title: The need for androgen deprivation therapy in patients with intermediate-risk prostate cancer treated with dose-escalated external beam radiation therapy.
abstract: BACKGROUND
  To evaluate if androgen deprivation therapy (ADT) improves outcomes for patients with localized, intermediate-risk prostate cancer treated with definitive external beam radiation therapy (EBRT) in the dose-escalated era.
  
  
  METHODS
  This is a retrospective study using a single institutional database. We included patients with localized, intermediate-risk prostate cancer treated with dose-escalated radiation therapy (RT) with 3D conformal radiotherapy or intensity-modulated radiotherapy (74-80 Gy in daily fraction of 1.8 Gy-2.0 Gy, or 70.2 Gy in daily fraction of 2.7 Gy) from 1992 to 2013. To further risk stratify the patients, PSA 10 ng/mL-20 ng/mL, Gleason 3+4, and T2b-T2c were assigned risk score (RS) of 1, while Gleason 4+3 was assigned RS of 2. Patients with prior treatment for prostate cancer, those on long term ADT (>= 23 months), or those with follow up < 1 year were excluded. We defined initial ADT as initiation within 9 months prior to the start of RT, during RT, or within 2 months after the completion of RT. Outcomes for patients who received initial ADT were compared to men treated with RT alone. Covariates included number of intermediate risk factors, age, and baseline comorbidities. Kaplan Meier estimates were compared using log rank tests. Competing risk regression and Cox proportional hazards regression were used to estimate hazard ratios adjusted for covariates.
  
  
  RESULTS
  Of 1,134 patients included in this study, 155 received initial ADT with median duration of 4.0 months (m) (range 0.5 m-22.0 m). The median follow up was 56.4 m (range 12.3 m-200.7 m). Patients on ADT had higher RS compared to those with radiation alone (RS 1: 48% versus 58%; RS 2: 35% versus 32%; RS 3: 14% versus 9%; RS 4: 3% versus 1%; p=0.01). When patients with ADT were compared to those treated with radiation alone, there were no significant differences in freedom from biochemical failure (FFBF) (84.0% versus 87.3%, p = 0.83), freedom from distant metastasis (FFDM) (94.4% versus 96.9%, p = 0.41), or overall survival (OS) (92.3% versus 90.7%, (p = 0.48) at 5 years. Among patients with RS >= 2, there were still no significant differences in FFBF, FFDM, or OS when patients treated with ADT were compared to those treated with radiation alone. In multivariable analyses adjusting for RS and age, the adjusted hazard ratio for ADT use was sHR = 0.89 (95% CI = 0.64-1.66, p = 0.64) for BCF; sHR = 1.13 (95% CI = 0.48-2.65, p = 0.77) for DM. For overall mortality, adjusted HR = 1.23 (95% CI = 0.76-2.01, p = 0.40) where comorbidities (including diabetes, cardiac disease, and hypertension) were also included as covariates.
  
  
  CONCLUSIONS
  Our study suggested that treatment of intermediate-risk prostate cancer with definitive dose-escalated EBRT alone resulted in acceptable outcomes, and it failed to show improved outcomes in patients who received short term ADT.
authors.affiliation: Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
authors.forename: Yanqun
authors.initials: Y
authors.lastname: Dong
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Ruth
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Churilla
authors.forename: Rosalia
authors.initials: R
authors.lastname: Viterbo
authors.forename: Mark L
authors.initials: ML
authors.lastname: Sobczak
authors.forename: Marc C
authors.initials: MC
authors.lastname: Smaldone
authors.forename: David Y T
authors.initials: DY
authors.lastname: Chen
authors.forename: Robert G
authors.initials: RG
authors.lastname: Uzzo
authors.forename: Mark H
authors.initials: MH
authors.lastname: Hallman
authors.forename: Eric M
authors.initials: EM
authors.lastname: Horwitz
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D015897:Comorbidity; D003920:Diabetes Mellitus / Q000453:epidemiology; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D005500:Follow-Up Studies; D006331:Heart Diseases / Q000453:epidemiology; D006801:Humans; D006973:Hypertension / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology / Q000532:radiotherapy*; D050397:Radiotherapy, Intensity-Modulated; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D000726:Androgen Antagonists; D017430:Prostate-Specific Antigen