Since the implementation of PSA testing, the number of PCa diagnoses has multiplied. Biomarkers are increasingly used to prevent overdiagnosis and overtreatment. New approaches, but also limitations, of microbiological testing were discussed at the 2018 AUA Annual Meeting.
Prostate cancer is the most commonly diagnosed cancer in men in industrialized countries [1]. After prostate-specific antigen (PSA) became detectable in 1986, its detection rapidly advanced to become the favored method for the early detection of prostate cancer. Metastases were reduced by nearly half as a result, and the prostate cancer-specific mortality rate decreased [2,3]. However, the method is criticized for its inaccuracy, especially since PSA is a non-cancer-specific glycoprotein whose presence does not necessarily indicate prostate cancer. Unnecessary biopsies and overdetection will now be reduced by working with more precise biomarkers. In addition, new molecular biological test methods should allow assessments regarding prognosis and facilitate the decision as to whether a patient requires therapy or whether active surveillance (AS) is sufficient. Perspectives opened the annual meeting of the American Urological Association (AUA) in San Francisco.
New approach to specifying PSA values
The structure-based biomarker IsoPSA™ may, among other things, provide the ability to distinguish high-grade (Gleason ≥7) from lower-grade carcinomas. This is the conclusion of a multicenter study conducted by the developer Cleveland Diagnostics and led by Mark Stovsky, MD [4]. Patients whose PSA level exceeded 2 ng/ml were studied. The study contrasted isoPSA analyses with results from punch biopsies with TRUS. Both the preliminary (n=261) and validation (n=123) studies showed that an IsoPSA test would have eliminated the need for nearly half of the biopsies. ROC analysis showed an AUC of 0.82 in the validation study, with a negative predictive value of 93.3%. The discriminatory ability of the new biomarker can thus be considered high.
It is envisaged that IsoPSA will be used as soon as a patient has critical PSA levels. If the test is negative, further observation is sufficient. However, if it is positive, MRI and biopsies are useful for further evaluation. Eric Klein, MD, director of the Glickman Urological & Kidney Institute at the Cleveland Clinic, hopes that combining new molecular biology approaches with MRI imaging will help discriminate against those patients not previously detected by MRI.
Genome testing on the test bench
Despite promising approaches, comparatively few biomarkers are actually used in clinical practice internationally. This is due to the lack of broad, cross-institutional studies on the cost-benefit ratio of such methods [5]. No statistically significant result, but food for thought was provided by a study at Hartford Hospital in Connecticut.
Three early diagnostic genomic tests – Oncotype DX, Prolaris, and Decipher – were reviewed for concordance. To do this, 22 patients who had undergone at least two of the three tests between 2014 and 2017 were selected after a retrospective review of patient records from Hartford Hospital. Of these, 21 met criteria for AS according to the National Comprehensive Cancer Network (NCCN). In their study, lead investigator Joseph Wagner, MD, and his team compared the extent to which genomic tests performed confirmed this assessment. Here, “considerable differences” became apparent: while Prolaris tests were 75% compliant with NCCN recommendations for AS, Decipher was 60%, and Oncotype DX was only half. However, that doesn’t make Prolaris the better process, Wagner says. However, the study suggests that “Prolaris tends most to confirm the NCCN recommendations, while Oncotype DX tends to contradict them.” Test results could also be contradictory at the individual level. For example, patients who underwent both Decipher and Prolaris testing received divergent results in one-third of cases. Although a sample of 22 subjects is not very informative, the result of the study nevertheless emphasizes the complexity of molecular biological methods for risk assessment.
Source: American Urological Association (AUA) Annual Meeting, May 18-21, 2018, San Francisco.
Literature:
- Torre LA, et al: Global Cancer Statistics, 2012. CA Cancer J Clin 2015; 65: 87-108.
- Welch HG, Gorski DH, Albertsen PC: Trends in Metastatic Breast and Prostate Cancer – Lessons in Cancer Dynamics. N Engl J Med 2015; 373(18): 1685-1687.
- Etzioni R, et al: Quantifying the role of PSA screening in the US prostate cancer mortality decline. Cancer Causes Control 2008; 19(2): 175-181.
- Klein EA, et al: The Single-parameter, Structure-based IsoPSA Assay Demonstrates Improved Diagnostic Accuracy for Detection of Any Prostate Cancer and High-grade Prostate Cancer Compared to a Concentration-based Assay of Total Prostate-specific Antigen: A Preliminary Report. European Urology 2017; 72: 942-949.
- Cucchiara V, et al: Genomic markers in prostate cancer decision making. European Urology 2018; 73: 572-582.
HAUSARZT PRAXIS 2018; 13(6): 46-47
