Não há medidas preventivas primárias comprovadas para o câncer de ovário, mas várias abordagens podem reduzir o risco de desenvolvimento.
O uso de contraceptivos orais por um período de 5 anos está associado a uma diminuição de 50% no risco de câncer de ovário, que diminui ainda mais com maior tempo de uso.[38]Beral V, Doll R, Hermon C, et al; Collaborative Group on Epidemiological Studies of Ovarian Cancer. Ovarian cancer and oral contraceptives: collaborative reanalysis of data from 45 epidemiological studies including 23,257 women with ovarian cancer and 87,303 controls. Lancet. 2008 Jan 26;371(9609):303-14.
http://www.ncbi.nlm.nih.gov/pubmed/18294997?tool=bestpractice.com
[39]Havrilesky LJ, Moorman PG, Lowery WJ, et al. Oral contraceptive pills as primary prevention for ovarian cancer: a systematic review and meta-analysis. Obstet Gynecol. 2013 Jul;122(1):139-47.
http://www.ncbi.nlm.nih.gov/pubmed/23743450?tool=bestpractice.com
[40]Michels KA, Pfeiffer RM, Brinton LA, et al. Modification of the associations between duration of oral contraceptive use and ovarian, endometrial, breast, and colorectal cancers. JAMA Oncol. 2018 Apr 1;4(4):516-21.
https://jamanetwork.com/journals/jamaoncology/fullarticle/2669779
http://www.ncbi.nlm.nih.gov/pubmed/29346467?tool=bestpractice.com
[41]Ness RB, Grisso JA, Klapper J, et al; SHARE Study Group. Risk of ovarian cancer in relation to estrogen and progestin dose and use characteristics of oral contraceptives. Am J Epidemiol. 2000 Aug 1;152(3):233-41.
https://academic.oup.com/aje/article/152/3/233/73169
http://www.ncbi.nlm.nih.gov/pubmed/10933270?tool=bestpractice.com
[42]Crane K. Oral contraceptives as ovarian cancer prevention. J Natl Cancer Inst. 2011 Sep 7;103(17):1286-8.
https://academic.oup.com/jnci/article/103/17/1286/2516764
http://www.ncbi.nlm.nih.gov/pubmed/21852259?tool=bestpractice.com
A laqueadura tubária e a histerectomia estão associadas à diminuição do risco de câncer de ovário.[54]Hankinson SE, Hunter DJ, Colditz GA, et al. Tubal ligation, hysterectomy, and risk of ovarian cancer. A prospective study. JAMA. 1993 Dec 15;270(23):2813-8.
http://www.ncbi.nlm.nih.gov/pubmed/8133619?tool=bestpractice.com
[55]Rice MS, Murphy MA, Tworoger SS. Tubal ligation, hysterectomy and ovarian cancer: a meta-analysis. J Ovarian Res. 2012 May 15;5(1):13.
https://ovarianresearch.biomedcentral.com/articles/10.1186/1757-2215-5-13
http://www.ncbi.nlm.nih.gov/pubmed/22587442?tool=bestpractice.com
Contudo, esses procedimentos só devem ser realizados por razões clínicas válidas, e não por seu efeito sobre o risco de câncer de ovário.
Com base em dados que implicam a extremidade fimbriada da tuba uterina como fonte do câncer de ovário seroso, o American College of Obstetricians and Gynecologists (ACOG) e a Society of Gynecologic Oncology têm recomendado que os médicos discutam a salpingectomia oportunista para todos os pacientes com risco médio de câncer de ovário submetidos a histerectomia.[56]Society of Gynecologic Oncology. SGO clinical practice statement: salpingectomy for ovarian cancer prevention. Nov 2013 [internet publication].
https://www.sgo.org/clinical-practice/guidelines/sgo-clinical-practice-statement-salpingectomy-for-ovarian-cancer-prevention
[57]American College of Obstetricians and Gynecologists. ACOG committee opinion no. 774: opportunistic salpingectomy as a strategy for epithelial ovarian cancer prevention. Obstet Gynecol. 2019 Apr;133(4):e279-84.
