Ovarian Cancer Markers Validated for Early Detection

A rigorous validation study of more than 50 potential markers for detecting early signs of ovarian cancer in blood has found that the most accurate marker is CA-125, a protein that is already routinely monitored in women with the disease. Panels of markers tested in the study offered, at best, only marginal improvements in the ability to detect the disease over CA-125 alone.

CA-125 remains the single best biomarker for the early detection of this cancer, but its performance was nearly matched by HE4, and several other candidates showed promise, Dr. Daniel W. Cramer of the Brigham and Women’s Hospital said yesterday at the 100th Annual Meeting of the American Association for Cancer Research (AACR) in Denver.

Dr. Cramer presented the results on behalf of five research groups that have been evaluating the most promising markers for the early detection of ovarian cancer.

“The validation study was an incredibly useful experiment,” commented Dr. Michael Seiden, president of Fox Chase Cancer Center and a leader in NCI’s SPORE program for ovarian cancer. He noted that whether screening women for ovarian cancer saves lives is a question that can only be answered through large prospective screening trials such as one underway in the United Kingdom.

The study—a joint project of NCI’s Early Detection Research Network (EDRN) and the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial—was closely watched because it included many of the field’s experts and used high-quality PLCO blood samples, including prediagnostic samples from women who developed ovarian cancer during the trial.

“This was the first time a disparate group of investigators was brought together in an effort to systematically evaluate a panel of biomarkers,” said Dr. Sudhir Srivastava, who heads the EDRN program. In general, the performance of markers on prediagnostic blood drawn within 6 months of a diagnosis of ovarian cancer was comparable to the performance of markers assessed at the time of diagnosis.

Following the presentation at AACR, Dr. David Sidransky of the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center and chair of the EDRN called the study a “tour de force” and said the results deserve close attention. He pointed out that the vast majority of cancer biomarker candidates that are discovered and reported in the scientific literature never make it through systematic validation. Now there are several for ovarian cancer.

Nonetheless, he added, “it’s a little sobering at the end of all this to say that we’re back to CA-125.” Clearly, a high priority for the field is to find noninvasive markers for detecting the most deadly types of ovarian cancer in women before the disease is diagnosed. This is particularly challenging in ovarian cancer because many tumors may progress rapidly, he noted.

In women diagnosed with the cancer, blood levels of CA-125 are routinely measured to monitor how well a treatment is working or whether the cancer has come back. Only some women with ovarian cancer develop elevated levels, however, and levels can rise for reasons other than cancer.

The current guidelines of the U.S. Preventive Services Task Force do not recommend ovarian cancer screening with CA-125. Earlier this month another study using PLCO data concluded that screening women for ovarian cancer often led to unnecessary surgeries and failed to detect the disease in its early stages.

See also Ovarian Cancer Study Could Speed Early Detection (June 10, 2008).

—Edward R. Winstead