Ovarian, Fallopian Tube, and Peritoneal Cancer

If early cancer is suspected, ultrasonography is done first; the following findings suggest cancer:

If advanced cancer is suspected (eg, based on ascites, abdominal distention, or nodularity or fixation detected during physical examination), CT or MRI is usually done before surgery to determine extent of the cancer.

Tumor markers for nonepithelial tumors (eg, germ cell tumors, stromal tumors) include the beta subunit of human chorionic gonadotropin (beta-hCG), lactic dehydrogenase (LDH), alpha-fetoprotein, and inhibin; they are typically measured in young patients, who are at higher risk of these cancers. CA 125 is also measured. In perimenopausal and postmenopausal patients, only CA 125 is measured because most ovarian cancers in this age group are epithelial tumors. CA 125 is elevated in 80% of advanced epithelial ovarian cancers but may be within normal range in early stages. It may also be mildly elevated in endometriosis, pelvic inflammatory disease, pregnancy, fibroids, peritoneal inflammation, or nonovarian peritoneal cancer.

A mixed solid and cystic pelvic mass in postmenopausal women, especially if CA 125 is elevated, raises suspicion of ovarian cancer.

A biopsy is not routinely recommended unless a patient is not a surgical candidate, because it may cause leakage of cells and upstaging of the cancer. Rarely, when biopsy is done, samples are obtained by needle biopsy for masses or by needle aspiration for ascitic fluid.

For masses that appear benign on ultrasonography, ultrasonography is repeated after 6 weeks and then every 3 to 6 months until it confirms that no malignant features are developing. Such benign-appearing masses include benign cystic teratomas (dermoid cysts), follicular cysts, and endometriomas. Masses that are indeterminate may require exploratory surgery and unilateral salpingo-oophorectomy to confirm histology.

Ovarian cancer is staged surgically (see table FIGO Surgical Staging of Ovarian, Fallopian Tube, and Peritoneal Cancer FIGO Surgical Staging of Ovarian, Fallopian Tube, and Peritoneal Cancer ).

If early-stage cancer is suspected, staging may be done by laparoscopy or robotic-assisted laparoscopic surgery. Otherwise, an abdominal midline incision that allows adequate access to the upper abdomen is required.

The staging procedure includes hysterectomy and bilateral salpingo-oophorectomy. All peritoneal surfaces, hemidiaphragms, and abdominal and pelvic viscera are inspected and palpated. Washings from the pelvis, abdominal gutters, and diaphragmatic recesses are obtained, and multiple biopsies of the peritoneum in the central and lateral pelvis and in the abdomen are done. For early-stage cancer, the infracolic omentum is removed, and pelvic and para-aortic lymph nodes are sampled. Sentinel lymph node biopsy is not routinely done in patients with ovarian cancer.

Cancers are also graded histologically, and epithelial ovarian cancers are classified as low-grade (grade 1) or high-grade (grade 2 or 3).

The surgical procedure for ovarian, fallopian tube, and peritoneal cancers includes staging and cytoreduction (all visibly involved tissue is surgically removed if possible). Cytoreduction is associated with increased survival time; the volume of residual disease remaining after cytoreduction correlates inversely with survival time.

Cytoreductive surgery for ovarian cancer usually includes

Cytoreduction may be

Because cytoreduction is associated with increased survival, being able to predict when cytoreduction to no gross residual disease can be done is important, but doing so is difficult; there are no uniform criteria.

Optimal cytoreduction is less likely if patients have the following:

The Fagotti score, based on seven laparoscopic findings, can help predict the likelihood of optimal cytoreduction in patients with advanced ovarian cancer. This scoring system assigns a value of 0 or 2 depending on whether disease is present in certain locations. If patients score ≥ 10, optimal cytoreduction is very unlikely. If they score < 10, they are considered candidates for cytoreductive surgery (2 Treatment references Ovarian cancer is often fatal because it is usually advanced when diagnosed. The most common histology—high-grade serous epithelial ovarian cancer—is considered as a single clinical entity along... read more ).

Diagnostic laparoscopy before laparotomy can spare patients an unnecessary laparotomy, which would result in suboptimal cytoreduction. Laparoscopy enables clinicians to do a tissue biopsy, make a definitive diagnosis, and analyze the biopsy sample. Thus, patients who are not candidates for cytoreduction can begin chemotherapy treatment earlier. Laparoscopic findings indicating that optimal cytoreduction is unlikely include

In most patients with newly diagnosed ovarian cancer, the disease has spread widely throughout the peritoneum; thus, treatment involves one of the following (see table Postoperative Treatment of Ovarian Cancer by Stage and Type Postoperative Treatment of Ovarian Cancer by Stage and Type ):

Standard chemotherapy is 6 courses of paclitaxel and carboplatin. Other chemotherapy drugs may be used depending on patient characteristics.

