1. Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin 2024;74:12-49. |
Review/Other-Dx |
N/A |
Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence and outcomes using incidence data collected by central cancer registries (through 2020) and mortality data collected by the National Center for Health Statistics (through 2021). In 2024, 2,001,140 new cancer cases and 611,720 cancer deaths are projected to occur in the United States. Cancer mortality continued to decline through 2021, averting over 4 million deaths since 1991 because of reductions in smoking, earlier detection for some cancers, and improved treatment options in both the adjuvant and metastatic settings. However, these gains are threatened by increasing incidence for 6 of the top 10 cancers. Incidence rates increased during 2015-2019 by 0.6%-1% annually for breast, pancreas, and uterine corpus cancers and by 2%-3% annually for prostate, liver (female), kidney, and human papillomavirus-associated oral cancers and for melanoma. Incidence rates also increased by 1%-2% annually for cervical (ages 30-44 years) and colorectal cancers (ages <55 years) in young adults. Colorectal cancer was the fourth-leading cause of cancer death in both men and women younger than 50 years in the late-1990s but is now first in men and second in women. Progress is also hampered by wide persistent cancer disparities; compared to White people, mortality rates are two-fold higher for prostate, stomach and uterine corpus cancers in Black people and for liver, stomach, and kidney cancers in Native American people. Continued national progress will require increased investment in cancer prevention and access to equitable treatment, especially among American Indian and Alaska Native and Black individuals. |
No results stated in abstract. |
4 |
2. Clarke-Pearson DL. Clinical practice. Screening for ovarian cancer. N Engl J Med. 2009; 361(2):170-177. |
Review/Other-Dx |
N/A |
Review the usefulness of screening for ovarian cancer. |
Routine screening of the general population for ovarian cancer is not recommended. Studies show that screening with serum tumor markers (especially CA-125), ovarian imaging with TVUS or a multimodal strategy can detect ovarian cancer at an earlier stage, but trials that have been completed to date have not included a control group for direct comparison. There is no trial that has yet shown improved overall survival for women undergoing screening. |
4 |
3. Antoniou A, Pharoah PD, Narod S, 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;72:1117-30. |
Meta-analysis |
22 studies |
To analyze the average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations. |
The average cumulative risks in BRCA1-mutation carriers by age 70 years were 65% (95% confidence interval 44%-78%) for breast cancer and 39% (18%-54%) for ovarian cancer. The corresponding estimates for BRCA2 were 45% (31%-56%) and 11% (2.4%-19%). Relative risks of breast cancer declined significantly with age for BRCA1-mutation carriers (P trend.0012) but not for BRCA2-mutation carriers. |
Good |
4. Chen S, Parmigiani G. Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol. 2007; 25(11):1329-1333. |
Meta-analysis |
10 studies |
Meta-analysis was performed to facilitate clinical management and counseling of individuals at high risk of carrying a BRCA1 or BRCA2 mutation. |
Meta-analytic mean cumulative cancer risks for mutation carriers at age 70 years were as follows: breast cancer risk of 57% (95% CI, 47% to 66%) for BRCA1 and 49% (95% CI, 40% to 57%) for BRCA2 mutation carriers; and ovarian cancer risk of 40% (95% CI, 35% to 46%) for BRCA1 and 18% (95% CI, 13% to 23%) for BRCA2 mutation carriers. |
M |
5. US Preventive Services Task Force, Owens DK, Davidson KW, et al. Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 322(7):652-665, 2019 08 20. |
Review/Other-Dx |
N/A |
To update the 2013 US Preventive Services Task Force (USPSTF) recommendation on risk assessment, genetic counseling, and genetic testing for BRCA-related cancer. |
