title: External-beam radiation therapy and high-dose rate brachytherapy combined with long-term androgen deprivation therapy in high and very high prostate cancer: preliminary data on clinical outcome.
abstract: OBJECTIVE
  To determine the feasibility of combined long-term androgen deprivation therapy (ADT) and dose escalation with high-dose-rate (HDR) brachytherapy.
  
  
  METHODS
  Between 2001 and 2007, 200 patients with high-risk prostate cancer (32.5%) or very high-risk prostate cancer (67.5%) were prospectively enrolled in this Phase II trial. Tumor characteristics included a median pretreatment prostate-specific antigen of 15.2 ng/mL, a clinical stage of T2c, and a Gleason score of 7. Treatment consisted of 54 Gy of external irradiation (three-dimensional conformal radiotherapy [3DCRT]) followed by 19 Gy of HDR brachytherapy in four twice-daily treatments. ADT started 0-3 months before 3DCRT and continued for 2 years.
  
  
  RESULTS
  One hundred and ninety patients (95%) received 2 years of ADT. After a median follow-up of 3.7 years (range, 2-9), late Grade ≥2 urinary toxicity was observed in 18% of the patients and Grade ≥3 was observed in 5%. Prior transurethral resection of the prostate (p = 0.013) and bladder D(50) ≥1.19 Gy (p = 0.014) were associated with increased Grade ≥2 urinary complications; age ≥70 (p = 0.05) was associated with Grade ≥3 urinary complications. Late Grade ≥2 gastrointestinal toxicity was observed in 9% of the patients and Grade ≥3 in 1.5%. CTV size ≥35.8 cc (p = 0.007) and D(100) ≥3.05 Gy (p = 0.01) were significant for increased Grade ≥2 complications. The 5-year and 9-year biochemical relapse-free survival (nadir + 2) rates were 85.1% and 75.7%, respectively. Patients with Gleason score of 7-10 had a decreased biochemical relapse-free survival (p = 0.007).
  
  
  CONCLUSIONS
  Intermediate-term results at the 5-year time point indicate a favorable outcome without an increase in the rate of late complications.
authors.affiliation: Department of Radiation Oncology, Clínica Universitaria de Navarra, University of Navarra, Pamplona, Navarre, Spain. rmartinezm@unav.es
authors.forename: Rafael
authors.initials: R
authors.lastname: Martínez-Monge
authors.forename: Marta
authors.initials: M
authors.lastname: Moreno
authors.forename: Raquel
authors.initials: R
authors.lastname: Ciérvide
authors.forename: Mauricio
authors.initials: M
authors.lastname: Cambeiro
authors.forename: José Luis
authors.initials: JL
authors.lastname: Pérez-Gracia
authors.forename: Ignacio
authors.initials: I
authors.lastname: Gil-Bazo
authors.forename: Miren
authors.initials: M
authors.lastname: Gaztañaga
authors.forename: Leire
authors.initials: L
authors.lastname: Arbea
authors.forename: Ignacio
authors.initials: I
authors.lastname: Pascual
authors.forename: Javier
authors.initials: J
authors.lastname: Aristu
mesh_terms: D000726:Androgen Antagonists / Q000627:therapeutic use*; D001918:Brachytherapy / Q000379:methods*; D003131:Combined Modality Therapy / Q000379:methods; D018572:Disease-Free Survival; D005240:Feasibility Studies; D006801:Humans; D008297:Male; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D058958:Organs at Risk / Q000528:radiation effects; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D012372:ROC Curve; D011879:Radiotherapy Dosage; D012007:Rectum / Q000528:radiation effects; D016896:Treatment Outcome; D014521:Urethra / Q000528:radiation effects; D001743:Urinary Bladder / Q000528:radiation effects; D014555:Urination Disorders / Q000209:etiology
chemical_list: D000726:Androgen Antagonists; D017430:Prostate-Specific Antigen