EPITHELIAL OVARIAN CANCER :
SIXTH MOST COMMON CANCER IN WOMEN. RISK IS INCREASED IN WOMEN WHO HAVE NOT HAD CHILDREN & POSSIBLY THOSE WITH EARLY MENARCHE OR LATE MENOPAUSE. WOMEN WITH H/O BREAST CANCER HAVE AN INCREASED RISK OF EOC.
Lactose consumption and the use of talcum powder on the vulva and perineum may be associated with increased risk. A steady decreased risk is observed with increasing parity and with use of the combined oral contraceptive pill.
Disorders of the genes associated with breast cancer, BRCA1 and BRCA2, and more rarely, genes within the Lynch II syndrome complex, are associated with ovarian cancer. Mutations in these genes are inherited in an autosomal dominant pattern, with the mutated gene coming from either parent.
PREVENTION & SCREENING :
CA125 is not useful when used alone as a single one-time test for ovarian cancer screening, but it may have increased value when serial measurements are performed over time and if it is incorporated into a risk of ovarian cancer algorithm. Other markers have been investigated, including lysophosphatidic acid, tumor-associated glycoprotein 72 (TAG 72), OVX1, and macrophage colony-stimulating factor (M-CSF). Still, other markers are undergoing active investigation
The risk of developing EOC is significantly reduced by bearing children, using the combined oral contraceptive pill, undergoing tubal ligation, and undergoing bilateral oophorectomy.
Evidence suggests that taking the oral contraceptive pill for at least 5 years reduces the relative risk of developing EOC to 50% of the risk for a woman who has never taken it.
For patients who are known carriers of BRCA1 or BRCA2 mutations, bilateral oophorectomy may be performed as soon as childbearing is complete, and probably before the patient is aged 35 years. This reduces the chance of developing EOC, but it does not prevent carcinoma of the peritoneum.
STAGING :
EOC is staged according to Federation International de Gynecologie et Obstetrique (FIGO) (ie, International Federation of Gynecology and Obstetrics) rules as follows:
Stage I - Growth limited to the ovaries
IA - Growth limited to 1 ovary, no ascites present containing malignant cells, no tumor on the external surface, capsule intact
IB - Growth limited to both ovaries, no ascites present containing malignant cells, no tumor on the external surfaces, capsules intact
IC* - Tumor either stage IA or IB, but with tumor on surface of 1 or both ovaries with capsule ruptured, with ascites present containing malignant cells, or with positive peritoneal washings
Stage II - Growth involving 1 or both ovaries with pelvic extension
IIA - Extension and/or metastases to the uterus and/or tubes
IIB - Extension to other pelvic tissues
IIC* - Tumor either stage IIA or IIB, but with tumor on surface of 1 or both ovaries, with capsule(s) ruptured, with ascites present containing malignant ovaries, or with positive peritoneal washings
Stage III - Tumor involving 1 or both ovaries with histologically confirmed peritoneal implants outside pelvis and/or positive retroperitoneal or inguinal nodes; superficial liver metastasis equals stage III; tumor limited to true pelvis, but with histologically proven malignant extension to small bowel and omentum
IIIA - Tumor grossly limited to the true pelvis, with negative nodes, but with histologically confirmed microscopic seeding of abdominal peritoneal surfaces, or histologically proven extension to small bowel mesentery
IIIB - Tumor of 1 or both ovaries with histologically confirmed implants, peritoneal metastasis of abdominal peritoneal surfaces, none exceeding 2 cm in diameter; nodes are negative
IIIC - Peritoneal metastasis beyond the pelvis larger than 2 cm in diameter and/or positive retroperitoneal or inguinal nodes
Stage IV - Growth involving 1 or both ovaries with distant metastases; if pleural effusion is present, positive cytology must be apparent to allot a case to stage IV; parenchymal liver metastasis qualifies as stage IV disease
*In order to evaluate the prognostic impact of the different criteria for allotting cases to stage IC or IIC, knowing if rupture of the capsule was spontaneous or caused by the surgeon is of value. Also of value is knowing if the source of malignant cells detected was peritoneal washings or ascites.
