Effective Ovarian Cancer Screening Still Elusive, New Results Show

A new report in the Journal of the American Medical Association (JAMA) found that a combination of screening tests for ovarian cancer had no benefit over the usual medical check-ups most women would have received.

The large study – part of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial – looked at the potential for annual screening with a cancer antigen 125 (CA-125) blood test and transvaginal ultrasound to reduce mortality from ovarian cancer (1) (study link).

Over 78,000 women aged 55 to 74 years were randomly assigned to undergo either annual screening (n=39,105) or usual care (n=39,111). A trial of this magnitude required collaboration from women and investigators at 10 screening centers.

The women in the intervention group were offered annual screening with CA-125 for 6 years and transvaginal ultrasound for 4 years. Test results were managed by the women and their providers. The women in the comparison group received their usual medical care. All participants were followed for up to 13 years for cancer diagnoses and death. Follow-up ended February 28, 2010, making the results timely and inline with recent health care in the United States.

Consistent with the rigorous evaluation of screening, mortality from ovarian cancer was used as the main outcome.

During follow-up, 212 women in the screening group were diagnosed with ovarian cancer, giving an incidence of 57 new cases per 100 000 women per year. Women in the comparison group had fewer cases of ovarian cancer diagnosed (176 cases, giving an incidence of 47 per 100 000 women per year). In the screening group, 118 women died due to ovarian cancer while in the usual care group only 100 women died from ovarian cancer.

The overall ratio for deaths in the intervention compared to the control group was 1.18 – meaning there was a greater, but non-significant, excess risk of death in the screening group.

Of course screening interventions have both positive results and false positive test results. Overall 3,285 women (out of the 39,000) had false-positive results, of these 1080 underwent surgical follow-up and 163 women experienced at least 1 serious complication (2).

As in any prevention trial, participants die from causes other than the focus of the study. Here, for example, 2,924 women in the intervention group died from all causes (excluding ovarian, colorectal, and lung cancer) and 2,914 women in the usual care group died. As expected, screening for ovarian cancer did not impact on mortality from all causes.

This study highlights the hopes and pitfalls of cancer screening. As a news commentary blog, we could probably write three posts a week about new cancer screening tests that grab headlines. Yet, the small number of tests actually proven effective points to how difficult it is to develop a screening test that actually does what a screening test should do – lower disease mortality, or in other words: save lives.

Based on preliminary studies, the screening combination of a CA-125 blood test and transvaginal ultrasound held promise but was found in this large randomized trial to have no effect on mortality and actually raised the risk of harm related to screening. With ovarian cancer a leading cause of cancer death in women, an effective screening test could have a great impact on cancer burden. Unfortunately, effective screening for ovarian cancer would seem to lie in modalities other than the combination of CA-125 and ultrasound used in the PLCO study .


1. Buys SS, Partridge E, Black A, Johnson CC, Lamerato L, Isaacs C, 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):2295-303.

2. Nyante SJ, Black A, Kreimer AR, Duggan MA, Carreon JD, Kessel B, et al. Pathologic findings following false-positive screening tests for ovarian cancer in the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial. Gynecol Oncol. 2011 Mar;120(3):474-9.

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