ASCO 2023: A Multi-Center Natural History Study of Precision-Based Genomics in Prostate Cancer

(UroToday.com) The 2023 American Society of Clinical Oncology (ASCO) annual meeting held in Chicago, IL between June 2nd and June 6th was host to a prostate, testicular, and penile cancers poster session. Dr. Fatima Karzai presented the rationale and study framework for a prospective, multicenter cohort natural history study of precision-based genomics in prostate cancer.



Germline and somatic mutations have significant prognostic and predictive implications for treatment selection, particularly with the emergence of PARP inhibitors, and as such routine genetic testing is widely recommended for patients with evidence of advanced disease. Clinical genomic sequencing not only identifies actionable targets but also allows for the identification of less common mutations with unclear prognostic and/or prognostic values. Integrative genomic sequencing studies of uncommon subgroups of prostate cancer patients may allow for the identification of new predictive and resistance patterns, facilitating the development of new biomarkers in this space. As such, acceleration of precision management strategies in prostate cancer is key.

This study is a planned multi-institutional, prospective observational cohort study that will collect clinical and genomic data for prostate cancer patients across all stages of the disease. This study will focus on those patients with distinct molecular alterations and/or exceptional clinical responses (with or without molecular alterations). The eligibility criteria are as follows:

  • Mutations in PIK3A, PIK3CB, and/or AKT, PALB2, BRIP1, RAD50, RAD51, RAD54, RB1, SPOP, Wnt/B-catenin pathway, MMR genes (MLH1, MSH2, MSH6, PMS2), EPCAM and/or tumor mutational burden-high (as defined by TMB ≥ 10 mutations/Mb).
    • Any platform for genomic testing is acceptable
  • Exceptional responders, are defined as:
    • Complete response or partial response of any duration to systemic therapy
    • Response of an exceptional duration

The primary objectives are to:

  • Define the natural history of men with select alterations and/or exceptional responses
  • Establish a biospecimen repository for extensive molecular analyses

This study will allow for a better understanding of molecular genetics in a longitudinal cohort of prostate cancer patients and may assist with the future design of drug trials in this disease space, as well as deepen our understanding of the natural history of this disease. Dr. Karzai did note that correlative studies using tissue and blood samples are ongoing.NATURAL HISTORY STUDY

 

Presented by: Fatima Karzai MD, Associate Research Physician and Clinical Director in the Genitourinary Malignancies Branch, National Cancer Institute, Bethesda, MD

Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 2 – Tues, June 6, 2023.