For women whose family or personal history is associated with an increased risk for harmful mutations in the BRCA1/2 genes, or who have an ancestry associated with BRCA1/2 gene mutations, there is adequate evidence that the benefits of risk assessment, genetic counseling, genetic testing, and interventions are moderate. For women whose personal or family history or ancestry is not associated with an increased risk for harmful mutations in the BRCA1/2 genes, there is adequate evidence that the benefits of risk assessment, genetic counseling, genetic testing, and interventions are small to none. Regardless of family or personal history, the USPSTF found adequate evidence that the overall harms of risk assessment, genetic counseling, genetic testing, and interventions are small to moderate. |
4 |
6. Nebgen DR, Lu KH, Bast RC Jr. Novel Approaches to Ovarian Cancer Screening. [Review]. Curr Oncol Rep. 21(8):75, 2019 07 26. |
Review/Other-Dx |
N/A |
To review conventional and novel approaches to early detection of ovarian cancer. |
No results stated in abstract. |
4 |
7. Peres LC, Cushing-Haugen KL, Kobel M, et al. Invasive Epithelial Ovarian Cancer Survival by Histotype and Disease Stage. J Natl Cancer Inst 2019;111:60-68. |
Review/Other-Dx |
28118 cases |
To classify ovarian cancer histotypes in Surveillance, Epidemiology, and SEER cancer registry data and examine survival patterns by histotype and disease stage. |
Within two years after diagnosis, localized/regional-stage carcinosarcoma and distant-stage mucinous, clear cell, and carcinosarcoma had a higher risk of mortality compared with high-grade serous, with the most pronounced association for localized/regional carcinosarcoma (>1-2-year time period: HR = 3.81, 95% CI = 2.74 to 5.30) and distant-stage mucinous (0-1-year time period: HR = 3.87, 95% CI = 3.45 to 4.34). In the time period more than four to 10 years after diagnosis, hazard ratios for all histotypes relative to high-grade serous, irrespective of disease stage, were less than 1.00. Cumulatively, both localized/regional and distant-stage low-grade serous and endometrioid carcinomas had the most favorable outcomes. |
4 |
8. Torre LA, Trabert B, DeSantis CE, et al. Ovarian cancer statistics, 2018. CA: a Cancer Journal for Clinicians. 68(4):284-296, 2018 07. |
Review/Other-Dx |
N/A |
To provide an overview of ovarian cancer occurrence based on incidence data from nationwide population-based cancer registries and mortality data from the National Center for Health Statistics. |
No results stated in abstract. |
4 |
9. Allemani C, Weir HK, Carreira H, et al. Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2). Lancet 2015;385:977-1010. |
Observational-Dx |
25.7 million adults (age 15-99 years) and 75,000 children (age 0-14 years) diagnosed with cancer during 1995-2009 |
To initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control. |
5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005-09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15-19% in North America, and as low as 7-9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10-20% between 1995-99 and 2005-09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer, national estimates of 5-year survival range from less than 50% to more than 70%; regional variations are much wider, and improvements between 1995-99 and 2005-09 have generally been slight. For women diagnosed with ovarian cancer in 2005-09, 5-year survival was 40% or higher only in Ecuador, the USA, and 17 countries in Asia and Europe. 5-year survival for stomach cancer in 2005-09 was high (54-58%) in Japan and South Korea, compared with less than 40% in other countries. By contrast, 5-year survival from adult leukaemia in Japan and South Korea (18-23%) is lower than in most other countries. 5-year survival from childhood acute lymphoblastic leukaemia is less than 60% in several countries, but as high as 90% in Canada and four European countries, which suggests major deficiencies in the management of a largely curable disease. |
4 |
10. Forstner R. Early detection of ovarian cancer. Eur Radiol. 30(10):5370-5373, 2020 Oct. |
Review/Other-Dx |
N/A |
To review the importance of early detection of ovarian cancer. |
No results stated in abstract. |
4 |
11. Pickhardt PJ, Hanson ME. Incidental adnexal masses detected at low-dose unenhanced CT in asymptomatic women age 50 and older: implications for clinical management and ovarian cancer screening. Radiology 2010;257:144-50. |
Review/Other-Dx |
2869 women |
To determine the prevalence, work-up, and outcomes of indeterminate adnexal masses identified at low-dose unenhanced computed tomography (CT) in asymptomatic women age 50 and older undergoing colonography screening. |
