Does This Patient Really Need a Gyn Oncology Referral?

Increased use of two non-invasive laboratory tests would help internists and OB-GYN generalists better assess and monitor patients whose sonograms indicate an ovarian mass.

The tests, which are typically covered by insurance, monitor and assess risk of malignancy when masses have been identified by sonography, says Kevin Elias, MD, a Cleveland Clinic gynecologic oncologist and ovarian cancer researcher. They are especially useful for patients whose scan results are classified as “intermediate risk” using the Ovarian-Adnexal Reporting and Data System Ultrasound (O-RADS).

O-RADS scores are as follows:

0=Incomplete evaluation
1=Normal ovary
2=Almost certainly benign (less than 1% risk)
3=Low malignancy risk (1% to less than 10%)
4=Intermediate risk (10% to 50%)
5=High risk (more than 50%)

Any score up to 3 can be managed by the patient’s OB-GYN or internist; 5 should be referred directly to a gynecologic oncologist.

A score of 4, however, leads many doctors to automatically refer the patient to a specialist.

“When someone gets an O-RADS score of 4, it means the risk of cancer is anything from 10% to 50%, which is a very wide range,” says Dr. Elias. “But when we actually looked back at our data here at Cleveland Clinic, we found that when these patients had surgery, they had cancer 2% of the time.”

It is understandable that physicians want to avoid missing a malignancy. The result, however, is that “a lot of patients are sent to the Cancer Center who really don't need to be, thinking that they have cancer,” he says. “This creates a lot of anxiety for patients, and often it can take a little while for them to get in for an oncology appointment when a generalist could have managed them. It also makes it difficult for patients who actually have cancer to see us sooner. We want to enable those O-RADS 5 patients to get into the operating room right away. That's where these blood tests become really useful.”

Risk assessment

In 2009, the U.S. Food and Drug Administration approved a new blood test, Ova1® by Aspira Women’s Health, that uses proprietary software and tests for five biomarkers (transthyretin, apolipoprotein, beta 2-microglobulin, transferrin and cancer antigen) to assess the likelihood of malignancy in an ovarian mass.

“It has a bias toward sensitivity, meaning it is 97% sensitive for ovarian cancer,” says Dr. Elias. “If a patient comes back negative, there is really no need to send them to a GYN oncologist. It also considers whether a patient is pre-menopausal or post-menopausal.”

Ova1 has been added to Cleveland Clinic’s electronic medical record ordering system, and OB-GYN sonographers are now prompted to add a recommendation for it on reports when appropriate. The hope is that by reminding physicians of the test option, the health system can reduce financial and psychological stress associated with specialty referrals and open up more surgery slots for cases involving higher risk.

“As oncologists, we don’t mind operating on somebody who has benign disease. If every four out of five of these that we operated on were benign, that's OK. But if 49 out of 50 of them are benign, that's probably excessive. So we think these tests can really help make things more efficient and more convenient,” he says.

Ongoing monitoring

In 2022, Aspira Women’s Health introduced OvaWatch, which monitors patients with low-risk adnexal masses. The test incorporates the patient’s age, menopausal status and an additional series of protein biomarkers along with a proprietary algorithm to assess the probability of malignancy.

“In cases where you find an incidental cyst that is not particularly concerning, but you still want to observe the patient, the question becomes, how do I observe them?” Dr. Elias says. “Traditionally, we've repeated ultrasounds at six weeks, and then again at three months and six months. People have tended to want to use a CA-125 to monitor over time, but it's not approved for that nor shown to be helpful for serial monitoring of a cyst to determine the risk of cancer.”

Like Ova1, OvaWatch is biased toward sensitivity. “It has a greater than 99% negative-predictive value,” says Dr. Elias. “So if the test comes back negative, you can be reassured that it's perfectly safe to continue to observe.”

For patients, blood draws provide an alternative to transvaginal ultrasounds. “If the results change, then sending the patient for an oncology referral is totally appropriate,” he says. “The more we can help reassure people that low-risk masses are low-risk masses, and really cut down on people becoming over medicalized, the better. Even if a patient is ultimately referred to specialist, the test results provide helpful information."

“If you're still nervous and you want to send them to me in oncology, reviewing the lab result before I see the patient helps me considerably in counseling,” Dr. Elias adds. “It helps me prioritize. If I have two women in my clinic, and they both are coming in with a complex cyst on the ovary, I can now prioritize who needs to get onto the operating room schedule urgently. It can inform us about choosing where within the health system to do the surgery. Is this a surgery I really want to do at our Main Campus because it may turn into a significant ovarian cancer surgery, or can we do it someplace that might be more conveniently located for the patient?”

Addressing cost

It’s important for clinicians and patients to know the tests are covered by Medicare and most major insurers.

“Sometimes an alert will come up in the ordering system, suggesting the test could be expensive and might have to be paid out of pocket. It can often scare people by making them think it's going to cost thousands of dollars. Even for cash-paying patients, the cost is only about $200 dollars — compared to $100 for a CA-125 — and virtually every insurer will cover it,” says Dr. Elias. “Plus, the Ova1 includes a CA-125, so you do not need to order both tests.”

Markers for endometriosis

Soon, Cleveland Clinic expects to trial a lab test that can similarly help determine whether a patient has endometriosis, says Dr. Elias.
“Right now the only way to diagnose endometriosis is surgically, which usually involves laparoscopy and having a tissue diagnosis,” he says. “Many times, based on a woman's symptoms, she might be labeled as having endometriosis and be started on medical therapy. If she gets better, it’s assumed that that's what it was, and if she doesn't get better, then other causes or surgery are considered. The problem is that it takes the average patient about seven years from symptom onset to get an endometriosis diagnosis.”

Among those who go on to have surgery, negative results are found between 30% and 70% of the time.

A trial is planned to compare results of a lab test that aims to identify endometriosis against surgical results. The test is designed to work similarly to Ova1. A negative result would indicate no endometriosis, and other causes for symptoms should be investigated; a positive test would indicate that next steps should be taken to evaluate for endometriosis. Again, the hope is to provide decision-making tools to steer patients to the right clinicians sooner.