The IsoPSA assay better identified prostate cancer and benign disease than a PSA test, according to results of a prospective study.
These results suggest the novel assay may reduce the need for biopsy, thus leading to a reduction in the overtreatment and overdiagnosis of prostate cancer.
Eric L. Klein
“The methodology used in the IsoPSA assay represents a significant departure from conventional ways to define biomarkers in blood, and may be applicable to improving other cancer biomarkers,” Eric L. Klein, MD, chair of the Glickman Urological & Kidney Institute at Cleveland Clinic, said in a press release.
PSA has changed the detection, screening and management of prostate cancer. However, since it is not cancer specific, overdiagnosis and overtreatment of less detrimental cancers has called its clinical usefulness into question.
IsoPSA (Cleveland Diagnostics) is a blood- and structure-based assay that agnostically interrogates the entire spectrum of structural changes of complex PSA. It is used to predict prostate cancer risk by partitioning isoforms of PSA with an aqueous two-phase reagent.
Klein and colleagues enrolled 261 men scheduled for prostate biopsy — due to increased PSA level or abnormal digital rectal examination — from five urology centers. Researchers collected heparin plasma for IsoPSA between August 2015 and December 2016.
Efficacy of IsoPSA assay compared with a standard concentration–based assay for the detection of any prostate cancer compared with no cancer, as well as high-grade prostate cancer compared with low-grade cancer or benign disease, served as the primary endpoints.
Prostate cancer occurred in 53% of patients, and high-grade prostate cancer occurred in 34%.
Researchers used receiver-operating characteristic analysis to determine discrimination power and decision curve analysis to compare the net benefit of IsoPSA against other methods.
For cancer vs. no cancer, the area under the receiver-operating characteristic curve was 0.79 (95% CI, 0.73-0.84) for IsoPSA vs. 0.61 (95% CI, 0.54-0.67) for total PSA (P < .001). IsoPSA also outperformed total PSA in this measure for distinguishing high-grade cancer from low-grade cancer/benign disease (0.81; 95% CI, 0.74-0.86 vs. 0.69; 95% CI, 0.61-0.75; P < .005).
The decision curve analysis showed IsoPSA had a superior net benefit compared with no biopsy, all biopsy and the modified Prostate Cancer Prevention Trial Risk Calculator 2.0.
With the goal of detecting cancer vs. no cancer, the IsoPSA assay led to a 48% reduction in unneeded biopsies using a 35% cutoff for the assay compared with 4 ng/ml cutoff for PSA.
Further, for detecting high-grade prostate cancer vs. low-grade prostate cancer/benign disease, the assay led to a 45% reduction in unneeded biopsies at a 17% cutoff.
“Due to its inherent simplicity, requiring only a blood draw and presenting information to the physicians in familiar contest using a single number — just like PSA itself — we are quite hopeful in IsoPSA’s future utility after further validation studies,” study researcher Mark Stovsky, MD, MBA FACS, staff urologist at the Glickman Urological & Kidney Institute at Cleveland Clinic, said in the release.
While IsoPSA is an “intriguing” new option, more studies are needed to identify additional biomarkers, Devin N. Patel, MD, from the division of urology at Cedars-Sinai Medical Center, and Stephen J. Freeland, MD, director of the Center for Integrated Research in Cancer at Cedars-Sinai Medical Center, wrote in a related editorial.
“Until well-conducted comparative effectiveness studies are carried out, the field of prostate cancer biology will continue in the unfettered pursuit of more novel biomarkers and the medicine of diagnosing prostate cancer will be unmethodical in its use of these new tests,” Patel and Freeland wrote. – by Melinda Stevens
Disclosures: Klein reports no relevant financial disclosures. Stovsky is the chief medical officer of Cleveland Diagnostics and reports investment interest in the company. Other researcher report employment with Cleveland Diagnostics. Freeland reports a consultant role with and stock ownership in Armune BioScience, the manufacturer of the APIFINY blood test. Patel reports no relevant financial disclosures.