title: Urinary functional outcomes and toxicity five years after proton therapy for low- and intermediate-risk prostate cancer: results of two prospective trials.
abstract: BACKGROUND
  To assess genitourinary (GU) function and toxicity in patients treated with image-guided proton therapy (PT) for early- and intermediate-risk prostate cancer and to analyze the impact of pretreatment urinary obstructive symptoms on urinary function after PT.
  
  
  METHODS
  Two prospective trials accrued 171 prostate cancer patients from August 2006 to September 2007. Low-risk patients received 78 cobalt gray equivalent (CGE) in 39 fractions and intermediate-risk patients received 78-82 CGE. Median follow-up was five years. The International Prostate Symptom Score (IPSS) and GU toxicities (per CTCAE v3.0 and v4.0) were documented prospectively.
  
  
  RESULTS
  Five transient GU events were scored Gr 3 per CTCAE v4.0, for a cumulative late GU toxicity rate of 2.9% at five years. There were no Gr 4 or 5 events. On multivariate analysis (MVA), the only factor predictive of Gr 2 + GU toxicity was pretreatment GU symptom management (p = 0.0058). Patients with pretreatment IPSS of 15-25 had a decline (clinical improvement) in median IPSS from 18 before treatment to 10 at their 60-month follow-up. At last follow-up, 18 (54.5%) patients had a > 5-point decline, 14 (42.5%) remained stable, and two patients (3%) had a > 5-point rise (deterioration) in IPSS. Patients with IPSS < 15 had a stable median IPSS of 6 before treatment and at 60 months.
  
  
  CONCLUSIONS
  Urologic toxicity at five years with image-guided PT has been uncommon and transient. Patients with pretreatment IPSS of < 15 had stable urinary function five years after PT, but patients with 15-25 showed substantial improvement (decline) in median IPSS, a finding not explained by initiation or dose adjustment of alpha blockers. This suggests that PT provides a minimally toxic and effective treatment for low and intermediate prostate cancer patients, including those with significant pretreatment GU dysfunction (IPSS 15-25).
authors.affiliation: University of Florida Proton Therapy Institute, Jacksonville, Florida 32206, USA. menden@shands.ufl .edu
authors.forename: Randal H
authors.initials: RH
authors.lastname: Henderson
authors.forename: Bradford S
authors.initials: BS
authors.lastname: Hoppe
authors.forename: Robert B
authors.initials: RB
authors.lastname: Marcus
authors.forename: William M
authors.initials: WM
authors.lastname: Mendenhall
authors.forename: R Charles
authors.initials: RC
authors.lastname: Nichols
authors.forename: Zuofeng
authors.initials: Z
authors.lastname: Li
authors.forename: Zhong
authors.initials: Z
authors.lastname: Su
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Morris
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Williams
authors.forename: Joseph
authors.initials: J
authors.lastname: Costa
authors.forename: Nancy P
authors.initials: NP
authors.lastname: Mendenhall
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000503:physiopathology / Q000532:radiotherapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000401:mortality / Q000503:physiopathology / Q000532:radiotherapy*; D061766:Proton Therapy / Q000009:adverse effects* / Q000379:methods; D011832:Radiation Injuries / Q000453:epidemiology* / Q000209:etiology; D011879:Radiotherapy Dosage; D012307:Risk Factors; D016896:Treatment Outcome; D014555:Urination Disorders / Q000453:epidemiology* / Q000209:etiology; D014566:Urogenital System / Q000503:physiopathology / Q000528:radiation effects