title: Outcomes and predictive factors for biochemical relapse following  primary androgen deprivation therapy in men with bone scan  negative prostate cancer.
abstract: OBJECTIVE
  Primary androgen deprivation therapy (PADT) is an important treatment modality for men with localized or locally advanced prostate cancer and without bone metastasis. There is, however, a lack of data on the biochemical relapse (BR) outcomes in these patients. Here, we studied the outcome of a contemporary series of men treated by PADT and investigated predictive risk factors for BR.
  
  
  METHODS
  One hundred and fifty-five patients treated by PADT formed the initial study cohort, and BR outcomes in this group were reviewed. The outcomes of men with bone scan negative disease were specifically analysed. The predictive value of a panel of clinical risk factors for BR was evaluated using univariate and multivariate analysis. The results were further validated in a separate cohort of patients without bone metastasis from a second institution (n = 84).
  
  
  RESULTS
  Median follow-up was 70 months. In the first study cohort, 109/155 men (70%) had bone scan negative disease. In these patients, only 45% developed BR during the follow-up period with only 28% relapsing within 5 years of initiating PADT. Key-independent factors predicting BR were a high PSA nadir (p = 0.001) and a shorter time to nadir (p < 0.001). A nadir of ≤0.1 ng/ml and time to nadir of >24 months specifically identified men with a very good outcome from PADT. In a second-independent cohort, very similar overall and 5-year BR rates were observed in men without bone metastasis (39 and 35%, respectively). PSA nadir thresholds identified in the first cohort were again able to define a good prognostic group in this re-test cohort (p = 0.005 and p = 0.01, respectively).
  
  
  CONCLUSIONS
  Men treated by PADT and without bone metastasis can have very durable responses to PADT with the majority remaining BR free at 5 years. PSA nadir and time to nadir are key predictors of a good outcome in this group.
authors.affiliation: Translational Prostate Cancer Group, Department of Oncology, Hutchinson MRC Research Centre, University of Cambridge, Hills Road, Cambridge CB2 0XZ, UK.
authors.forename: S
authors.initials: S
authors.lastname: Hori
authors.forename: T
authors.initials: T
authors.lastname: Jabbar
authors.forename: N
authors.initials: N
authors.lastname: Kachroo
authors.forename: J C
authors.initials: JC
authors.lastname: Vasconcelos
authors.forename: C N
authors.initials: CN
authors.lastname: Robson
authors.forename: V J
authors.initials: VJ
authors.lastname: Gnanapragasam
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000726:Androgen Antagonists / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D001859:Bone Neoplasms / Q000175:diagnosis / Q000556:secondary; D015331:Cohort Studies; D018572:Disease-Free Survival; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009919:Orchiectomy; D011237:Predictive Value of Tests; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D015203:Reproducibility of Results; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D007987:Gonadotropin-Releasing Hormone; D017430:Prostate-Specific Antigen
references.citation: Cancer. 2006 Apr 15;106(8):1708-14
references.pmid: 16544313
references.citation: Urology. 2002 Jan;59(1):73-8
references.pmid: 11796285
references.citation: Int J Cancer. 2004 Mar 1;108(6):877-81
references.pmid: 14712491
references.citation: BJU Int. 2006 Sep;98(3):573-9
references.pmid: 16925756
references.citation: Prostate. 1985;7(2):131-41
references.pmid: 3931066
references.citation: BJU Int. 2007 Jul;100 Suppl 2:2-4
references.pmid: 17594347
references.citation: Cancer. 2005 Apr 15;103(8):1615-24
references.pmid: 15742331
references.citation: BJU Int. 2009 Nov;104(9):1208-14
references.pmid: 19388987
references.citation: Urology. 1989 May;33(5 Suppl):53-6
references.pmid: 2775378
references.citation: J Natl Cancer Inst. 2003 Jul 2;95(13):981-9
references.pmid: 12837834
references.citation: Eur Urol. 2003 Apr;43(4):337-41
references.pmid: 12667713
references.citation: Urology. 2002 Jul;60(1):120-4
references.pmid: 12100936
references.citation: J Urol. 1989 May;141(5):1139-42
references.pmid: 2651713
references.citation: Prostate Suppl. 1992;4:125-8
references.pmid: 1374175
references.citation: Int J Biol Markers. 2005 Oct-Dec;20(4):209-16
references.pmid: 16398402
references.citation: BJU Int. 2005 Sep;96(4):503-7
references.pmid: 16104900
references.citation: J Urol. 2003 Dec;170(6 Pt 2):S21-5; discussion S26-7
references.pmid: 14610406
references.citation: J Clin Oncol. 2006 Aug 20;24(24):3984-90
references.pmid: 16921051
references.citation: JAMA. 2005 Jul 13;294(2):238-44
references.pmid: 16014598
references.citation: Eur Urol. 2008 Jan;53(1):68-80
references.pmid: 17920184
references.citation: Cancer. 2009 Mar 1;115(5):981-7
references.pmid: 19152438
references.citation: J Urol. 2002 Sep;168(3):995-1000
references.pmid: 12187207