title: Functional heterogeneity of prostatic intraepithelial neoplasia: the duration of hormonal therapy influences the response.
abstract: OBJECTIVE
  To use a clinical model of androgen-deprivation therapy (ADT) followed by radical prostatectomy (RP) to test the hypothesis that prostatic intraepithelial neoplasia (PIN, a premalignant lesion of the prostate causally linked to prostate cancer) is heterogeneous for hormone responsiveness, which might explain aspects of the heterogeneity of the natural history of prostate cancer, for although ADT has been used to reduce prostate cancer, there are controversial data on the effect of ADT on PIN.
  
  
  METHODS
  We assessed retrospectively patients with biopsy-confirmed prostate cancer who had RP; some patients had received >or=3 months of ADT at the discretion of their surgeons, and patients from the same cohort who did not have ADT were used as controls. Patients were sequentially selected from the database and their pathology slides were reviewed by a pathologist unaware of the initial presence of PIN (assessed by an independent observer). Fisher's exact test was used to compare the proportions of patients who had residual PIN in the study and control groups. Exact logistic regression was used to evaluate the duration of ADT on PIN regression.
  
  
  RESULTS
  Eighteen patients initially diagnosed with PIN who had no ADT were identified, and 28 with PIN who had ADT were also assessed. All patients who had had no ADT had residual PIN, whereas seven of 28 receiving ADT had no residual PIN (P=0.043). The evaluation of ADT between responders and nonresponders showed a statistically significant association between PIN regression and the duration of ADT (P<0.001). However, the response of PIN to ADT was not uniform, as 16% of patients on ADT for >6 months had residual PIN, suggesting variable sensitivity of PIN to ADT.
  
  
  CONCLUSIONS
  These results show that ADT causes PIN to regress, and that there is heterogeneity in this effect with the duration of ADT. We propose future prospective, multicentre, randomized trials in which the effect of ADT on PIN is characterized further.
authors.affiliation: Cleveland Clinic Taussig Cancer Center, Cleveland, OH 44195, and University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA. kangt@ccf.org
authors.forename: Tyler Y
authors.initials: TY
authors.lastname: Kang
authors.forename: Peter
authors.initials: P
authors.lastname: Nichols
authors.forename: Eila
authors.initials: E
authors.lastname: Skinner
authors.forename: Susan
authors.initials: S
authors.lastname: Groshen
authors.forename: Greg
authors.initials: G
authors.lastname: Valin
authors.forename: Wei
authors.initials: W
authors.lastname: Ye
authors.forename: Derek
authors.initials: D
authors.lastname: Raghavan
mesh_terms: D000726:Androgen Antagonists / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D015331:Cohort Studies; D003131:Combined Modality Therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D011468:Prostatectomy; D019048:Prostatic Intraepithelial Neoplasia / Q000188:drug therapy* / Q000235:genetics / Q000601:surgery; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000601:surgery; D012044:Regression Analysis; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal