) was replaced with cervical intraepithelial neoplasia I to III, based on the replacement of each third of the epithelium. This has since been replaced by the present system of “abnormal squamous cells of unknown significance” (ASCUS), which represents two-thirds of all abnormal Pap smears, and squamous intraepithelial lesions (SILs), which can be further classified as low-grade SIL or high-grade SIL.
An ASCUS Pap should trigger HPV testing. If positive, the patient should be referred for colposcopy. Women older than 40 years with normal endometrial cells on Pap smear require endometrial biopsy. There is a clear correlation between cytologic diagnosis and histologic diagnosis at colposcopy in approximately half of patients.
C. Clinical disease and staging
1. Clinical presentation. The most common symptoms of invasive cervical cancer are abnormal vaginal bleeding, either postcoital or intramenstrual, and vaginal discharge. Larger tumors may also interfere with urination and defecation, and may be accompanied by pelvic pain. Once the disease has metastasized to the regional lymph nodes, unilateral leg swelling, back pain, neuropathic pain, and postobstructive renal failure are also common symptoms. It should be noted that many women with cervical cancer do not present with any symptoms, but rather with disease detected during pelvic examination or screening procedures. The most common clinical sign of cervical cancer is an abnormal lesion on the cervix, usually detected by a physician during a pelvic exam. The exophytic lesion often presents as necrotic and friable. Involvement of surrounding tissues should be assessed, including the parametria, sidewalls, and uterosacral ligaments, as well as the superficial groin and femoral lymph nodes and the supraclavicular region. Infiltration of surrounding tissues is the most common reason to consider chemotherapy over surgery.
2. Diagnosis. Once an abnormal cervical lesion has been assessed by a physician, a tissue biopsy should be performed to either
confirm or rule out malignancy. The physician should make sure the biopsy is deep enough so as to include non-necrotic tissue, thus ensuring a diagnostically relevant sample.
3. Prognostic factors. Stage, histologic grade and type, tumor size, depth of stromal invasion, involvement of parametrium, and lymphovascular space invasion all influence prognosis. Pelvic lymph node metastasis significantly decreases the survival rate of patients.
4. Staging (Table 10.1). Cervical cancer is staged clinically and includes palpation, colposcopy, cystoscopy, endocervical curettage, proctoscopy, hysteroscopy, intravenous (IV) urography, and radiograph. Many centers also use magnetic resonance imaging (MRI) to define the local extent of disease and positron emission tomography (PET)/computed tomography (CT) to determine if there is any metastatic spread. Postoperatively, pathologic staging does not change clinical International Federation of Gynecology and Obstetrics (FIGO) staging.
TABLE 10.1 2009 FIGO Staging for Carcinoma of the Cervix Uteri
FIGO Stages
I
Cervical carcinoma confined to the uterus (extension to corpus should be disregarded)
IA
Invasive carcinoma diagnosed only by microscopy. All macroscopically visible lesions—even with superficial invasion—are stage IB.
IA1
Stromal invasion ≤3.0 mm in depth and extension ≤7.0 mm
IA2
Stromal invasion >3.0 mm but ≤5.0 mm in depth with extension ≤7.0 mm
IB
Clinically visible lesion confined to the cervix uteri or preclinical cancers greater than stage IA
IB1
Clinically visible lesion ≤4.0 cm in greatest dimension
IB2
Clinically visible lesion >4 cm in greatest dimension
II
Tumor invades beyond the uterus, but not to pelvic wall or lower third of the vagina
IIA
Without parametrial invasion
IIA1
Clinically visible lesion ≤4.0 cm in greatest dimension
IIA2
Clinically visible lesion >4 cm in greatest dimension
IIB
With obvious parametrial invasion
III
Tumor extends to pelvic wall and/or involves lower third of vagina and/or causes hydronephrosis or nonfunctioning kidney
IIIA
Tumor involves lower third of vagina with no extension to pelvic wall
IIIB
Tumor extends to pelvic wall and/or causes hydronephrosis or nonfunctioning kidney
IV
Carcinoma has extended beyond true pelvis or has involved (biopsy proven) the mucosa of the bladder or rectum. A bullous edema, as such, does not permit a case to be allotted stage IV.
