To assess late gastrointestinal (GI) and genitourinary (GU) side effects in patients with organ-confined unfavorable prostate cancer (PCa) treated with single dose ablative radiotherapy (SDRT). Thirty patients enrolled in a single-arm prospective trial received 24 Gy SDRT to the whole prostate with urethra sparing and organ motion control delivered on a Linac platform with a 10MV FFF single partial arc. ADT was prescribed as per standard of care. Treatment-related acute and late GU and GI toxicities (CTCAE_v5 scale) and QoL outcomes (EORTC QLQ-PR25/C30, IPSS) were assessed at different time points. Minimal Important Difference (MID) was established as a change of >0.5 pooled SD from baseline. Statistical analysis included ANOVA test and logistic regression. Median follow-up was 18 months (range, 6-31), with no ≥G3 late side effects observed. G2 late GI and G2 late GU toxicities occurred in 1 and 2 patients, respectively. GI toxicity of any grade correlated with maximum rectal dose (P=0.021). Lower baseline QoL score (P=0.025), higher baseline IPSS score (P=0.049), acute GU toxicity (P=0.029), and acute urinary domain MID (P=0.045) predicted GU toxicity of any grade. In MVA, only baseline QoL score (OR, 0.95, P=0.031) and acute GU toxicity (OR, 8.4, P=0.041) remained significant. Significant QoL change was observed only in the urinary domain (P=0.005), with a median increase from 8 to 17. Late urinary MID correlated with acute urinary MID (P=0.003), acute QoL MID (P=0.029), acute GU toxicity (P=0.030), and lower baseline urinary score (P=0.033). In MVA, only acute urinary MID predicted late urinary MID (OR, 9.7, P=0.035). Our findings provide promising data on the feasibility and safety of 24 Gy whole gland SDRT with urethra sparing and organ motion control, in association with ADT and an adequate prophylactic medication, in organ confined unfavorable PCa. Long-term follow-up is needed to confirm these results.