Professional Documents
Culture Documents
Ovarian Cancer Prevention and Screening.22
Ovarian Cancer Prevention and Screening.22
There has been much progress in ovarian cancer screening and prevention in recent years. Improved
tools that combine genetic and epidemiologic factors to predict an individual’s ovarian cancer risk
are set to become available for tailoring preventive and screening approaches. The increasing evi-
Downloaded from https://journals.lww.com/greenjournal by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3XLe684GKHSWSPs4K0vGEry9Jz6zSk8gJSbZFSguGzpho8AwKWrVtpg== on 07/08/2018
dence on tubal origins of a proportion of ovarian cancer has paved the way to use of opportunistic
bilateral salpingectomy at tubal ligation and hysterectomy in the general population. Clinical trials
are in progress to estimate the long-term effects on endocrine function. In women at high risk, risk
reducing salpingo-oophorectomy remains the standard of care with the current focus on manage-
ment of resulting noncancer outcomes, especially sexual dysfunction in younger women. This has
led to evaluation of early bilateral salpingectomy and delayed oophorectomy in this population.
Meanwhile, modeling suggests that BRCA mutation carriers should consider using the oral contra-
ceptive pill for chemoprevention. In the general population, the largest ovarian cancer screening trial
to date, the UK Collaborative Trial of Ovarian Cancer Screening reported a stage shift with annual
multimodal screening using the longitudinal CA 125 Risk of Ovarian Cancer Algorithm but not with
annual transvaginal ultrasound screening. There was no definitive mortality reduction with either
screening strategy compared with no screening. Further follow-up until December 2018 in now
underway. Stage shift and higher rates of optimal cytoreduction were also reported during 3- to
4-monthly multimodal screening in the United Kingdom and U.S. high-risk screening trials. Although
all agree that there is not yet evidence to support general population screening, recommendations
for high-risk screening vary between countries. A key finding from the screening trials has been the
better performance of longitudinal algorithms compared with a single cutoff for CA 125. A major
focus of ovarian cancer biomarker discovery work has been tumor DNA markers in both plasma and
novel specimens such as cervical cytology samples.
(Obstet Gynecol 2018;131:909–27)
DOI: 10.1097/AOG.0000000000002580
910 Menon et al Ovarian Cancer Prevention and Screening OBSTETRICS & GYNECOLOGY
Effect on
Ovarian
Risk Factors Cancer risk Study Design OR/RR 95% CI Author, Year
(continued )
VOL. 131, NO. 5, MAY 2018 Menon et al Ovarian Cancer Prevention and Screening 911
(continued )
912 Menon et al Ovarian Cancer Prevention and Screening OBSTETRICS & GYNECOLOGY
VOL. 131, NO. 5, MAY 2018 Menon et al Ovarian Cancer Prevention and Screening 913
914 Menon et al Ovarian Cancer Prevention and Screening OBSTETRICS & GYNECOLOGY
VOL. 131, NO. 5, MAY 2018 Menon et al Ovarian Cancer Prevention and Screening 915
916 Menon et al Ovarian Cancer Prevention and Screening OBSTETRICS & GYNECOLOGY
VOL. 131, NO. 5, MAY 2018 Menon et al Ovarian Cancer Prevention and Screening 917
918 Menon et al Ovarian Cancer Prevention and Screening OBSTETRICS & GYNECOLOGY
VOL. 131, NO. 5, MAY 2018 Menon et al Ovarian Cancer Prevention and Screening 919
CA 125, HE4, EDRN, 118 women with invasive In PLCO samples predating Cramer et al,
transthyretin, SPORE, epithelial ovarian cancer/FT/ diagnosis by 6 mo, the 2011140
CA15.3, and CA72.4 PLCO PPC; 474 matched controls sensitivity for detection of
ovarian cancer was 86% for CA
125 and 73% for HE4
CA 125 and TP53 AOCS, MD 378 cases of invasive epithelial Using a cutoff of 78 units/mL and Yang et al, 2017141
Anderson, ovarian cancer; 944 age- specificity of 97.4%, TP53
UKCTOCS matched healthy controls (50 autoantibodies were elevated
cases—MD Anderson, 108 in 30% OCs from MD
cases—AOCS, 220 cases— Anderson, 21.3% AOCS, and
UKCTOCS) 21% UKCTOCS; in the
UKCTOCS screen-detected
cancers, TP53 autoantiobodies
were elevated 11 mo before CA
125. 16% of cases missed by
ROCA in UKCTOCS had
elevated TP53 autoantibodies,
22.9 mo before diagnosis
CA 125 and Protein Z UKCTOCS 482 serial serum samples from 49 CA 125 combined with protein Z Russell et al,
women with primary ovarian had a significantly higher AUC 2016142
cancer (30 type II, 19 type I—9 compared with that of CA 125
invasive ovarian cancer and 10 alone for both type I (0.82 vs
borderline) and 31 controls, 0.77, P5.00033) and type II
spanning up to 7 y before (0.82 vs 0.76, P5.00003) OCs;
diagnosis protein Z was downregulated
up to 2 y prediagnosis
(P5.000000411) in 8/19 type I
OCs; upregulated up to 4 y
before diagnosis in type II OCs
(P5.01)
CA 125, HE4, UKCTOCS 47 women who went on to A model combining CA 125, Blyuss et al,
glycodelin, develop primary invasive HE4, and glycodelin had 2015143
mesothelin, MMP7, epithelial ovarian cancer/FT/ slightly higher AUC (0.967)
and CYFRA 21-1 PPC (170 samples); 179 compared with that of CA 125
matched controls (893 alone (0.957), which decreased
samples) in samples greater than 6 mo
from diagnosis (0.789); HE4
was the only marker
significantly elevated in the
screen-negative OCs
CA 125, HE4, CA72-4, EDRN Cases with samples closest to Data being generated to allow https://edrn.nci.nih.