IVA
Spread of growth to adjacent organs
IVB
Spread to distant organs
D. Treatment
Over the last century, management of cervical cancer has changed significantly: (1) more precancerous disease is managed through colposcopy, (2) there is now a preference for surgery over primary radiation, and (3) there is new evidence in the last 10 years that chemoradiation is significantly superior to radiation as primary or adjuvant therapy.
1. Dysplasia and in situ carcinoma. Options for treatment include conization (loop diathermy or cold knife), loop electrosurgical excision procedure, or hysterectomy. Lymphadenectomy is not required if stage IA-1 disease is demonstrated, as risk of metastases is very small (1%). If margins are positive, completion of hysterectomy or chemoradiation is needed. With negative margins, careful follow-up is adequate.
2. Early-stage disease. Early-stage disease can be treated with either chemoradiation or surgery, both of which have similar survival rates but different morbidity. Surgery may better preserve sexual function, although this has not been confirmed in well-controlled studies. Surgery should also be considered in premenopausal women where ovarian function can be preserved, in patients with an undiagnosed pelvic mass, in patients with more risk of bowel toxicity from radiotherapy (RT; adhesions because of pelvic inflammatory disease, endometriosis, inflammatory bowel disease, or in very thin women), or when compliance with the RT schedule may be difficult (with socially disadvantaged patients, for example).
The only randomized controlled trial (RCT) to compare RT with surgery for treatment of stage IB cervical cancers reported equivalent survival (83%) and similar recurrence rates (surgery 25%; RT 26%). However, surgery was associated with more serious adverse events (28% versus 12%), and 64% of the surgical patients required postoperative radiation, likely associated with increased morbidity. An important goal is to identify patients who would likely need RT and then avoid surgery; most clinicians now use PET/CT scans to screen for metastatic disease and MRI to evaluate the extent of local disease. This allows patients with more advanced disease to be triaged and treated with primary chemotherapy.
Morbidly obese patients are typically not considered for standard surgery because of high surgical risk, though robotically assisted surgery may prove safer. Age does not appear to be a significant contraindication to radical hysterectomy. Treatment should be appropriately tailored in unusual circumstances such as pregnancy or patients with HIV.
Lymphadenectomy is a standard part of surgical management of any early-stage disease being treated with radical
hysterectomy. Sentinel node biopsy is still investigational. Retrospective analysis of lymph-node debulking of palpable nodes prior to RT suggests a survival advantage in the prechemoradiation era, but is now more controversial and obsolete with modern imaging (MRI and PET/CT) and chemotherapy.
Adjuvant chemotherapy is necessary for women who have high-risk features after radical hysterectomy (positive lymph nodes, margins, or parametrium). A Southwest Oncology Group RCT in 243 women revealed that chemoradiation with cisplatin and 5-fluorouracil (5-FU) was significantly superior to RT alone (overall survival [OS] at 4 years of 81% with chemoradiation versus 71% with RT), though it had more toxicity.
If preservation of fertility is desired, vaginal radical trachelectomy (removal of only the cervix) with lymphadenectomy for small (less than 2 cm) tumors appears to be associated with an increased fertility (with up to 50% of patients becoming pregnant postradical trachelectomy) along with acceptable risk of recurrence in carefully selected patients. Tumor size is the single most important criterion in considering fertility-preserving surgery, but other criteria, including grade, canal involvement, lymphovascular space invasion, and MRI, are increasingly considered.
3. Locally advanced disease (stage IIB-IVA). In 1999, the National Cancer Institute (NCI) released a clinical alert about the large survival advantage in five NCI-sponsored clinical trials of the administration of concurrent chemotherapy with RT. A systematic review of 18 randomized trials revealed absolute benefit in progression-free survival (PFS) and OS of 16% (95% confidence interval 13 to 19) and 12% (8% to 16%), respectively, but with twice the gastrointestinal (GI) toxicity. Late toxicity is anticipated to be less with concurrent chemotherapy because of the total lower dose of RT.
Weekly cisplatin 40 mg/m2 during RT has become the popular strategy because of its more favorable toxicity profile compared to cisplatin and 5-FU. There has not been a direct comparison of cisplatin versus cisplatin and 5-FU, though many extrapolate their equivalence from Gynecologic Oncology Group (GOG)-120, which compared RT with cisplatin versus the combination of cisplatin, 5-FU, and hydroxyurea versus hydroxyurea alone in 526 patients with stages IIB, III, IVA cancer. In both groups who received radiation and cisplatin, the 3-year survival rate was 65% compared to 47% for women receiving radiation and hydroxyurea.
