Introduction: To assess the impact of radiation dose and clinical parameters on rectal toxicity following salvage external beam radiation therapy (EBRT) with or without a brachytherapy (BT) boost for exclusive local failure after primary-EBRT for prostate cancer.

Materials and Methods: Fourteen patients with no residual toxicity after primary EBRT (±BT) were re-irradiated after a median time interval of 6.1 years (4.7-10.2). The median NTD2Gy was 74Gy (66-98.4) at primary-RT and 85.1Gy (70-93.4) at re-irradiation. Rectal dose volume histograms of both treatments (converted to NTD2Gy) and the corresponding normal-tissue-complication-probability (NTCP) values for gastro-intestinal (GI) toxicity were calculated.

Results: The 5-year Grade ≥3 GI toxicity-free survival rate was 57.1±13.1%. Five patients developed Grade 4 GI toxicity. Rectal V70Gy and the maximum dose to 1cc of rectum at primary EBRT were both predictive for Grade ≥3 GI toxicity; 12.2% vs. 3.8%, p=0.042 and 72.2 Gy vs. 66.8 Gy, p=0.0027, respectively. When adding primary-RT and re-irradiation plans, the median maximum dose to 1cc of rectum was 139.8 Gy (126.7-147.8) vs. 125.9 Gy (99.1-133.1) (p=0.0063) for Grade ≥3 and Grade ≤2 GI toxicity groups. Higher NTCP values at primary-RT were predictive for Grade ≥3 toxicity (p<0.05).

Conclusions: A higher rectal NTCP value, even in the absence of high-grade late-toxicity after primary-RT, is correlated with an increased risk of severe rectal side-effects after salvage re-irradiation. Rectum doses greater than 70Gy at primary-RT, and NTCP values of more than 10%, might predict for grade ≥3 rectal toxicity at re-irradiation, with a possible threshold for total rectum dose of around 130Gy.