We analyzed the acute and chronic genitourinary (GU) and gastrointestinal (GI) toxicity of prostate cancer patients treated with 3 different high-dose RT techniques at a single institution. From 1992-2003, 1232 patients with clinically localized prostate cancer were treated with ART (n=512), EBRT+HDR (n=421), or BT alone (n=299, 204 Pd103 implants, 95 HDR alone). Median delivered dose with ART was 75.6 Gy (minimal peripheral dose) to the prostate gland +/- seminal vesicles. For EBRT+HDR, the whole pelvis was treated to 46 Gy + a median of 9.5 Gy via 2 HDR prostate implants. The dose delivered with Pd103 was 120 Gy and with HDR, 38 Gy in 4 fractions and a single implant. Neoadjuvant androgen deprivation was used in 52% for EBRT+HDR, 37% for BT, and 32% for ART. NCI-CTC version 2 was used for toxicity scoring. Median age was 73, 68 and 66 years for ART, EBRT+HDR and BT patients (p<0.01). Median follow-up was 4.6 years (EBRT+HDR and BT) and 3.4 for ART with 31% of patients having a follow-up over 5 years. Grade ≥ 2 acute GU toxicity was greater for EBRT+HDR (52%) vs. BT (39%) vs. ART (40%, p<0.01) mainly due to more dysuria (26% vs 11% vs 2%, respectively). Grade ≥ 2 acute GI toxicity was greater for patients receiving EBRT (34% for EBRT+HDR and 28% for ART vs 4% for BT, p<0.01) primarily due to more diarrhea and tenesmus. Grade ≥ 2 chronic GU toxicity was greater in brachytherapy patients (29% for EBRT+HDR and 24% for BT vs 17% for ART, p<0.01) mainly due to more urinary retention (12% for EBRT+HDR and 10% for BT vs 3% for ART, p<0.01). Grade ≥ 2 chronic GI toxicity was higher for ART (19%) vs EBRT+HDR (10%) and BT (only 1%, p<0.01), mainly due to more rectal bleeding with EBRT (13% for ART vs 7% for EBRT+HDR vs 1% for BT, p<0.01). Grade ≥ 3 acute GU toxicity was higher with the use of brachytherapy (see table). Grade ≥ 3 chronic GU toxicity was also greater with brachytherapy primarily due to a higher rate of urethral dilatations in these patients (10% for EBRT+HDR). Grade ≥ 3 chronic GI toxicity was higher for ART due to more rectal bleeding.Tabled 1Toxicity gr≥3ARTBT AloneEBRT + HDRp-Valueany acute gr≥3 GU2%10%7%<0.01any acute gr≥3 GI0.3%0.3%2%<0.01Any Acute gr≥3 Toxicity3%10%10%<0.01Chronic gr≥3 GUretention2%3%5%0.02urethral dilatation1%3%10%<0.01any gr≥3 GU3%6%11%<0.01Chronic gr≥3 GIrectal bleeding3%0.4%0.3%<0.01any gr≥3 GI4%0.4%1%0.01Any Chronic Toxicity gr≥37%7%12%0.03 Open table in a new tab In hormone-naïve patients and no pre-RT erectile dysfunction (ED), EBRT+HDR had higher rate of ED (57%) than ART (38%) and BT (22%, p<0.01). Chronic grade ≥ 3 toxicity rates were low for all treatment modalities. Brachytherapy patients experienced more GU toxicity (more urethral strictures with EBRT+HDR) and patients receiving EBRT had more GI toxicity with a higher rate of rectal bleeding with ART. Patients treated with BT alone had the best GI toxicity profile and the lowest rate of ED compared with ART and EBRT+HDR.