title: Stereotactic Body Radiation Therapy for Prostate Cancer: What is the Appropriate Patient-Reported Outcome for Clinical Trial Design?
abstract: OBJECTIVE
  Stereotactic body radiation therapy (SBRT) is increasingly utilized as primary treatment for clinically localized prostate cancer. Consensus regarding the appropriate patient-reported outcome (PRO) endpoints for clinical trials evaluating radiation modalities for early stage prostate cancer is lacking. To aid in clinical trial design, this study presents PROs over a 36-month period following SBRT for clinically localized prostate cancer.
  
  
  METHODS
  Between February 2008 and September 2010, 174 hormone-naïve patients with clinically localized prostate cancer were treated with 35-36.25 Gy SBRT (CyberKnife, Accuray) delivered in 5 fractions. Patients completed the validated Expanded Prostate Cancer Index Composite (EPIC)-26 questionnaire at baseline and all follow-ups. The proportion of patients developing a clinically significant decline in each EPIC domain score was determined. The minimally important difference (MID) was defined as a change of one-half the standard deviation from the baseline. Per Radiation Therapy Oncology Group (RTOG) 0938, we also examined the patients who experienced a decline in EPIC urinary domain summary score of >2 points (unacceptable toxicity defined as ≥60% of all patients reporting this degree of decline) and EPIC bowel domain summary score of >5 points (unacceptable toxicity defined as >55% of all patients reporting this degree of decline) from baseline to 1 year.
  
  
  RESULTS
  A total of 174 patients at a median age of 69 years received SBRT with a minimum follow-up of 36 months. The proportion of patients reporting a clinically significant decline (MID for urinary/bowel are 5.5/4.4) in EPIC urinary/bowel domain scores was 34%/30% at 6 months, 40%/32.2% at 12 months, and 32.8%/21.5% at 36 months. The patients reporting a decrease in the EPIC urinary domain summary score of >2 points was 43.2% (CI: 33.7%, 54.6%) at 6 months, 51.6% (CI: 43.4%, 59.7%) at 12 months, and 41.8% (CI: 33.3%, 50.6%) at 36 months. The patients reporting a decrease in the EPIC bowel domain summary score of >5 points was 29.6% (CI: 21.9%, 39.3%) at 6 months, 29% (CI: 22%, 36.8%) at 12 months, and 22.4% (CI: 15.7%, 30.4%) at 36 months.
  
  
  CONCLUSIONS
  Following prostate SBRT, clinically significant urinary symptoms are more common than bowel symptoms. Our prostate SBRT treatment protocol meets the RTOG 0938 criteria for moving forward to a Phase III trial comparing it to conventionally fractionated radiation therapy. Notably, between 12 and 36 months, the proportion of patients reporting a significant decrease in both EPIC urinary and bowel domain scores declined, suggesting a late improvement in these symptom domains. Further investigation is needed to elucidate (1) which EPIC domains bear the greatest influence on post-treatment quality of life and (2) at what time point PRO endpoint(s) should be assessed.
authors: Department of Radiation Medicine, Georgetown University Hospital , Washington, DC , USA.
authors: Jennifer Ai-Lian
authors: JA
authors: Woo
authors: Department of Radiation Medicine, Georgetown University Hospital , Washington, DC , USA.
authors: Leonard N
authors: LN
authors: Chen
authors: Department of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University , Washington, DC , USA.
authors: Hongkun
authors: H
authors: Wang
authors: Department of Radiation Medicine, Georgetown University Hospital , Washington, DC , USA.
authors: Robyn A
authors: RA
authors: Cyr
authors: Department of Radiation Medicine, Georgetown University Hospital , Washington, DC , USA.
authors: Onita
authors: O
authors: Bhattasali
authors: Department of Radiation Medicine, Georgetown University Hospital , Washington, DC , USA.
authors: Joy S
authors: JS
authors: Kim
authors: Department of Radiation Medicine, Georgetown University Hospital , Washington, DC , USA.
authors: Rudy
authors: R
authors: Moures
authors: Department of Radiation Medicine, Georgetown University Hospital , Washington, DC , USA.
authors: Thomas M
authors: TM
authors: Yung
authors: Department of Radiation Medicine, Georgetown University Hospital , Washington, DC , USA.
authors: Siyuan
authors: S
authors: Lei
authors: Department of Radiation Medicine, Georgetown University Hospital , Washington, DC , USA.
authors: Brian Timothy
authors: BT
authors: Collins
authors: Department of Radiation Medicine, Georgetown University Hospital , Washington, DC , USA.
authors: Simeng
authors: S
authors: Suy
authors: Department of Radiation Medicine, Georgetown University Hospital , Washington, DC , USA.
authors: Anatoly
authors: A
authors: Dritschilo
authors: Department of Urology, Georgetown University Hospital , Washington, DC , USA.
authors: John H
authors: JH
authors: Lynch
authors: Department of Radiation Medicine, Georgetown University Hospital , Washington, DC , USA.
authors: Sean P
authors: SP
authors: Collins
keywords: CyberKnife; EPIC; SBRT; patient-reported outcome; prostate cancer; toxicity