Table 4.

Identification of predictive factors for late abdominal or rectal pain in patients with localized prostate cancer treated with pelvic radiotherapy.

Study	Design	No. of# patients	Received treatment (technique, dose, volumes and associated treatments)	Follow up(months)	Outcomes/Endpointdefinition	Evaluation method	Predictive factors identified in multivariate analysis
Peeters et al. (16)	Multicenter phase 3 RCT	641	3D Dose: 68 vs 78 Gy CTV1= prostate only; CTV2= prostate + SV up to 50 Gy then prostate only; CTV3= same as CTV3, treated to 68 Gy; CTV4= prostate + SV treated to total dose PTV= 10 mm margin coned down to 5 mm for delivery of the last 10 Gy (in 78 Gy arm) Anal canal = most distal 3 cm of the anorectal volume HT for grade groups 3 and 4	44	Grade ≥ 2 rectal bleeding, requiring treatment by laser coagulation and/or blood transfusion	Modified RTOG/EORTC score	1. Acute GIT (HR=1.9; p ≤ 0.01) 2. GI symptoms prior to radiotherapy 2. No association found with dosimetric parameters (HR=6.4; p ≤ 0.01)
Ebert et al. (27)	Multicenter phase 3 RCT	754	3D Dose: 66, 70, 74 or 78 Gy CTV= prostate only +/− SV; PTV= 10 mm margin reduced to 5 mm posteriorly Anal canal = most distal 3 cm of the anorectal volume HT for 6 vs 18 months	72	Prevalence of peak toxicity grade at 36 months	SOMAT LENT and CTCAE V2.0	1. No predictive factors identified
Schaake et al. (30)	Prospective cohort	262	IMRT Dose: 78 Gy CTV= prostate only +/− SV; PTV= 10 mm isotropic margin Pelvic floor muscles were defined retrospectively Anal canal = most distal 3 cm of the anorectal volume HT was allowed	> 36 months	Prevalence grade ≥2 toxicities after 36 months	CTCAE V3.0 and patient questionnaire	1. No clinical or dosimetric correlation with rectal pain
Thor et al. (29)	Prospective cohorts	212 in the Danish cohort 277 in the Swedish cohort	3DCRT Dose: 70 to 78 Gy CTV= prostate only +/− SV PTV= For the Danish cohort, 7 mm margin but 9 mm cranio-caudally. For the Swedish cohort, 20 mm margin but 15 mm posteriorly Definition of the anal sphincter (AS) and of external/internal sphincter muscles definition du sphincter anal (AS)	42 months for the Danish cohort 76 months for the Swedish cohort	Prevalence of moderately severe symptoms (occurring at least once/week) and the use of diapers/pads	Questionnaires specific to the Danish and Swedish cohorts	1. HT, tobacco and V15 Gy are predictive of pain

RCT, randomized controlled trial; 3D, tridimensional radiotherapy; RT, radiotherapy; CTV, clinical target volume; PTV, planning target volume; SV, seminal vesicles; HT, hormonotherapy; GIT, gastrointestinal toxicities; OR, odds ratio; HR, hazard ratio.