title: Clinical characteristics and management of late urinary symptom flare following stereotactic body radiation therapy for prostate cancer.
abstract: OBJECTIVE
  Stereotactic body radiation therapy (SBRT) is increasingly utilized as primary treatment for clinically localized prostate cancer. While acute post-SBRT urinary symptoms are well recognized, the late genitourinary toxicity of SBRT has not been fully described. Here, we characterize the clinical features of late urinary symptom flare and recommend conservative symptom management approaches that may alleviate the associated bother.
  
  
  METHODS
  Between February 2008 and August 2011, 216 men with clinically localized prostate cancer were treated definitively with SBRT at Georgetown University Hospital. Treatment was delivered using the CyberKnife with doses of 35-36.25 Gy in five fractions. The prevalence of each of five Common Terminology Criteria for Adverse Events (CTCAE) graded urinary toxicities was assessed at each follow-up visit. Medication usage was documented at each visit. Patient-reported urinary symptoms were assessed using the American Urological Association (AUA) symptom score and the Expanded Prostate Cancer Index Composite (EPIC)-26 at 1, 3, 6, 9, 12, 18, and 24 months. Late urinary symptom flare was defined as an increase in the AUA symptom score of ≥5 points above baseline with a degree of severity in the moderate to severe range (AUA symptom score ≥15). The relationship between the occurrence of flare and pre-treatment characteristics were examined.
  
  
  RESULTS
  For all patients, the AUA symptom score spiked transiently at 1 month post-SBRT. Of the 216 patients, 29 (13.4%) experienced a second transient increase in the AUA symptom score that met the criteria for late urinary symptom flare. Among flare patients, the median age was 66 years compared to 70 for those without flare (p = 0.007). In patients who experienced flare, CTCAE urinary toxicities including dysuria, frequency/urgency, and retention peaked at 9-18 months, and alpha-antagonist utilization increased at 1 month post-treatment, rose sharply at 12 months post-treatment, and peaked at 18 months (85%) before decreasing at 24 months. The EPIC urinary summary score of flare patients declined transiently at 1 month and experienced a second, more protracted decline between 6 and 18 months before returning to near baseline at 2-year post-SBRT. Statistically and clinically significant increases in patient-reported frequency, weak stream, and dysuria were seen at 12 months post-SBRT. Among flare patients, 42.9% felt that urination was a moderate to big problem at 12 months following SBRT.
  
  
  CONCLUSIONS
  In this study, we characterize late urinary symptom flare following SBRT. Late urinary symptom flare is a constellation of symptoms including urinary frequency/urgency, weak stream, and dysuria that transiently occurs 6-18 months post-SBRT. Provision of appropriate anticipatory counseling and the maintenance of prophylactic alpha-antagonists may limit the bother associated with this syndrome.
authors.affiliation: Department of Radiation Medicine, Georgetown University Hospital , Washington, DC , USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Woo
authors.affiliation: Department of Radiation Medicine, Georgetown University Hospital , Washington, DC , USA.
authors.forename: Leonard N
authors.initials: LN
authors.lastname: Chen
authors.affiliation: Department of Radiation Medicine, Georgetown University Hospital , Washington, DC , USA.
authors.forename: Aditi
authors.initials: A
authors.lastname: Bhagat
authors.affiliation: Department of Radiation Medicine, Georgetown University Hospital , Washington, DC , USA.
authors.forename: Eric K
authors.initials: EK
authors.lastname: Oermann
authors.affiliation: Department of Radiation Medicine, Georgetown University Hospital , Washington, DC , USA.
authors.forename: Joy S
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Department of Radiation Medicine, Georgetown University Hospital , Washington, DC , USA.
authors.forename: Rudy
authors.initials: R
authors.lastname: Moures
authors.affiliation: Department of Radiation Medicine, Georgetown University Hospital , Washington, DC , USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Yung
authors.affiliation: Department of Radiation Medicine, Georgetown University Hospital , Washington, DC , USA.
authors.forename: Siyuan
authors.initials: S
authors.lastname: Lei
authors.affiliation: Department of Radiation Medicine, Georgetown University Hospital , Washington, DC , USA.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Collins
authors.affiliation: Cancer Research Laboratory, Department of Biology, University of the District of Columbia , Washington, DC , USA.
authors.forename: Deepak
authors.initials: D
authors.lastname: Kumar
authors.affiliation: Department of Radiation Medicine, Georgetown University Hospital , Washington, DC , USA.
authors.forename: Simeng
authors.initials: S
authors.lastname: Suy
authors.affiliation: Department of Radiation Medicine, Georgetown University Hospital , Washington, DC , USA.
authors.forename: Anatoly
authors.initials: A
authors.lastname: Dritschilo
authors.affiliation: Department of Urology, Georgetown University Hospital , Washington, DC , USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Lynch
authors.affiliation: Department of Radiation Medicine, Georgetown University Hospital , Washington, DC , USA.
authors.forename: Sean P
authors.initials: SP
authors.lastname: Collins
keywords: AUA symptom score; CyberKnife; EPIC; SBRT; bother; genitourinary toxicity; late urinary symptom flare; prostate cancer