One hundred eighteen women (mean age, 56.2 years), representing 4.1% of the screening cohort, had an indeterminate adnexal mass (108 unilateral, 10 bilateral; mean size, 4.1 cm) at prospective CT interpretation. A total of 80 women underwent some combination of further imaging evaluation (n = 76) (transvaginal ultrasonography [n = 71], pelvic magnetic resonance imaging [n = 7], contrast material-enhanced CT [n = 7]) and/or surgery (n = 26). Mean serum CA-125 level in 33 women was 12.8 U/mL; levels were normal (<35 U/mL) in 32 (97%) cases (range, 3-26 U/mL) and mildly elevated (41 U/mL) in one case. Final pathologic findings of surgically excised lesions were cystadenoma or cystadenofibroma (n = 14; 11 serous, three mucinous); nonneoplastic cysts (n = 5; two endometriomas); mature teratoma (n = 3); hydrosalpinx (n = 2); fibroma (n = 1); and benign Brenner tumor (n = 1). Three additional teratomas were diagnosed at index CT only. No ovarian cancers were prospectively identified, although four cases of ovarian cancer developed subsequent to a negative adnexal finding at CT examination during a 15-44-month interval among the remaining 2751 women. |
4 |
12. Buys SS, Partridge E, Black A, et al. Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial. JAMA. 2011; 305(22):2295-2303. |
Experimental-Dx |
78,216 women assigned to either annual screening (n=39,105) or usual care (n=39,111) |
To evaluate the effect of screening for ovarian cancer on mortality in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. |
Ovarian cancer was diagnosed in 212 women (5.7 per 10,000 person-years) in the intervention group and 176 (4.7 per 10,000 person-years) in the usual care group (rate ratio, 1.21; 95% CI, 0.99-1.48). There were 118 deaths caused by ovarian cancer (3.1 per 10,000 person-years) in the intervention group and 100 deaths (2.6 per 10,000 person-years) in the usual care group (mortality rate ratio, 1.18; 95% CI, 0.82-1.71). Of 3,285 women with false-positive results, 1,080 underwent surgical follow-up; of whom, 163 women experienced at least one serious complication (15%). There were 2,924 deaths due to other causes (excluding ovarian, colorectal, and lung cancer) (76.6 per 10,000 person-years) in the intervention group and 2,914 deaths (76.2 per 10,000 person-years) in the usual care group (rate ratio, 1.01; 95% CI, 0.96-1.06). Among women in the general US population, simultaneous screening with CA-125 and TVUS compared with usual care did not reduce ovarian cancer mortality. Diagnostic evaluation following a false-positive screening test result was associated with complications. |
1 |
13. Jacobs IJ, Menon U, Ryan A, et al. Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial.[Erratum appears in Lancet. 2016 Mar 5;387(10022):944], [Erratum appears in Lancet. 2016 Mar 5;387(10022):944; PMID: 28832000]. Lancet. 387(10022):945-956, 2016 Mar 05. |
Observational-Dx |
202, 638 women |
To establish the effect of early detection by screening on ovarian cancer mortality. |
Between June 1, 2001, and Oct 21, 2005, we randomly allocated 202 638 women: 50 640 (25.0%) to MMS, 50 639 (25.0%) to USS, and 101 359 (50.0%) to no screening. 202 546 (>99.9%) women were eligible for analysis: 50 624 (>99.9%) women in the MMS group, 50 623 (>99.9%) in the USS group, and 101 299 (>99.9%) in the no screening group. Screening ended on Dec 31, 2011, and included 345 570 MMS and 327 775 USS annual screening episodes. At a median follow-up of 11.1 years (IQR 10.0-12.0), we diagnosed ovarian cancer in 1282 (0.6%) women: 338 (0.7%) in the MMS group, 314 (0.6%) in the USS group, and 630 (0.6%) in the no screening group. Of these women, 148 (0.29%) women in the MMS group, 154 (0.30%) in the USS group, and 347 (0.34%) in the no screening group had died of ovarian cancer. The primary analysis using a Cox proportional hazards model gave a mortality reduction over years 0-14 of 15% (95% CI -3 to 30; p=0.10) with MMS and 11% (-7 to 27; p=0.21) with USS. The Royston-Parmar flexible parametric model showed that in the MMS group, this mortality effect was made up of 8% (-20 to 31) in years 0-7 and 23% (1-46) in years 7-14, and in the USS group, of 2% (-27 to 26) in years 0-7 and 21% (-2 to 42) in years 7-14. A prespecified analysis of death from ovarian cancer of MMS versus no screening with exclusion of prevalent cases showed significantly different death rates (p=0.021), with an overall average mortality reduction of 20% (-2 to 40) and a reduction of 8% (-27 to 43) in years 0-7 and 28% (-3 to 49) in years 7-14 in favour of MMS. |