TREATMENT :
Treatment of ovarian cancer is undertaken after consideration of many factors, including the extent of disease spread, symptoms, and patients' wishes and fitness to undergo treatment.
Surgery
Surgery is the initial treatment of choice, provided patients are medically fit. Patients who are not fit for surgery may be given chemotherapy and considered for surgery later. The aim of surgery is to confirm the diagnosis, define the extent of disease, and resect all visible tumor. The role of cytoreduction was demonstrated by Griffiths in 1975 and has been confirmed by many others.
The incision for surgery should be midline abdominal. In young women with early-stage disease, a transverse incision may be considered. Careful inspection and/or palpation of the abdominal contents should be performed, including all peritoneal surfaces, the liver, large and small bowel and mesentery, stomach, appendix, kidneys, spleen, retroperitoneal spaces, and all pelvic structures.
Appropriate surgery, depending on whether or not disease is visible outside the ovaries, is described below. It is essential that where no disease is visible outside the ovaries, the patient be adequately surgically staged because the incidence of microscopic metastases is significant. Surgery for patients with stage IV disease should be individualized, particularly when disease is in the liver and above the diaphragm. Patients who are in stage IV because of small-volume disease in the liver, abdominal wall, or lung should undergo cytoreductive surgery if medically fit.
Surgery for ovarian cancer
No visible disease outside of an ovary
Aspirate ascitic fluid for cytology studies.
Perform peritoneal washings* for cytology if ascites is not present.
Remove the ovary and ovarian tumor intact.
Perform diaphragmatic scraping for cytology studies.
Obtain peritoneal biopsy specimens.
Perform a subcolic omentectomy.
Obtain bilateral para-aortic and pelvic node samples.
Obtain biopsy samples of adhesions or other suspicious areas.
If the patient does not desire future fertility, perform a total abdominal hysterectomy and excise the opposite ovary.
Remove the appendix if mucinous tumor is present.
Macroscopic disease outside of the ovary
All visible tumor should be removed. This may require extensive surgery, including bowel resection, excision of peritoneal implants, liver resection, omentectomy, and splenectomy.
The extent of bowel resection should depend on the role this plays in achieving maximal cytoreduction.
*Fluid must have been in contact with broad surfaces of the peritoneum above the liver, the paracolic gutters, and the pelvis. All specimens may be placed in the same container with heparin at a concentration of 1 U/mL of aspirate and sent for cytology studies.
Role of laparoscopy
Laparoscopy may be used for diagnostic purposes in a patient with low risk for ovarian cancer and to remove cystic masses, according to guidelines developed by the American College of Obstetricians and Gynecologists. The mass must be 10 cm or smaller as viewed by a sonogram, must have a distinct border and no solid parts, and must not be associated with ascites. The serum CA125 level must be normal (<35 U/mL), and the patient must have no family history of ovarian cancer. If chance exists that ovarian cancer is present, such surgery is best arranged in conjunction with a specialist in gynecologic cancer surgery. The patient then can undergo all necessary surgery for her cancer under a single anesthetic, without delay. Laparoscopy also has a role in second-look inspection and in the staging of apparently early-stage disease found by chance during another surgery.
Chemotherapy
Only a small percentage of women with EOC can be treated with surgery alone. These include patients with stage IA grade 1 and stage IB grade 1 serous, mucinous, endometrioid, and Brenner tumors. Clear-cell carcinomas are associated with a significantly worse prognosis in stage I, and patients with subtypes should be considered for chemotherapy at all stages.
Patients not treated with chemotherapy should be monitored closely with clinical examination, serum CA125 estimation, and ultrasonography of the residual ovary at regular intervals. Surgery to remove the uterus and residual ovary should be considered when the patient no longer desires to remain fertile.