https://journals.lww.com/greenjournal/Fulltext/2019/04000/ACOG_Committee_Opinion_No__774__Opportunistic.59.aspx
http://www.ncbi.nlm.nih.gov/pubmed/30913199?tool=bestpractice.com
No entanto, as evidências de salpingectomia oportunista para prevenção do câncer de ovário são oriundas principalmente de estudos observacionais.[58]van Lieshout LAM, Steenbeek MP, De Hullu JA, et al. Hysterectomy with opportunistic salpingectomy versus hysterectomy alone. Cochrane Database Syst Rev. 2019 Aug 28;8(8):CD012858.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD012858.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/31456223?tool=bestpractice.com
Cirurgia redutora de risco para mulheres com alto risco
A salpingo-ooforectomia redutora de risco (RRSO) pode diminuir o risco de câncer de ovário em pacientes de alto risco, como aquelas com: mutações BRCA1 ou BRCA2; mutações associadas com a síndrome de Lynch; ou outras variantes genéticas de suscetibilidade a câncer de ovário.[16]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: genetic/familial high-risk assessment: colorectal, endometrial, and gastric [internet publication].
https://www.nccn.org/guidelines/category_2
[17]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: genetic/familial high-risk assessment: breast, ovarian, pancreatic, and prostate [internet publication].
https://www.nccn.org/guidelines/category_2
[59]Rebbeck TR, Kauff ND, Domchek SM. Meta-analysis of risk reduction estimates associated with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 mutation carriers. J Natl Cancer Inst. 2009 Jan 21;101(2):80-7.
https://academic.oup.com/jnci/article/101/2/80/1206374
http://www.ncbi.nlm.nih.gov/pubmed/19141781?tool=bestpractice.com
[60]Kauff ND, Satagopan JM, Robson ME, et al. Risk-reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med. 2002 May 23;346(21):1609-15.
https://www.nejm.org/doi/full/10.1056/NEJMoa020119
http://www.ncbi.nlm.nih.gov/pubmed/12023992?tool=bestpractice.com
[61]Ludwig KK, Neuner J, Butler A, et al. Risk reduction and survival benefit of prophylactic surgery in BRCA mutation carriers, a systematic review. Am J Surg. 2016 Oct;212(4):660-9.
http://www.ncbi.nlm.nih.gov/pubmed/27649974?tool=bestpractice.com
[62]Paluch-Shimon S, Cardoso F, Sessa C, et al; ESMO Guidelines Committee. Prevention and screening in BRCA mutation carriers and other breast/ovarian hereditary cancer syndromes: ESMO clinical practice guidelines for cancer prevention and screening. Ann Oncol. 2016 Sep;27(suppl 5):v103-10.
https://www.annalsofoncology.org/article/S0923-7534(19)31645-X/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/27664246?tool=bestpractice.com
[63]Eleje GU, Eke AC, Ezebialu IU, et al. Risk-reducing bilateral salpingo-oophorectomy in women with BRCA1 or BRCA2 mutations. Cochrane Database Syst Rev. 2018 Aug 24;8(8):CD012464.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD012464.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/30141832?tool=bestpractice.com
A decisão de realizar a RRSO (com ou sem histerectomia concomitante) e o seu momento deve ser individualizada (por exemplo, com base na idade, se a idade fértil tiver se completado, status de menopausa, comorbidades, mutação genética específica e história familiar).[16]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: genetic/familial high-risk assessment: colorectal, endometrial, and gastric [internet publication].
https://www.nccn.org/guidelines/category_2
[17]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: genetic/familial high-risk assessment: breast, ovarian, pancreatic, and prostate [internet publication].
https://www.nccn.org/guidelines/category_2
[64]National Institute for Health and Care Excellence. Ovarian cancer: identifying and managing familial and genetic risk. Mar 2024 [internet publication].
