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Less is more when it comes to serial CA125 testing in ovarian cancer

Less is more when it comes to serial CA125 testing in ovarian cancer

ABSTRACT: Oncologists need to reconsider how to use a long-standing test, according to trial results that indicated no survival benefit for early detection of ovarian cancer recurrence.

ORLANDO—For the majority of women who undergo ovarian cancer treatment, disease relapse is a matter of when rather than if. These women could spend the rest of their lives undergoing regular CA125 serum marker testing. A recent study that compares the quality of life in early- and advanced-stage ovarian cancer survivors found that CA125 marker measurements for recurrence were, understandably, a source of anxiety for both groups.

Will the results of a European trial showing that detecting recurrence early did not lead to better overall survival free women from the clutches of CA125 testing? Gordon J. Rustin, MD, who presented the study results at ASCO 2009, certainly thinks so.

“For the first time, women can be reassured that there is no benefit to early detection of recurrence with routine CA125,” Dr. Rustin said during an ASCO press conference. “Even if the CA125 rises, chemotherapy can be safely delayed until they have signs and symptoms of recurrence. Women now have informed choices to be able to decide.”

Of course, the offer of that reassurance falls on the shoulders of physicians. “This is not going to result in a 180° change in behavior in the U.S. This is something that medical oncologists and gynecologic oncologists need to talk about,” said ASCO press conference moderator Eric Winer, MD, director, Breast Oncology Center, and chief, division of women’s cancers at Boston’s Dana-Farber Cancer Institute.

‘Far more chemo in their lifetimes’
For the MRC OV05/EORTEC 55955 trial, Dr. Rustin and colleagues enrolled 1,400 ovarian cancer patients who were in clinical complete remission after first-line platinum-based chemotherapy and showed a normal CA125. CA125 was measured every three months; patients and physicians were blinded to the results.

“If CA125 levels rose to more than twice the upper limit of normal, patients were randomized either to an early-treatment arm or a delayed-treatment arm, where they continued having blood tests every three months and started Rx only when they started showing signs and symptoms of relapse,” said Dr. Rustin, who is based at Mount Vernon Cancer Centre at Mount Vernon Hospital in London. His co-lead investigator was Maria van der Burg, MD, from Erasmus Medical Center and Daniel den Hoed Cancer Center in Rotterdam, the Netherlands.

Patients did not undergo CT scan confirmation of complete clinical remission, he explained. The primary outcome was overall survival. Additional endpoints were time to second-line treatment and time to third-line treatment or death. Quality of life assessments were also measured.

The investigators found that patients in the early-treatment arm started their second-line chemotherapy, based on the rising CA125, 4.8 months earlier than those who waited until they had signs and symptoms. “Although many of these women go on to have third- or fourth-line chemotherapy, the time to third-line chemotherapy was 4.6 months earlier in the early (treatment) group, indicating that early institution of chemotherapy did not induce a longer remission,” Dr. Rustin said.

The researchers concluded that early treatment based on rising CA125 did not improve survival and may have even decreased quality of life. “Women in the early arm got far more chemo in their lifetimes,” he said. Dr. Rustin told Oncology News International that he hopes to see the trial results published by the end of 2009.

What to tell patients?
In Dr. Winer’s estimation, gynecologic oncologists should take a cue from their breast cancer counterparts. “This puts ovarian cancer on the same playing field as breast cancer. When a woman is treated for breast cancer, we follow to detect the second primary. We’ve learned from randomized studies that there is no value in obtaining extensive diagnostic tests after treatment. This is always a long conversation with patients.”

Dr. Rustin said that he discourages patients in his practice from serial CA125 testing. “Most of my patients, when I give them the information, they say, ‘I do not want routine serial CA125 measurements.’ But I do tell them to look for likely signs of relapse. We offer rapid access to CA125 and blood tests to get them back on chemotherapy.”

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