Higher-risk early-stage disease includes all histologic subtypes with stage IA and stage IB grade 2 and all stage I grade 3. These patients should be treated with front-line chemotherapy with a taxane/platinum combination for a minimum of 3 courses. They should consider participating in clinical trials.
Patients with stage II cancer and greater should receive front-line chemotherapy and should strongly consider participation in clinical trials. Standard therapy is currently a taxane/platinum combination, usually with carboplatin and either paclitaxel or docetaxel for a minimum of 6 courses. Carboplatin is given at an area under the curve (AUC) of 6-7.5 mg/mL/min (using the Calvert formula). Paclitaxel is dosed at 175 mg/m2 and docetaxel at 60-75 mg/m2. Cisplatin at 50-75 mg/m2 can be substituted for carboplatin. Docetaxel in combination with carboplatin has been shown to provide equivalent survival rates with less neurotoxicity but greater neutropenia.
Calvert formula for calculating total dose of carboplatin: Total dose (mg) = target AUC x (GFR + 25), where GFR = glomerular filtration rate, taken to be the creatinine clearance in mL/min and AUC in mg/mL/min. The normal range of AUC for treatment of ovarian carcinoma varies from 5-8. Patients who have received extensive prior chemotherapy or radiation should start with an AUC of less than 5.
Neoadjuvant chemotherapy
This is given to patients with disease that is initially considered inoperable or it is given if the patient is unfit for surgery at the time of diagnosis. If the patient has a good response to 3 or more cycles of chemotherapy, surgery, called interval debulking, may be performed followed by further chemotherapy.
Intraperitoneal chemotherapy
Use of chemotherapy agents instilled into the peritoneal cavity has the theoretical advantage that much higher concentrations can be obtained locally without the risk of adverse systemic effects; however, the agents are unable to penetrate more than a few millimeters. At least 3 randomized studies comparing chemotherapy regimens, including the intraperitoneal route with the intravenous route, have shown a survival advantage for the arms receiving intraperitoneal chemotherapy. Thus, intraperitoneal chemotherapy should be strongly considered for the treatment of front-line disease following surgery where 5 mm of less-residual disease exists. This route of chemotherapy administration requires the placement of a subcutaneous tube into the peritoneal cavity; this is associated with a number of complications including infection, blockage, and discomfort. Nevertheless, randomized studies show a survival benefit and disease-free survival benefit.
Radiation therapy
Radiation has not been widely accepted as a routine treatment modality in the initial treatment of patients with EOC, despite reports of efficacy for higher-risk stage I and II disease and in stage III disease where small-volume residual disease is present after surgery.
Second-look laparotomy
Second-look laparotomy is performed at the end of initial treatment when no disease is evident. The aim is to inspect the abdominal cavity for disease and perform an extensive biopsy when no macroscopic disease is found. This surgery went out of fashion because (1) at this time, no adequate treatment exists for patients found to have the disease; and (2) of those patients who had negative findings at surgery (a complete pathologic response), 50% would have recurrence by 5 years and 60% would have recurrence by 10 years. However, research is producing novel potential therapeutic options and second-look laparotomy should still be considered when performed as part of a research protocol.
Consolidation chemotherapy
Ovarian cancer has a very high response rate, but most patients have recurrent cancer following initial therapy. Much interest abounds in research into treatments to prevent or prolong the interval of recurrence. A Gynecologic Oncology Group protocol was discontinued when a statistical improvement in disease-free survival was demonstrated in patients receiving 12 months versus 3 months of additional monthly paclitaxel after initial therapy. However, questions remain about this study, which was not completed as designed. Since no consensus on management in this situation exists, patients should be encouraged to participate in clinical trials of consolidation therapy.
Estrogen replacement therapy after treatment of epithelial ovarian cancer
The safety of estrogen replacement therapy (ERT) after treatment for EOC has not been tested in a randomized trial, but current evidence suggests that the benefits of ERT outweigh the risks.
Younger women with endometrioid subtypes are of concern because these tumors theoretically are estrogen-sensitive. If estrogen is used in such patients, a progestogen probably should be given with it.
Recurrent disease
In most patients, ovarian cancer recurs, and the prognosis for these patients is poor. The goal of further therapy is to achieve a response to treatment and to prolong meaningful quality survival.
Treatment of recurrent disease may involve surgery, chemotherapy, and radiation. If a localized mass is present, surgery may play a role prior to the initiation of further chemotherapy. Response is more likely in patients who previously had a good response to first-line therapy and who had a long interval between the completion of initial therapy and the time of recurrence.
Patients whose previous response to platinum agents was good and who have gone at least 6 months since completing initial therapy may be re-treated with a taxane together with carboplatin or cisplatin. Patients with platinum-resistant disease who respond poorly to treatment with platinum agents initially and have a short interval to recurrence, do poorly. These patients should be offered participation in clinical trials. Agents with some activity in this situation include topotecan, etoposide, liposomal doxorubicin, and docetaxel and altretamine. Single-agent therapy is usually given for recurrent disease.
Samples of recurrent tumor or ascitic fluid can be sent to one of several laboratories for chemotherapeutic assay. This assay involves culturing tumor cells in media containing a range of chemotherapy agents. This allows chemotherapy agents to be offered to patients with the greatest potential for activity, and, conversely, this allows for drugs with extreme resistance to be avoided. These assays have a controversial role in the initial treatment of ovarian cancer.
Patients who are sensitive to chemotherapy have overall response rates of 30-60%, with an overall survival of 12-24 months, whereas patients resistant to chemotherapy have expected response rates of 12-32%, with an overall survival of 7-12 months.
The finding of elevated CA125 in the serum in the absence of clinical or radiographic disease is a relatively common situation in patients with EOC following initial treatment. Treatment of these patients is controversial. No current evidence indicates that treating the patient at this time affects survival.
Radiation
Radiation has a palliative role in recurrent disease for symptomatic and persistent masses. Emerging evidence suggests that radiation may improve the prognosis for women with recurrent disease that can be surgically debulked to microscopic disease only. However, morbidity may be high, and each case should be considered individually.
Hyperthermic intraperitoneal chemotherapy
The instillation into the peritoneal cavity of chemotherapeutic agents in a solution heated to between 40Β°C and 43Β°C was first introduced in an attempt to induce longer survival in patients with gastric carcinomas that had spread to the peritoneal cavity. Considerable experimental evidence shows that not only is heat alone tumoricidal, but it also increases the activity of many different chemotherapeutic agents, several of which have activity in ovarian cancer. Over the last 25 years, many reports have surfaced on the use of such therapy in combination with debulking surgery in diseases such as malignant mesothelioma, appendiceal cancer, and colorectal cancer.
In 2003, findings from a randomized controlled trial on patients with peritoneal carcinomatosis from colorectal cancer was published. The trial demonstrated a significant prolongation of life in patients undergoing surgical debulking with hyperthermic chemotherapy in comparison with patients treated with standard palliative surgery and chemotherapy.
Ovarian cancer is a good theoretical target for surgical debulking combined with hyperthermic chemotherapy because it combines 3 separately useful modalities: surgical debulking, intraperitoneal chemotherapy, and heat. Several reports on ovarian cancer have documented promising results. However, no randomized, phase III studies have been performed in ovarian cancer cases and more research is warranted.
LOW MALIGNANT POTENTIAL CARCINOMA OF OVARIES :
Tumors of low malignant potential (LMP) are a distinct variety of EOC that behave in a much less aggressive fashion. These tumors cause great anxiety to patients, and the concept of LMP sometimes is difficult to explain. They comprise approximately 20% of malignant ovarian tumors. The mean age of diagnosis is younger than for invasive EOC, at approximately 48 years, and no large peak of incidence is observed.
