title: Understanding heterogeneity of treatment effect in prostate cancer.
abstract: OBJECTIVE
  In the era of personalized medicine, oncologists seek to tailor treatments for their patients based on indicators of differential response to treatment. We first provide a conceptual explanation of heterogeneity of treatment effect using prostate cancer as a case study and review studies that test whether Gleason score has a role in modifying the effectiveness of androgen deprivation therapy in men newly diagnosed with metastatic prostate cancer.
  
  
  RESULTS
  Depending on the study design, setting, and population, the median time to develop castration-resistant prostate cancer ranges from 12 to 23 months among men with M1 disease on androgen deprivation therapy, and the median time from diagnosis to mortality in such patients ranges from 23 to 37 months. Patients with higher Gleason scores have a significantly shorter time to developing castration-resistant prostate cancer compared with patients with lower Gleason scores. However, data suggest that Gleason score does not have a role in modifying the survival benefit associated with androgen deprivation therapy.
  
  
  CONCLUSIONS
  Androgen deprivation therapy has heterogeneous effects in men with metastatic prostate cancer related to the time of developing castration resistance. However, survival benefit from androgen deprivation therapy does not appear to depend on Gleason score.
authors.affiliation: aDepartment of Pharmaceutical Health Services Research, School of Pharmacy bMarlene and Stewart Greenebaum Cancer Center, School of Medicine, University of Maryland cVeterans Affairs Medical Center, Baltimore, Maryland, USA.
authors.forename: Abdalla
authors.initials: A
authors.lastname: Aly
authors.forename: C Daniel
authors.initials: CD
authors.lastname: Mullins
authors.forename: Arif
authors.initials: A
authors.lastname: Hussain
mesh_terms: D000726:Androgen Antagonists / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D018450:Disease Progression; D018740:Genetic Heterogeneity; D006801:Humans; D008297:Male; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D064887:Observational Studies as Topic; D011237:Predictive Value of Tests; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D017430:Prostate-Specific Antigen