 "New diagnostic tools for prostate cancer")
Dan Woska was weighing his treatment options after he was found to have prostate cancer two years ago when a friend mentioned a new genomic test that could gauge how lethal his tumour was.
The test, called Oncotype DX, which looks at the expression of 17 genes in a tumour, cost about $4,000 and was not covered by Woska's insurance. But through a patient assistance programme, the company that created it, Genomic Health, ran it for him free, using a tiny grain of tissue left over from his biopsy. The results indicated there was an 81 per cent probability that his tumour would not spread beyond the prostate. On an aggressiveness scale of zero to 100, the tumour was an indolent 15.
Thrilled and relieved, Woska decided to forgo radiation and surgery.
"Everybody gets completely flipped out, 'I have cancer, I gotta get it out,'" said Woska, 63, a lawyer in Oklahoma City who now watches his condition closely with frequent checkups and a blood test every 90 days. "I am double-minded," he said. "I really don't want to have this cancer in my body, but everything is telling me this appears to be a low-risk cancer."
Decisions about prostate cancer treatment are fraught with such conundrums. Every year, about 220,800 American men receive a diagnosis of the disease, but one-third to one-half of all prostate cancers are not life-threatening, and most of those who have the disease do not die from it. The problem for patients is that doctors do not know how to distinguish the life-threatening cancers from the slow-growing ones.
Now, a plethora of new diagnostic tools aimed at distinguishing the aggressive cancers from the indolent ones - tests that "help tell us which ones are the bad guys," as the Genomic Health co-founder Steve Shak put it, are becoming available and more are in development.
But while they promise to help guide decisions like Woska's about whether to pursue treatment or engage in what doctors call "active surveillance," some experts advise that they may not have been adequately studied.
"A lot of companies are developing tests that may be promising, but they push them out the door into clinical practice without really doing all their homework," said David F Penson, the chairman of urologic surgery at Vanderbilt University Medical Center, who added, "The rules for new lab tests aren't as rigorous as the rules for new drugs."
The Food and Drug Administration does not regulate tests that are developed and manufactured in a single laboratory, but the agency is seeking to extend its oversight into this rapidly growing field to ensure that these tests are not only accurate and reliable but clinically meaningful in guiding treatment decisions.
In November, the agency issued a report criticising 20 lab-developed tests for various diseases that mentioned Myriad's Prolaris prostate cancer biomarker test, saying it had not been studied adequately for clinical use and could lead to overtreatment or undertreatment of cancer. (Myriad officials say the test has been validated and studied in thousands of patients, with 10 retrospective studies published in peer-reviewed journals.)
Much of the interest in new screening stems from the reality that the Prostate Specific Antigen, or PSA, blood test used to screen men at annual checkups can be misleading, often suggesting cancer where there is none. Even pathology reports on tissue from biopsies that confirm prostate cancer often fail to provide a clear picture of how the cancer is likely to behave.
The fog of information is particularly problematic because surgery and radiation treatments for prostate cancer can have serious side effects, like incontinence and sexual dysfunction. In 2012, a national task force found the risks of routine PSA blood screening tests outweighed the benefits, but last month, some experts expressed concern when studies found that fewer early-stage prostate cancers are being detected and fewer men are being screened.
The holy grail test for prostate cancer that scientists are seeking is a "liquid biopsy" - a minimally invasive test that can be performed on blood or urine and is capable of detecting "the prostate cancers that kill and need to be treated, versus those that don't kill," said Dr. Otis Brawley, chief medical officer for the American Cancer Society.
Researchers, often working in collaboration with industry, are inching closer to this goal. The company MDxHealth plans to introduce a noninvasive urine-based molecular test called SelectMDx in the United States early next year. The test, which is already available outside the country, measures messenger RNA levels of biomarkers associated with an increased probability of aggressive disease. It is intended to help determine whether an initial prostate biopsy is needed - gauging not just the likelihood of detecting cancer upon biopsy, but the probability of high-grade versus a low-grade tumor.
Dr. Philip Ginsburg, executive vice president and chief medical officer of MDxHealth, based in Irvine, Calif., said the tests were designed to be prognostic rather than diagnostic.
"At the end of the day, our test, and most other tests, should be seen as aids to patient management," he said, "and not regarded as a sine qua non."
Last month, Swedish researchers reported good results with their new version of a liquid biopsy, a blood test that analyzes more than 200 genetic markers called S.N.P.s (or single nucleotide polymorphisms) associated with prostate cancer, as well as six prostate protein markers. The researchers also incorporate personal medical information like age and family history into the calculations.
The scientists ran both the P.S.A. blood test and the new test, called the STHLM3 test, on 58,818 men in their 50s and 60s, and reported that the STHLM3 test reduced false positives, cutting the number of biopsies by nearly one-third while finding aggressive cancers in men with low P.S.A. levels who would have been missed. The study was published in The Lancet Oncology.
Dr. Joseph Presti, lead urologic surgeon at the Kaiser Permanente Oakland Medical Center, said the test had enormous potential because it was "just like walking in and getting your P.S.A." but is far more accurate and precise. He hopes to start a clinical trial in the United States soon.
But even as new tests are being developed, existing technologies, like magnetic resonance imaging scans of the prostate, are being improved and retooled. The P.S.A. test may be flawed, but most physicians say it is a valuable tool. The challenge is to use it more wisely, said Dr. James Eastham, chief of urology at Memorial Sloan Kettering Cancer Center. "It's probably one of the better screening tools we have, but it comes with a big asterisk: It has to be used appropriately."
©2015 The New York Times News Service
