Figure 1 – Role of biomarkers in prostate cancer:
Biomarkers in focal therapy can be used for localization of occult clinically significant prostate cancer and characterization of occult biological potential. Biomarkers used for localization should risk stratify to make sure we are not missing anything more aggressive than we know about. These include:
- Multiparametric MRI
- Serum markers: PHI and 4K score
- Urine markers: SelectMDX
- Tissue markers – ConfirmMDX
Biomarkers used for the characterization of biological potential should be able to help patients and surgeons quantify the potential risk of cancer progression. These include tissue markers (PTEN, LPL/8p loss, Myc/8q gain, PROLARIS, OncotypeDX prostate, Decipher prostate).
Next, Dr. Siddiqui elaborated on several select biomarkers. The first was the PHI – prostate health index biomarker. This is a blood test, and it is composed of total PSA, free PSA, and the PSA isoform [-2]proPSA. It has better accuracy for the identification of Gleason group >2 than PSA. When it is elevated in primarily very low-risk patients, it has been shown to be correlated with grade reclassification.
4K score is similar to PHI in concept and performance. It uses free PSA, Intact PSA, total PSA, and Hk2. The area under the curve (AUC) for identification of group grade >2 disease is 0.82 in an analysis of screened men from the ProtecT trial1 and in 15000 men reported in over ten publications2.
vSelectMDX (urine HOXC6 and DLX1) is another diagnostic tool performed in a urine sample after a digital rectal examination. It measures mRNAs and combines clinical features into an algorithm. The AUC is significantly higher than for that of PCA3 biomarker for the detection of grade group >2 prostate cancer.
CONFIRM MDX is an epigenetic test in tissue obtained from biopsies. It searches for methylation patterns in genes of the surrounding tissue of the biopsy (GSTP, APC, and RASSF1). It has been shown to have a negative predictive value of 90% and is currently available for repeat biopsy after a negative biopsy. It is useful for confirmation of negative biopsies in patients with a high clinical suspicion but with a negative biopsy.
Prolaris is a real-time quantitative reverse transcription PCR test measuring 31 cell-cycle genes normalized to 15 housekeeping genes. It provides an independent prediction of prostate cancer-specific mortality in patients being followed with progression after radical prostatectomy. It is currently marketed for use in men diagnosed with very low risk and low-risk prostate cancer.
OncotypeDX is also a real-time quantitative reverse transcription PCR test of 12 genes and five house-keeping genes. It predicts favorable pathology (pT2 and grade group of 2 or less). Each 20-point increase in the genomic prostate score (GPS) equals a 2-fold increased risk of >=4+3 Gleason disease or pT3 disease at radical prostatectomy. It is currently marketed for men with low- to low-intermediate risk disease considering active surveillance.
Decipher is a high-density array (1.4 million probes) predicting high-grade disease, 5-year metastasis rate, and 10-year prostate cancer-specific mortality rate. It reports 22 genomic marker signatures, and it correlates with grade and stage. It is an independent predictor of metastatic progression and prostate cancer-specific mortality following therapy.
Summarizing this talk, Dr. Siddiqui reiterated that the role of biomarkers in patient selection for focal therapy is not defined yet. Studies are needed to test the utility of these tests/biomarkers in this specific population. In select clinical scenarios, biomarkers may hold significant benefit to guide patients and physicians in decision-making.
Presented by: Minhaj Siddiqui, MD, University of Maryland, Baltimore, MD
Written by: Hanan Goldberg, MD, MSc, Assistant Professor, Urology Department, SUNY Upstate Medical University, Syracuse, NY, USA @GoldbergHanan at the 2020 Society of Urologic Oncology Annual Meeting – December 2-5, 2020 – Washington, DC
- Bryant RJ, Sjoberg DD, Vickers AJ, et al. Predicting high-grade cancer at ten-core prostate biopsy using four kallikrein markers measured in blood in the ProtecT study. Journal of the National Cancer Institute 2015; 107(7).
- Punnen S, Pavan N, Parekh DJ. Finding the Wolf in Sheep's Clothing: The 4Kscore Is a Novel Blood Test That Can Accurately Identify the Risk of Aggressive Prostate Cancer. Reviews in urology 2015; 17(1): 3-13.