3 |
14. Jacobs IJ, Skates SJ, MacDonald N, et al. Screening for ovarian cancer: a pilot randomised controlled trial. Lancet. 1999; 353(9160):1207-1210. |
Experimental-Dx |
Screened group (n=10,958) Control group (n=10,977) |
Pilot randomized trial to assess multimodal screening with sequential CA 125 antigen and US. |
Of 468 women in the screened group with a raised CA 125, 29 were referred for a gynaecological opinion; screening detected an index cancer in 6 and 23 had false-positive screening results. The PPV was 20.7%. During 7-year follow-up, 10 further women with index cancers were identified in the screened group and 20 in the control group. Median survival of women with index cancers in the screened group was 72.9 months and in the control group was 41.8 months (P=0.0112). The number of deaths from an index cancer did not differ significantly between the control and screened groups (18/10,977 vs 9/10,958, relative risk 2.0 [95% CI, 0.78-5.13]). Results show that a multimodal approach to ovarian cancer screening in a randomized trial is feasible and justify a larger randomized trial to see whether screening affects mortality. |
1 |
15. Kobayashi H, Yamada Y, Sado T, et al. A randomized study of screening for ovarian cancer: a multicenter study in Japan. Int J Gynecol Cancer. 2008; 18(3):414-420. |
Experimental-Dx |
Intervention group (n=41,688) Control group (n=40,799) |
Prospective randomized controlled trial of ovarian cancer screening to establish an improved strategy for the early detection of cancers. |
27 cancers were detected in the 41,688-screened women. 8 more cancers were diagnosed outside the screening program. Detection rates of ovarian cancer were 0.31 per 1,000 at the prevalent screen and 0.38-0.74 per 1,000 at subsequent screens; they increased with successive screening rounds. Among the 40,779 control women, 32 women developed ovarian cancer. The proportion of stage I ovarian cancer was higher in the screened group (63%) than in the control group (38%), which did not reach statistical significance (P=0.2285). The rise in the detection of early-stage ovarian cancer in asymptomatic postmenopausal women is not significant, but future decisions on screening policy should be informed by further follow-up from this trial. |
1 |
16. Lu KH, Skates S, Hernandez MA, et al. A 2-stage ovarian cancer screening strategy using the Risk of Ovarian Cancer Algorithm (ROCA) identifies early-stage incident cancers and demonstrates high positive predictive value. Cancer 2013;119:3454-61. |
Observational-Dx |
4051 women |
To determine if this 2-step strategy has sufficiently high specificity and PPV for screening postmenopausal women at general population risk in the U.S. |
A total of 4051 women participated over 11 years. The average annual rate of referral to a CA125 test in 3 months was 5.8%, and the average annual referral rate to TVS and review by a gynecologic oncologist was 0.9%. Ten women underwent surgery on the basis of TVS, with 4 invasive ovarian cancers (1 with stage IA disease, 2 with stage IC disease, and 1 with stage IIB disease), 2 ovarian tumors of low malignant potential (both stage IA), 1 endometrial cancer (stage I), and 3 benign ovarian tumors, providing a positive predictive value of 40% (95% confidence interval = 12.2%, 73.8%) for detecting invasive ovarian cancer. The specificity was 99.9% (95% confidence interval = 99.7%, 100%). All 4 women with invasive ovarian cancer were enrolled in the study for at least 3 years with low-risk annual CA125 test values prior to rising CA125 levels. |
2 |
17. Menon U, Gentry-Maharaj A, Hallett R, 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(4):327-340. |
Experimental-Tx |
202,638 post-menopausal women |
Results of the prevalence (initial) screen of the UKCTOCS. Post-menopausal women were randomly assigned to no treatment (control; n=101,359); annual CA-125 screening (interpreted using a risk of ovarian cancer algorithm) with TVUS as a second-line test (multimodal screening; n=50,640); or annual screening with TVUS (US screening; n=50,639) alone in a 2:1:1 ratio using a computer-generated random number algorithm. |
