title: Tri-Modality therapy with I-125 brachytherapy, external beam radiation therapy, and short- or long-term hormone therapy for high-risk localized prostate cancer (TRIP): study protocol for a phase III, multicenter, randomized, controlled trial.
abstract: BACKGROUND
  Patients with high Gleason score, elevated prostate specific antigen (PSA) level, and advanced clinical stage are at increased risk for both local and systemic relapse. Recent data suggests higher radiation doses decrease local recurrence and may ultimately benefit biochemical, metastasis-free and disease-specific survival. No randomized data is available on the benefits of long-term hormonal therapy (HT) in these patients. A prospective study on the efficacy and safety of trimodality treatment consisting of HT, external beam radiation therapy (EBRT), and brachytherapy (BT) for high-risk prostate cancer (PCa) is strongly required.
  
  
  METHODS
  This is a phase III, multicenter, randomized controlled trial (RCT) of trimodality with BT, EBRT, and HT for high-risk PCa (TRIP) that will investigate the impact of adjuvant HT following BT using iodine-125 ((125)I-BT) and supplemental EBRT with neoadjuvant and concurrent HT. Prior to the end of September 2012, a total of 340 patients with high-risk PCa will be enrolled and randomized to one of two treatment arms. These patients will be recruited from more than 41 institutions, all of which have broad experience with (125)I-BT. Pathological slides will be centrally reviewed to confirm patient eligibility. The patients will commonly undergo 6-month HT with combined androgen blockade (CAB) before and during (125)I-BT and supplemental EBRT. Those randomly assigned to the long-term HT group will subsequently undergo 2 years of adjuvant HT with luteinizing hormone-releasing hormone agonist. All participants will be assessed at baseline and every 3 months for the first 30 months, then every 6 months until 84 months from the beginning of CAB.The primary endpoint is biochemical progression-free survival. Secondary endpoints are overall survival, clinical progression-free survival, disease-specific survival, salvage therapy non-adaptive interval, and adverse events.
  
  
  CONCLUSIONS
  To our knowledge, there have been no prospective studies documenting the efficacy and safety of trimodality therapy for high-risk PCa. The present RCT is expected to provide additional insight regarding the potency and limitations of the addition of 2 years of adjuvant HT to this trimodality approach, and to establish an appropriate treatment strategy for high-risk PCa.
  
  
  BACKGROUND
  UMIN000003992.
authors.affiliation: Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Japan. h-konaka@med.kanazawa-u.ac.jp
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Konaka
authors.forename: Shin
authors.initials: S
authors.lastname: Egawa
authors.forename: Shiro
authors.initials: S
authors.lastname: Saito
authors.forename: Atsunori
authors.initials: A
authors.lastname: Yorozu
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Keiko
authors.initials: K
authors.lastname: Miyakoda
authors.forename: Masanori
authors.initials: M
authors.lastname: Fukushima
authors.forename: Takushi
authors.initials: T
authors.lastname: Dokiya
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Yamanaka
authors.forename: Nelson N
authors.initials: NN
authors.lastname: Stone
authors.forename: Mikio
authors.initials: M
authors.lastname: Namiki
mesh_terms: D000328:Adult; D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D001918:Brachytherapy / Q000379:methods*; D003131:Combined Modality Therapy / Q000379:methods; D018572:Disease-Free Survival; D007987:Gonadotropin-Releasing Hormone / Q000627:therapeutic use*; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000473:pathology / Q000628:therapy*; D050397:Radiotherapy, Intensity-Modulated
chemical_list: D000726:Androgen Antagonists; D007457:Iodine Radioisotopes; D007987:Gonadotropin-Releasing Hormone