To investigate the impact of reducing CTV to PTV margins on dosimetry and patient reported Quality of Life (QOL) for patients with localized prostate cancer. Twenty patients were included in a single institution IRB-approved prospective study. Nine were planned using reduced margins (5 mm uniformly except 4 mm at prostate/rectum boundary), and 11 were control patients with standard margins (10/6 mm). Cumulative delivered dose was calculated using deformable dose accumulation. Each daily CBCT dataset was deformed to the planning CT (pCT), dose was computed, and accumulated on the resampled pCT using a parameter-optimized, B-spline algorithm (Elastix, ITK/VTK). EPIC-26 based patient reported QOL data was collected pre-treatment, post-treatment, and at 2, 6, 12, 18, 24, 36, 48 and 60 months follow-up. Post-radiation therapy (RT) QOL scores were baseline corrected and standardized to a [0-100] scale using EPIC-26 methodology. QOL comparisons between the margin-reduced and the standard cohorts including the averages within each arm and the overall mean QOL differences between the groups (QOLM-R-QOLcontrol) were made at each time point. The median QOL follow-up length for the 20 patients was 48 months. Cumulative delivered dose and planned dose did not reach statistical significance (p>0.1) for targets and organs at risk, for both mean and maximum dose. At 4 years after RT, standardized and baseline-corrected mean QOLM-R-QOLcontrol were improved for “Urinary Incontinence”, “Urinary Irritative/Obstructive”, “Bowel”, and “Sexual” EPIC domains by 3.5, 14.8, 10.2, and 16.1, respectively (higher value is better). The control group showed larger PTV/rectum and PTV/bladder intersection volumes (7.2±5.8, 18.2±8.1 cc) than the margin-reduced group (2.6±1.8, 12.5±8.3 cc), though the dose to these intersection volumes did not reach statistical significance (p>0.1) between the groups. PTV/rectum intersection volume showed a moderate correlation (R = -0.6) to “Bowel” EPIC domain. Margin-reduced group exhibited clinically meaningful improvement of QOL without compromising the target dose coverage.Abstract 4152; TableTime PointUrinary IncontinenceUrinary Irritative/ObstructiveBowelSexualHormonalEnd of RT (N = 20)-6.413.46.36.6-2.62-month post RT (N = 20)3.18.26.68.3-3.26-month post RT (N = 19)-2.08.519.014.94.412-month post RT (N = 19)5.510.38.019.97.124-month post RT (N = 17)-1.59.515.614.6-13.036-month post RT (N = 16)5.616.59.020.2-13.848-month post RT (N = 13)-3.96.34.96.2-14.2Mean QOLM-R - QOLcontrol3.514.810.216.1-4.9Minimally important difference range [Skolarus et al. Urology 2015]6-95-74-610-124-6 Open table in a new tab