Sensitivity, specificity, and PPVs for all primary ovarian and tubal cancers were 89.4%, 99.8%, and 43.3% for multimodal screening, and 84.9%, 98.2%, and 5.3% for US screening, respectively. For primary invasive epithelial ovarian and tubal cancers, the sensitivity, specificity, and PPVs were 89.5%, 99.8%, and 35.1% for multimodal screening, and 75.0%, 98.2%, and 2.8% for US screening, respectively. Significant difference in specificity (P<0.0001) but not sensitivity between the two screening groups for both primary ovarian and tubal cancers as well as primary epithelial invasive ovarian and tubal cancers. |
1 |
18. Menon U, Skates SJ, Lewis S, et al. Prospective study using the risk of ovarian cancer algorithm to screen for ovarian cancer. J Clin Oncol. 2005; 23(31):7919-7926. |
Experimental-Dx |
13,582 women recruited |
To evaluate prevalence screening in the first prospective trial of a new ovarian cancer screening strategy (risk of ovarian cancer or ROC algorithm) on the basis of age and CA 125 profile. |
Of 6,682 women randomly assigned to screening, 6,532 women underwent the first screen. After the initial CA 125, 5,213 women were classified as normal risk, 91 women elevated, and 1,228 women intermediate. On repeat CA 125 testing of the latter, a further 53 women were classified as elevated risk. All 144 women with elevated risk had TVUS. Sixteen women underwent surgery. Eleven women had benign pathology; one woman had ovarian recurrence of breast cancer; one woman had borderline; and three women had primary invasive epithelial ovarian cancer. The specificity and PPV for primary invasive epithelial ovarian cancer were 99.8% (95% CI, 99.7 to 99.9) and 19% (95% CI, 4.1 to 45.6), respectively. An ovarian cancer screening strategy using the ROC algorithm is feasible and can achieve high specificity and PPV in postmenopausal women. |
1 |
19. van Nagell JR, Jr., Miller RW, DeSimone CP, et al. Long-term survival of women with epithelial ovarian cancer detected by ultrasonographic screening. Obstet Gynecol 2011;118:1212-21. |
Observational-Dx |
37,293 women |
To estimate the effect of ultrasonographic screening on stage at detection and long-term disease-specific survival of women with epithelial ovarian cancer. |
Forty-seven invasive epithelial ovarian cancers and 15 epithelial ovarian tumors of low malignant potential were detected. No women with low malignant potential tumors experienced recurrent disease. Stage distribution for invasive epithelial cancers was: stage I, 22 (47%); stage II, 11 (23%); stage III, 14 (30%), and stage IV, 0 (0%). Follow-up varied from 2 months to 20.1 years (mean, 5.8 years). The 5-year survival rate for invasive epithelial ovarian cancers detected by screening was: stage I, 95%+/-4.8%; stage II, 77.1%+/-14.5%; and stage III, 76.2%+/-12.1%. The 5-year survival rate for all women with invasive epithelial ovarian cancer detected by screening as well as interval cancers was 74.8%+/-6.6% compared with 53.7%+/-2.3% for unscreened women with ovarian cancer from the same institution treated by the same surgical and chemotherapeutic protocols (P<.001). |
3 |
20. Reade CJ, Riva JJ, Busse JW, Goldsmith CH, Elit L. Risks and benefits of screening asymptomatic women for ovarian cancer: a systematic review and meta-analysis. Gynecol Oncol 2013;130:674-81. |
Meta-analysis |
10 trials |
To perform a systematic review and meta-analysis to quantify risks and benefits of screening asymptomatic women for ovarian cancer. |
Ten randomized trials proved eligible. Screening did not reduce all-cause mortality (relative risk (RR)=1.0, 95% confidence interval (CI) 0.96-1.06), ovarian cancer specific mortality (RR=1.08, 95% CI 0.84-1.38), or risk of diagnosis at an advanced stage (RR of diagnosis at FIGO stages III-IV=0.86, 95% CI 0.68-1.11). Transvaginal ultrasound resulted in a mean of 38 surgeries per ovarian cancer detected (95% CI 15.7-178.1) while screening with CA-125 led to 4 surgeries per ovarian cancer detected (95% CI 2.7-4.5). Surgery was associated with severe complications in 6% of women (95% CI 1%-11%). Quality of life was not affected by screening; however, women with false-positive results had increased cancer-specific distress compared to those with normal results (odds ratio (OR)=2.22, 95% CI 1.23-3.99). |