Combining cisplatin with another agent improves response at the expense of considerably worse toxicity, but many clinicians suspect that two drugs are better than one. A provocative RCT presented at the 2009 meeting of the American Society of Clinical Oncology suggested a 32% improvement in OS for
cisplatin 40 mg/m2 and gemcitabine 124 mg/m2 (both weekly for 6 weeks) over cisplatin alone 40 mg/m2 weekly for 6 weeks as chemotherapy (p = 0.0220). Typically half of the operative specimens from bulky tumors contain residual carcinoma after chemoradiation, and an adjuvant extrafascial hysterectomy is typically recommended.
4. Adenocarcinoma. Adenocarcinoma is associated with a worse prognosis, with no clear data that a more aggressive approach results in a better outcome. Treatment is typically the same as that for squamous cell carcinomas.
5. Neoadjuvant and adjuvant chemotherapy. Primary chemotherapy (neoadjuvant) with combination platinum-based chemotherapy (cisplatin, vincristine, bleomycin) can have a very high response rate (90% in stage IB2) with consolidative adjuvant radiation. However, early positive results could not be confirmed and this approach has fallen out of favor.
6. Palliative chemotherapy. For recurrent tumors, the ultimate goals of treatment are palliative, and the most active single agents are cisplatin, ifosfamide, paclitaxel, vinorelbine, and topotecan with response rates of 15% to 23%. Response rates of tumors located within a radiation field are typically halved; in the chemotherapy era, palliative chemotherapy is less effective. Combination platinum-based therapy with ifosfamide, paclitaxel, or topotecan is associated with higher response rates for all three agents, but cisplatin 50 mg/m2 on day 1 with topotecan 0.75 mg/m2 on days 1 to 3 is the only combination associated with an OS advantage (9.4 months versus 6.5 months). Despite this, the standard of care is cisplatin 50 mg/m2 on day 2 and paclitaxel 135 mg/m2 on day 1 as a 3- or 24-hour infusion because of its better toxicity profile. Single-agent, nonplatinum combination or paclitaxel and carboplatin are reasonable options. A newer study (GOG-240) compares cisplatin and paclitaxel with topotecan and paclitaxel, with and without bevacizumab, because with cisplatin as the standard in chemotherapy, response rates to platinum combination regimens has fallen.
7. Novel biologics. There is a desperate need for more effective therapy for recurrent cervical cancer. Agents that target the vascular endothelial growth factor, epidermal growth factor, and HER2/neu receptors are currently in clinical trial and look promising.
8. Palliative care. Supportive care, which addresses physical, psychological, social, and spiritual issues, is an essential part of the holistic care of patients as they approach the end of their life. Common medical problems include pain, nausea and vomiting, lymphedema, obstruction (genitourinary and GI), and fistulae, and require multiprofessional care.
II. ENDOMETRIAL CANCER
Endometrial cancer is the most common gynecologic malignancy. The ACS estimates that there were 42,160 new cases in 2009 in the United States, with 7780 deaths attributable to the disease. The cancer typically presents at an early stage with vaginal bleeding in postmenopausal women. Because it usually presents while still confined to the uterus, it is often readily cured with surgery alone. Prior treatment with tamoxifen is a significant risk factor for developing endometrial cancer. As tamoxifen has been used in the prevention and treatment of all stages of breast cancer, a significant population of women has been exposed to this drug and is therefore at increased risk of developing endometrial cancer.
A. Histology
Endometrial cancer includes endometrial carcinomas (95%) and mesenchymal tumors (5%). Mesenchymal tumors are comprised of uterine sarcomas (leiomyosarcomas and endometrial stromal sarcoma) and mixed epithelial/stromal tumors (carcinosarcomas and adenosarcomas). Histologic subtypes of endometrial carcinomas include endometrioid (75% to 80%), serous (5% to 10%), clear cell (1% to 5%), and other rare carcinomas (less than 2%), such as mucinous, squamous cell, transitional cell, and small-cell cancers. Endometrial carcinomas are also designated as types I and II, with type I being an estrogen-driven, endometrioid tumor occurring in obese women, and type II referring to all other, more aggressive histologic subtypes.
