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Ovarian cancer ‘biomarker’ screening works to find disease early

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A two-step process that begins by looking for a sudden change in a cancer marker may hold the key to detecting ovarian cancer earlier in its development, when this often-lethal cancer is easier to treat successfully, says a new study published in the journal Cancer.

The study used a growing body of research on ovarian cancer to devise a strategy to identify women who need more intensive monitoring and not raise alarms or increase invasive surgery among women who are not likely to have developed the disease. It was conducted at seven sites in Texas, Iowa, Rhode Island and Florida.

Currently, some 70% of ovarian cancers are caught in advanced stages, when the prospects for a long-term cure are dismal -- less than 30%. When the disease is caught early, prompt treatment can raise the odds of a patient surviving to between 75% and 90%.

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But ovarian cancer’s early symptoms are not readily recognizable, and tests that might detect the disease early are costly, invasive and potentially dangerous. So cancer researchers have come to believe that an effective screening method for the disease must first use some reliable “biomarker” in the blood to narrow down the population at higher-than-usual risk of having the disease. That smaller set of women, in turn, would be monitored more intensively and if a second red flag appeared, physicians would act more aggressively to ferret out the disease while it still can be treated.

The biomarker used in this study -- carbohydrate antigen 125, or CA125 -- has been recognized for some years as a telltale sign of ovarian cancer. But only in recent studies have researchers begun to zero in on how it might be used to detect the active presence of ovarian cancer.

Led by researchers at M.D. Anderson Cancer Center in Houston, the team conducting the latest study looked not at absolute values of CA125 in women’s blood, but for changes in CA125. All the study’s 4,051 participants were post-menopausal, when the risk for ovarian cancer takes a sudden upturn.

Between 2001 and 2011, each woman had a baseline CA125 level taken and was tested thereafter once a year. Based on recent studies conducted in Great Britain and Sweden, the study authors stipulated a jump in a woman’s CA125 level above a certain point would place her in a higher-risk group, in which case her CA125 level would be checked every three months.

A steeper jump in CA125 would classify a woman as high-risk and steer her toward a transvaginal ultrasound, in which a radiologist and gynecologic oncologist would assess the need for exploratory surgery by looking for certain cystic formations or solid areas that could be clusters of cancerous cells.

Over the 11-year study period, 83.4% of the participants never tripped the alarm that called for CA125 testing more than once a year. Another 13.7% did trip that alarm, but never returned CA125 results that suggested the need for an ultrasound. Some 2.9% of the women -- 117 of 4,051 participants--were labeled as high-risk and thus recommended for a transvaginal ultrasound. The ultrasounds of 10 of those women led to surgery.

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Four of those 10 women were found to have early-stage high grade ovarian cancers, and one was ultimately found to have endometrial cancer. Three had benign cysts and two had ovarian tumors unlikely ever to become malignant. All the women with invasive ovarian cancers were treated and reported to be free of the disease anywhere from four to 42 months after treatment.

In recent years, cancer screening has come in for heightened scrutiny, in part because early detection does not always save lives and in part because early detection sometimes sets up a dragnet that sweeps many patients unnecessarily into procedures that are costly and risky. Researchers proposing screening protocols for ovarian cancer know that they will have to demonstrate that widespread screening of women passes muster on both counts -- that it saves womens’ lives and that it does so without costing too much or subjecting women who are healthy to intrusive, risky and costly surgery.

“More definitive data....is required” before those requirements can be satisfied, write the authors of the current study, led by gynecological oncologist Karen H. Lu of M.D. Anderson. Biomarkers other than CA125 still are being explored, the authors note, and may prove more telling than CA125. And in 2015, the results should be in from a 200,000-woman British study that will gauge whether earlier detection saves lives.

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