CA15-3, and VTCN1 diagnosis (average 9 mo); 951 algorithm development gov/biomarkers/
(Cramer 5-marker controls (475 general cramer-5-marker-
panel for ovarian population, 238 with false- panel-for-
cancer) positive CA 125, and 238 with ovarian-cancer
a family history of breast or
ovarian cancer; 90 quality
controls)
AOCS, Australian Ovarian Cancer Study; EDRN, Early Detection Research Network; PLCO, Prostate Lung Colorectal and Ovarian Cancer
Screening Trial; SPORE, Ovarian Cancer Specialized Program of Research Excellence; UKCTOCS, UK Collaborative Trial of Ovarian
Cancer Screening.
incidence screening) and specificity (99.8% prevalence 4.4 operations per cancer detected.127 A similar high
screening, 99.8% incidence screening) for detection of specificity and positive predictive value of the Risk of
invasive epithelial ovarian, tubal, and peritoneal Ovarian Cancer Algorithm was reported from a pro-
cancers diagnosed within 1 year of screening with spective single-arm U.S. study of 4,051 low-risk
920 Menon et al Ovarian Cancer Prevention and Screening OBSTETRICS & GYNECOLOGY
VOL. 131, NO. 5, MAY 2018 Menon et al Ovarian Cancer Prevention and Screening 921
922 Menon et al Ovarian Cancer Prevention and Screening OBSTETRICS & GYNECOLOGY
VOL. 131, NO. 5, MAY 2018 Menon et al Ovarian Cancer Prevention and Screening 923
57. Davies SD. Annual report of the Chief Medical Officer 2016, 74. Zakhour M, Danovitch Y, Lester J, Rimel BJ, Walsh CS, Li AJ,
generation genome. London (UK): Department of Health; 2016. et al. Occult and subsequent cancer incidence following risk-
reducing surgery in BRCA mutation carriers. Gynecol Oncol
58. Cancer Taskforce. Statement of intent: cancer strategy for 2016;143:231–5.
England: 2015–2020. London (UK): Cancer Strategy Task-
75. Manchanda R, Drapkin R, Jacobs I, Menon U. The role of
force; 2015.
peritoneal cytology at risk-reducing salpingo-oophorectomy
59. Clinicaltrials.gov. Women informed to screen depending on (RRSO) in women at increased risk of familial ovarian/tubal
measures of risk (WISDOM). Available at: https://clinical- cancer. Gynecol Oncol 2012;124:185–91.
trials.gov/ct2/show/NCT02620852. Retrieved July 24, 2017.
76. Powell CB, Swisher EM, Cass I, McLennan J, Norquist B,
60. Parmigiani G, Chen S, Iversen ES Jr, Friebel TM, Finkelstein Garcia RL, et al. Long term follow up of BRCA1 and BRCA2
DM, Anton-Culver H, et al. Validity of models for predicting mutation carriers with unsuspected neoplasia identified at risk
924 Menon et al Ovarian Cancer Prevention and Screening OBSTETRICS & GYNECOLOGY
VOL. 131, NO. 5, MAY 2018 Menon et al Ovarian Cancer Prevention and Screening 925
926 Menon et al Ovarian Cancer Prevention and Screening OBSTETRICS & GYNECOLOGY
VOL. 131, NO. 5, MAY 2018 Menon et al Ovarian Cancer Prevention and Screening 927