Ovarian cancer overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Huda A. Karman, M.D. Alberto Castro Molina, M.D.
Overview
Ovarian cancer is a malignant tumor arising from the ovary, fallopian tube, or peritoneum. In contemporary classification, epithelial ovarian carcinoma is considered together with fallopian tube and primary peritoneal carcinomas as a single disease entity because these tumors share similar molecular features, patterns of spread, and clinical behavior.[1][2] Epithelial malignancies account for roughly 90% of ovarian cancers, of which 70% to 80% are high-grade serous carcinomas; other major histologic types include endometrioid, clear cell, mucinous, and low-grade serous carcinomas, as well as borderline tumors.[1][3]
Globally, ovarian cancer is an important cause of cancer morbidity and mortality in women. GLOBOCAN 2022 estimates more than 320,000 new cases and over 200,000 deaths worldwide, corresponding to age-standardized incidence and mortality rates of approximately 6–7 and 4 per 100,000 women-years, respectively.[4][5] In the United States, ovarian cancer remains a leading cause of gynecologic cancer death, but both incidence and mortality have declined by roughly 3% per year since the mid-2000s, a trend attributed largely to increased use of oral contraceptives and uptake of risk-reducing salpingo-oophorectomy among women with high-risk genetic variants.[6][1]
The understanding of epithelial ovarian cancer pathogenesis has shifted from the traditional concept of an origin in the ovarian surface epithelium to a model in which many high-grade serous carcinomas arise from serous tubal intraepithelial carcinoma (STIC) in the fimbrial end of the fallopian tube, with subsequent implantation on the ovary and peritoneal surfaces.[7][2] Endometrioid and clear cell carcinomas are strongly associated with endometriosis, whereas some mucinous tumors may originate in the ovary or represent metastases from gastrointestinal primaries.[8] Approximately 50% of high-grade serous ovarian cancers are characterized by homologous recombination deficiency (HRD), including germline or somatic variants in BRCA1, BRCA2, and other DNA-repair genes, which has important implications for platinum sensitivity and benefit from poly (ADP-ribose) polymerase (PARP) inhibitors.[9][10]
Hereditary factors account for roughly one quarter of epithelial ovarian cancers, most commonly germline variants in BRCA1 and BRCA2, although pathogenic variants in other homologous recombination and mismatch repair genes also contribute.[11][12] Current guidelines recommend that all patients with epithelial ovarian, fallopian tube, or peritoneal carcinoma undergo germline testing (and, when indicated, somatic tumor testing) for hereditary cancer susceptibility genes, as this information influences treatment decisions, surveillance strategies, and cascade testing of relatives.[13]
Beyond genetic predisposition, risk factors for ovarian cancer include reproductive and hormonal factors such as endometriosis, infertility, and use of postmenopausal estrogen therapy without adequate progestin, as well as lifestyle and environmental exposures.[8][14] Protective factors include multiparity, breastfeeding, and use of combined oral contraceptives, which are associated with substantial relative risk reductions in both the general population and among BRCA1/2 carriers.[15][16] Risk-reducing salpingo-oophorectomy significantly decreases ovarian cancer risk and overall mortality in BRCA1/2 mutation carriers and is a cornerstone of preventive strategies in this population.[17][18][19]
Early detection of ovarian cancer is challenging because there are no effective screening tests for average-risk women. Large randomized trials of screening with CA-125 and transvaginal ultrasonography have not demonstrated a clear mortality benefit and have led to false-positive results and unnecessary surgery; therefore, routine screening is not recommended for asymptomatic women at average risk.[20][1] Instead, clinical attention is focused on timely evaluation of symptoms and risk assessment in women with hereditary predisposition.[21]
