If adopted, the active surveillance threshold would give physicians a tool in the management of men with localized prostate cancer and could spare many aggressive therapy or radiation and its side effects.
Data presented today at the American Urological Association (AUA) in New Orleans, Louisiana, showed how Myriad Genetics’ Prolaris test, which guides treatment for prostate cancer, can be incorporated into a composite score to gauge whether active surveillance (AS) is the best option for men with localized cancer.
In a 2-part process, researchers first established an AS threshold, which combines a Prolaris score and certain clinical features derived from evaluating data on 505 conservatively managed men with localized prostate cancer. To test the effectiveness of the AS threshold, researchers then evaluated it in 765 different conservatively managed men to see if the composite accurately predicted that AS was appropriate.
Not only did the AS threshold work, but when researchers evaluated their tool against additional patient data it performed better than even modeling suggested, according to results presented at AUA.
Finally, a separate analysis of data from 4218 patients who have been tested with Prolaris suggests that many more men could be candidates for AS than are referred for this option based solely on an evaluation of clinical features. Thus, use of the AS threshold could potentially spare more men the effects of cancer treatment and bring savings to the healthcare system.
“This is a very significant positive result in the management of patients with localized prostate cancer,” Michael Brawer, MD, vice president for Medical Affairs Myriad Genetic Laboratories, told The American Journal of Managed Care in an interview. Providing a cutoff point for determining who should be a candidate for AS gives doctors a new treatment tool, he said. Brawer said use of the new AS threshold is being discussed with physician groups.
Active surveillance, according to the American Cancer Society, consists of have a prostate-specific antigen (PSA) test and a digital rectal exam (DRE) every 3 to 6 months to check for any change in status. This approach has gained ground in clinical guidelines as both clinicians and patients have questioned whether patients should suffer the side effects of cancer therapy or radiation for slow-growing cancers, which can include erectile dysfunction and incontinence.
Creating the AS threshold. Myriad set out to give clinicians a clear benchmark to help them determine “who is a candidate for active surveillance and who is not,” said Brawer. Such a threshold has many advantages: it can clearly identify patients who need treatment, but it can also provide reassurance for patients who are candidates for active surveillance, but hear the word “cancer” and don’t want to feel they aren’t doing something.
To establish the AS threshold, researchers developed a measurement that combined the Prolaris score with clinical risk to predict prostate cancer mortality. This was developed by reviewing data from a group of 505 men in the United Kingdom who might be candidates for AS based on clinical results only: Gleason score of ≤ 3+4, PSA of < 10 ng/ml, < 25% cores positive, and clinical stage ≤ T2a. The resulting combined clinical risk or CCR score of 0.80 became the “cutoff” for which 90% of the men were below the threshold.
Validating the threshold. To test this cutoff point, researchers evaluated it against 765 conservatively managed prostate cancer patients. The predicted 10-year survival rate of these patients was 97%. However, among the 62 men in the group who were below the AS threshold, there were no deaths over 10 years.
A separate analysis of 4218 commercial patients who have received the Prolaris test found that 36% qualified for active surveillance based on clinical features. But if the AS threshold were applied instead, 60% fell below the level that could be considered eligible for this less aggressive approach to care.
Other results scheduled for presentation include the final data from PROCEDE 1000, the ongoing clinical utility study that includes data from 1206 patients. Neal Shore, MD, presented data showing that Prolaris tests caused physicians to change treatment plans in 48% of cases, with 72.1% opting for less aggressive treatment and 26.9% seeking more aggressive treatment.
“You want the treatment changes to be moving in both directions,” Brawer explained. “The clinical utility study shows that Prolaris does that.”
A major milestone awaiting the test will be Medicare reimbursement. Until now, Myriad has made the test available without reimbursement from the nation’s largest payer. Prolaris has passed muster with Palmetto GBA, whose MolDx program is highly influential in diagnostic testing decision-making. Myriad awaits the final local coverage determination from Noridian, which covers its territory. The company’s third-quarter update said Medicare revenue was not anticipated before the first quarter of fiscal 2016.
Cuzick J, Stone S, Fisher G, et al. Validation of an active surveillance threshold for the CCP score in conservatively managed men with localized prostate cancer. Presented at the Annual Meeting of the American Urological Association, New Orleans, Louisiana, May 15, 2015.