title: Proton Therapy as Salvage Treatment for Local Relapse of Prostate Cancer Following Cryosurgery or High-Intensity Focused Ultrasound.
abstract: OBJECTIVE
  Local recurrence of prostate cancer after cryosurgery (CS) and high-intensity focused ultrasound (HIFU) is an emerging problem for which optimal management is unknown. Proton therapy (PT) may offer advantages over other local therapeutic options. This article reviews a single institution's experience using PT for salvage of local recurrent disease after HIFU or CS.
  
  
  METHODS
  We reviewed the medical records of 21 consecutive patients treated with salvage PT following a local recurrence of prostate cancer after CS (n=12) or HIFU (n=9) between January 2007 and July 2014. Patients were treated to a median dose of 74 Gy(relative biological effectiveness [RBE]; range: 74-82 Gy[RBE]) and 8 patients received androgen deprivation therapy with radiation therapy. Patients were evaluated for quality of life (QOL) by using the Expanded Prostate Index Composite questionnaire and toxicity by using Common Terminology Criteria for Adverse Events, version 3.0, weekly during treatment, every 6 months for 2 years after treatment, and then annually.
  
  
  RESULTS
  Median follow-up was 37 months (range: 6-95 months). The 3-year biochemical progression-free survival (bPFS) rate was 77%. The 3-year grade 3 toxicity rate was 17%; however, 2 of these patients had pre-existing grade 3 GU toxicities from their HIFU/CRYO prior to PT. At 1 year, bowel summary, urinary incontinence, and urinary obstructive QOL scores declined, but only the bowel QOL score at 12 months met the minimally important difference threshold.
  
  
  CONCLUSIONS
  PT achieved a high rate of bPFS with acceptable toxicity and minimal changes in QOL scores compared with baseline pre-PT functions. Although most patients have done fairly well, the study size is small, follow-up is short, and early results suggest that outcomes with PT for salvage after HIFU or CS failure are inferior to outcomes with PT given in the de novo setting with respect to disease control, toxicity, and QOL.
authors.affiliation: University of Florida Health Proton Therapy Institute, University of Florida College of Medicine, Jacksonville, Florida.
authors.forename: Adam L
authors.initials: AL
authors.lastname: Holtzman
authors.affiliation: University of Florida Health Proton Therapy Institute, University of Florida College of Medicine, Jacksonville, Florida. Electronic address: bhoppe@floridaproton.org.
authors.forename: Bradford S
authors.initials: BS
authors.lastname: Hoppe
authors.affiliation: University of Florida Health Proton Therapy Institute, University of Florida College of Medicine, Jacksonville, Florida.
authors.forename: Haley P
authors.initials: HP
authors.lastname: Letter
authors.affiliation: University of Florida Health Proton Therapy Institute, University of Florida College of Medicine, Jacksonville, Florida.
authors.forename: Curtis
authors.initials: C
authors.lastname: Bryant
authors.affiliation: University of Florida Health Proton Therapy Institute, University of Florida College of Medicine, Jacksonville, Florida.
authors.forename: Romaine C
authors.initials: RC
authors.lastname: Nichols
authors.affiliation: University of Florida Health Proton Therapy Institute, University of Florida College of Medicine, Jacksonville, Florida.
authors.forename: Randal H
authors.initials: RH
authors.lastname: Henderson
authors.affiliation: University of Florida Health Proton Therapy Institute, University of Florida College of Medicine, Jacksonville, Florida.
authors.forename: William M
authors.initials: WM
authors.lastname: Mendenhall
authors.affiliation: University of Florida Health Proton Therapy Institute, University of Florida College of Medicine, Jacksonville, Florida.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Morris
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Jacksonville, Florida.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Williams
authors.affiliation: University of Florida Health Proton Therapy Institute, University of Florida College of Medicine, Jacksonville, Florida.
authors.forename: Zuofeng
authors.initials: Z
authors.lastname: Li
authors.affiliation: University of Florida Health Proton Therapy Institute, University of Florida College of Medicine, Jacksonville, Florida.
authors.forename: Nancy P
authors.initials: NP
authors.lastname: Mendenhall
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use; D003452:Cryosurgery; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D057086:High-Intensity Focused Ultrasound Ablation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000532:radiotherapy*; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000532:radiotherapy* / Q000628:therapy; D061766:Proton Therapy / Q000009:adverse effects / Q000379:methods*; D011788:Quality of Life; D011879:Radiotherapy Dosage; D012062:Relative Biological Effectiveness; D016879:Salvage Therapy / Q000009:adverse effects / Q000379:methods*; D013997:Time Factors; D014549:Urinary Incontinence / Q000209:etiology; D016055:Urinary Retention / Q000209:etiology
chemical_list: D000726:Androgen Antagonists; D017430:Prostate-Specific Antigen