https://www.nice.org.uk/guidance/ng241
Para mulheres com mutação de BRCA1, as diretrizes recomendam a RRSO aos 35 a 40 anos de idade (levando em consideração o desejo de ter filhos).[17]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: genetic/familial high-risk assessment: breast, ovarian, pancreatic, and prostate [internet publication].
https://www.nccn.org/guidelines/category_2
As variantes do BRCA2 estão associadas a um início tardio do câncer de ovário, e pode-se considerar o adiamento da RRSO até os 40 a 45 anos de idade nessas pacientes (a menos que haja uma história familiar de diagnóstico precoce). A histerectomia no momento da RRSO para reduzir o risco de câncer de útero grave nas mulheres com mutação de BRCA pode ser discutida. As evidências que sugerem um aumento do risco de câncer de útero seroso nas pessoas com BRCA1/2 são limitadas.[17]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: genetic/familial high-risk assessment: breast, ovarian, pancreatic, and prostate [internet publication].
https://www.nccn.org/guidelines/category_2
Para mulheres com mutação BRIP1, RAD51C ou RAD51D, a RRSO é recomendada aos 45 a 50 anos de idade.[17]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: genetic/familial high-risk assessment: breast, ovarian, pancreatic, and prostate [internet publication].
https://www.nccn.org/guidelines/category_2
A RRSO pode ser considerada entre os 45 e 50 anos nas mulheres com mutação em PALB2. As discussões sobre cirurgia para redução do risco devem começar mais cedo se houver uma história familiar de doença de início precoce.[17]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: genetic/familial high-risk assessment: breast, ovarian, pancreatic, and prostate [internet publication].
https://www.nccn.org/guidelines/category_2
Para mulheres com síndrome de Lynch, as diretrizes recomendam discutir a cirurgia redutora de risco com mulheres do início a meados dos 40 anos.[20]American College of Obstetricians and Gynecologists. ACOG practice bulletin no. 147: Lynch syndrome. Obstet Gynecol. 2014 Nov;124(5):1042-54.
http://www.ncbi.nlm.nih.gov/pubmed/25437740?tool=bestpractice.com
As evidências dão suporte ao uso da RRSO em pacientes com as variantes MLH1, MSH2 e EPCAM, mas não são suficientes para recomendar a cirurgia redutora de risco para aquelas com as variantes MSH6 e PMS2 (que estão associadas com um risco mais baixo de câncer de ovário).[16]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: genetic/familial high-risk assessment: colorectal, endometrial, and gastric [internet publication].
https://www.nccn.org/guidelines/category_2
Além da RRSO, a histerectomia deve ser considerada para todos os pacientes com síndrome de Lynch para reduzir o risco de câncer de endométrio.[16]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: genetic/familial high-risk assessment: colorectal, endometrial, and gastric [internet publication].
https://www.nccn.org/guidelines/category_2
Redução de risco não cirúrgico para mulheres de alto risco
Para mulheres de alto risco que recusam ou não podem ser submetidas à RRSO, às vezes é considerado o rastreamento de rotina com ultrassonografia transvaginal e CA-125.[18]Sessa C, Balmaña J, Bober SL, et al. Risk reduction and screening of cancer in hereditary breast-ovarian cancer syndromes: ESMO clinical practice guideline. Ann Oncol. 2023 Jan;34(1):33-47.
https://www.annalsofoncology.org/article/S0923-7534(22)04193-X/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/36307055?tool=bestpractice.com
[62]Paluch-Shimon S, Cardoso F, Sessa C, et al; ESMO Guidelines Committee. Prevention and screening in BRCA mutation carriers and other breast/ovarian hereditary cancer syndromes: ESMO clinical practice guidelines for cancer prevention and screening. Ann Oncol. 2016 Sep;27(suppl 5):v103-10.
https://www.annalsofoncology.org/article/S0923-7534(19)31645-X/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/27664246?tool=bestpractice.com
[65]American College of Radiology. ACR appropriateness criteria: ovarian cancer screening. 2024 [internet publication].
