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Ovarian, Fallopian Tube, and Peritoneal Cancer

By

Pedro T. Ramirez

, MD, The University of Texas MD Anderson Cancer Center;


Gloria Salvo

, MD, MD Anderson Cancer Center

Last full review/revision Jul 2022| Content last modified Sep 2022
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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 with fallopian tube and peritoneal cancers because of shared clinical features. Symptoms are usually absent or nonspecific. Evaluation usually includes ultrasonography, CT or MRI, and measurement of tumor markers (eg, cancer antigen 125). Diagnosis is by histologic analysis. Staging is surgical. Treatment requires hysterectomy, bilateral salpingo-oophorectomy, excision of as much involved tissue as possible (cytoreduction), and usually chemotherapy.

In the US, ovarian cancer is the 2nd most common gynecologic cancer (affecting about 1/70 women). It is the 5th leading cause of cancer-related deaths in women and, in the US, will cause an estimated 19,880 new cases and 12,810 deaths in 2022 (1 General 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 ). Incidence is higher in developed countries.

General reference

Etiology of Ovarian Cancer

Ovarian cancer affects mainly perimenopausal and postmenopausal women.

Risk of ovarian cancer is increased by

  • A history of ovarian cancer in a 1st-degree relative

  • Nulliparity

  • Delayed childbearing

  • Early menarche

  • Delayed menopause

  • A personal or family history of endometrial, breast, or colon cancer

Risk is decreased by

  • Oral contraceptive use

Germline alterations in breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) genes are identified in 14 to 18% of patients with high-grade serous ovarian cancer; 3% have somatic BRCA mutations (BRCAm) or inactivation due to methylation (1 Etiology 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 ). Deficiency of homologous recombination (which is involved in the repair of DNA damage and replication) is detected in about half of patients with high-grade serous ovarian cancer (2 Etiology 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 ).

Mutations in the autosomal dominant BRCA gene are associated with a 50 to 85% lifetime risk of developing breast cancer. Women with BRCA1 mutations have a 20 to 40% lifetime risk of developing ovarian cancer; risk among women with BRCA2 mutations is 11 to 20%. Incidence of these mutations is higher in people with Ashkenazi Jewish ancestry than in the general population. Mutations in several other genes, including TP53, PTEN, STK11/LKB1, CDH1, CHEK2, ATM, MLH1, and MSH2, have been associated with hereditary breast and/or ovarian cancer.

Etiology references

  • 1. Cancer Genome Atlas Research Network: Integrated genomic analyses of ovarian carcinoma. Nature 474 (7353):609–615, 2011. doi: 10.1038/nature10166

  • 2. Li X, Heyer WD: Homologous recombination in DNA repair and DNA damage tolerance. Cell Res 18 (1):99–113, 2008. doi: 10.1038/cr.2008.1

Pathology of Ovarian Cancer

Ovarian cancers are histologically diverse (see table Types of Ovarian Cancer Types of Ovarian Cancers Types of Ovarian Cancers ).

Most (90%) ovarian cancers develop from epithelial cells; the rest (germ cell tumors, sex-cord stromal tumors) develop from other ovarian cell types.

Epithelial ovarian carcinoma may be divided into five subtypes:

  • High-grade serous

  • Low-grade serous

  • Endometrioid

  • Clear cell

  • Mucinous

High-grade serous ovarian carcinoma is the most common subtype (> 70%) of epithelial carcinomas and usually manifest at an advanced stage. High-grade serous epithelial ovarian, fallopian tube, and peritoneal carcinomas share clinical behavior and treatment. Most high-grade serous carcinomas that manifest as an ovarian mass or as peritoneal disease originate in the fallopian tubes, based on studies of women with BRCA mutations after risk-reducing bilateral salpingo-oophorectomy.

Mucinous ovarian cancers are more likely to manifest at stage I than other histologies and account for nearly 27% of patients with stage I epithelial ovarian cancer.

