Experts keep lamenting this well-known problem. This spring, for example, a major report by the Institute of Medicine said that although women who receive care according to national guidelines have “improved survival, less than one-half of women with ovarian cancer receive such care.”
What the report didn’t say is that, since 2009, the U.S. Food and Drug Administration has approved two sophisticated blood tests that can help women get the optimal surgery for ovarian cancer. But the tests – OVA1 and ROMA – have not been widely adopted, largely because they haven’t been recommended by the physician groups that write the care guidelines.
The reasons are nearly as complex as ovarian cancer, a disease with 22,000 new U.S. diagnoses and 14,000 deaths a year. Some experts say that the tests’ track records are too short, or worry that the technology could be misused, leading to unnecessary surgery or delayed diagnosis.
In any case, the Texas-based company that developed OVA1 is trying hard to get traction for its test, and a “next-generation” version called Overa, which it says will be available “in the coming year.” Vermillion is marketing directly to women, hiring celebrity ovarian cancer survivors for an awareness campaign with the catchphrase “Know Pelvic Mass.”
Pelvic mass is a catchall term for an abnormal growth in the ovaries or pelvic area.
These lumps and enlargements are common and often get discovered incidentally during, say, a gynecological checkup. But some masses are tough to diagnose with certainty. Every year, an estimated 100,000 women have surgery to do that.
That’s where OVA1 or ROMA come in. They are approved to help decide whether the woman’s surgery should be done by a gynecologic oncologist instead of an obstetrician-gynecologist or general surgeon.
The referral to a gyn-onc can be crucial. Ovarian cancer has no early-detection screening test, so it is usually found after it has spread through the pelvis or beyond. Thus, the operation to diagnose a suspicious mass may turn into a marathon cancer surgery called “debulking.”
Gyn-oncs are trained in debulking, removing all visible cancer in hopes that aggressive chemotherapy can kill remaining cells. The operation may involve taking out the spleen, abdominal membranes and digestive organs, as well as reproductive organs.
OVA1 and ROMA fill “a pretty small niche, but an important one,” said Calaneet Balas, vice president of the National Ovarian Cancer Research Fund Alliance, an advocacy group. “We know that if women have the surgery by a gynecologic oncologist first, their outcomes are much better.”
ROMA, sold by Fujirebio Diagnostics, measures two blood proteins (CA125 and HE4). OVA1 measures those two and three more. The data are plugged into a proprietary formula to tell the patient whether she’s at high or low risk of having a malignancy.
ROMA is $65 to $275, OVA1 is $1,495, and insurance coverage varies, according to the test-makers. Vermillion says a patient without insurance coverage pays a maximum of $450 for OVA1.
Company-sponsored studies have shown that each test is better than physicians’ clinical judgment alone at identifying women who have cancer, although the tests aren’t so good at ruling out noncancers.
In studies that led to FDA approval, combining ROMA or Ova1 with clinicians’ assessments better determined the patients who should be referred to a gyn-onc, identifying well over 90 percent of the women who actually had cancer. “Whether it’s ROMA or OVA1, I think these tests are useful,” said Richard Moore, a University of Rochester gyn-onc who led Fujirebio’s approval study.
The Fine Print
Still, he and others recognize that the technology could be misused for screening or diagnosis – purposes far beyond guiding the choice of a surgeon. That’s why the FDA requires each test to warn that “incorrect use . . . carries the risk of unnecessary testing, surgery, and/or delayed diagnosis.”
“We are extremely careful when we explain what its use is for, and not for,” said gyn-onc Judy Wolf, Vermillion’s chief medical officer. “But you can’t control what doctors do.” She said some doctors use the CA125 blood test for screening.
Though CA125 is valuable to look for recurrence of cancer, it is not recommended for screening because it can surge, for example, during menstruation. However, guidelines from the American College of Obstetricians and Gynecologists and the National Comprehensive Cancer Network (NCCN) recommend a CA125 test plus vaginal ultrasound imaging for a woman with nonspecific symptoms that could signal ovarian cancer, such as bloating and pain. A CT or MRI scan may be added, although these are expensive. A biopsy is usually avoided because it could spread cancer cells.
If the diagnostic workup is worrisome, or if the woman has a strong family history of breast or ovarian cancer, the guidelines call for referral or consultation with a gyn-onc.
But guidelines aren’t always followed.
Consider ovarian cancer survivor Sherry Pollex, 37. Two summers ago, she was caught in what her boyfriend, NASCAR driver Martin Truex Jr., calls “patient pinball” – bouncing between family doctor, ob-gyn and gastroenterologist near their home in Mooresville, NC., with no definite diagnosis.
Ovarian cancer is rare in women under 40, so it wasn’t an obvious suspect. However, she says her ob-gyn didn’t order a CA125 test even though she had ascites – fluid – in her abdomen and severe pelvic pain. She says he did multiple vaginal ultrasounds, reassuring her that she had benign ovarian cysts.
In desperation – and in retrospect, luckily – she called a family friend, a gastric surgeon, who ordered a CT scan. That test led to an immediate referral to a gyn-onc, which led to a seven-hour debulking surgery followed by chemotherapy.
The CT scan image “looked like a bomb went off in my body,” she said. “From my pelvis to my diaphragm, I was covered in tumors.”
Vermillion has hired Pollex and two other young, high-profile ovarian cancer survivors – Olympic gymnast Shannon Miller and Broadway star Valisia LeKae – for the awareness campaign.
Robert E. Bristow, a gyn-onc at the University of California-Irvine, has published much-cited studies showing that most women with ovarian cancer receive suboptimal care, shortening their lives by at least a year.
In some cases, women don’t go to a gyn-onc for surgery because of distance; there are only about 1,200 in the United States.
But subtler problems persist.
Some physicians “don’t have a full appreciation of the complexities of treatment,” said Bristow, a paid consultant to Vermillion. “It’s this antiquated thinking: ‘Oh, we just go in and do a hysterectomy and send the patient for chemo.’ ”
Such thinking is a bigger problem than identifying which women are likely to have cancer, said David O’Malley, an Ohio State gyn-onc who helped write the NCCN’s care guidelines.
“The problem is that sometimes even when they [ob-gyns] know there is ovarian cancer, they aren’t making the referral,” O’Malley said.
So far, the closest that ROMA and Ova1 have gotten to acceptance by physician groups is a 2013 statement by the Society of Gynecologic Oncology. It says tests that measure blood proteins “may be useful” in making referrals to gyn-oncs.
Moore, the Rochester gyn-onc, said he believes the tests just need more time to build a following.
“In 2011, we had a few publications on ROMA,” Moore said. “Since then, we’ve probably had over 200 independent validations worldwide. As the validation is more evident, you’ll see the community using these tests more and more.”
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