https://acsearch.acr.org/docs/69463/Narrative
No entanto, os estudos não mostram um benefício claro e isso não é recomendado de maneira rotineira.[16]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: genetic/familial high-risk assessment: colorectal, endometrial, and gastric [internet publication].
https://www.nccn.org/guidelines/category_2
[17]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: genetic/familial high-risk assessment: breast, ovarian, pancreatic, and prostate [internet publication].
https://www.nccn.org/guidelines/category_2
A eficácia do rastreamento das mulheres com alto risco de câncer de ovário usando exame pélvico, teste de CA-125 e ultrassonografia transvaginal não foi demonstrada; a doença em estádio inicial é difícil de detectar e pode passar despercebida com essas abordagens.[17]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: genetic/familial high-risk assessment: breast, ovarian, pancreatic, and prostate [internet publication].
https://www.nccn.org/guidelines/category_2
[66]Cannistra S. Medical progress: cancer of the ovary. N Engl J Med. 2004 Dec 9;351(24):2519-29.
http://www.ncbi.nlm.nih.gov/pubmed/15590954?tool=bestpractice.com
O algoritmo de risco de câncer de ovário (ROCA) pode ser potencialmente útil como ferramenta de vigilância em mulheres de alto risco (por exemplo, com variantes de linha germinativa patogênicas de BRCA1/2) que adiam ou recusam a cirurgia redutora de risco.[67]Philpott S, Raikou M, Manchanda R, et al. The avoiding late diagnosis of ovarian cancer (ALDO) project; a pilot national surveillance programme for women with pathogenic germline variants in BRCA1 and BRCA2. J Med Genet. 2023 May;60(5):440-9.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10176325
http://www.ncbi.nlm.nih.gov/pubmed/36319079?tool=bestpractice.com
No Reino Unido, as diretrizes do National Institute of Health and Care Excellence (NICE) recomendam considerar a vigilância com teste de CA125 longitudinal (a cada 4 meses) usando um algoritmo (como o ROCA) para pacientes nos seguintes grupos de alto risco que postergam ou recusam a cirurgia redutora de risco:[64]National Institute for Health and Care Excellence. Ovarian cancer: identifying and managing familial and genetic risk. Mar 2024 [internet publication].
https://www.nice.org.uk/guidance/ng241
Variante patogênica de BRCA1 e idade acima de 35 anos
Variante patogênica de BRCA2 e idade acima de 40 anos
Variante patogênica de RAD51C, RAD51D, BRIP1 ou PALB2 e idade acima de 45 anos.
Além disso, uma revisão anual com discussão da cirurgia redutora de risco é recomendada para esses pacientes.
A vigilância de mulheres com alto risco de câncer de ovário representa uma medida temporária e não deve ser considerada como uma alternativa à cirurgia redutora de risco.[68]Manning-Geist BL, Flint M, Roche KL. Prevention over screening for ovarian cancer in patients with high-risk germline mutations: misinterpreting the findings of ALDO. Gynecol Oncol Rep. 2023 Apr;46:101157.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10020112
http://www.ncbi.nlm.nih.gov/pubmed/36938343?tool=bestpractice.com
É recomendável considerar a contracepção oral combinada ou um dispositivo intrauterino (DIU) hormonal como medida de redução de risco nas mulheres com mutação de BRCA.[15]American College of Obstetricians and Gynecologists. Practice bulletin no 182: hereditary breast and ovarian cancer syndrome. Obstet Gynecol. 2017 Sep;130(3):e110-26.
http://www.ncbi.nlm.nih.gov/pubmed/28832484?tool=bestpractice.com
[17]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: genetic/familial high-risk assessment: breast, ovarian, pancreatic, and prostate [internet publication].