For certain patients at higher risk of recurrence (eg, those who have pleural effusions or ascites and do not have a BRCA mutation), adding bevacizumab to chemotherapy and continuing it as maintenance therapy is an option.

PARP (polyadenosine diphosphate-ribose polymerase) enzymes are essential to the repair of single-strand breaks in DNA. Inhibition of PARP enzymes leads to persistent single-strand breaks, which cause double-strand breaks to accumulate during DNA replication and ultimately lead to tumor cell death.

In several clinical trials, a PARP inhibitor (PARPi) after chemotherapy improved progression-free survival in women who have serous or high-grade endometrioid ovarian cancer and who completed first-line chemotherapy, even if they did not have a BRCA1 or BRCA2 mutation (3 Treatment references Ovarian cancer is often fatal because it is usually advanced when diagnosed. The most common histology—high-grade serous epithelial ovarian cancer—is considered as a single clinical entity along... read more , 4 Treatment references Ovarian cancer is often fatal because it is usually advanced when diagnosed. The most common histology—high-grade serous epithelial ovarian cancer—is considered as a single clinical entity along... read more , 5 Treatment references Ovarian cancer is often fatal because it is usually advanced when diagnosed. The most common histology—high-grade serous epithelial ovarian cancer—is considered as a single clinical entity along... read more , 6 Treatment references Ovarian cancer is often fatal because it is usually advanced when diagnosed. The most common histology—high-grade serous epithelial ovarian cancer—is considered as a single clinical entity along... read more ).

Two placebo-controlled studies evaluated maintenance therapy with a PARPi in patients who responded to first-line platinum therapy. The SOLO1 study evaluated olaparib in patients with somatic and germline BRCAm (7 Treatment references Ovarian cancer is often fatal because it is usually advanced when diagnosed. The most common histology—high-grade serous epithelial ovarian cancer—is considered as a single clinical entity along... read more ), and the PRIMA/ENGOT-Ov26 study evaluated niraparib in patients with newly diagnosed advanced ovarian cancer (not restricted to BRCAm carriers [ 4 Treatment references Ovarian cancer is often fatal because it is usually advanced when diagnosed. The most common histology—high-grade serous epithelial ovarian cancer—is considered as a single clinical entity along... read more ]).

The VELIA trial included patients with previously untreated stage III or IV high-grade serous ovarian carcinoma. This three-arm trial compared standard chemotherapy alone versus standard chemotherapy plus veliparib versus standard chemotherapy plus veliparib followed by maintenance therapy with veliparib (3 Treatment references Ovarian cancer is often fatal because it is usually advanced when diagnosed. The most common histology—high-grade serous epithelial ovarian cancer—is considered as a single clinical entity along... read more ). Progression-free survival was longest with veliparib chemotherapy plus veliparib maintenance therapy.

Intraperitoneal chemotherapy using a catheter has been suggested as an alternative to IV chemotherapy. Intraperitoneal chemotherapy delivers the chemotherapy drugs directly to the peritoneal surface and thus eliminates residual microscopic disease. In advanced-stage ovarian cancer, combination treatment with IV and intraperitoneal chemotherapy appears to prolong overall survival after primary cytoreductive surgery (8 Treatment references Ovarian cancer is often fatal because it is usually advanced when diagnosed. The most common histology—high-grade serous epithelial ovarian cancer—is considered as a single clinical entity along... read more ). This approach is not without complications; catheter-related complications can limit its use (9 Treatment references Ovarian cancer is often fatal because it is usually advanced when diagnosed. The most common histology—high-grade serous epithelial ovarian cancer—is considered as a single clinical entity along... read more ).

Direct delivery of chemotherapy to the abdominal cavity under hyperthermic conditions (HIPEC) intraoperatively after cytoreduction has been used in patients with colon cancer and is under study for ovarian cancer. The potential benefit of HIPEC is increased sensitivity to chemotherapy by impairing DNA repair, it induces apoptosis and activates heat-shock proteins.

