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PURPOSE/OBJECTIVE(S) The use/prolongation of androgen deprivation therapy (ADT) with external beam radiotherapy (EBRT) improves distant metastasis outcomes in patients with high-risk prostate cancer. The optimal duration of ADT when adding a brachytherapy boost (EBRT+BT) remains unknown. MATERIALS/METHODS A total of 2935 patients who received treatment across 15 institutions between 2000-2014 were identified (1827 treated with EBRT and 1108 with EBRT+BT). Three broad ADT strata were defined: no ADT, 1-18 months ADT, and 18-36 months ADT. Fine-Gray competing risk regression models evaluating the association between differing ADT duration strata and time to distant metastasis (DM) were developed. Models were adjusted for ln (initial PSA), clinical T stage, Gleason grade group, age at treatment, treatment type, and interaction between ADT duration and treatment. A continuous, non-linear relationship between ADT duration and DM was investigated in the overall cohort and within the EBRT and EBRT+BT cohorts using a restricted cubic spline transformation with 4 knots. Splines were adjusted for the same covariates. RESULTS Median follow-up was 8 years (IQR, 5-11.3 years). ADT duration was significantly greater in patients treated with EBRT (median 18 months vs. 8 months, P < 0.001). A substantial proportion of patients did not receive any ADT (26.2% and 14.9% of those undergoing EBRT and EBRT+BT, respectively). Overall, DM rates were improved with adding 1-18 months of ADT or 18-36 months of ADT versus no ADT (sHR 0.66 and 0.43, respectively). DM rates were also lower after 18-36 months vs. 1-18 months (sHR 0.64). No significant interaction between treatment type and ADT duration was seen. Based on spline analysis, the optimal durations of ADT were 26 months for the total cohort and patients receiving EBRT and 22.5 months for patients receiving EBRT+BT. However, the incremental benefit of prolonged time to DM per month ADT added appears to be more pronounced in patients receiving EBRT than in those undergoing combined EBRT+BT treatment. CONCLUSION A clear relationship between ADT duration and DM risk following definitive radiotherapy in patients with HRPCa was seen, with durations of 18-36 months being associated with the lowest risk of DM. The lack of a significant interaction between ADT duration and treatment type implies this relationship persists even in patients receiving EBRT+BT. However, the magnitude of this benefit may differ, and prospective evidence seems warranted to determine the optimal duration of ADT in patients receiving of EBRT+BT.

Introduction To identify differences in acute urinary and sexual toxicity between a 6-fraction and 2-fraction high-dose-rate brachytherapy monotherapy regimen and correlate dosimetric constraints to short-term toxicity. Methods A single institution retrospective study of 116 men with prostate cancer treated with HDR monotherapy from 2010 to 2015 was conducted. Eighty-one men had 7.25 Gy × 6-fractions and 35 men had 13.5 Gy × 2-fractions. Patients had two CT-planned implants spaced 1–2 weeks apart. Patient baseline characteristics, International Prostate Symptom Scores (IPSS) and Sexual Health Inventory for Men (SHIM) scores were collected pre-treatment and 3, 6 and 12 months post-implantation. Mixed effect modelling was undertaken to compare baseline, 1–6 month and 7–12 month scores between groups. Poisson regression analysis was performed to correlate dosimetric constraints with acute toxicity. Results There was no difference between baseline and post-implantation IPSS scores between 6-fraction and 2-fraction groups. SHIM scores for men treated with 6-fractions had a steeper decline at 1–6 months, but resolved at 7–12 months. Pre-treatment alpha-blocker use correlated with worse short-term acute urinary toxicity. Worsened SHIM score correlated with increasing age, diabetes mellitus and androgen-deprivation therapy. In a dosimetric analysis of outcomes, prostate V150 dose and bladder wall (D01.cc, D1cc, D2cc) dose correlated with increased IPSS score. Conclusion No increased acute genitourinary or sexual dysfunction has been observed in men when transitioning from 6-fraction to 2-fraction HDR monotherapy. A dosimetric correlation was found between the V150 and bladder wall doses for acute urinary toxicity. Future research should continue to standardize and validate dose constraints for prostate HDR monotherapy patients.

