Prognostic factors for acute toxicity in prostate cancer patients treated with high-dose hypofractionated radiotherapy.

Purpose: To prospectively study acute genitourinary (GU) and gastrointestinal (GI) toxicity during hypofractionated radiotherapy.
Patients and Materials: One-hundred and seventy-one consecutive men with cT1-T3cN0cM0 prostate cancer were treated at 2.6 Gy/fraction to a total dose of 67.6 for low risk (EQD2 = 79 Gy) and 70.2 Gy for intermediate-high risk (EQD2 = 82 Gy) over 5.2-5.4 weeks (α/β 1.5). Acute toxicity was scored according to RTOG/EORTC toxicity extended criteria after completing a 22-item questionnaire (basal, weekly, at 6 months).
Results: Minimum and median follow-up were 36 and 54.2 months, respectively. GU toxicity grades 0, 1, 2 and 3 were found in 30.4, 37, 32 and 0.6 % of patients, respectively. The figures for grades 0, 1, 2 and 3 GI toxicity were 66, 24, 10 and 0 %. The highest degree of acute reactions was reached at 4-5 weeks. At 6 months, 15 % of patients had GU toxicity (11 % grade 1, 4 % grade 2) and 5.8 % GI toxicity (5.3 % grade 1, 0.5 % grade 2). Multivariate analysis shows that bladder volume receiving ≥65 Gy (V 65) is associated with an increased risk of GU complications (p = 0.017, HR = 1.143, 95 % CI = 1.025-1.276), while history of TURP is linked to lower risk (p = 0.002, HR = 0.310, 95 % CI 0.004-0.370). Mean rectal dose (p = 0.013, HR = 1.089, 95 % CI 1.018-1.116) and total dose (p = 0.019, HR = 0.734, 95 % CI 0.567-0.950) are significantly related to GI toxicity.
Conclusions: This 5-week dose-escalation hypofractionated radiotherapy schedule that uses 3D-conformal radiotherapy without IGRT has resulted in <1 % grade 3 acute complications. Our study suggests that reducing the mean rectal dose and the bladder V 65 helps prevent acute toxicity. TURP before radiotherapy was associated with lower acute GU toxicity.