These tumors are staged identically to EOC, using the FIGO system (see Staging), but unlike with EOC, the majority of tumors are stage I at presentation (IA, 51%; IB, 6%; IC, 18%; II, 8%; III, 15%; IV, 2%).
Surgery
Surgery begins with a full assessment of the pelvis and abdominal contents as for EOC and is carried out as described in Surgery for ovarian cancer.
Patients who are premenopausal and desire preservation of fertility can be treated with unilateral oophorectomy alone. In selected cases, ovarian cystectomy may be enough for stage IA serous tumors of LMP. Hysterectomy and removal of the other ovary can be performed if the patient no longer desires to remain fertile.
When complete surgical staging is performed in patients with LMP tumors, some patients with disease originally thought to be confined to the ovaries are found to have disease that has spread. However, the value of this has not been defined in early-stage disease.
In advanced disease, patients should undergo cytoreductive surgery, as for invasive EOC, to remove all visible tumor.
Adjuvant therapy
Chemotherapy and radiation therapy are not indicated for LMP tumors following complete resection for stage I and II disease. In cases where disease has spread from the ovaries at the time of surgery, and particularly where implants are found to be invasive, chemotherapy can be considered, but data establishing its efficacy are absent.
Follow-up after initial treatment
Regular follow-up care includes clinical examination and serum CA125 estimation, especially if the original tumor was serous and/or the CA125 was elevated. If a patient retains 1 or both ovaries, annual ultrasound examination may be indicated.
Treatment of recurrence
LMP tumors do not recur in the majority of patients. When they do, initial debulking surgery usually is indicated. Chemotherapy has no proven role.
MALIGNANT GERM CELL TUMORS :
Treatment
Surgery is the initial treatment for GCT, and, in young patients, this can be conservative, with preservation of the uterus and contralateral ovary, because chemotherapy is very effective. Second-look surgery generally is not indicated following initial treatment.
Dysgerminoma
This is the most common malignant GCT and represents 3-5% of all ovarian malignancies. Ninety percent occur in people younger than 30 years, and 75% occur in the second and third decades, with a median age of 22 years.
Dysgerminomas are bilateral in 10-35% of cases. Five percent occur in phenotypic females with abnormal gonads. They may have a 46XY karyotype with pure gonadal dysgenesis or androgen insensitivity syndrome, or, they may have a 45X, 46XY karyotype with mixed gonadal dysgenesis. Dysgerminomas may be large and usually are solid with a smooth external surface and a fleshy pink-tan color inside. The majority are confined to the ovary at diagnosis, but approximately 25% of otherwise stage I dysgerminomas have lymph node metastasis.
Surgery
Surgery is the initial management of a tumor that possibly is a dysgerminoma. Assessment of the abdominal and pelvic contents is made as for EOC (see Surgery for ovarian cancer).
Where no macroscopic disease exists outside the ovary, unilateral oophorectomy should be performed, excising the tumor intact and without rupture. Staging procedures include washings, omental biopsy, and sampling of paraaortic and pelvic lymph nodes. The opposite ovary should be carefully inspected, and a biopsy should be performed if necessary. However, in young patients, the uterus and opposite ovary should be left in situ.
If disease is present outside the ovary, make an attempt to remove all visible tumor while maintaining fertility for the patient. In a young patient, debulking disease from the contralateral ovary, without performing oophorectomy, should be safe.
Many patients present having already undergone a unilateral oophorectomy that uncovered the dysgerminoma. Consideration should be given to staging these patients laparoscopically if possible, if a negative result will spare the patient from receiving chemotherapy. If chemotherapy will be given regardless, initial staging surgery is not warranted.
Postsurgical treatment
Adequately staged patients with stage IA disease can be monitored without further therapy, whatever the size of the primary tumor. However, 15-20% of tumors recur, mostly in the first 2 years after treatment.