M |
21. Partridge E, Kreimer AR, Greenlee RT, et al. Results from four rounds of ovarian cancer screening in a randomized trial. Obstet Gynecol. 2009; 113(4):775-782. |
Experimental-Dx |
34,261 women |
Randomized trial to test whether annual screening with TVUS and CA-125 reduces ovarian cancer mortality. |
Among 34,261 screening arm women without prior oophorectomy, compliance with screening ranged from 83.1% (T0) to 77.6% (T3). Screen positivity rates declined slightly with TVUS, from 4.6 at T0 to 2.9-3.4 at T1-T3; CA 125 positivity rates (range 1.4%-1.8%) showed no time trend. 89 invasive ovarian or peritoneal cancers were diagnosed; 60 were screen detected. PPV and cancer yield per 10,000 women screened on the combination of tests were similar across screening rounds (range 1.0%-1.3% for PPV and 4.7-6.2 for yield); however, the biopsy (surgery) rate among screen positives decreased from 34% at T0 to 15-20% at T1-T3. The overall ratio of surgeries to screen-detected cancers was 19.5:1. 72% of screen-detected cases were late stage (III/IV). Through 4 screening rounds, the ratio of surgeries to screen-detected cancers was high, and most cases were late stage. However, the effect of screening on mortality is as yet unknown. |
1 |
22. Gaarenstroom KN, van der Hiel B, Tollenaar RA, et al. Efficacy of screening women at high risk of hereditary ovarian cancer: results of an 11-year cohort study. Int J Gynecol Cancer. 2006; 16 Suppl 1:54-59. |
Observational-Dx |
269 women |
Outcome of an 11-year cohort study on the value of screening women at high risk of hereditary ovarian cancer using TVUS and serum CA-125 testing. |
113 (42%) of 269 women had a pathogenic BRCA1 or BRCA2 mutation, and 127 (47%) of 269 women had salpingo-oophorectomy. Malignancy was found in 8 women having both elevated CA-125 levels and abnormal US findings. 4 of these cancers (one borderline, one stage Ia, one stage IIIb, and one stage IIIc ovarian or peritoneal cancer) were detected at the first screening visit. One stage IIIb and one stage IIIc cancer were detected at the second screening visit after 12 months, and two interval stage IIIc and IV cancers were detected 8 and 10 months after the first screening visit.). Because most cancers were detected at an advanced stage, value of screening women at high risk of ovarian cancer seems poor. |
3 |
23. Olivier RI, Lubsen-Brandsma MA, Verhoef S, van Beurden M. CA125 and transvaginal ultrasound monitoring in high-risk women cannot prevent the diagnosis of advanced ovarian cancer. Gynecol Oncol. 2006; 100(1):20-26. |
Observational-Dx |
312 women |
To evaluate ovarian cancer screening by means of pelvic examination, serum CA 125 and TVUS in a consecutive series of high-risk women. |
Among 10 women with an elevated CA 125 level and a positive TVUS, 3 screening carcinomas (one FIGO stage IC, one stage IIIB and one stage IV) and one interval carcinoma (stage IV) were detected. Five occult ovarian/fallopian tube carcinomas (two stage IA, one stage IC, one stage IIIB and one stage IV) after bilateral prophylactic (salpingo-) oophorectomy have been found in 152 women. The sensitivity, specificity, PPV and NPV of the combination of CA 125 and TVUS were the highest (40%, 99%, 40% and 99%) followed by CA 125 alone (50%, 96%, 13% and 99%), pelvic exam (40%, 98%, 21% and 99%) and TVUS, separately (40%, 90%, 6% and 99%). By combining CA 125 with TVUS results, a PPV of 40% was achieved. However, the diagnostic tools appear to be only sensitive in detecting ovarian cancer at an advanced stage, while three of four tumors with early-stage disease in this series had normal screening tests prior to the diagnosis. |
3 |
24. Stirling D, Evans DG, Pichert G, et al. Screening for familial ovarian cancer: failure of current protocols to detect ovarian cancer at an early stage according to the international Federation of gynecology and obstetrics system. J Clin Oncol 2005;23:5588-96. |
Observational-Dx |
1110 women |
To assess the effectiveness of annual ovarian cancer screening (transvaginal ultrasound and serum CA-125 estimation) in detecting presymptomatic ovarian cancer in women at increased genetic risk. |