https://www.nccn.org/guidelines/category_2
[62]Paluch-Shimon S, Cardoso F, Sessa C, et al; ESMO Guidelines Committee. Prevention and screening in BRCA mutation carriers and other breast/ovarian hereditary cancer syndromes: ESMO clinical practice guidelines for cancer prevention and screening. Ann Oncol. 2016 Sep;27(suppl 5):v103-10.
https://www.annalsofoncology.org/article/S0923-7534(19)31645-X/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/27664246?tool=bestpractice.com
O uso de um contraceptivo com estrogênio/progestina ou um DIU com levonorgestrel (DIU-LNG) nas mulheres com mutações de BRCA1 ou BRCA2 reduz o risco de câncer de ovário em comparação ao relatado para a população em geral.[69]Moorman PG, Havrilesky LJ, Gierisch JM, et al. Oral contraceptives and risk of ovarian cancer and breast cancer among high-risk women: a systematic review and meta-analysis. J Clin Oncol. 2013 Nov 20;31(33):4188-98.
https://ascopubs.org/doi/10.1200/JCO.2013.48.9021
http://www.ncbi.nlm.nih.gov/pubmed/24145348?tool=bestpractice.com
[70]Huber D, Seitz S, Kast K, et al. Use of oral contraceptives in BRCA mutation carriers and risk for ovarian and breast cancer: a systematic review. Arch Gynecol Obstet. 2020 Apr;301(4):875-84.
http://www.ncbi.nlm.nih.gov/pubmed/32140806?tool=bestpractice.com
[71]Wheeler LJ, Desanto K, Teal SB, et al. Intrauterine device use and ovarian cancer risk: a systematic review and meta-analysis. Obstet Gynecol. 2019 Oct;134(4):791-800.
http://www.ncbi.nlm.nih.gov/pubmed/31503144?tool=bestpractice.com
[72]Balayla J, Gil Y, Lasry A, et al. Ever-use of the intra-uterine device and the risk of ovarian cancer. J Obstet Gynaecol. 2021 Aug;41(6):848-53.
http://www.ncbi.nlm.nih.gov/pubmed/33045859?tool=bestpractice.com
[73]van Bommel MHD, IntHout J, Veldmate G, et al. Contraceptives and cancer risks in BRCA1/2 pathogenic variant carriers: a systematic review and meta-analysis. Hum Reprod Update. 2023 Mar 1;29(2):197-217.
https://pmc.ncbi.nlm.nih.gov/articles/PMC9976973
http://www.ncbi.nlm.nih.gov/pubmed/36383189?tool=bestpractice.com
Os benefícios e malefícios devem ser ponderados e discutidos com pacientes de alto risco, inclusive o aumento do risco de câncer de mama associado com o uso de contraceptivos orais em longo prazo.[64]National Institute for Health and Care Excellence. Ovarian cancer: identifying and managing familial and genetic risk. Mar 2024 [internet publication].
https://www.nice.org.uk/guidance/ng241
[70]Huber D, Seitz S, Kast K, et al. Use of oral contraceptives in BRCA mutation carriers and risk for ovarian and breast cancer: a systematic review. Arch Gynecol Obstet. 2020 Apr;301(4):875-84.
http://www.ncbi.nlm.nih.gov/pubmed/32140806?tool=bestpractice.com
[73]van Bommel MHD, IntHout J, Veldmate G, et al. Contraceptives and cancer risks in BRCA1/2 pathogenic variant carriers: a systematic review and meta-analysis. Hum Reprod Update. 2023 Mar 1;29(2):197-217.
https://pmc.ncbi.nlm.nih.gov/articles/PMC9976973
http://www.ncbi.nlm.nih.gov/pubmed/36383189?tool=bestpractice.com
Para mulheres com síndrome de Lynch, as estratégias alternativas de redução de risco devem ser discutidas se a RRSO for recusada ou não for possível.[16]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: genetic/familial high-risk assessment: colorectal, endometrial, and gastric [internet publication].
https://www.nccn.org/guidelines/category_2
Isso deve incluir educação sobre os sintomas associados ao câncer de ovário.