All patients at a stage greater than IA require combination chemotherapy, with the most accepted regimen in the United States being bleomycin, etoposide, and cisplatin (BEP). In patients with advanced disease, the combination of vincristine, actinomycin D, and cyclophosphamide (VAC) has been used following BEP as consolidation therapy. Dysgerminoma is very radiosensitive, but radiation rarely is used, especially in young patients, because of its effect on future fertility.
Prognosis
Stage IA disease is associated with a 5-year survival rate of higher than 95%, but even with advanced disease, the 5-year survival rate is good following surgery and chemotherapy.
Immature teratoma
This is the second most common GCT. It occurs mostly in people aged 10-20 years but may occur postmenopausally. Tumor markers are not elevated unless the tumor contains elements of other GCTs. The cardinal histologic feature is immature elements, mostly of neural tissue. The tumor spreads most commonly to peritoneal surfaces.
In the patient who is premenopausal, treatment should include unilateral oophorectomy and surgical staging (see Surgery for ovarian cancer). The contralateral ovary rarely is involved, and biopsy of the other ovary is not necessary. If a patient no longer desires to remain fertile or is postmenopausal, hysterectomy with removal of both ovaries is sensible.
Patients with stage IA grade 1 disease do not need adjuvant therapy postoperatively. The standard of care for high-grade stage I disease postoperatively has been chemotherapy with BEP. Evidence is accumulating that such patients can be treated more conservatively following surgery, provided good follow-up care is maintained. Patients with stage IA grade 2 disease can be monitored only.
The conservative management of stage IA grade 3 is more controversial.
Follow-up
No tumor markers exist for immature teratoma, and follow-up care should include clinical examination together with ultrasound at regular intervals.
Second-look laparoscopy or laparotomy may be considered, particularly in patients who had macroscopic residual disease at the end of surgery. Immature teratoma may be associated with the development of benign teratomatous masses and peritoneal glial implants that may remain for a long time. All masses at second surgery should be removed to be sure that no immature (malignant) elements are present. If such elements are present, the patient should have further chemotherapy with VAC.
The prognosis depends on the extent of the tumor and the grade. Stage I grades 1 and 2 have almost 100% survival. Patients with incompletely resected tumor have a 50% chance of survival.
Other germ cell tumors
Endodermal sinus tumor occurs at a mean age of 18 years, and one third occur before puberty. The tumors secrete alpha-fetoprotein. Following standard surgery, all patients should be treated with BEP. Other chemotherapy regimens may be necessary. Embryonal carcinoma and choriocarcinoma are extremely rare.
SEX-CORD STROMAL TUMORS :
These include tumors arising from the sex cords; granulosa cells; Sertoli cells; and the specialized stroma of the genital ridge, theca, and Leydig cells. They comprise fewer than 5% of all ovarian tumors.
Although granulosa cell tumors are malignant and Sertoli-Leydig cell tumors less so, they behave in a much less malignant fashion than EOC. Benign tumors in the group include thecoma and fibroma. Granulosa cell tumors and pure Sertoli cell tumors commonly secrete estrogen, while Leydig cell tumors and combined Sertoli-Leydig tumors often secrete androgens.
Granulosa cell tumor
This is the most common malignant sex-cord stromal tumor. It can occur at any age, with a mean age of the early fifties. Because of the secretion of estrogen, the presenting features depend on the patient's age. Prepubertal girls typically present with precocious sexual development, women of reproductive age have heavy or irregular periods, and postmenopausal women may have postmenopausal bleeding. At all ages, the tumor may present with acute abdominal pain due to rupture or hemorrhage.
The tumors vary in size and may be solid or partially cystic. The cut surface may be grey-white or yellow, depending on lipid content. Necrosis and hemorrhage often are present, with cystic compartments filled with fluid or clotted blood. The microscopic features are granulosa cells in a wide variety of patterns, and characteristic Call-Exner bodies may be present.
Juvenile granulosa cell tumor is a variant of granulosa cell tumor that is rarely malignant. It most often presents in young girls with isosexual precocious puberty. The tumor usually is unilateral and confined to the ovary and can be managed with surgery alone.
