CA 125 – to test or not to test

Dr. Weeks’ Comment:  A critically important part of the art of medicine is knowing what and when to test for disease markers or progression of an illness.  In men, the merit of th PSA, a screen for prostate cancer has come under scrutiny and now the merit of the ovarian cancer screen – the CA 125 is being challenged.  If you or someone you know has ovarian cancer, study this post and send it to your oncologist.

“The findings of the study are then best framed as routine surveillance with CA-125 testing is harmful in patients diagnosed with ovarian cancer in remission after initial treatment,” 

 

The ‘Fatal Attraction’ of an Ovarian Cancer Test

Nick Mulcahy

August 18, 2016

Use of a blood test in the monitoring of ovarian cancer patients who are in remission is an example of the “fatal attraction of more information” in medicine, according to an editorial published July 21 in JAMA Oncology.

The commonly used cancer antigen 125 (CA-125) test is irresistibly and destructively attractive to both oncologists and patients, suggests editorialist James Goodwin, MD, from the University of Texas Medical Branch, Galveston.

He explains that the routine use of the CA-125 test was proven to be “harmful” in this setting in a major clinical trial in 2009  ( ASCO Ann Meet Proc. 2009;27[18s]:1).

In that trial, patients randomized to routine CA-125 testing had no better survival and worse quality of life compared with patients who were randomized to clinical observation (and did not receive test results) because, overall, the test results triggered earlier second-line chemotherapy, which was not efficacious.

Now, 7 years later, a new study has been published as follow-up on this subject ”” to learn if the evidence from 2009 changed practice.

This new study, also published online in JAMA Oncology, prompted Dr Goodwin’s “fatal attraction” comment in the accompanying editorial.

The researchers, led by Katharine Esselen, MD, MBA, from Harvard Medical School in Boston, reviewed the use and frequency of CA-125 testing in 1241 women in remission after initial treatment of ovarian cancer at six National Cancer Institute-designated cancer centers from 2004 to 2011. They found that almost all of the study’s patients received CA-125 testing every 3 to 4 months, both before and after the 2009 study.

In short, the 2009 study results did not change CA-125 testing.

This becomes the leaping off point for Dr Goodwin’s editorial as he asks: “Why did practice not change?”

Physicians are capable of “rapid change in practice in the face of new information,” he says.

He cites an example: When a study showed an absolute survival improvement of 2% at 18 months after treatment with a taxane plus doxorubicin compared with doxorubicin alone in node-positive breast cancer, there was a doubling of use of the combination therapy within 3 months of an oral report of the findings (J Natl Cancer Inst. 2006;98[6]:382-388).

Dr Goodwin then proposes that two sets of factors contribute to the lack of change after the 2009 ovarian cancer study; the first is “the fundamental attractiveness of testing.”

Physicians practice in a sea of uncertainty.

“Physicians practice in a sea of uncertainty. Making life-altering decisions based on incomplete information is one of the major stresses of becoming a physician,” he writes. Thus physicians seek “more information through testing to reduce uncertainty.

This seems benign, suggests Dr Goodwin, who asks, “How could more information possibly hurt?” He also says that avoiding information “sounds antiscientific” and doctors are confident that they can interpret results “wisely.”

But these sentiments are not borne out by the new study.

When CA-125 tests revealed increased levels, second-line chemotherapy was initiated equally rapidly after and before the 2009 study results. And those results showed that this management (test followed by second-line chemotherapy) was inconsequential in terms of survival and detrimental to overall well-being.

This is where the metaphor of fatal attraction, which is a reference to a 1987 film about an extramarital affair, applies. Dr Goodwin suggests that the object of clinicians’ desire (in this case, a test result) can destructively backfire.

In discussing the second set of factors influencing the lack of practice change, Dr Goodwin faults the authors of the 2009 study results for not effectively “framing” the results of the study.

He explains that the approaches examined in the study were characterized as early versus delayed chemotherapy instead of CA-125 surveillance testing every 3 months versus no testing information.

“The findings of the study are then best framed as routine surveillance with CA-125 testing is harmful in patients diagnosed with ovarian cancer in remission after initial treatment,” he writes.

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Dr. Weeks’ Comment:  A critically important part of the art of medicine is knowing what and when to test for disease markers or progression of an illness.  In men, the merit of th PSA, a screen for prostate cancer has come under scrutiny and now the merit of the ovarian cancer screen – the CA…
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