Introduction
- Prostate cancer is the most commonly diagnosed cancer in men in the United States (~174,650 in 2019), nearly 20% of all new cancers, and the second leading cause of cancer-related death (~31,620 in 2019).
- At diagnosis, there is a diverse spectrum of clinical course ranging from indolent features with a negligible likelihood of morbidity or mortality to characteristics reflecting near certitude of eventual metastases and cancer-specific death.
- Predicting future clinical behavior is imperfect but constitutes the foundation of physician counseling and patient management decisions.
- By utilizing additional biopsy data (e.g., total number or percent of positive cores), more nuanced risk stratification can be achieved (e.g., CAPRA score [www.guidelinecentral.com/CAPRA], nomograms [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2242430/figure/F1/]).
- A variety of molecular biomarkers have been developed, evaluated, and commercialized with an overarching aim to further personalize risk stratification, more comprehensively inform management decisions, and consequently improve quality of care.
Table 1. Definitions and Terms
| Molecular biomarker | A biological molecule found in blood, body fluid or tissue that provides information regarding presence or absence of a disease, prognosis, or likelihood to respond to a specific treatment. Molecular biomarkers broadly encompass DNA, transcriptome, protein, metabolic, and other tissue-based or cellular biomarkers |
| Cellular biomarker | Cells found in blood, body fluid or tissue that provide information regarding presence or absence of a disease, prognosis, or likelihood to respond to a specific treatment |
| Genomic biomarker | Genetic material (including DNA or RNA) found in blood, body fluid or tissue that provides information regarding presence or absence of a disease, prognosis, or likelihood to respond to a specific treatment |
| Active surveillance | Monitoring prostate cancer rather than immediately treating it |
| prostate cancer | Various definitions: in general, clinical, pathologic, or biomarker features of prostate cancer suggesting a possibility of becoming clinically relevant (symptoms or metastases) |
| Low-risk prostate cancer | Gleason score ≤6 (Grade group 1), PSA <10 ng/ml, and non-palpable or only palpable in less than half of one lobe of the prostate (clinical stage T1c or T2a) |
| Intermediate-risk prostate cancer | PSA 10-20 ng/ml, a clinical stage of T2b-T2c, or a Gleason score 7 (Grade group 2-3) grade without meeting any criteria for high-risk |
| High-risk prostate cancer | Clinical stage T3a, Gleason score ≥8 (Grade group ≥4), or PSA ≥20 ng/ml |
| Very high-risk prostate cancer | Clinical stage T3b-T4, any primary Gleason pattern 5 (Grade group 5) or >4 cores of Gleason score 8-10 (Grade group ≥4) |
| Assay validity | Comprehensive experiments that evaluate and document the quan-titative performance of an assay, including sensitivity, specificity, accuracy, precision, reproducibility, detection limit, range and limits of quantitation. |
| Analytic validity | How well a test predicts the presence or absence of a particular disease, condition, or state |
| Clinical validity | How well the test result is related to the presence, absence, or risk of a specific disease |
| Clinical utility | The ability of a screening or diagnostic test to prevent or ameliorate adverse health outcomes such as mortality, morbidity, or disability |
| Tumor heterogeneity | Variability amongst cancer cells including cellular morphology, genomic alterations, gene expression, metabolism, proliferation, and metastatic potential |
| Predictive Biomarker | Provides information regarding response to a specific treatment |
| Diagnostic Biomarker | Provides information regarding the likelihood of disease presence or absence |
| Prognostic Biomarker | Provides information about the patient’s overall cancer outcome (e.g., disease recurrence, progression, death) independent of treatment received. |
Diagnosis
- Commercially available molecular biomarkers (i.e., Oncotype Dx Prostate, Prolaris, Decipher, ProMark) may be offered in situations where the assay result, when considered in toto with routine clinical factors, is likely to impact management. Routine ordering of molecular biomarkers is not recommended (Moderate Recommendation; EB-I).
- Any additional molecular biomarkers evaluated do not have sufficient data to be clinically actionable or are not commercially available, thus should not be offered. (Moderate Recommendation; EB-Ins)
- The Expert Panel recommends consideration of a commercially available molecular biomarker (e.g., Decipher Genomic Classifier) in situations where the assay result, when considered in toto with routine clinical factors, is likely to impact management. In the absence of prospective clinical trial data, routine use of genomic biomarkers in the post-prostatectomy setting to determine adjuvant versus salvage radiation or to initiate systemic therapies should not be offered. (Moderate Recommendation; EB-I)
- In men with newly diagnosed prostate cancer eligible for active surveillance, both MRI and genomics intend to identify clinically significant cancers. The Expert Panel endorses their use only in situations where the result, when considered with routine clinical factors, is likely to impact management. This may include, for instance, in the initial management of men potentially eligible for active surveillance, where each of these approaches may provide clinically relevant and actionable information. These tests may provide information independent of routine clinical parameters and independent of one another. (Weak Recommendation; IC-U-L)
Table 2. Description of Assays
| Test(s) | Decipher Biopsy and Decipher PostOp | Oncotype Dx Genomic Prostate Score (GPS) | Prolaris Biopsy and Prolaris Postprostatectomy | ProMark, Proteomic Prognostic Test for Prostate Cancer |
|---|---|---|---|---|
| Company | Decipher Biosciences (formally Genome Dx Inc) | Genomic Health Inc. | Myriad Genetics, Inc. | MetaMark Genetics, Inc. |
| List price* (USD) | $5150 | $4520 | $3900 | $3900 |
| Sample requirement | FFPE tissue from:
| Tumor tissue from original biopsy in neutral buffered formalin prostatectomy specimens not accepted | FFPE tissue from:
| Requires tissue collected with patented biopsy kit available from MetaMark |
| Clinical utility/ Intended use |
| Biopsy-based likelihood of adverse pathologic features (grade group ≥3 or extracapsular extension). Identifies those who may benefit from surveillance vs treatment. | Aggressiveness of cancer: Provides 10-year risk of metastasis after definitive therapy and disease-specific mortality under conservative management. | Uses automated image recognition technology to determine likelihood of Grade Group ≥2 or stage ≥T3b. |
| Comments | Evaluates mRNA expression levels of 22 genes from FFPE tissue. Generates score from 0–1.0. | GPS ranges from 0–100 based on mRNA expression of 17 genes across four pathways. | mRNA expression of cell cycle progression genes is used to calculate the score. Clinical factors are subsequently added for risk assessment. | Expression of 8 proteins: Uses automated image recognition technology to generate a score from 1–100 indicating aggressiveness of prostate cancer. |