Ultrasound is the most useful preoperative investigation in a patient found to have a pelvic mass. Ultrasound studies may show the presence of ascites and may help define the morphology of the pelvic tumor. In addition, it can determine whether large masses are present in other parts of the abdomen, including the liver, and it can help evaluate the kidneys for evidence of ureteric obstruction. CT scan can detect enlarged pelvic masses and other evidence of intra-abdominal metastasis and disease within the chest.
Ninety percent of granulosa cell tumors are stage I at the time of diagnosis. Surgery is performed as described in Surgery for ovarian cancer. Because bilateral involvement of the ovaries is observed in only 2% of cases, the opposite ovary can be conserved in younger women. If the uterus is to be left behind, endometrium biopsy should be performed because of the synchronous occurrence of endometrial adenocarcinoma associated with estrogen secretion.
No adjuvant therapy is available for early-stage disease that is completely excised. Patients with recurrent disease or residual disease after surgery should be treated with BEP. No evidence demonstrates that treatment with progesterone is beneficial. Radiation has a definite role, especially for palliation in recurrent disease in the pelvis.
Granulosa cell tumors typically recur a long time after primary treatment. Factors reported to be associated with outcome include stage at presentation, age older than 40 years, tumor size, tumor rupture, histologic pattern, high mitotic count, and nuclear atypicality.
The 5-year survival rate for stage I is 86-96%, and for all other stages, it is 26-46%.
Inhibin
Inhibin is a glycoprotein produced by granulosa cells that can be used as a tumor marker. It is undetectable in the serum of postmenopausal women without ovaries and returns to normal 1 week after removal of a granulosa cell tumor. The best discrimination is made with assays detecting the alpha subunit of inhibin. Inhibin also may be elevated in postmenopausal women with mucinous carcinomas.
Recurrence
Granulosa cell tumors can recur a long time after initial treatment, with an average time interval of 5-10 years. The longest reported interval is 37 years, and lifelong follow-up care, therefore, is necessary. Recurrences can be treated with surgery and/or chemotherapy and radiation. The combination of BEP is the most active chemotherapy regimen.
Sertoli-Leydig cell tumors
These tumors are rare. They are a form of low-grade malignancy that typically produces androgens and rarely estrogens.
The surgery is unilateral oophorectomy, and, if patients' childbearing has been completed, total hysterectomy and bilateral oophorectomy is performed. The overall 5-year survival rate is 70-90%.
Other rare tumors
Small-cell carcinoma: This is a rare type of carcinoma that occurs in females aged 2-46 years. It often is associated with hypercalcemia. Treatment is with surgery and chemotherapy, but the prognosis is poor.
Sarcoma: The most common form of this rare tumor in the ovary is the mixed mesodermal sarcoma or carcinosarcoma. Patients should be treated with surgery as described in Surgery for ovarian cancer, followed by platinum-containing chemotherapy. Prognosis is poor.
Metastatic: Metastatic tumors of the ovary arise from direct extension and spread within the bloodstream or lymphatic system or within the peritoneal cavity. Sites of origin include the endometrium; cervix; and nongynecologic sites such as breast, colon, and stomach. The classic Krukenberg tumor refers to bilateral enlargement of the ovaries from metastases from a signet-ring carcinoma of the stomach. Treatment of metastatic disease relates to the primary site.
Effects of chemotherapy on ovarian function, fertility, and the fetus
Many women experience symptoms of ovarian dysfunction, ie, amenorrhea and hot flashes, during treatment with chemotherapy. The younger the woman at the time of treatment, the more likely the return of normal ovarian function and the more tolerant the ovaries are to higher doses of alkylating agents.
An increase in congenital anomalies in babies conceived following treatment with chemotherapy does not seem to occur. The necessity for chemotherapy during a preexisting pregnancy fortunately is rare, but antifolate drugs such as methotrexate probably should be avoided during the first trimester.