Thirteen epithelial ovarian malignancies (12 invasive and one borderline), developed in the cohort. Ten tumors were detected at screening: three International Federation of Gynecology and Obstetrics (FIGO) stage I (including borderline), two stage II, four stage III, and one stage IV. Of the three cancers not detected by screening, two were stage III and one was stage IV; 29 women underwent diagnostic surgery but were found not to have ovarian cancer. Annual surveillance by transvaginal ultrasound scanning and serum CA-125 measurement in women at increased familial risk of ovarian cancer is ineffective in detecting tumors at a sufficiently early stage to influence prognosis. With a positive predictive value of 17% and a sensitivity of less than 50%, the performance of ultrasound does not satisfy the WHO screening standards. In addition, the combined protocol has a particularly high false-positive rate in premenopausal women, leading to unnecessary surgical intervention. |
3 |
25. van der Velde NM, Mourits MJ, Arts HJ, et al. Time to stop ovarian cancer screening in BRCA1/2 mutation carriers? Int J Cancer. 2009; 124(4):919-923. |
Observational-Dx |
241 consecutive women |
To determine the effectiveness of ovarian cancer screening in women with a BRCA1/2 mutation. |
3 ovarian cancers were detected during the surveillance period; 1 prevalent cancer, 1 interval cancer and 1 screen-detected cancer, all in an advanced stage (FIGO stage IIIc). A PPV of 20% was achieved for pelvic examination, 33% for TVUS and 6% for CA 125 estimation alone. The NPV were 99.4% for pelvic examination, 99.5% for TVUS and 99.4% for CA 125. All detected ovarian cancers were in an advanced stage, and sensitivities and PPVs of the screening modalities are low. Restricting the analyses to incident contacts that contained all 3 screening modalities did not substantially change the outcomes. Annual gynecological screening of women with a BRCA1/2 mutation to prevent advanced stage ovarian cancer is not effective. |
3 |
26. Rosenthal AN, Fraser L, Manchanda R, et al. Results of annual screening in phase I of the United Kingdom familial ovarian cancer screening study highlight the need for strict adherence to screening schedule. J Clin Oncol 2013;31:49-57. |
Observational-Dx |
3,563 women |
To establish the performance characteristics of annual transvaginal ultrasound and serum CA125 screening for women at high risk of ovarian/fallopian tube cancer (OC/FTC) and to investigate the impact of delayed screening interval and surgical intervention. |
Sensitivity for detection of incident OC/FTC at 1 year after last annual screen was 81.3% (95% CI, 54.3% to 96.0%) if occult cancers were classified as false negatives and 87.5% (95% CI, 61.7% to 98.5%) if they were classified as true positives. Positive and negative predictive values of incident screening were 25.5% (95% CI, 14.3 to 40.0) and 99.9% (95% CI, 99.8 to 100) respectively. Four (30.8%) of 13 incident screen-detected OC/FTCs were stage I or II. Compared with women screened in the year before diagnosis, those not screened in the year before diagnosis were more likely to have >/= stage IIIc disease (85.7% v 26.1%; P = .009). Screening interval was delayed by a median of 88 days before detection of incident OC/FTC. Median interval from detection screen to surgical intervention was 79 days in prevalent and incident OC/FTC. |
3 |
27. Rosenthal AN, Fraser LSM, Philpott S, et al. Evidence of Stage Shift in Women Diagnosed With Ovarian Cancer During Phase II of the United Kingdom Familial Ovarian Cancer Screening Study. Journal of Clinical Oncology. 35(13):1411-1420, 2017 May 01. |
Observational-Dx |
4348 women |
To establish the performance of screening with serum cancer antigen 125 (CA-125), interpreted using the risk of ovarian cancer algorithm (ROCA), and transvaginal sonography (TVS) for women at high risk of ovarian cancer (OC) or fallopian tube cancer (FTC). |
