A pilot randomized trial in the United Kingdom randomly assigned 10,977 women to a control group and 10,958 women to a screened group in 1989. The primary screen was the CA 125 test, followed by ultrasonography when CA 125 levels were elevated. Women were offered three annual screening rounds, and both groups were followed for 7 years. Compliance was 70.7% for all three screenings and 85.5% for at least one screening. There were 20 ovarian cancers in the control group and 16 in the screened group, only six of which were detected by screening. There was a higher proportion of stage I/II cancers in the screened group (31.3% vs. 10.0%). There were 18 ovarian cancer deaths in the control group and nine in the screened group (relative risk = 2.0; 95% confidence interval [CI], 0.78-5.13). The outcome for women with ovarian cancer in the control group, however, was unexpectedly poor.
Women with mutations in genes associated with breast and ovarian cancer family syndromes or hereditary nonpolyposis colorectal cancer are at an increased risk for the development of ovarian cancer. No controlled studies have evaluated the efficacy of ovarian cancer screening in this population. A Dutch study of BRCA1- or BRCA2-mutation carriers involved surveillance via annual TVUs and serum CA 125 measurements beginning in women aged 30 to 35 years. Six cases of ovarian cancer were detected, all of which were in the advanced stage of disease.[22,23]
Combined Screening With CA 125 and TVU
The objective of the ovarian component of the PLCO trial was to evaluate the effect of screening on ovarian cancer mortality. The trial included 78,216 women aged 55 to 74 years who were randomly assigned to undergo either annual screening (n = 39,105) or usual care (n = 39,111) at ten screening centers across the United States between November 1993 and July 2001. The intervention group was offered annual screening with CA 125 for 6 years and TVU for 4 years. Participants and their health care practitioners received the screening test results and managed evaluation of abnormal results. The usual care group was not offered screening with CA 125 or TVU but received their usual medical care. Participants were followed for a maximum of 13 years (median, 12.4 years; range, 10.9-13.0 years) for cancer diagnoses and death until February 28, 2010. Mortality from ovarian cancer, including primary peritoneal and fallopian tube cancers, was the main outcome measure. Secondary outcomes included ovarian cancer incidence and complications associated with screening examinations and diagnostic procedures.
Compliance with screening ranged from 85% at the initial round to 73% at the sixth round, while contamination in the usual care group ranged from about 3.0% for CA 125 to 4.6% for TVU. Across the first four screening rounds, 11.1% of women had at least one positive test, 8.1% had at least one positive TVU, and 3.4% had at least one positive CA 125 test. The yields of both tests were similar. Ovarian cancer was diagnosed in 212 women (5.7 per 10,000 person-years) in the intervention group and 176 women (4.7 per 10,000 person-years) in the usual care group (rate ratio [RR], 1.21; 95% CI, 0.99-1.48). The stage distributions were similar by study group with stage III and IV cancers comprising the majority of cases in both the intervention group (163 cases, 77%) and the usual care group (137 cases, 78%). The cancer case treatment distributions were very similar between groups within each stage. 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 RR, 1.18; 95% CI, 0.82-1.71). Of the 3,285 women with false-positive results, 1,080 underwent surgical follow-up; of whom, 163 women experienced at least one serious complication (15%). A total of 1,771 women in the intervention group (7.7%) and 1,304 in the usual care group (5.8%) reported oophorectomy. 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 such deaths (76.2 per 10,000 person-years) in the usual care group (RR, 1.01; 95% CI, 0.96-1.06).[6,24]