Table 1.

Identification of predictive factors for rectorrhagia 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/Endpoint definition	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 group 3 and 4	44	Grade ≥ 2 rectal bleeding, requiring treatment by laser coagulation and/or blood transfusion	Modified RTOG/EORTC score	1. History of abdominal surgery (HR =2.7; 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, sometimes requiring iron supplements	SOMAT LENT and CTCAE V2.0	1. V40 Gy to V65 Gy was predictive of anorectal bleeding ay 36 months
Schaake et al. (30)	Prospective cohort	262	IMRT Dose: 78 Gy CTV= prostate only +/− SV; PTV= 10 mm isotropic margin Pelvic floor muscles were contoured retrospectively Anal canal = most distal 3 cm of the anorectal volume HT was allowed	> 36 months	Prevalence of grade ≥2 toxicities after 36 months	CTCAE V3.0 and patient questionnaire	1. The use of anticoagulants increases the risk of rectorrhagia (OR=3 ; p=0.06)
Defraene et al. (28)	Phase 3 RCT	512	3D Dose: 68 vs 78 Gy CTV1= prostate only; CTV2= prostate + SV up to 50 Gy then prostate only; CTV3= same up to 68Gy; CTV4= prostate + SV for 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	> 36 months	Prevalence of the critical event	Subjective	History of abdominal surgery or cardiovascular risk/disease V65Gy to the anal canal (p=0.002)

RCT, randomized controlled trial; 3D, tridimensional radiotherapy; RT, radiotherapy; CTV, clinical target volume; PTV, Planning Target Volume, SV, seminal vesicles; H, hormonotherapy; OR, odds ratio; HR, hazard ratio.