Between June 14, 2007, and May 15, 2012, 4,348 women underwent 13,728 women-years of screening. The median follow-up time was 4.8 years. Nineteen patients were diagnosed with invasive OC/FTC within 1 year of prior screening (13 diagnoses were screen-detected and six were occult at RRSO). No symptomatic interval cancers occurred. Ten (52.6%) of the total 19 diagnoses were stage I to II OC/FTC (CI, 28.9% to 75.6%). Of the 13 screen-detected cancers, five (38.5%) were stage I to II (CI, 13.9% to 68.4%). Of the six occult cancers, five (83.3%) were stage I to II (CI, 35.9% to 99.6%). Modeled sensitivity, positive predictive value, and negative predictive value for OC/FTC detection within 1 year were 94.7% (CI, 74.0% to 99.9%), 10.8% (6.5% to 16.5%), and 100% (CI, 100% to 100%), respectively. Seven (36.8%) of the 19 cancers diagnosed < 1 year after prior screen were stage IIIb to IV (CI, 16.3% to 61.6%) compared with 17 (94.4%) of 18 cancers diagnosed > 1 year after screening ended (CI, 72.7% to 99.9%; P < .001). Eighteen (94.8%) of 19 cancers diagnosed < 1 year after prior screen had zero residual disease (with lower surgical complexity, P = .16) (CI, 74.0% to 99.9%) compared with 13 (72.2%) of 18 cancers subsequently diagnosed (CI, 46.5% to 90.3%; P = .09). |
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28. Lacey JV, Jr., Greene MH, Buys SS, et al. Ovarian cancer screening in women with a family history of breast or ovarian cancer. Obstet Gynecol. 2006; 108(5):1176-1184. |
Experimental-Dx |
28,460 women |
To evaluate PPVs of CA 125 or TVUS screening for ovarian cancer according to family history of breast or ovarian cancer. |
Similar proportions (4.8%-5.0%) of women in each group had abnormal screening results. Higher-risk women were more likely than lower-risk women to undergo biopsy after a positive screen. Screening identified 43 invasive ovarian cancers. The PPVs for abnormal screening results were 0.7% in average-risk, 1.3% in moderate-risk, and 1.6% in high-risk groups; one ovarian cancer occurred among the breast cancer survivors. The PPVs for postbaseline abnormal screening results were also higher in the higher-risk groups. The PPVs did not significantly differ across risk groups. Probabilities of abnormal annual CA 125 and TVUS screens were similar across groups based on family history of breast or ovarian cancer. However, ovarian cancer was more likely to be diagnosed after an abnormal screening result among women at higher family history-based risk than among women at lower risk. |
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29. Lai T, Kessel B, Ahn HJ, Terada KY. Ovarian cancer screening in menopausal females with a family history of breast or ovarian cancer. J Gynecol Oncol 2016;27:e41. |
Observational-Dx |
78216 women |
To determine whether annual screening reduces ovarian cancer mortality in women with a family history of breast or ovarian cancer. |
There was no significant difference in overall mortality or disease specific mortality between the two arms. Ovarian cancer was diagnosed in 48 patients in the screening arm and 44 patients in the usual care arm. Screened patients were more likely to be diagnosed at an earlier stage than usual care patients. Patients in the screening arm diagnosed with ovarian cancer experienced a significantly improved survival compared to patients in the usual care arm; relative risk 0.66 (95% CI, 0.47 to 0.93). |
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30. National Academies of Sciences, Engineering, and Medicine; Division of Behavioral and Social Sciences and Education; Committee on National Statistics; Committee on Measuring Sex, Gender Identity, and Sexual Orientation. Measuring Sex, Gender Identity, and Sexual Orientation. In: Becker T, Chin M, Bates N, eds. Measuring Sex, Gender Identity, and Sexual Orientation. Washington (DC): National Academies Press (US) Copyright 2022 by the National Academy of Sciences. All rights reserved.; 2022. |
Review/Other-Dx |
N/A |
Sex and gender are often conflated under the assumptions that they are mutually determined and do not differ from each other; however, the growing visibility of transgender and intersex populations, as well as efforts to improve the measurement of sex and gender across many scientific fields, has demonstrated the need to reconsider how sex, gender, and the relationship between them are conceptualized. |
No abstract available. |
4 |
31. American College of Radiology. ACR Appropriateness Criteria® Radiation Dose Assessment Introduction. Available at: https://edge.sitecorecloud.io/americancoldf5f-acrorgf92a-productioncb02-3650/media/ACR/Files/Clinical/Appropriateness-Criteria/ACR-Appropriateness-Criteria-Radiation-Dose-Assessment-Introduction.pdf. |
Review/Other-Dx |
N/A |
To provide evidence-based guidelines on exposure of patients to ionizing radiation. |
No abstract available. |
4 |