Advertisement

Why have ovarian cancer mortality rates declined? Part III. Prospects for the future

      Highlights

      • Up to 17% of ovarian cancers are potentially preventable through population-based genetic testing of known cancer genes.
      • To improve the cure rate there must be an increase in the proportion of women with no residual disease after primary surgery.
      • This may be achieved through a combination of aggressive surgery and wider application of the CA125 screening test.

      Abstract

      Over the last 40 years, the age-adjusted ovarian cancer mortality rate in the USA declined by 23%. The decline in mortality paralleled a decline in incidence, which was largely due to changes in reproductive risk factors. There was no reduction in ovarian cancer case-fatality at 12 years, indicating that improvements in early detection or in treatment did not contribute to the decline in mortality. Here, we discuss potential strategies to further reduce ovarian cancer mortality through prevention, early detection and treatment. The first approach is to increase genetic testing, in order to identify women who are at a high risk of developing ovarian cancer and offer them preventive bilateral salpingo-oophorectomy. At present, up to 17% of ovarian cancers are potentially preventable through population-based genetic testing of known ovarian cancer susceptibility genes. The second approach is to increase the proportion of ovarian cancer patients who achieve a status of no residual disease through primary debulking surgery and subsequently receive adjuvant intraperitoneal chemotherapy. We believe that through a combination of screening to better identify low-volume advanced stage ovarian cancer, aggressive surgery to leave no residual disease and adjuvant intraperitoneal chemotherapy, the cure rate of ovarian cancer might be improved significantly.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Gynecologic Oncology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Sopik V.
        • et al.
        Why have ovarian cancer mortality rates declined? Part I. Incidence.
        Gynecol. Oncol. 2015; 138: 741-749
        • Sopik V.
        • et al.
        Why have ovarian cancer mortality rates declined? Part II. Case-fatality.
        Gynecol. Oncol. 2015; 138: 750-756
        • Parker W.H.
        • et al.
        Ovarian conservation at the time of hysterectomy and long-term health outcomes in the nurses' health study.
        Obstet. Gynecol. 2009; 113: 1027-1037
        • Giannakeas V.
        • et al.
        A model for estimating ovarian cancer risk: application for preventive oophorectomy.
        Gynecol. Oncol. 2015; (submitted for publication)
        • Zhang S.
        • et al.
        Frequencies of BRCA1 and BRCA2 mutations among 1,342 unselected patients with invasive ovarian cancer.
        Gynecol. Oncol. 2011; 121: 353-357
        • Antoniou A.
        • et al.
        Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies.
        Am. J. Hum. Genet. 2003; 72: 1117-1130
        • Pal T.
        • et al.
        Frequency of mutations in mismatch repair genes in a population-based study of women with ovarian cancer.
        Br. J. Cancer. 2012; 107: 1783-1790
        • Bonadona V.
        • et al.
        Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome.
        JAMA. 2011; 305: 2304-2310
        • Daly M.B.
        • et al.
        Genetic/familial high-risk assessment: breast and ovarian, version 1.2014.
        J. Natl. Compr. Cancer Netw. 2014; 12: 1326-1338
        • Lindor N.M.
        • et al.
        Recommendations for the care of individuals with an inherited predisposition to Lynch syndrome: a systematic review.
        JAMA. 2006; 296: 1507-1517
        • Loveday C.
        • et al.
        Germline RAD51C mutations confer susceptibility to ovarian cancer.
        Nat. Genet. 2012; 44 (author reply 476): 475-476
        • Loveday C.
        • et al.
        Germline mutations in RAD51D confer susceptibility to ovarian cancer.
        Nat. Genet. 2011; 43: 879-882
        • Akbari M.R.
        • et al.
        PPM1D mutations in circulating white blood cells and the risk for ovarian cancer.
        J. Natl. Cancer Inst. 2014; 106: djt323
        • Ruark E.
        • et al.
        Mosaic PPM1D mutations are associated with predisposition to breast and ovarian cancer.
        Nature. 2013; 493: 406-410
        • Antoniou A.C.
        • et al.
        Breast-cancer risk in families with mutations in PALB2.
        N. Engl. J. Med. 2014; 371: 497-506
        • Rafnar T.
        • et al.
        Mutations in BRIP1 confer high risk of ovarian cancer.
        Nat. Genet. 2011; 43: 1104-1107
        • Olivier M.
        • et al.
        Li–Fraumeni and related syndromes: correlation between tumor type, family structure, and TP53 genotype.
        Cancer Res. 2003; 63: 6643-6650
        • Finch A.
        • et al.
        Preventing ovarian cancer through genetic testing: a population-based study.
        Clin. Genet. 2014; 86: 496-499
        • Jervis S.
        • et al.
        A risk prediction algorithm for ovarian cancer incorporating BRCA1, BRCA2, common alleles and other familial effects.
        J. Med. Genet. 2015; 52: 465-475
        • Kuchenbaecker K.B.
        • et al.
        Identification of six new susceptibility loci for invasive epithelial ovarian cancer.
        Nat. Genet. 2015; 47: 164-171
        • Pearce C.L.
        • et al.
        Population distribution of lifetime risk of ovarian cancer in the United States.
        Cancer Epidemiol. Biomarkers Prev. 2015; 24: 671-676
        • Berek J.S.
        • et al.