Most patients lack specific symptoms until disease is advanced, and approximately 70% to 80% of epithelial ovarian cancers are diagnosed at stage III or IV.[1][22] When present, symptoms are typically nonspecific and may include abdominal bloating or distension, early satiety, pelvic or abdominal pain, urinary urgency or frequency, changes in bowel habits, and unintentional weight loss.[22][21] Definitive diagnosis and staging require surgical exploration to determine the origin and extent of disease and to obtain tissue for histopathologic and molecular evaluation.[3][23]
Early-stage disease (confined to the ovaries or fallopian tubes) is primarily managed with comprehensive surgical staging and, in selected stage I cases, adjuvant platinum-based chemotherapy; 5-year overall survival for appropriately treated early-stage disease is approximately 70% to 95%.[23][1] Advanced-stage disease typically requires cytoreductive surgery combined with platinum-taxane chemotherapy, delivered either as primary debulking surgery followed by adjuvant chemotherapy or as neoadjuvant chemotherapy followed by interval debulking in patients with high tumor burden or poor performance status.[3][24] For patients with advanced-stage high-grade serous carcinoma who respond to initial platinum-based chemotherapy, maintenance therapy with PARP inhibitors, with or without the anti-angiogenic agent bevacizumab, improves progression-free survival, particularly in those with BRCA1/2 variants or HRD-positive tumors.[10][1] Nonetheless, most patients with advanced epithelial ovarian cancer eventually relapse, and 5-year overall survival in this group remains approximately 10% to 40% despite modern systemic therapy.[3][23]
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 Caruso G, Weroha SJ, Cliby W (2025). "Ovarian cancer: a review". JAMA.
- ↑ 2.0 2.1 WHO Classification of Tumours Editorial Board (2020). "Female genital tumours". World Health Organization Classification of Tumours. IARC Press. 5th ed.
- ↑ 3.0 3.1 3.2 3.3 González-Martín A, Harter P, Leary A, et al; ESMO Guidelines Committee (2023). "Newly diagnosed and relapsed epithelial ovarian cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up". Ann Oncol. 34 (10): 833–848. doi:10.1016/j.annonc.2023.07.011.
- ↑ Bray F, Laversanne M, Sung H; et al. (2024). "Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries". CA Cancer J Clin. 74 (3): 229–263. doi:10.3322/caac.21834.
- ↑ Cabasag CJ, Fagan PJ, Ferlay J; et al. (2022). "Ovarian cancer today and tomorrow: a global assessment by world region and Human Development Index using GLOBOCAN 2020". Int J Cancer. 151 (9): 1535–1541. doi:10.1002/ijc.34002.
- ↑ Siegel RL, Kratzer TB, Giaquinto AN, Sung H, Jemal A (2025). "Cancer statistics, 2025". CA Cancer J Clin. 75 (1): 10–45. doi:10.3322/caac.21871.
- ↑ Karnezis AN, Cho KR, Gilks CB, Pearce CL, Huntsman DG (2017). "The disparate origins of ovarian cancers: pathogenesis and prevention strategies". Nat Rev Cancer. 17 (1): 65–74. doi:10.1038/nrc.2016.113.
- ↑ 8.0 8.1 Barnard ME, Farland LV, Yan B; et al. (2024). "Endometriosis typology and ovarian cancer risk". JAMA. 332 (6): 482–489. doi:10.1001/jama.2024.9210.
- ↑ Konstantinopoulos PA, Ceccaldi R, Shapiro GI, D’Andrea AD (2015). "Homologous recombination deficiency: exploiting the fundamental vulnerability of ovarian cancer". Cancer Discov. 5 (11): 1137–1154. doi:10.1158/2159-8290.CD-15-0714.
- ↑ 10.0 10.1 Caruso G, Tomao F, Parma G; et al. (2023). "Poly (ADP-ribose) polymerase inhibitors in ovarian cancer: lessons learned and future directions". Int J Gynecol Cancer. 33 (4): 431–443. doi:10.1136/ijgc-2022-004149.
