title: Dose escalation with external beam radiation therapy and high-dose-rate brachytherapy combined with long-term androgen deprivation therapy in high and very high risk prostate cancer: Comparison of two consecutive high-dose-rate schemes.
abstract: OBJECTIVE
  To compare rectal toxicity, urinary toxicity, and nadir+2 PSA relapse-free survival (bRFS) in two consecutive Phase II protocols of high-dose-rate (HDR) brachytherapy used at the authors institution from 2001 to 2012.
  
  
  METHODS
  Patients with National Comprehensive Cancer Network high risk and very high risk prostate cancer enrolled in studies HDR4 (2001-2007, n = 183) and HDR2 (2007-2012, n = 56) were analyzed. Patients received minipelvis external beam radiation therapy/intensity-modulated external radiotherapy to 54 Gy and 2 years of androgen blockade along with HDR brachytherapy. HDR4 protocol consisted of four 4.75 Gy fractions delivered in 48 hours; the HDR2 protocol delivered two 9.5 Gy fractions in 24 hours. Average 2-Gy equivalent dose (α/β = 1.2) prostate D90 doses for the HDR4 and HDR2 groups were 89.8 Gy and 110.5 Gy, respectively (p = 0.0001). Both groups were well balanced regarding risk factors. Prior transurethral resection of the prostate was more frequent in the HDR2 group (p = 0.001).
  
  
  RESULTS
  After a median followup of 7.4 years (range, 2-11.2), there was no difference in adverse grade ≥ 2 rectal events (HDR4 = 10.4% vs. HDR2 = 12.5%; p = ns) or grade ≥3 (HDR4 = 2.2% vs. HDR2 = 3.6%; p = ns). No differences in urinary grade ≥2 adverse events (HDR4 = 23% vs. HDR2 = 26.8%; p = ns) or grade ≥3 (HDR4 = 7.7% vs. HDR2 = 8.9%; p = ns) were detected. The 7-year bRFS for HDR4 and HDR2 protocols was 88.7% and 87.8%, respectively (p = ns).
  
  
  CONCLUSIONS
  HDR4 and HDR2 protocols produce similar results in terms of toxicity and bRFS at the intermediate time point of 7 years.
authors.affiliation: Department of Radiation Oncology, Clínica Universitaria de Navarra, University of Navarra, Pamplona, Navarre, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Olarte
authors.affiliation: Department of Radiation Oncology, Clínica Universitaria de Navarra, University of Navarra, Pamplona, Navarre, Spain.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Cambeiro
authors.affiliation: Department of Radiation Oncology, Clínica Universitaria de Navarra, University of Navarra, Pamplona, Navarre, Spain; Instituto de Investigación Biosanitaria de Navarra (IdiSNA), Pamplona, Navarre, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Moreno-Jiménez
authors.affiliation: Department of Radiation Oncology, Clínica Universitaria de Navarra, University of Navarra, Pamplona, Navarre, Spain.
authors.forename: Leire
authors.initials: L
authors.lastname: Arbea
authors.affiliation: Department of Medical Oncology, Clínica Universitaria de Navarra, University of Navarra, Pamplona, Navarre, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Pérez-Gracia
authors.affiliation: Department of Medical Oncology, Clínica Universitaria de Navarra, University of Navarra, Pamplona, Navarre, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Gil-Bazo
authors.affiliation: Department of Urology, Clínica Universitaria de Navarra, University of Navarra, Pamplona, Navarre, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Pascual
authors.affiliation: Department of Radiation Oncology, Clínica Universitaria de Navarra, University of Navarra, Pamplona, Navarre, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Aristu
authors.affiliation: Department of Radiation Oncology, Clínica Universitaria de Navarra, University of Navarra, Pamplona, Navarre, Spain. Electronic address: rmartinezm@unav.es.
authors.forename: Rafael
authors.initials: R
authors.lastname: Martínez-Monge
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use*; D001918:Brachytherapy / Q000009:adverse effects* / Q000379:methods*; D059248:Chemoradiotherapy; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000209:etiology; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000209:etiology*; D011879:Radiotherapy Dosage; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects / Q000379:methods; D012007:Rectum / Q000528:radiation effects*; D012307:Risk Factors; D016896:Treatment Outcome; D001743:Urinary Bladder / Q000528:radiation effects*
chemical_list: D000726:Androgen Antagonists; D017430:Prostate-Specific Antigen
keywords: 3DCRT; Androgen deprivation therapy; HDR brachytherapy; High risk; Prostate cancer