Even if chemotherapy results in a complete clinical response (ie, normal physical examination, normal serum CA 125, negative CT scan of the abdomen and pelvis), about 50% of patients with stage III or IV cancer have residual tumor. Of patients with persistent elevation of CA 125, 90 to 95% have residual tumor.

Recurrence of ovarian cancer can be detected serologically with tumor markers (eg, CA 125) and/or by radiologic signs of progression. Treatment of recurrence depends on the time between the completion of platinum-based treatment and detection of recurrence (platinum-free interval [PFI]):

The main treatment for patients with recurrent ovarian cancer has been systemic therapy. If cancer recurs or progresses after effective chemotherapy, chemotherapy is restarted. Useful drugs for ovarian cancer may include liposomal doxorubicin, docetaxel, paclitaxel, gemcitabine, bevacizumab, and a combination of cyclophosphamide plus bevacizumab or of gemcitabine plus cisplatin (10 Treatment references Ovarian cancer is often fatal because it is usually advanced when diagnosed. The most common histology—high-grade serous epithelial ovarian cancer—is considered as a single clinical entity along... read more ). Targeted therapy with biologic agents is under study.

If platinum-sensitive ovarian cancer recurs, a PARP inhibitor—olaparib, niraparib, or rucaparib—is used for maintenance therapy (11 Treatment references Ovarian cancer is often fatal because it is usually advanced when diagnosed. The most common histology—high-grade serous epithelial ovarian cancer—is considered as a single clinical entity along... read more , 12 Treatment references Ovarian cancer is often fatal because it is usually advanced when diagnosed. The most common histology—high-grade serous epithelial ovarian cancer—is considered as a single clinical entity along... read more ).

Randomized trials of secondary cytoreductive surgery in patients with platinum-sensitive ovarian cancer have had variable results. Several trials compared surgical cytoreduction followed by chemotherapy versus chemotherapy alone, In one trial (GOG-0213), overall survival time did not increase, but in other trials, there were significant increases in overall survival time (in DESKTOP III, 53.7 versus 46.0 months) or progression-free survival time (in SOC-1, 17.4 versus 11.9 months [ 13 Treatment references Ovarian cancer is often fatal because it is usually advanced when diagnosed. The most common histology—high-grade serous epithelial ovarian cancer—is considered as a single clinical entity along... read more , 14 Treatment references Ovarian cancer is often fatal because it is usually advanced when diagnosed. The most common histology—high-grade serous epithelial ovarian cancer—is considered as a single clinical entity along... read more , 15 Treatment references Ovarian cancer is often fatal because it is usually advanced when diagnosed. The most common histology—high-grade serous epithelial ovarian cancer—is considered as a single clinical entity along... read more ]).

There is no screening test for ovarian cancer. However, women with a known hereditary risk, such as those with BRCA mutations, should be followed closely.

Although data from large trials indicate that CA 125 has a high specificity (up to 99.9% in one study), sensitivity is only moderate (71% in one study), and positive predictive value is low; thus, CA 125 is not recommended as a screening test for asymptomatic, average-risk women.

Multimodal screening has been studied but has not been determined to be effective. A large randomized trial compared annual multimodal screening (CA 125, transvaginal ultrasonography [TVUS]) with no screening. At a median follow-up of 16.3 years, multimodal screening detected more women with early stage ovarian or fallopian tube cancer; however, there was no significant reduction in deaths due to ovarian or fallopian tube cancer (1 Prevention reference Ovarian cancer is often fatal because it is usually advanced when diagnosed. The most common histology—high-grade serous epithelial ovarian cancer—is considered as a single clinical entity along... read more ).

Most breast and ovarian cancers are sporadic; only about 6% of breast cancer and 15% of ovarian cancer cases are caused by BRCA mutations. However, evaluation for a hereditary cancer syndrome should be considered in all women diagnosed with ovarian, fallopian tube, or peritoneal cancer, and they should have a genetic risk evaluation. A germline or somatic BRCA1 or BRCA2 mutation may affect treatment and maintenance therapy. A detailed personal and family history of other cancers should be obtained to identify women who are more likely to have a hereditary cancer syndrome (eg, one involving BRCA1 or BRCA2 mutations, Lynch syndrome [hereditary nonpolyposis colorectal cancer]).

Women should be screened for abnormalities in the BRCA gene if their family history includes any of the following:

Also, if Ashkenazi Jewish women have one family member with breast cancer diagnosed before age 50 or with ovarian cancer, screening for abnormalities in the BRCA gene should be considered.