Annual Meeting of the NCI Cohort Consortium (Abstract Submission): Submission #4

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data:
  list_of_additional_authors:
    - add_author_degrees: M.D.
      affiliation: 'Department of Pathology, Johns Hopkins University School of Medicine'
      first_name: Lia
      last_name: 'De Paula Oliveria'
    - add_author_degrees: ''
      affiliation: 'Department of Epidemiology, Harvard T.H. Chan School of Public Health'
      first_name: Aidan
      last_name: Daluiski
    - add_author_degrees: M.D.
      affiliation: 'Department of Pathology, Johns Hopkins University School of Medicine'
      first_name: Adrianna
      last_name: 'Amaral de Aragao'
    - add_author_degrees: M.P.H.
      affiliation: 'Department of Epidemiology, Harvard T.H. Chan School of Public Health'
      first_name: 'Jane B.'
      last_name: Vaselkiv
    - add_author_degrees: 'M.B. B.Ch B.A.O., M.P.H.'
      affiliation: 'Department of Histopathology and Morbid Anatomy, Trinity Translational Medicine Institute, Trinity College Dublin'
      first_name: Sinead
      last_name: Flanagan
    - add_author_degrees: M.S.
      affiliation: 'Department of Epidemiology, Harvard T.H. Chan School of Public Health'
      first_name: Colleen
      last_name: McGrath
    - add_author_degrees: M.S.
      affiliation: 'Department of Epidemiological Methods and Etiological Research, Leibniz Institute for Prevention Research and Epidemiology – BIPS and Faculty of Human and Health Sciences, University of Bremen'
      first_name: Magdalena
      last_name: Brinker
    - add_author_degrees: 'M.D., Ph.D.'
      affiliation: 'Pathology Unit, Maggiore Hospital-AUSL Bologna and Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna'
      first_name: Michelangelo
      last_name: Fiorentino
    - add_author_degrees: M.D.
      affiliation: 'Department of Pathology and Laboratory Medicine, New York Presbyterian Hospital, Weill Cornell Medicine'
      first_name: Massimo
      last_name: Loda
    - add_author_degrees: 'Ph.D., M.P.H., M.A.'
      affiliation: 'Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins'
      first_name: Corinne
      last_name: Joshu
    - add_author_degrees: 'Sc.D., M.P.H.'
      affiliation: 'Department of Epidemiology, Harvard T.H. Chan School of Public Health'
      first_name: Lorelei
      last_name: Mucci
    - add_author_degrees: 'M.D., M.P.H.'
      affiliation: 'Department of Epidemiological Methods and Etiological Research, Leibniz Institute for Prevention Research and Epidemiology – BIPS and Faculty of Human and Health Sciences, University of Bremen'
      first_name: Konrad
      last_name: Stopsack
    - add_author_degrees: M.D.
      affiliation: 'Department of Pathology, Johns Hopkins University School of Medicine'
      first_name: Tamara
      last_name: Lotan
  degree_s_: M.S.
  email: hguard@hsph.harvard.edu
  first_name: Hannah
  last_name: Guard
  middle_initial: E.
  organization: 'Department of Epidemiology, Harvard T.H. Chan School of Public Health'
  summary: |-
    Background: Tumor biomarkers, including PTEN loss and TP53 mutations, can identify prognostic subtypes of prostate cancer. We evaluated p53 and PTEN loss with or without ERG tumor protein expression and lethal prostate cancer in two prospective cohort studies. 

    Methods: 1,085 participants of the Health Professionals Follow-up Study and Physicians’ Health Study diagnosed with prostate cancer (1986-2017) and treated surgically were followed for lethality (metastasis or prostate cancer death) through 2022. PTEN loss, ERG, and p53-mutations in prostate tumors were assessed using validated immunohistochemistry assays on tissue microarrays. We estimated hazard ratios (HR) and 95% confidence intervals (CI) for associations between each biomarker and lethality using Cox proportional hazards models adjusted for Gleason score, pathologic TNM stage, and the other biomarkers. We also assessed the joint association of PTEN loss and ERG with lethality. We evaluated prognostic discrimination of the biomarkers in addition to clinical factors across time using time-varying area-under-the-curve (tAUC).

    Results: Over median 19 years follow-up, 113 lethal events occurred. The prevalence of each subtype was: 53% ERG-positive, 4% p53-positive, 14% complete PTEN loss (overall), 9% PTEN loss/ERG-positive, 5% PTEN loss/ERG-negative. PTEN loss (HR: 2.3, 95% CI: 1.5, 3.6) and p53 (HR: 2.9, 95% CI: 1.7, 5.1) were associated with lethal prostate cancer. PTEN loss/ERG-negative tumors had 4.3-fold higher risk of lethality (95% CI: 2.4, 7.8) compared to PTEN intact/ERG-negative tumors. The risk was not elevated in PTEN loss/ERG-positive tumors (HR: 1.3, 95% CI: 0.7, 2.3). tAUCs for p53 (0.55-0.57) and PTEN (0.59-0.65) were low. tAUCs for clinical factors ranged from 0.80 to 0.86 over time. The addition of the biomarkers did not add information for prognosis.

    Conclusion/Discussion: Complete PTEN loss in ERG-negative tumors and p53 were associated with higher risk of lethal prostate cancer, but they did not meaningfully improve prediction of lethality beyond Gleason grade and stage.
  title: 'Research Assistant IV'
  ttile: 'Tumor expression of ERG, PTEN, and p53 and lethal prostate cancer in two prospective cohort studies'