        Prophylactic and risk-reducing bilateral salpingo-oophorectomy: recommendations based on risk of ovarian cancer.
        Obstet. Gynecol. 2010; 116: 733-743
      1. ACOG Practice Bulletin No. 89. Elective and risk-reducing salpingo-oophorectomy.
        Obstet. Gynecol. 2008; 111: 231-241
        • Salvador S.
        • et al.
        The fallopian tube: primary site of most pelvic high-grade serous carcinomas.
        Int. J. Gynecol. Cancer. 2009; 19: 58-64
        • Madsen C.
        • et al.
        Tubal ligation and salpingectomy and the risk of epithelial ovarian cancer and borderline ovarian tumors: a nationwide case–control study.
        Acta Obstet. Gynecol. Scand. 2015; 94: 86-94
        • Falconer H.
        • et al.
        Ovarian cancer risk after salpingectomy: a nationwide population-based study.
        J. Natl. Cancer Inst. 2015; 107
        • Narod S.A.
        Salpingectomy to prevent ovarian cancer: a countercurrents series.
        Curr. Oncol. 2013; 20: 145-147
        • Buys S.S.
        • et al.
        Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial.
        JAMA. 2011; 305: 2295-2303
        • Moyer V.A.
        Screening for ovarian cancer: U.S. Preventive Services Task Force reaffirmation recommendation statement.
        Ann. Intern. Med. 2012; 157: 900-904
        • Menon U.
        • et al.
        Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer, and stage distribution of detected cancers: results of the prevalence screen of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).
        Lancet Oncol. 2009; 10: 327-340
        • Rosen D.G.
        • et al.
        Potential markers that complement expression of CA125 in epithelial ovarian cancer.
        Gynecol. Oncol. 2005; 99: 267-277
        • Van Calster B.
        • et al.
        A novel approach to predict the likelihood of specific ovarian tumor pathology based on serum CA-125: a multicenter observational study.
        Cancer Epidemiol. Biomarkers Prev. 2011; 20: 2420-2428
        • Fader A.N.
        • et al.
        The prognostic significance of pre- and post-treatment CA-125 in grade 1 serous ovarian carcinoma: a gynecologic Oncology Group study.
        Gynecol. Oncol. 2014; 132: 560-565
        • Escudero J.M.
        • et al.
        Comparison of serum human epididymis protein 4 with cancer antigen 125 as a tumor marker in patients with malignant and nonmalignant diseases.
        Clin. Chem. 2011; 57: 1534-1544
        • Bon G.G.
        • et al.
        Serum tumor marker immunoassays in gynecologic oncology: establishment of reference values.
        Am. J. Obstet. Gynecol. 1996; 174: 107-114
        • Skates S.
        Personal Communication.
        2014
        • Rosen B.
        • et al.
        The impacts of neoadjuvant chemotherapy and of debulking surgery on survival from advanced ovarian cancer.
        Gynecol. Oncol. 2014; 134: 462-467
        • du Bois A.
        • et al.
        Role of surgical outcome as prognostic factor in advanced epithelial ovarian cancer: a combined exploratory analysis of 3 prospectively randomized phase 3 multicenter trials: by the Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR) and the Groupe d'Investigateurs Nationaux Pour les Etudes des Cancers de l'Ovaire (GINECO).
        Cancer. 2009; 115: 1234-1244
        • Vergote I.
        • et al.
        Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer.
        N. Engl. J. Med. 2010; 363: 943-953
        • Kehoe S.
        • et al.
        Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): an open-label, randomised, controlled, non-inferiority trial.
        Lancet. 2015; https://doi.org/10.1016/S0140-6736(14)62223-6
        • Chi D.S.
        • et al.
        An analysis of patients with bulky advanced stage ovarian, tubal, and peritoneal carcinoma treated with primary debulking surgery (PDS) during an identical time period as the randomized EORTC-NCIC trial of PDS vs neoadjuvant chemotherapy (NACT).
        Gynecol. Oncol. 2012; 124: 10-14
        • Fagotti A.
        • et al.
        Introduction of staging laparoscopy in the management of advanced epithelial ovarian, tubal and peritoneal cancer: impact on prognosis in a single institution experience.
        Gynecol. Oncol. 2013; 131: 341-346
        • Hendrickson A.W.
        • et al.
        Assessment of published models and prognostic variables in epithelial ovarian cancer at Mayo Clinic.
        Gynecol. Oncol. 2015; 137: 77-85
        • Suidan R.S.
        • et al.
        A multicenter prospective trial evaluating the ability of preoperative computed tomography scan and serum CA-125 to predict suboptimal cytoreduction at primary debulking surgery for advanced ovarian, fallopian tube, and peritoneal cancer.
        Gynecol. Oncol. 2014; 134: 455-461
        • Nick A.M.
        • et al.
        A framework for a personalized surgical approach to ovarian cancer.
        Nat. Rev. Clin. Oncol. 2015; 12: 239-245
        • Horowitz N.S.
        • et al.
        Does aggressive surgery improve outcomes? Interaction between preoperative disease burden and complex surgery in patients with advanced-stage ovarian cancer: an analysis of GOG 182.
        J. Clin. Oncol. 2015; 33: 937-943
        • Tewari D.
        • et al.
        Long-term survival advantage and prognostic factors associated with intraperitoneal chemotherapy treatment in advanced ovarian cancer: a Gynecologic Oncology Group study.
        J. Clin. Oncol. 2015; 33: 1460-1466
        • Chin S.N.
        • et al.
        Evaluation of an intraperitoneal chemotherapy program implemented at the Princess Margaret Hospital for patients with epithelial ovarian carcinoma.
        Gynecol. Oncol. 2009; 112: 450-454