Table

Ovarian cancer spreads by

  • Direct extension

  • Exfoliation of cells into the peritoneal cavity (peritoneal seeding)

  • Lymphatic dissemination to the pelvis and around the aorta

  • Less often, hematogenously to the liver or lungs

Symptoms and Signs of Ovarian Cancer

Ovarian cancer may be asymptomatic. When symptoms are present, they are nonspecific (eg, dyspepsia, bloating, early satiety, change in bowel habits, urinary frequency). Later, pelvic pain, anemia, cachexia, and abdominal swelling due to ovarian enlargement or ascites usually occur.

An adnexal mass, often solid, irregular, and fixed, may be discovered incidentally. Pelvic and rectovaginal examinations typically detect diffuse nodularity. A few women present with severe abdominal pain secondary to torsion of the ovarian mass Adnexal Torsion Adnexal torsion is twisting of the ovary and sometimes the fallopian tube, interrupting the arterial supply and causing ischemia. Adnexal torsion is uncommon, occurring most often during reproductive... read more .

Germ cell or stromal tumors that produce hormones may have functional effects (eg, hyperthyroidism, feminization, virilization).

Diagnosis of Ovarian Cancer

  • Ultrasonography (for suspected early cancers) or CT or MRI (for suspected advanced cancers)

  • Tumor markers (eg, cancer antigen [CA] 125)

Ovarian cancer is suspected in women with the following:

  • Unexplained adnexal masses

  • Unexplained abdominal bloating

  • Changes in bowel habits

  • Unintended weight loss

  • Unexplained abdominal pain

A pelvic mass plus ascites usually indicates ovarian cancer but sometimes indicates Meigs syndrome (a benign fibroma with ascites and right hydrothorax).

Imaging

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

  • A solid component

  • Surface excrescences

  • Size > 6 cm

  • Irregular shape

  • Low vascular resistance detected by transvaginal Doppler flow studies

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

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.

Histology

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.

Staging

Table

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).

Prognosis for Ovarian Cancer

In women with ovarian cancer, the 5-year survival rates with treatment are

  • Stage I: 85 to 95%

  • Stage II: 70 to 78%

  • Stage III: 40 to 60%

  • Stage IV: 15 to 20%

Prognosis is worse when tumor grade is higher or when surgery cannot remove all visibly involved tissue; in such cases, prognosis is best when the involved tissue can be reduced to < 1 cm in diameter or ideally to a microscopic residual amount (cytoreductive surgery).

With stage III or IV ovarian cancer, recurrence rate is about 70%.

Treatment of Ovarian Cancer

  • Usually hysterectomy and bilateral salpingo-oophorectomy

  • Cytoreductive surgery

  • Usually postoperative chemotherapy, often with carboplatin and paclitaxel

(See also National Comprehensive Cancer Network (NCCN): NCCN Clinical Practice Guidelines in Oncology: Ovarian Cancer.)

Treatment of ovarian, fallopian tube, and peritoneal cancer is based on stage, grade, and histology:

  • For stage IA or IB ovarian tumors (confined to the ovary) and/or grade 1 endometrioid tumors, prognosis is excellent (survival 90%) after surgery alone.

  • For patients with stage IC, II, grade 3, or clear cell histology, adjuvant chemotherapy treatment (eg, with carboplatin and paclitaxel) is recommended.

  • For stage III or IV, primary surgical cytoreduction followed by systemic chemotherapy is the standard treatment. Neoadjuvant chemotherapy followed by cytoreductive surgery is the preferred option for patients who are not candidates for surgical resection (due to location and volume of the cancer or because of comorbidities).

Hysterectomy and bilateral salpingo-oophorectomy are usually indicated, but fertility preservation by conserving the unaffected ovary and uterus may be considered for stage I nonepithelial or low-grade unilateral epithelial ovarian cancers in young patients.

Potential indications for neoadjuvant chemotherapy include one or more of the following:

  • Multiple liver metastases

  • Lymphadenopathy in the porta hepatis

  • Suprarenal para-aortic lymph nodes

  • Diffuse mesenteric disease

  • Evidence of pleural or parenchymal lung disease

In a large randomized trial, neoadjuvant chemotherapy followed by surgery had less perioperative morbidity than primary surgery followed by chemotherapy and similar long-term survival rates (1 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 ).

