By Marilynn Larkin
NEW YORK (Reuters Health) - 6/9/2019
Two prostate cancer risk calculators that estimate the probability of reclassification with or without biopsy were validated in five large cohorts, researchers say - but using the calculators in the clinic can be complicated.
"Both Canary Prostate Active Surveillance Study Risk Calculators (PASS-RCs) were externally validated by state-of-the-art statistical analyses in a broad spectrum of different real-life active surveillance cohorts," Dr. Frank-Jan Drost of Erasmus University Medical Center in Rotterdam told Reuters Health by email. "We showed that the use of the PASS-RCs could reduce the number of unnecessary surveillance biopsies."
That said, he noted, "the benefit coincided with some harm, and it cannot be ruled out that reclassification to a higher Gleason grade will be missed. Therefore, it is the balance between detecting reclassification and performing surveillance biopsies that is improved."
"The balance between reducing surveillance prostate biopsies and missing reclassification at that point in time- i.e., the net benefit - can be quantified with a so-called decision curve analysis, where net benefit is calculated for different risk thresholds," he explained. "Clinicians and patients should discuss their preferred risk threshold by shared decision-making and use the risk calculators accordingly."
"It is advised that the PASS risk calculators be implemented into daily practice after checking calibration in the local setting," he added. "This is to avoid suboptimal performance and a potential detrimental effect on individual risk assessment and subsequent shared decision making."
"This calibration can be done by a local statistician," he said.
The risk calculators are available at https://canarypass.org/pass-risk-calculator/.
Dr. Drost and colleagues used data up to November 2017 from the Movember Foundation's Global Action Plan active surveillance database to assess the external validity of two PASS-RCs. Specifically, the tools estimate the probability of reclassification (Gleason grade of 7 or greater, with or without >34% of biopsy cores positive for prostate cancer) on a surveillance biopsy, using a mix of months since last biopsy, age, body mass index, prostate-specific antigen, prostate volume, number of prior negative biopsies, and percentage (or ratio) of positive cores on last biopsy.
As reported online August 24 in European Urology, five validation cohorts involving 5,105 men on active surveillance were included in the analysis: Prostate Cancer Research International: Active Surveillance, Johns Hopkins, Toronto, Memorial Sloan Kettering Cancer Center, and University of California San Francisco.
Cohort sizes varied from 429 to 2,416 men. The median follow-up was 36 to 84 months, in both community and academic practices, and mainly in western countries.
The PASS-RCs were able to discriminate reasonably well between men with and without reclassification on biopsy (area under the receiver operating characteristic curve values of 0.68 and 0.65 for the two tools).
"The tools were moderately well calibrated, and had a greater net benefit than most default strategies, between a predicted 10% and 30% risk of reclassification," the authors concluded.
Dr. Drost said, "Further research incorporating contemporary methods of risk assessment such as MRI or DNA tests might further improve the balance between reducing surveillance biopsies while maintaining optimal and timely detection of disease progression."
David Y.T. Chen, Director, Urologic Oncology Fellowship Program at Fox Chase Cancer Center in Philadelphia, told Reuters Health, "The key limitation of this study is the recognition by the authors that the outcome of the calculator is variable, based on the aspects of the parameters of the cohort of men being examined. The risk calculators need to be examined in a local patient dataset first to determine their accuracy in a specific hospital or region (i.e., recalibration), before they can be clinically applied."
"The need for local validation is a major barrier to implementation," he said by email. "If these risk calculators are not ready for immediate use because the results...in a local practice may not mirror the results found in the study, then they unfortunately have no immediate clinical utility."
Echoing Dr. Drost, Dr. Chen noted that the current versions of the risk calculators do not include newer test information such as biomarkers and multiparametric MRI.
"So, this is an incremental advance on the current standard, but not practice-changing, and warrants further development of tools that incorporate additional tests," he concluded.
Eur Urol 2019.
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