title: Multimodal treatment for high-risk prostate cancer with high-dose intensity-modulated radiation therapy preceded or not by radical prostatectomy, concurrent intensified-dose docetaxel and long-term androgen deprivation therapy: results of a prospective phase II trial.
abstract: BACKGROUND
  The optimal management of high-risk prostate cancer remains uncertain. In this study we assessed the safety and efficacy of a novel multimodal treatment paradigm for high-risk prostate cancer.
  
  
  METHODS
  This was a prospective phase II trial including 35 patients with newly diagnosed high-risk localized or locally advanced prostate cancer treated with high-dose intensity-modulated radiation therapy preceded or not by radical prostatectomy, concurrent intensified-dose docetaxel-based chemotherapy and long-term androgen deprivation therapy. Primary endpoint was acute and late toxicity evaluated with the Common Terminology Criteria for Adverse Events version 3.0. Secondary endpoint was biochemical and clinical recurrence-free survival explored with the Kaplan-Meier method.
  
  
  RESULTS
  Acute gastro-intestinal and genito-urinary toxicity was grade 2 in 23% and 20% of patients, and grade 3 in 9% and 3% of patients, respectively. Acute blood/bone marrow toxicity was grade 2 in 20% of patients. No acute grade ≥ 4 toxicity was observed. Late gastro-intestinal and genito-urinary toxicity was grade 2 in 9% of patients each. No late grade ≥ 3 toxicity was observed. Median follow-up was 63 months (interquartile range 31-79). Actuarial 5-year biochemical and clinical recurrence-free survival rate was 55% (95% confidence interval, 35-75%) and 70% (95% confidence interval, 52-88%), respectively.
  
  
  CONCLUSIONS
  In our phase II trial testing a novel multimodal treatment paradigm for high-risk prostate cancer, toxicity was acceptably low and mid-term oncological outcome was good. This treatment paradigm, thus, may warrant further evaluation in phase III randomized trials.
authors.affiliation: Department of Oncological, Surgical and Gastroenterological Sciences, Urology Clinic, University of Padua, Padua 35128, Italy. andrea.guttilla@gmail.com.
authors.forename: Andrea
authors.initials: A
authors.lastname: Guttilla
authors.forename: Roberto
authors.initials: R
authors.lastname: Bortolus
authors.forename: Gianluca
authors.initials: G
authors.lastname: Giannarini
authors.forename: Pirus
authors.initials: P
authors.lastname: Ghadjar
authors.forename: Fabio
authors.initials: F
authors.lastname: Zattoni
authors.forename: Michele
authors.initials: M
authors.lastname: Gnech
authors.forename: Vito
authors.initials: V
authors.lastname: Palumbo
authors.forename: Francesca
authors.initials: F
authors.lastname: Valent
authors.forename: Antonio
authors.initials: A
authors.lastname: Garbeglio
authors.forename: Filiberto
authors.initials: F
authors.lastname: Zattoni
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D002277:Carcinoma / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy; D003131:Combined Modality Therapy; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D008875:Middle Aged; D011468:Prostatectomy / Q000379:methods; D011471:Prostatic Neoplasms / Q000473:pathology / Q000628:therapy*; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant; D050397:Radiotherapy, Intensity-Modulated; D012306:Risk; D043823:Taxoids / Q000008:administration & dosage*
chemical_list: D000726:Androgen Antagonists; D043823:Taxoids; D000077143:Docetaxel