Surgical staging and cytoreduction

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

  • Supracolic omentectomy, sometimes with rectosigmoid resection (usually with primary reanastomosis)

  • Radical peritoneal stripping

  • Resection of diaphragmatic peritoneum or splenectomy

Cytoreduction may be

  • Complete: Cytoreduction to no grossly visible disease

  • Optimal: Cytoreduction with residual disease that is ≤ 1 cm in maximum tumor diameter, as defined by the Gynecologic Oncology Group

  • Suboptimal: Cytoreduction with any visible tumor nodules > 1 cm remaining

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:

  • Poor performance status

  • Age > 60 years

  • American Society of Anesthesiologists physical status 3 or 4

  • Medical comorbidities

  • Poor nutritional status

  • Extra-abdominal disease

  • Large tumor bulk

  • Involvement of large bowel

  • Metastases to retroperitoneal lymph nodes above the renal vessels and > 1 cm in largest dimension

  • Parenchymal liver involvement

  • A preoperative CA 125 > 500 U/mL

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

  • Omental cake

  • Extensive peritoneal or diaphragmatic carcinomatosis

  • Mesenteric retraction

  • Bowel and stomach infiltration

  • Spleen and/or liver superficial metastasis

Systemic or intraperitoneal chemotherapy

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 Postoperative Treatment of Ovarian Cancer by Stage and Type ):

  • Staging and cytoreduction, followed by 6 cycles of IV chemotherapy

  • 3 cycles of neoadjuvant chemotherapy, followed by surgery and 3 more chemotherapy cycles

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.

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.

Table

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.

Recurrent disease

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]):

  • A PFI of ≥ 6 months suggests platinum-sensitive disease.

  • A PFI of < 6 months suggests platinum-resistant disease.

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.

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 ]).

Treatment references

  • 1. Vergote I, Tropé CG, Amant F, et al; Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med 2010;363 (10):943–953, 2010. doi:10.1056/ NEJMoa0908806

  • 2. Petrillo M, Vizzielli G, Fanfani F, et al: Definition of a dynamic laparoscopic model for the prediction of incomplete cytoreduction in advanced epithelial ovarian cancer: Proof of a concept. Gynecol Oncol. 139 (1):5–9, 2015. doi:10.1016/j.ygyno.2015.07.095 Epub 2015 Jul 18.

  • 3. Coleman RL, Fleming GF, Brady MF, et al: Veliparib with first-line chemotherapy and as maintenance therapy in ovarian cancer. N Engl J Med 381 (25):2403–2415, 2019. doi: 10.1056/NEJMoa1909707 Epub 2019 Sep 28.

  • 4. González-Martín A, Pothuri B, Vergote I, et al: Niraparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med 381 (25):2391–2402, 2019. doi: 10.1056/NEJMoa1910962 Epub 2019 Sep 28.

  • 5. Ray-Coquard I, Pautier P, Pignata S, et al: Olaparib plus bevacizumab as first-line maintenance in ovarian cancer. N Engl J Med 381 (25):2416–2428, 2019. doi: 10.1056/NEJMoa1911361

  • 6. Moore K, Colombo N, Scambia G, et al: Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med 379 (26):2495–2505, 2018. doi: 10.1056/NEJMoa1810858 Epub 2018 Oct 21.

  • 7. Banerjee S, Moore KN, Colombo N, et al: Maintenance olaparib for patients with newly diagnosed advanced ovarian cancer and a BRCA mutation (SOLO1/GOG 3004): 5-year follow-up of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 22 (12):1721–1731, 2021. doi: 10.1016/S1470-2045(21)00531-3 Epub 2021 Oct 26

  • 8. Armstrong DK, Bundy B, Wenzel L, et al: Intraperitoneal cisplatin and paclitaxelin in ovarian cancer. N Engl J Med 354:34–43, 2006. doi: 10.1056/NEJMoa052985

  • 9. Wright AA, Cronin A, Milne DE, et al: Use and effectiveness of intraperitoneal chemotherapy for treatment of ovarian cancer. J Clin Oncol 33:2841–2847, 2015. doi: 10.1200/JCO.2015.61.4776

  • 10. Zsiros E, Lynam S, Attwood KM, et al: Efficacy and safety of pembrolizumab in combination with bevacizumab and oral metronomic cyclophosphamide in the treatment of recurrent ovarian cancer: A phase 2 nonrandomized clinical trial. JAMA Oncol 7 (1):78–85, 2021. doi: 10.1001/jamaoncol.2020.5945

  • 11. Ledermann J, Harter P, Gourley C, et al: Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med 366 (15):1382–1392, 2012. doi: 10.1056/NEJMoa1105535 Epub 2012 Mar 27.

