San Diego, CA USA (UroToday.com) In today’s International Prostate Forum at the 2016 AUA, Dr. Stephen Freedland discussed reclassification of genetic heterogeneity. Using breast cancer as an example, the historic treatment for all cancers was surgical resection; however as an understanding of tumor biology developed, molecular markers entered the management algorithm, and patients are now genetically risk stratified to guide treatment and prognosis.
Classic prognostic markers for prostate cancer are PSA, stage and grade. In the 2000s, we developed more sensitive markers such as PSA density, % cores, and tertiary patterns. Analogous to the sophistication of prognostic capability in breast cancer, the modern era of prostate cancer management now incorporates molecular markers.
Prostate markers for men with CaP include Prolaris, OncotypeDx, and Decipher. Prolaris is a tissue-based (biopsy) RT-PCR assay that includes 31 genes, and provides 10-year probability of CSM with conservative management. OncotypeDx is a tissue-based (biopsy) RT-PCR assay that includes 17 genes, and was developed for Gleason 3+3 and 3+4 disease with <=30% cores positive; OncotypeDx provides risk of adverse final pathology. Decipher uses tissue from prostatectomy in men with adverse pathology, and with a 22-gene RNA assay, provides 5-year probability of metastatic disease.
AR-V7 is another predictive marker which is a splice variant of the androgen receptor where the ligand binding domain has been eliminated, but the receptor remains persistently activated. DNA damage repair can be measured in the tumor sample, and confers sensitivity to PARP inhibitors. Alternatively, TMPRS2-ERG/ETS and SPINK1 status can be incorporated into management algorithms.
A novel classification system for CaP includes identification of subtypes 1, 2, or 3 (2 luminal and basal subtypes). Even within each subtype, there remains a degree of heterogeneity in aggressiveness. Despite this, models that incorporate these subtypes can predict progression to metastatic disease. The ultimate goal is to distill down the heterogeneity to understand the biology of disease.
Dr. Freedland concluded that cancer is heterogeneous by nature. Understanding heterogeneity can lead to better prognosis and treatment options. A clearer picture of prostate cancer heterogeneity is emerging, and we can take advantage of this to develop more predictive biomarkers.
Presented By: Stephen Freedland, MD