title: Salvage prostate re-irradiation using high-dose-rate brachytherapy or focal stereotactic body radiotherapy for local recurrence after definitive radiation therapy.
abstract: BACKGROUND
  Optimal management of locally recurrent prostate cancer after definitive radiation therapy is still challenging. With the development of highly accurate radiotherapy devices, prostate salvage re-irradiation might generate lower toxicity rates than classical salvage therapies. We retrospectively evaluated the toxicity and the feasibility of a prostate re-irradiation after definitive radiation therapy failure. Two modalities were investigated: high-dose-rate brachytherapy (HDRB) on whole prostate gland and focal stereotactic radiotherapy (SBRT) using CyberKnife® linac.
  
  
  METHODS
  Between 2011 and 2015, 28 patients with imaged and/or biopsy-proven intra-prostatic recurrence of cancer after definitive radiation therapy underwent a salvage re-irradiation using HDRB (n = 10) or focal SBRT (n = 18). The schedule of re-irradiation was 35 Gy in 5 fractions. Biological response (defined as post-salvage radiation PSA variation) and biochemical no-evidence of disease (bNED) were evaluated in the whole cohort. For patients who had a positive biological response after salvage radiation, biochemical recurrence (BCR) and survival after salvage radiotherapy were evaluated. Post-salvage toxicities were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.03 and were compared to baseline status.
  
  
  RESULTS
  Within a median follow-up of 22.5 months (IQR = 8-42), 9 (90%) patients experienced a positive biological response after salvage HDRB and 5 (50%) remained bNED at the end of the follow-up. Among patients who initially responded to salvage HDRB, the BCR rate was 44.4% after a median interval of 19.5 months (IQR = 11.5-26). Only one patient experienced a transient grade 3 urinary complication. In the SBRT group, the median follow-up was 14.5 months (IQR = 7-23) and 10 (55.6%) out of the 18 patients remained bNED. Among the 15 patients who initially responded to salvage SBRT, 5 (33.3%) experienced a BCR. One patient experienced a transient grade 4 urinary complication. At the end of the follow-up, all evaluated patients had a urinary status grade variation ≤ +1 grade. No grade 3-4 digestive toxicity was observed.
  
  
  CONCLUSIONS
  Salvage prostate re-irradiation for locally recurrent cancer is feasible and generate low toxicities rates when using with HDRB or focal SBRT. However, further investigations are necessary to confirm these findings and to determine predictive features for patients who might benefit from such an approach.
authors.affiliation: Department of Radiation Oncology, Antoine-Lacassagne Cancer Canter, University of Nice Sophia-Antipolis, 33, avenue Valombrose, 06189, Nice Cedex 2, Nice, France.|Department of Urology, Hôpital Pasteur 2, Centre Hospitalier Universitaire de Nice, University of Nice Sophia-Antipolis, Nice, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Mbeutcha
authors.affiliation: Department of Radiation Oncology, Clinique Hartmann, Levallois-Perret, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Chauveinc
authors.affiliation: Department of Radiation Oncology, Antoine-Lacassagne Cancer Canter, University of Nice Sophia-Antipolis, 33, avenue Valombrose, 06189, Nice Cedex 2, Nice, France.
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Bondiau
authors.affiliation: Department of Radiation Oncology, Antoine-Lacassagne Cancer Canter, University of Nice Sophia-Antipolis, 33, avenue Valombrose, 06189, Nice Cedex 2, Nice, France.
authors.forename: Marie-Eve
authors.initials: ME
authors.lastname: Chand
authors.affiliation: Department of Urology, Hôpital Pasteur 2, Centre Hospitalier Universitaire de Nice, University of Nice Sophia-Antipolis, Nice, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Durand
authors.affiliation: Department of Urology, Hôpital Pasteur 2, Centre Hospitalier Universitaire de Nice, University of Nice Sophia-Antipolis, Nice, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Chevallier
authors.affiliation: Department of Urology, Hôpital Pasteur 2, Centre Hospitalier Universitaire de Nice, University of Nice Sophia-Antipolis, Nice, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Amiel
authors.affiliation: Department of Radiation Oncology, Antoine-Lacassagne Cancer Canter, University of Nice Sophia-Antipolis, 33, avenue Valombrose, 06189, Nice Cedex 2, Nice, France.
authors.forename: Daniel Lam Cham
authors.initials: DL
authors.lastname: Kee
authors.affiliation: Department of Radiation Oncology, Antoine-Lacassagne Cancer Canter, University of Nice Sophia-Antipolis, 33, avenue Valombrose, 06189, Nice Cedex 2, Nice, France. jean-michel.hannoun-levi@nice.unicancer.fr.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Hannoun-Lévi
mesh_terms: D000368:Aged; D001918:Brachytherapy / Q000009:adverse effects / Q000379:methods*; D018572:Disease-Free Survival; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000532:radiotherapy*; D011471:Prostatic Neoplasms / Q000401:mortality / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000453:epidemiology; D016634:Radiosurgery / Q000009:adverse effects / Q000379:methods*; D011879:Radiotherapy Dosage; D000069475:Re-Irradiation / Q000009:adverse effects / Q000379:methods; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000009:adverse effects / Q000379:methods*
keywords: CyberKnife; High-dose-rate brachytherapy; Local recurrence; Prostate cancer; Salvage therapy; Stereotactic body radiation therapy