  • 12. Pujade-Lauraine E, Ledermann JA, Selle F, et al: Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): A double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol 18 (9):1274–1284, 2017. doi: 10.1016/S1470-2045(17)30469-2 Epub 2017 Jul 25.

  • 13. Coleman RL, Spirtos NM, Enserro D, et al: Secondary surgical cytoreduction for recurrent ovarian cancer. N Engl J Med 381 (20):1929–1939, 2019. doi: 10.1056/NEJMoa1902626

  • 14. Harter P, Sehouli J, Vergote I, et al: Randomized trial of cytoreductive surgery for relapsed ovarian cancer. N Engl J Med 385 (23):2123–2131, 2021. doi: 10.1056/NEJMoa2103294

  • 15. Shi T, Zhu J, Feng Y, et al: Secondary cytoreduction followed by chemotherapy versus chemotherapy alone in platinum-sensitive relapsed ovarian cancer (SOC-1): A multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 22 (4):439–449, 2021. doi: 10.1016/S1470-2045(21)00006-1 Epub 2021 Mar 8.

Prevention of Ovarian Cancer

For patients with BRCA1 or BRCA2 gene mutations, risk of ovarian and, to a lesser degree, breast cancer is reduced if prophylactic bilateral salpingo-oophorectomy is done after childbearing is completed. Patients with BRCA1 or BRCA2 gene mutations should be referred to a gynecologic oncologist for counseling.

Screening

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:

  • Diagnosis of ovarian cancer in a 1st-degree relative before age 40

  • Diagnosis of breast and ovarian cancer in only one 1st-degree relative if one of the cancers was diagnosed before age 50

  • Two cases of ovarian cancer among 1st- and 2nd-degree relatives of the same lineage

  • Two cases of breast cancer and one case of ovarian cancer among 1st- or 2nd-degree relatives of the same lineage

  • One case of breast and one case of ovarian cancer among 1st- or 2nd-degree relatives of the same lineage if breast cancer was diagnosed before age 40 or if ovarian cancer was diagnosed before age 50

  • Two cases of breast cancer among 1st- or 2nd-degree relatives of the same lineage if both cases were diagnosed before age 50

  • Two cases of breast cancer among 1st- or 2nd-degree relatives of the same lineage if one was diagnosed before age 40

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.

Prevention reference

  • 1. Menon U, Gentry-Maharaj A, Burnell M, et al : Ovarian cancer population screening and mortality after long-term follow-up in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): A randomised controlled trial. Lancet 397 (10290):2182–2193, 2021. doi: 10.1016/S0140-6736(21)00731-5 Epub 2021 May 12.

Key Points

  • Ovarian cancer affects mostly postmenopausal and perimenopausal women; nulliparity, delayed childbearing, early menarche, delayed menopause, and certain genetic markers (BRCA mutations) increase risk.

  • Symptoms (eg, dyspepsia, bloating, early satiety, gas pains, backache) are nonspecific.

  • If cancer is suspected, do ultrasonography first (sometimes followed by CT or MRI) and measure tumor markers (eg, CA 125).

  • Typically, treatment is surgical staging (including hysterectomy, bilateral salpingo-oophorectomy, pelvic washings, and peritoneal biopsy) and cytoreductive surgery followed by chemotherapy (eg, carboplatin, paclitaxel, and bevacizumab).

  • Effective screening is not available for average-risk women; screen women at high risk (eg, BRCA mutation carriers) with ultrasonography and/or CA 125.

More Information

The following is an English-language resource that may be useful. Please note that THE MANUAL is not responsible for the content of this resource.

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