title: PSA response to neoadjuvant androgen deprivation therapy is a strong independent predictor of survival in high-risk prostate cancer in the dose-escalated radiation therapy era.
abstract: OBJECTIVE
  The aim of the study was to evaluate the prognostic value of prostate-specific antigen (PSA) response to neoadjuvant androgen deprivation therapy (ADT) prior to dose-escalated radiation therapy (RT) and long-term ADT in high-risk prostate cancer.
  
  
  METHODS
  We reviewed the charts of all patients diagnosed with high-risk prostate cancer and treated with a combination of long-term ADT (median, 24 months) and dose-escalated (median, 75.6 Gy) RT between 1990 and 2007. The associations among patient, tumor, and treatment characteristics with biochemical response to neoadjuvant ADT and their effects on failure-free survival (FFS), time to distant metastasis (TDM), prostate cancer-specific mortality (PCSM) and overall survival (OS) were examined.
  
  
  RESULTS
  A total of 196 patients met criteria for inclusion. Median follow-up time for patients alive at last contact was 7.0 years (range, 0.5-18.1 years). Multivariate analysis identified the pre-RT PSA concentration (<0.5 vs ≥0.5 ng/mL) as a significant independent predictor of FFS (P=.021), TDM (P=.009), PCSM (P=.039), and OS (P=.037). On multivariate analysis, pretreatment PSA (iPSA) and African-American race were significantly associated with failure to achieve a pre-RT PSA of <0.5 ng/mL.
  
  
  CONCLUSIONS
  For high-risk prostate cancer patients treated with long-term ADT and dose-escalated RT, a pre-RT PSA level≥0.5 ng/mL after neoadjuvant ADT predicts for worse survival measures. Both elevated iPSA and African-American race are associated with increased risk of having a pre-RT PSA level≥0.5 ng/mL. These patients should be considered for clinical trials that test newer, more potent androgen-depleting therapies such as abiraterone and MDV3100 in combination with radiation.
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030-4009, USA. semcguir@mdanderson.org
authors.forename: Sean E
authors.initials: SE
authors.lastname: McGuire
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Lee
authors.forename: Jasmina Z
authors.initials: JZ
authors.lastname: Cerne
authors.forename: Mark F
authors.initials: MF
authors.lastname: Munsell
authors.forename: Lawrence B
authors.initials: LB
authors.lastname: Levy
authors.forename: Rajat J
authors.initials: RJ
authors.lastname: Kudchadker
authors.forename: Seungtaek L
authors.initials: SL
authors.lastname: Choi
authors.forename: Quynh N
authors.initials: QN
authors.lastname: Nguyen
authors.forename: Karen E
authors.initials: KE
authors.lastname: Hoffman
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Pugh
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Frank
authors.forename: Paul G
authors.initials: PG
authors.lastname: Corn
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Logothetis
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Kuban
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000726:Androgen Antagonists / Q000627:therapeutic use*; D044383:Black People; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D017430:Prostate-Specific Antigen / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000208:ethnology / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D011879:Radiotherapy Dosage; D016019:Survival Analysis; D013997:Time Factors; D001741:Black or African American
chemical_list: D000726:Androgen Antagonists; D017430:Prostate-Specific Antigen