Choo, Richard

305 Background: Toxicity due to radiotherapy (RT) may differ in patients (pts) with prostate cancer who receive intensity-modulated radiotherapy (IMRT) or proton beam therapy (PBT). Methods: Patient-reported bowel function (BF), urinary incontinence (UI), and urinary irritative/obstructive symptoms (UO) domains of the Expanded Prostate Index Composite Questionnaire (EPIC-26) were prospectively collected in pts with localized prostate cancer receiving either IMRT (n=157) or PBT (n=105) to the prostate +/- proximal seminal vesicles for clinical stage T1-T2 N0 prostate cancer at a single tertiary cancer center between 2015 and 2018. Changes in domain scores were analyzed from pretreatment to the end of RT and 3 months post-RT, assessing the acute effects of each modality. A clinically relevant change was defined as a score change that exceeded 50% of the standard deviation of a baseline value. Results: At baseline there was no difference in the scores of BF, UI, and UO domains between IMRT and PBT cohorts. At the end of RT, pts treated with either modality had a statistically significant and clinically relevant worsening of BF and UO compared to baseline. Pts treated with IMRT experienced a significantly greater decrement in BF compared to the PBT cohort (-13 vs -9, p<0.01), including significantly more IMRT pts having a clinically relevant deterioration in BF compared to PBT pts (58% vs 40%, p=0.01). Though there was a statistically significant deterioration in UI in the IMRT cohort (-4, p<0.001), this did not reach the predefined threshold for clinical relevance. Three months following RT, the IMRT group continued to have statistically significant and clinically relevant worsening of BF (-9, p<0.001), whereas the change in BF domain score of the PBT cohort was no longer statistically significant or clinically relevant compared to baseline (-1, p=0.25). There were no statistically significant or clinically relevant changes in UO or UI in either cohort at three months when compared to baseline. Conclusions: Pts who received IMRT or PBT reported unique patterns of toxicity, and pts treated with IMRT had worse decrement in BF immediately after and three months following RT, compared to those treated with PBT.

75 Background: Combined radiotherapy (RT) and long-term hormonal therapy (HT) is a standard treatment option for high-risk prostate cancer. Dose escalated RT alone has been shown to improve disease free survival. Increased sensitivity of prostate cancer to high doses per fraction has led to hypofractionation as a method to radiobiologically escalate dose.We report on the quality of life of patients treated with combined hypofractionated RT and HT. Methods: A prospective phase I/II study enrolling patients with any of: clinical T3, PSA ≥20, or Gleason 8-10. Forty-five Gy (1.8 Gy/fraction) was delivered to the pelvic nodes with a concomitant 22.5 Gy intensity-modulated RT boost to the prostate, for a total of 67.5 Gy (2.7 Gy/fraction) in 25 fractions over 5 weeks. Hormonal therapy was administered for 2-3 years. Patient reported outcomes were measured at baseline and every 6 months using the validated Expanded Prostate Cancer Index Composite (EPIC) questionnaire, which measures urinary, bowel, sexual, and hormonal domains. Results: Sixty patients with a minimum 24 months of patient-reported outcomes were analyzed. Mean scores comparing baseline to 24 month values are reported. There were no statistically significant changes in the urinary summary scores (86.3 vs. 86.0, p=0.45) or any of the urinary subscales (function, bother, incontinence, irritative/obstructive). Domain summary score decreases were observed in: bowel by 4.4% (94.7 vs. 90.3, p<0.01), sexual by 27% (44.5 vs. 17.5, p<0.01), and hormonal by 11.9% (93.1 vs. 81.2, p<0.01). Examining time trends in outcomes, most changes occurred within the first 6 months with smaller changes thereafter. Conclusions: Hypofractionated RT combined with long-term HT is associated with good patient-reported urinary and bowel outcomes at 24 months. Sexual and hormonal summary scores are affected, largely due to continued androgen deprivation therapy. Further follow-up is needed to document patient reported outcomes after testosterone recovery. No significant financial relationships to disclose.

277 Background: For patients (pts) with LRR or advanced primary tumors of the UB or ureter, limited therapeutic options exist. Outcomes of combined SR and IOERT are reported here. Methods: From 1983 to 2009, a total of 17 pts with urothelial (16 pts) or squamous cell carcinoma (1 pt) of the UB (n=13) or ureter (n=4) were treated with SR and IOERT. Pts had LRR after radical cystoprostatectomy or nephroureterectomy (n=15) or advanced primary tumor (n=2). Extent of SR was R0 (microscopic negative margins), R1 (microscopic positive margins), and R2 (gross residual tumor) in 7, 1, and 9 pts, respectively. After maximal SR, IOERT was delivered to the tumor bed. Median IOERT dose and energy delivered were 12.5 Gy (range; 10-20) and 9 MeV (range; 6-18), respectively, with 1 (n=15), 2 (n=1), or 3 (n=1) IOERT fields. Sixteen pts also received perioperative external beam radiotherapy (EBRT) with a median dose of 50.4 Gy (range; 21.6- 60). Five pts received concurrent chemotherapy (CT) with perioperative EBRT. Overall (OS), disease-free survival (DFS) and relapse patterns were estimated from the date of SR and IOERT using the Kaplan-Meier method. Results: The median pt age was 63 years (yrs) (range; 51-76). The median follow-up of surviving pts was 3.6 yrs (range; 1.1-10.0). OS and DFS at 1, 2, and 5 yrs were 53%, 31%, and 16%, and 24%, 18%, and 18%, respectively. Central (within the IOERT field), locoregional (tumor bed or first echelon draining lymphatics), and distant relapse at 2 yrs were 15%, 49%, and 67%, respectively. Seven pts received systemic CT after relapse. Mortality within 30 days of SR and IOERT was 0%. Two pts (12%) experienced grade 4-5 (NCI-CTCAE v. 4) toxicity potentially related to the multimodality therapy. Conclusions: For pts with LRR or advanced primary tumor of the UB or ureter, this multimodality therapy including SR and IOERT resulted in durable OS and DFS in a small but significant number of pts. Both LRR and distant relapse were common, indicating a need for more effective systemic therapy along with more refined locoregional therapy. No significant financial relationships to disclose.

