Washington, DC (UroToday.com): Dr. Himisha Beltran gave an overview on the molecular and histological heterogeneity in prostate cancer. Prostate cancer is a multifocal disease with wide clinical variability between patients. Additionally, there is clonal heterogeneity in advanced prostate cancer. For example, about 20% have BRCA2 defects and others have several DNA-Repair defects.
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Prostate cancer is a multi-focal disease with distinct genomics. Phylogenies of multi-focal prostate cancer by whole genome sequencing are revealing tumor evolution. Currently, no single genomic mutation is shown to predict prognosis but requires combinations of mutation. Assays for risk stratification is dependent on tissue availability and even then on which tumor nodule to evaluate. Risk stratification may be different dependent on which nodule is evaluated. Question remains whether one or more tumor nodules are responsible for aggressive nature or metastasis. If so, do we need to identify the dominant lesion at diagnosis or do we need to assess multiple or all lesions.
Dr. Beltran then describes the monoclonal and polyclonal seeding model theory. Monoclonal theory suggests that metastatic cells share lesions from founding clonal and all metastatic cells are similar. Polyclonal theory suggests a higher genomic diversity in metastatic cells, which may come from several founding clones. There is evidence for both of these theories. Haffner et al (JCI 2013) described one patient that they followed from initial presentation to tumor progression to death due to malignancy. Mutation analysis at serial time-points in this patient identified the founding lethal clone. However, what was revealing was that the founding lethal clone was from the tumor nodule that was not the largest.
Dr. Beltran, therefore, suggests that dominant lesion may not be the one with the largest size or highest Gleason Grade but is one based on molecular features. This has implications clinically when one triages patient to active surveillance or to therapy.
Dr. Beltran concludes that molecular heterogeneity in prostate cancer is common. Opportunities exist for clinical investigation and assay development that captures tumor biology.
Himisha Beltran, MD.
Weill Cornell Medical College, James Buchanan Brady Foundation Department of Urology.
Mohammed Haseebuddin, MD. from the Society of Urologic Oncology Meeting - December 2 - 4, 2015 – Washington, DC.
Fox Chase Cancer Center, Philadelphia, PA.