title: Hypofractionated external beam radiotherapy to boost the prostate with ≥85 Gy/equivalent dose for patients with localised disease at high risk of lymph node involvement: feasibility, tolerance and outcome.
abstract: OBJECTIVE
  To evaluate the tolerance and preliminary outcome of prostate cancer patients at high risk of lymph node involvement treated with normofractionated whole pelvic radiotherapy (WPRT) followed by a hypofractionated boost to the prostate with an intensity-modulated radiotherapy (IMRT) technique.
  
  
  METHODS
  Between 2004 and 2011, 78 T1-4N0M0 prostate cancer patients at high risk of lymph node involvement (70 patients with a Roach index ≥ 15%; 57 with T-stage ≥ 3a; 40 with Gleason score ≥ 8) underwent WPRT to a median normofractionated dose of 50.4 Gy (range 48.0-50.4 Gy) with conformal three-dimensional techniques for most patients. A 24 Gy boost (4 Gy/six fractions, twice weekly) was delivered to the prostate with IMRT. The total median delivered dose was 74.4 Gy, equivalent to 85.2 Gy in 2 Gy/fractions (α/β = 1.5 Gy). All patients underwent androgen deprivation for a total median time of 10.8 months. The maximum gastrointestinal and genitourinary acute and late toxicity scores were recorded according to the Radiation Therapy Oncology Group scoring system.
  
  
  RESULTS
  All patients completed treatment as planned. Only 1% of patients presented with grade 3 genitourinary or gastrointestinal acute toxicity and none scored ≥ grade 4. With a median follow-up of 57 months, the 5 year probability of late grade ≥2 genitourinary and gastrointestinal toxicity-free survival was 79.1 ± 4.8% and 84.1 ± 4.5%, respectively. The 5 year biochemical disease-free survival, local relapse-free survival and distant metastasis-free survival were 84.5 ± 4.5%, 96.0 ± 2.8% and 86.4 ± 4.4%, respectively. A pre-radiotherapy prostate-specific antigen ≤0.3 ng/ml was associated with a better 5 year biochemical disease-free survival (P = 0.036) and distant metastasis-free survival (P = 0.049).
  
  
  CONCLUSIONS
  The use of a hypofractionated IMRT boost after WPRT may allow a minimally invasive dose escalation to successfully treat patients with non-metastatic prostate cancer at high risk of lymph node involvement. Higher prostate-specific antigen values before radiotherapy may require alternative adjuvant treatments to further optimise the outcome of this high-risk group of patients.
authors.affiliation: Radiation Oncology Department, Geneva University Hospital, Geneva, Switzerland. Electronic address: Thomas.Zilli@hcuge.ch.
authors.forename: T
authors.initials: T
authors.lastname: Zilli
authors.affiliation: Servei de Radio-oncologia, Institut Oncològic Teknon, Barcelona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Jorcano
authors.affiliation: Servei de Radio-oncologia, Institut Oncològic Teknon, Barcelona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Escudé
authors.affiliation: Servei de Radio-oncologia, Institut Oncològic Teknon, Barcelona, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Linero
authors.affiliation: Radiation Oncology Department, Geneva University Hospital, Geneva, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Rouzaud
authors.affiliation: Radiation Oncology Department, Geneva University Hospital, Geneva, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Dubouloz
authors.affiliation: Radiation Oncology Department, Geneva University Hospital, Geneva, Switzerland; Servei de Radio-oncologia, Institut Oncològic Teknon, Barcelona, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Miralbell
mesh_terms: D000328:Adult; D000368:Aged; D000726:Androgen Antagonists / Q000008:administration & dosage; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D005240:Feasibility Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis / Q000517:prevention & control* / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011471:Prostatic Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000453:epidemiology; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects / Q000379:methods*; D012189:Retrospective Studies; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal
keywords: HDR; IMRT; WPRT; hypofractionation; prostate cancer; toxicity