327 Background: To report long-term outcomes of patients (pts) treated with radiotherapy (RT) for stage II testicular seminoma. Methods: Between 1974 and 2007, 52 pts received RT for clinical stage II testicular seminoma after radical inguinal orchiectomy; 3 pts were excluded due to no clinical follow-up. CT staging was used for 46 pts (94%). Estimates of overall (OS), relapse-free (RFS), and cause-specific (CSS) survival were determined using the Kaplan-Meier technique. Major cardiac event (MCE) was defined as myocardial infarction, coronary artery bypass grafting or stenting, or valve replacement. Second malignancy (SM) was defined as biopsy-confirmed malignancy occurring in the RT field. Results: The median pt age was 35 years. AJCC stage was IIA (n=23), IIB (n=7), IIC (n=15), and unknown (n=4). Three pts were treated for paraortic recurrence during surveillance for stage I seminoma. Four pts with IIB (n=1) or IIC (n=3) disease were treated with chemotherapy in addition to RT. The median total RT dose was 30.4 Gy. Prophylactic mediastinal/supraclavicular (MSCV) RT was given to 24 pts (49%). The median follow-up was 18 years (range 0.4-37). Estimates of OS, RFS, and CSS at 10 and 20 years were 94% and 81%, 79% and 70%, and 96% and 96%, respectively. OS, RFS, and CSS were not significantly different between stage groups. Recurrence occurred in 9 pts (18%); sites were MSCV (n=6), para-aortic (n=1), lung (n=1), and peritoneal cavity (n=1). Seven pts were successfully salvaged, while 2 pts died of seminoma. No patient with stage IIA/B that received prophylactic MSCV RT (n=11) experienced MSCV relapse. Among patients that did not receive prophylactic MSCV RT, 2 of 13 (15%) with stage IIA and 3 of 6 (50%) with stage IIB experienced MSCV relapse. MCE occurred in 10 pts (20%) at a median of 18 years (range 7-30) after RT. SM occurred in 5 pts (10%) at a median of 27 years (range 20-34) after RT. Conclusions: Infradiaphragmatic RT alone was associated with a significant risk of MSCV failure, particularly in patients with stage IIB disease, suggesting that chemotherapy may be the optimal treatment in this patient cohort. Most MCE and SM events occurred more than 20 years after RT, highlighting the importance of vigilant long-term follow-up.

Purpose To describe outcomes of salvage radiotherapy (SRT) for men with detectable prostate-specific antigen (PSA) after radical prostatectomy for prostate cancer and identify associations with outcomes. Patients and Methods A total of 1,106 patients received SRT between January 1987 and July 2013, with median follow-up 8.9 years. Outcomes were estimated using Kaplan-Meier for overall survival (OS) and cumulative incidence for biochemical recurrence (BcR), distant metastases (DM), and cause-specific mortality (CSM). Variable associations with outcomes used Cox or Fine-Gray methods, as appropriate. Multiple variable analyses used backward selection with P < .05 for retention. Results In multiple variable analyses, pathologic tumor stage, Gleason score, and pre-SRT PSA were associated with BcR, DM, CSM, and OS; androgen suppression and SRT doses > 68 Gy were associated with BcR; and age was associated with OS. Each pre-SRT PSA doubling increased significantly the relative risk of BcR (hazard ratio [HR], 1.30; P < .001), DM (HR, 1.32; P < .001), CSM (HR, 1.40; P < .001), and all-cause mortality (HR, 1.12; P = .02). Using a pre-SRT PSA cutoff ≤ 0.5 versus > 0.5 ng/mL, 5-year and 10-year cumulative incidences for BcR were 42% versus 56% and 60% versus 68% ( P < .001), DM 7% versus 14% and 13% versus 25% ( P < .001), CSM 1% versus 4% and 6% versus 13% ( P < .001), and OS of 94% versus 92% and 83% versus 73% ( P > .05). Conclusion SRT outcomes are in part affected by factors associated with prostatectomy findings but may be positively affected by using SRT at lower PSA levels, including reductions in BcR, DM, CSM, and all-cause mortality. These findings argue against prolonged monitoring of detectable postprostatectomy PSA levels that delay initiation of SRT.