- ↑ Kotsopoulos J, Gronwald J, Karlan B, et al; Hereditary Ovarian Cancer Clinical Study Group (2018). "Age-specific ovarian cancer risks among women with a BRCA1 or BRCA2 mutation". Gynecol Oncol. 150 (1): 85–91. doi:10.1016/j.ygyno.2018.05.011.
- ↑ Bonadona V, Bonaïti B, Olschwang S, et al; French Cancer Genetics Network (2011). "Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome". JAMA. 305 (22): 2304–2310. doi:10.1001/jama.2011.743.
- ↑ Konstantinopoulos PA, Norquist B, Lacchetti C; et al. (2020). "Germline and somatic tumor testing in epithelial ovarian cancer: ASCO guideline". J Clin Oncol. 38 (11): 1222–1245. doi:10.1200/JCO.19.02960.
- ↑ Tanha K, Mottaghi A, Nojomi M; et al. (2021). "Investigation on factors associated with ovarian cancer: an umbrella review of systematic review and meta-analyses". J Ovarian Res. 14 (1): 153. doi:10.1186/s13048-021-00911-z.
- ↑ van Bommel MH, IntHout J, Veldmate G; et al. (2023). "Contraceptives and cancer risks in BRCA1/2 pathogenic variant carriers: a systematic review and meta-analysis". Hum Reprod Update. 29 (2): 197–217. doi:10.1093/humupd/dmac038.
- ↑ Iodice S, Barile M, Rotmensz N; et al. (2010). "Oral contraceptive use and breast or ovarian cancer risk in BRCA1/2 carriers: a meta-analysis". Eur J Cancer. 46 (12): 2275–2284. doi:10.1016/j.ejca.2010.04.018.
- ↑ Marchetti C, De Felice F, Palaia I; et al. (2014). "Risk-reducing salpingo-oophorectomy: a meta-analysis on impact on ovarian cancer risk and all-cause mortality in BRCA1 and BRCA2 mutation carriers". BMC Womens Health. 14: 150. doi:10.1186/s12905-014-0150-5.
- ↑ Walker JL, Powell CB, Chen LM; et al. (2015). "Society of Gynecologic Oncology recommendations for the prevention of ovarian cancer". Cancer. 121 (13): 2108–2120. doi:10.1002/cncr.29321.
- ↑ American College of Obstetricians and Gynecologists (2019). "ACOG Committee Opinion No. 774: opportunistic salpingectomy as a strategy for epithelial ovarian cancer prevention". Obstet Gynecol. 133 (4): e279–e284. doi:10.1097/AOG.0000000000003164.
- ↑ US Preventive Services Task Force (2018). "Screening for ovarian cancer: US Preventive Services Task Force recommendation statement". JAMA. 319 (6): 588–594. doi:10.1001/jama.2017.21926.
- ↑ 21.0 21.1 Huepenbecker SP, Sun CC, Fu S; et al. (2021). "Factors impacting the time to ovarian cancer diagnosis based on classic symptom presentation in the United States". Cancer. 127 (22): 4151–4160. doi:10.1002/cncr.33778.
- ↑ 22.0 22.1 Goff BA, Mandel LS, Melancon CH, Muntz HG (2004). "Frequency of symptoms of ovarian cancer in women presenting to primary care clinics". JAMA. 291 (22): 2705–2712. doi:10.1001/jama.291.22.2705.
- ↑ 23.0 23.1 23.2 Berek JS, Renz M, Kehoe S, Kumar L, Friedlander M (2021). "Cancer of the ovary, fallopian tube, and peritoneum: 2021 update". Int J Gynaecol Obstet. 155 (suppl 1): 61–85. doi:10.1002/ijgo.13878.
- ↑ Fleming ND, Nick AM, Coleman RL; et al. (2018). "Laparoscopic surgical algorithm to triage the timing of tumor reductive surgery in advanced ovarian cancer". Obstet Gynecol. 132 (3): 545–554. doi:10.1097/AOG.0000000000002796.