FDA Recommends Against Ovarian Cancer Screening and Industry Emphasizes Risk-Based Testing

The U.S. Food and Drug Administration (FDA) recommends against using currently available tests to screen for ovarian cancer, according to a safety communication the agency issued at the beginning of September. The FDA says there are risks associated with currently marketed, but not approved, ovarian cancer screening tests and the agency is especially concerned about inaccurate results that may delay effective, preventive treatments for asymptomatic women at increased risk for developing ovarian cancer.

Despite the fact that ovarian cancer is the fifth-leading cause of cancer-related deaths among women, there is no approved or recommended screening test for the disease. Yet, cancer antigen (CA) 125 tests are extensively used.

"From what we know anecdotally, in spite of the fact that CA 125 isn't really meant to be used that way, many women who are concerned about the risk of ovarian cancer are getting the test every year,'' Sarah DeFeo, vice president of scientific affairs for the Ovarian Cancer Research Fund Alliance, told STAT News. "In practice, lots of people are doing it."

Current recommendations against screening for ovarian cancer are based on the large U.S. Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, which found that annual CA 125 measurement (using a fixed cutoff value for a positive test result) and vaginal ultrasound were not associated with a reduction in ovarian cancer mortality. Additionally, screening was tied to significant harms from surgeries resulting from false-positive results.

However, the United Kingdom Collaborative Trial of Ovarian Cancer Screening, published in The Lancet in December 2015, similarly used multimodal screening—CA 125 and ultrasound—but relied on a risk of ovarian cancer algorithm (ROCA) instead of a fixed cutoff. Use of the algorithm did increase sensitivity and led to fewer unnecessary surgeries and a positive trend towards earlier diagnosis, but led to questionable improvements in mortality—only seen after seven to 10 years of screening. While the authors concluded by saying further follow-up was necessary "before firm conclusions can be reached on the efficacy and cost-effectiveness of ovarian cancer screening," the algorithm at the center of the protocol began to be commercially marketed, in the United Kingdom and in the United States (for $295).

Abcodia (United Kingdom), the company marketing the ROCA test, announced in mid-September that it was temporarily suspending its test in the United States while the company continues to engage with the FDA and the clinical community for further evaluation of the ROCA test.

With women concerned about ovarian cancer still left without a viable screening option, the industry is emphasizing availability of risk-based testing—either to assess for hereditary cancer risk using BRCA testing, or likelihood of an ovarian cancer malignancy in women presenting with a pelvic mass.

"We believe this clarity around the use of non-FDA approved test for ovarian cancer screening, demonstrates the need to manage high-risk, pelvic mass patients at the onset with our FDA-cleared technology," said Valerie Palmieri, CEO of Vermillion/ASPiRA Labs (Austin, Texas), which markets OVA1 and OVERA tests, in a statement. "No technology exists today to support screening, but we believe that our technology is the best available to assess risk, optimally manage patients, and lower overall healthcare costs."

Takeaway: Research continues to develop a sensitive screening test to evaluate the general population for ovarian cancer. In the absence of such a test, industry does have available tests to evaluate risk of hereditary ovarian cancer and the likelihood an ovarian mass is cancerous.