February 27, 2020

Ovarian Cancer: Challenges in Diagnostic Innovation

By Melissa Laitner, PhD, MPH, SWHR Director of Science Policy

In 2020, SWHR is bringing attention to the need for advances in diagnostic and screening tests across a variety of diseases and conditions to improve the health of women. In part two of our two-part blog series on ovarian cancer, we delve deeper into screening and diagnostics for the disease. For more information on ovarian cancer risk and mortality, see part one here.

Most women will never be screened for ovarian cancer. Unlike breast and cervical cancers — both of which have safe and effective screening tests — ovarian cancer research has struggled to produce reliable methods of screening.

The United States Preventative Services Task Force (USPSTF) currently advises against screening for asymptomatic women without a previously determined risk for the disease, a recommendation largely based on the high prevalence of inaccurate results.

Of all the women screened for ovarian cancer using current technology — including transvaginal ultrasound and the blood test for tumor marker CA-125 — a number of patients are likely to receive false-positives. Dr. Julia Smith, a medical oncologist at NYU Langone Health, told SWHR that neither test is specific enough and highly sensitive enough for reliably detecting early ovarian cancer.

Therefore, for many women, ovarian cancer screening comes down to dependence on screening mechanisms that may yield inaccurate results, and those results will likely lead to potentially invasive biopsies and surgeries to determine a definitive diagnosis.

“We need new, advanced techniques to detect ovarian cancer when it’s still in the early stages, confined to the ovary and the fallopian tube, so that it is highly curable,” Smith said.

Innovation has been slow for ovarian cancer, despite some promising recent breakthroughs. These advances include new ultrasound technology, including the use of photoacoustic imaging that uses laser pulses to help health care providers to better “see” if a tumor is forming. Scientists are also attempting to identify new ovarian cancer biomarkers — other than the questionably reliable CA-125 — that could be found using a simple urine or blood test. Other possibilities may one day include the ability to screen for certain rare mutations via a routine Pap test.

“We’ve been looking for a long time for tests looking at signals in the serum — in the blood — for early detection of abnormal markers,” Smith said. “That’s probably the most promising line.”

However, she warned that these types of new screening and diagnostics are far from reality. “Nobody should be relying on that at this point,” she said. “We’ve had promising results over the last 20 years, but there have been a number of times when a test has looked promising in early trials and has not panned out.”

When screening and diagnostic tests don’t meet certain efficacy standards, there can be consequences for patients. For example, in 2016, a laboratory-developed test that measures changes in CA-125 levels in the blood was pulled from the market after the FDA warned that false negatives resulting from such tests might delay necessary treatment.

These types of laboratory-developed tests (LDTs) used for screening and diagnostics have historically fallen outside FDA review. Instead, the laboratories that develop and perform these tests as services receive government oversight through the Centers for Medicare and Medicaid Services (CMS). However, over the past decade, the FDA and Congress have been working to develop a new regulatory paradigm for LDTs.

To promote both patient safety as well as timely innovation, there is a need for a sophisticated understanding of these laboratory developed tests. LDT-related legislation currently under development in the House and the Senate must encourage the development of LDTs that may be of great significance to women worried about possible cancer diagnoses. Legislation must ensure patient protection while still allowing test developers to maintain flexibility and efficiency when managing innovative technology. Tests must be able to evolve in a way that adheres to the latest science and evidence.

Another challenge for innovation in ovarian cancer is that gynecologic cancer research broadly remains underfunded compared to other cancer types. Prostate and breast cancers receive almost 20 times the research funding of that allocated for ovarian cancer when considering years of life lost to each disease. Recent gynecological cancer funding is actually declining when using similar funding versus lethality metrics.

In comparison, prostate cancer demonstrated the highest funding score using these methods and its mortality rate has decreased by 51% over the past 25 years. Mortality rates for ovarian cancer have largely remained steady — showing only a 1-2% decline — over a similar time frame.

“It’s always hard with things like ovarian cancer because it’s very rare compared to the number of cases for breast cancer,” Smith said. “But I do think that there’s also less attention than there should be to women’s illnesses in medical research, and we have to change that.”

More can also be done for patients — and especially those with genetic mutations, including those on the BRCA 1 and 2 genes, which put them at higher risk for both breast and ovarian cancer. Despite national guidelines encouraging genetic testing for women diagnosed with certain cancers, only about one-quarter of women with breast cancer and one-third of women with ovarian cancer receive this genetic testing.

This disparity between recommendation and reality suggests that many women may not understand their true cancer risk and may not have discussions about the risks and benefits of screening and preventative care with their health care provider. “Many health care providers are still not really familiar enough with who should be tested and where to get them tested, and how to get them to follow up on this,” Smith said.

Despite these challenges, she remains optimistic that ovarian cancer care is on the brink of a breakthrough. “It’s getting much better — I’ve been in this field since the BRCA genes were cloned in the mid-1990s and became available for commercial testing in the late ’90s,” Smith said. “The changes are enormous. In those days, it was very hard to convince doctors and patients of the usefulness and the validity of these tests. … There’s no question in my mind it’s hugely different now.”

But for now, ovarian cancer screening and diagnosis remains a grey area. Given that patients are unlikely to notice symptoms until the disease has spread, the lack of progress in this field is untenable if we seek to improve the health and longevity of women worldwide. There is hope to be found in new research, but policymakers must act to ensure appropriate funding, adequate oversight of current guidelines, and sophisticated and expedient regulation of new technologies. Until then, we can expect to see stagnant mortality rates and continued difficulty diagnosing the disease until the latest stages.