B. Screening
Screening is not necessary for endometrial cancer as the disease typically presents early with postmenopausal vaginal (PMV) bleeding and has a good prognosis with effective treatment (surgery). Although screening patients by ultrasound for thickened endometrial stripe has been advocated for patients who are on tamoxifen and are at increased risk of endometrial cancer, there is no clear survival advantage over clinical surveillance for PMV bleeding. Therefore, the role of ultrasound is probably limited to surveillance of pre-existing benign lesions. By contrast, in patients at higher than average risk of endometrial cancer because of a family history of colorectal cancer (Lynch II syndrome), prophylactic hysterectomy and bilateral salpingo-oophorectomy (BSO) prevents all (100%) uterine cancers.
C. Clinical disease
1. Clinical presentation. The most common symptoms of invasive endometrial cancer are abnormal vaginal bleeding and discharge. Because such bleeding can be caused by disorders other than cancer, special attention should be paid to women with abnormal bleeding who are either postmenopausal or who are at high risk for endometrial cancer and are over the age
of 40 years. Metastatic intraperitoneal disease may also cause symptoms similar to ovarian cancer, including abdominal distension, pelvic pressure, and pelvic pain. On pelvic ultrasound, a thickened endometrium is a sign of possible endometrial cancer and should be followed up by a gynecologic oncologist.
2. Diagnosis. For a definitive diagnosis of endometrial cancer, a tissue biopsy must be performed, usually through an endometrial biopsy (EMB) or fractional dilation and curettage (D&C). Today, EMB is the preferred method of evaluating abnormal uterine bleeding. It should be noted that EMB has proven more effective in postmenopausal, rather than premenopausal, women and is better at confirming the presence of cancer rather than its absence. In cases where outpatient EMB is not possible, or if abnormal bleeding persists despite negative biopsy, fractional D&C should be performed. Tissue samples from either diagnostic method allow for pathologic evaluation of the endometrium, which can help determine the cause of the patient’s symptoms, even if they are not the result of cancer.
3. Prognostic factors. The 5-year survival rate for endometrial cancer is 83%, and tumor-related prognostic factors at diagnosis include histologic subtype, stage, grade, depth of myometrial invasion, and lymphovascular space invasion. The prognosis of type I carcinomas is more favorable than that of type II because of their lower grade and sensitivity to hormone therapy. The presence of certain molecular abnormalities also contributes to poor prognosis. One such abnormality is the overexpression of the epidermal growth factor receptor (EGFR). In endometrioid adenocarcinomas, overexpression of EGFR decreases the overall 5-year survival rate from 89% to 69%; in serous and clear cell, the presence of EGFR overexpression decreases the survival rate from 86% to 27%.
4. Staging (Table 10.2). Endometrial cancer is surgically staged. As per FIGO recommendation, the surgery is done via an abdominal incision, followed by parametrial washings along with examination and palpation of omentum, liver, adnexal surfaces, peritoneal cul-de-sac, and enlarged aortic and pelvic nodes. Total abdominal hysterectomy (TAH) with BSO and complete lymphadenectomy are also standard in the United States. It should be noted, however, that the benefits of complete lymphadenectomy have been challenged with two negative randomized studies and are not standard in Europe. Further pathologic examination and frozen section assessment also contribute to accurate staging.
D. Treatment
1. Surgery. Surgery is most commonly all that is needed to cure endometrial cancer. Although ACOG recommends at least a TAH-BSO and node dissection, the role of nodal dissection is increasingly controversial. Laparoscopic surgery is associated with significantly shorter hospital stays and better quality of life. The use of robotically-assisted laparoscopic hysterectomy has increased dramatically, especially in the obese patient population, and has resulted in significantly lower perioperative complications (4% versus 21%, p = 0.007).
TABLE 10.2 2009 FIGO Staging for Carcinoma of the Epithelium of the Corpus Uteri
FIGO Stages
I
Tumor confined to the corpus uteri
IA
No invasion of or invasion is less than half of myometrium
IB
Invasion equal to or more than half of myometrium
II
Tumor invades cervical stroma but does not extend beyond uterus (endocervical glandular involvement only is considered stage I)
III
Local and/or regional spread of tumor
IIIA
Tumor involves serosa of corpus and/or adnexa
IIIB
Vaginal and/or parametrial involvement
IIIC
Metastases to pelvic and/or para-aortic lymph nodes
IIIC-1
Positive pelvic nodes
IIIC-2
Positive para-aortic lymph nodes with or without positive pelvic lymph nodes
IV
Tumor invades bladder mucosa and/or bowel mucosa and/or distant metastases
IVA
Tumor invades bladder mucosa and/or bowel mucosa
IVB
Distant metastases, including intra-abdominal metastases and/or inguinal lymph nodes
Debulking involved lymph node metastases (greater than 8 mm) may have an impact on prognosis, but lymphadenectomy for patients with stage I and II disease is not associated with a survival advantage in a recent RCT, and a growing consensus appears to support less aggressive surgical approaches in women with grade 1 or 2 endometrioid tumors with less than 50% myometrial invasion, less than 2 cm in tumor length, and no obvious other macroscopic disease.
