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Blood test superior to PSA for detecting high-grade prostate cancer
A novel blood test was more accurate than PSA screening for identifying patients with high-risk prostate cancer, according to findings presented at the Annual Meeting of the American Urological Association.
IsoPSA, (Cleveland Diagnostics) — a blood- and structure-based assay — could reduce the necessity of biopsies for prostate cancer, thereby reducing overdetection and overtreatment of the disease, researchers reported.
“To be clinically useful, a biomarker must be both tissue specific and cancer specific,” Eric Klein, MD, chairman of the Glickman Urological & Kidney Institute at Cleveland Clinic, said in a press release. “While PSA is prostate specific, it is not specific for prostate cancer, leading to diagnostic inaccuracy and too many unneeded biopsies.”
Klein and colleagues performed a prospective validation of the IsoPSA assay, evaluating plasma samples from multiple centers in both preliminary (n = 261) and validation (n = 123) trials. Researchers collected all samples within 30 days before prostate biopsy from patients with PSA levels of 2 ng/ml to 62.8 ng/ml.
Klein and colleagues evaluated the assay against 12 biopsy results as the gold standard, with a subset of 10 MRI-guided biopsies in the preliminary cohort and 42 in the validation cohort. The prevalence of high-grade patients was 33.7% in the preliminary cohort and 32.6% in the validation cohort.
A receiver operating characteristic curve analysis showed an area under the curve of 0.81 in the preliminary group and 0.82 in the validation group.
Nearly half of biopsies in both the preliminary and validation studies could have been avoided with the novel assay (45.1% vs. 47%).
“IsoPSA fulfills both the tissue and cancer specificity needed for a useful biomarker, and this validation study shows that it can more accurately detect high-grade cancer and reduce the rate of unneeded biopsies [among] patients at low risk of this disease,” Klein said. – by Andy Polhamus
Reference:
Klein E, et al. Abstract PD60-05. Presented at: Annual Meeting of the American Urological Association; May 18-21, 2018; San Francisco.
Disclosures: Cleveland Diagnostics, a company co-founded by Cleveland Clinic, developed IsoPSA and funded the study. Klein reports no relevant financial disclosures. One author is the chief medical officer of Cleveland Diagnostics and holds financial interest in the company.
Perspective
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PSA is a unique biomarker; it is produced almost entirely by the prostate gland and, hence, affords nearly 100% specificity to the prostate. Unfortunately, the PSA protein is produced by normal prostate tissue, and elevations in PSA can only hint at the possible presence of underlying carcinoma. Indeed, the sensitivity and specificity of PSA for detecting clinically significant prostate cancer is only moderately better than a flip of a coin. The result is that many insignificant cancers are detected because clinicians and patients fear missing more meaningful disease. Further, the harms of overdiagnosis have been heavily documented in the field of prostate cancer.
Clearly, there is space for more robust biomarker development. Over the past decade, there have been several PSA-based and non-PSA-based tests that have demonstrated some improvement in predictive abilities for prostate cancer. Work by Dr. Eric Klein’s group at Cleveland Clinic, along with a multi-institutional collaboration and in conjunction with commercial biomarker developer Cleveland Diagnostics, is taking a unique approach to identifying a better screening biomarker. Their biomarker, IsoPSA, is the result of partitioning isoforms of PSA in a two-phased aqueous solution and analyzing/quantitating the structural differences in PSA rather than quantifying total PSA, as is the standard of care.
The research group has previously published work on the development of IsoPSA and, at this meeting, they presented their validation of the test with a new cohort of men screened for prostate cancer. Researchers collected IsoPSA and total PSA blood tests and analyzed their ability to predict Gleason score of 7 or greater from Gleason 6 cancer/benign tissue using prostate biopsy tissue as the gold standard. The prevalence of high-grade disease was approximately 33% for both preliminary and validation cohorts. The area under the curve for the receiver operating characteristic curve for IsoPSA was 0.82, compared with 0.69 for total PSA seen in the preliminary cohort. At their chosen reference cutoff, the negative predictive value was 93.3%. Clinically, this meant that up to 47% of biopsies targeting high-risk disease could have been avoided.
This is a dramatic improvement over the use of total PSA, and an incremental improvement over the use of other potential biomarkers and PSA-based metrics. For screening, it is a test that I would gladly offer patients rather than total PSA. But, despite having a promising future, IsoPSA is fundamentally limited by the fact that it is a service offered by a single company. Its impact, therefore, will be limited until it can be performed in routine clinical labs, which would require the manufacturer to share their intellectual property. We should look forward to seeing how this test is unfolded in the years to come.