Prophylactic TAH-BSO has been reported to prevent 100% of uterine cancers of women undergoing risk-reducing surgery for hereditary nonpolyposis colon cancer.
2. RT. Radiation is given adjuvantly to reduce the risk of local recurrence (brachytherapy to the vaginal vault postoperatively). External-beam RT (EBRT) is indicated for completely resected, node-positive disease (stage IIIC) and is also considered for higher risk patients (poor grade, or adverse histology, deep invasion, advanced age) with early-stage disease. However, this is increasingly controversial as there is no proven survival
advantage. RT in the form of brachytherapy is administered to the vaginal vault for high-risk tumors and tumors involving the lower uterine segment. More extensive RT (extended field) may be indicated in carefully selected patients with small volume residual disease, but the benefit has to be weighed against the risk of late complications.
Medically unfit patients with serious comorbidities can be treated with primary RT with good clinical benefit, and radiation is very good palliation of symptomatic metastases (brain or bone metastases, pelvic pain, or bleeding).
3. Hormonal therapy. Hormonal therapy is recommended only for patients with recurrent or inoperable tumor that is estrogen receptor (ER)/progesterone receptor (PR) positive. Adjuvant progestin therapy is not recommended because of excess cardiovascular mortality. Clinical responses to progestins (such as medroxyprogesterone acetate 80 mg twice a day) are consistently reported in approximately one-third of patients (15% to 34%), similar to other agents, such as tamoxifen, and probably no better than the highest reported response rate with tamoxifen alternating with a progestin. Aromatase inhibitors and gonadotropin-releasing hormone agonists are reasonable alternatives.
4. Chemotherapy (Table 10.3). The role of systemic therapy for endometrial cancer is changing and controversial. Adjuvant chemotherapy has been reported to increase 5-year survival rates (from 78% to 88%, hazard ratio [HR] 0.51, p = 0.02) in high-risk early-stage disease and is commonly recommended for deep penetrative, node-positive, poor-grade tumors. Although one standard combination is paclitaxel, doxorubicin, and cisplatin, paclitaxel and carboplatin is the most popular choice because of a better toxicity profile. These are being compared in GOG-209.
TABLE 10.3 Chemotherapy Regimens for Endometrial Cancer
1.
Doxorubicin and cisplatin:
Doxorubicin 60 mg/m2 IV every 3 weeks
Cisplatin 50 mg/m2 IV every 3 weeks
2.
Megestrol acetate 80 mg twice a day
3.
Topotecan 1.2-1.5 mg/m2/d IV on days 1-5 every 3 weeks
4.
TC:
Carboplatin AUC 6 IV on day 1
Paclitaxel 175 mg/m2 IV on day 1 every 4 weeks
5.
TAP:
Doxorubicin 45 mg/m2 IV on day 1
Cisplatin 50 mg/m2 IV on day 1
Paclitaxel 160 mg/m2 IV on day 2
AUC, area under the curve; IV, intravenous; TAP, paclitaxel, doxorubicin, and cisplatin; TC, carboplatin and paclitaxel.
Recurrent disease (especially ER/PR-negative disease) is often treated with further palliative chemotherapy such as weekly paclitaxel, liposomally encapsulated doxorubicin, topotecan, low-dose gemcitabine, and cisplatin. However, response rates are very low and benefit is rarely durable.
5. Uterine papillary serous carcinoma. All uterine papillary serous carcinomas, except those limited to a polyp, are typically treated with chemotherapy after initial surgery. Although they more commonly have HER2/neu overexpression or amplification, trastuzumab has no proven role.
6. Novel biologics. The role of mTOR, AKT inhibitors, and PI3 kinase inhibitors looks promising for endometrioid tumors, but remains investigational. One report suggests that with a 16% response rate, bevacizumab is worthy of further study.
7. Multimodality therapy. GOG-122 (doxorubicin-cisplatin versus whole-abdominal irradiation [WAI]) changed the landscape of endometrial cancer treatment with proof that chemotherapy improved survival compared to radiation alone for stage III and IV disease, with 50% compared to 38% of patients alive at 5 years (HR 0.68, p <0.01). These patients need tailored multimodality therapy; however, the sequence and schedule are not optimally defined. Therapy most commonly consists of surgery, followed by chemotherapy and tailored RT. Paclitaxel, doxorubicin, and cisplatin (TAP) is thought to be more toxic than the more popular regimen of paclitaxel and carboplatin.
8. Follow-up. Surveillance requires a pelvic exam every 3 months in the first 2 years to detect a potentially curable local recurrence, and supportive care should address functional, psychological, social, and spiritual issues.
III. UTERINE SARCOMAS
A. Histology
Endometrial stromal sarcomas (ESSs) and undifferentiated endometrial sarcomas are rare forms of uterine sarcomas. ESSs, whose cells resemble endometrial stromal cells, are low-grade. Other uterine sarcomas include malignant mixed müllerian tumor (MMMT) and leiomyosarcomas.
B. Clinical disease
1. Clinical presentation and diagnosis. ESSs are a specific histologic subtype within the larger group of mesenchymal tumors of the uterine corpus. The most common symptom experienced by women with ESS is abnormal vaginal bleeding. ESS tumors
are almost always low-grade and on gross examination usually present as a single mass. They can occur in sites other than the uterus, including the ovary, fallopian tube, cervix, vagina, vulva, pelvis, abdomen, retroperitoneum, placenta, sciatic nerve, or round ligament. ESS can be mistaken for endometrial stromal nodules; two distinguishing characteristics are infiltrating margins with or without angioinvasion, both of which are found in sarcomas but are absent in nodules. A definitive diagnosis of ESS is not possible from endometrial curettage specimens alone, and a full hysterectomy is required.
Undifferentiated endometrial sarcomas are marked by extensive cytologic atypia to the point where they can no longer be recognized as arising from the endometrial stroma. Grossly, these tumors resemble undifferentiated mesenchymal tumors and mimic high-grade sarcomas in behavior.
2. Prognostic factors. Stage and grade for all three types are important when considering a patient’s prognosis. ESS has a good prognosis, in part due to its low-grade characteristics, and most are cured surgically. However, low-grade ESS behaves aggressively if the following characteristics are present: high expression of androgen receptors or low expression of estrogen receptors. The relapse rate for ESS is 62%. Recurrence commonly includes pulmonary metastases and responds to hormonal therapy (progestins or aromatase inhibitors). MMMTs, which behave in a manner similar to high-grade sarcomas, are often fatal and have a relapse rate of 85%.
3. Staging is according to FIGO criteria.
C. Treatment
ESS is typically treated with surgery and possible hormonal therapy, including progestins or aromatase inhibitors. Leiomyosarcoma is treated with surgery, RT, and palliative chemotherapies. These include gemcitabine with docetaxel and occasionally hormonal therapy, as with ESS. MMMT is treated with surgery followed by multimodal therapies, including RT and chemotherapy. Chemotherapy includes carboplatin with paclitaxel or ifosfamide with cisplatin, although the latter combination is much more toxic. Chemotherapy (cisplatin-ifosfamide and mesna) may be superior to other regimens as postsurgical therapy in stage I to IV carcinosarcoma (MMMT) of the uterus (52% versus 58% [WAI], HR 0.789, p = 0.245).
IV. OVARIAN CANCER
Ovarian cancer is a relatively rare disease, with an incidence of about 1 in 70 women. In the United States, there were 21,550 new cases of ovarian cancer and 14,600 deaths attributable to the disease in 2009, according to the ACS. As early-stage ovarian cancer is rarely symptomatic, and due to the fact that there are no effective screening
protocols, ovarian cancer patients typically present with advanced stage disease (stages II to IV). Although the tumors are very responsive to chemotherapy, thus enabling the majority of patients to live for years with their disease (overall 5-year survival rate is 45.6%), the patients are rarely cured. The cause of epithelial ovarian cancer remains unknown, but theories relate it to incessant ovulation or abnormalities in the fallopian tube fimbria.
A. HistologyRelated posts:
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