BackgroundThe long natural history of prostate cancer (CaP) limits comparisons of efficacy between radical prostatectomy (RP) and external beam radiotherapy (EBRT), since patients treated years ago received treatments considered suboptimal by modern standards (particularly with regards to androgen deprivation therapy [ADT] and radiotherapy dose-escalation]. Gleason score (GS) 9-10 CaP is particularly aggressive, and clinically-relevant endpoints occur early, facilitating meaningful comparisons.ObjectiveTo compare outcomes of patients with GS 9-10 CaP following EBRT, extremely-dose escalated radiotherapy (as exemplified by EBRT+brachytherapy [EBRT+BT]), and RP.Design, setting, participantsRetrospective analysis of 487 patients with biopsy GS 9-10 CaP treated between 2000 and 2013 (230 with EBRT, 87 with EBRT+BT, and 170 with RP). Most radiotherapy patients received ADT and dose-escalated radiotherapy.Outcome measurements and statistical analysisKaplan-Meier analysis and multivariate Cox regression estimated and compared 5-yr and 10-yr rates of distant metastasis-free survival, cancer-specific survival (CSS), and overall survival (OS).Results and limitationsThe median follow-up was 4.6 yr. Local salvage and systemic salvage were performed more frequently in RP patients (49.0% and 30.1%) when compared with either EBRT patients (0.9% and 19.7%) or EBRT+BT patients (1.2% and 16.1%, p

208 Background: Treatment of high risk prostate cancer (HRPCa) with external beam radiotherapy (EBRT) plus brachytherapy (BT) boost (EBRT+BT) has been prospectively associated with lower rates of BCR, albeit potentially with increased toxicity, and retrospectively linked to decreased distant metastasis (DM) and PCa-specific mortality (PCSM) compared to EBRT alone. However, it is unclear whether patients who develop BCR following either approach have similar downstream oncologic outcomes. Methods: We identified 706 out of 3820 men with HRPCa treated at 13 institutions from 1998-2015 with EBRT (n=468/2134) or EBRT+BT (n=238/1686) who developed BCR. We compared rates of DM, PCSM, and all-cause mortality (ACM) after BCR between treatment groups using Fine-Gray competing risk regression. Models were adjusted for age, Gleason grade group, initial PSA (iPSA), clinical T stage, time-dependent use of systemic salvage, and interval to BCR using inverse probability of treatment weighting. Results: Median follow-up was 9.9 years from RT and 4.8 years from BCR. Groups were similar in age, iPSA, presence of ≥2 HR features, and median interval to BCR (3.3 years). Most men received neoadjuvant/concurrent androgen deprivation therapy (ADT), 92.5% and 91.0% for EBRT and EBRT+BT, respectively, though for a longer duration with EBRT (median 14.7 vs. 9.0 months, p=0.0012). Local and systemic salvage rates were 2.3% and 36.3% after EBRT, and 2.6% and 43.6% after EBRT+BT, respectively. Initial EBRT+BT was associated with significantly lower rates of DM after BCR (HR 0.48, 95% CI 0.36-0.64, p

109 Background: While level one evidence has shown an overall survival (OS) advantage with the addition of androgen deprivation therapy (ADT) to radiotherapy (RT) for intermediate risk prostate cancer (PCa), the benefit in the era of modern dose escalation is controversial, especially given the heterogeneity within this risk group. We assessed the impact of adding ADT to high dose RT on OS for intermediate risk PCa stratified by number of intermediate risk factors (IRF). Methods: We identified 114,339 men with intermediate risk PCa (Gleason 7, clinical stage T1-2, PSA < 20 ng/mL) using the National Cancer Database. Men were stratified into the following subgroups based on the number of IRFs (Gleason 7, cT2b-c, PSA > 10-20 ng/mL): A) Gleason 3+4 and no other IRF, B) Gleason 4+3 and no other IRF, C) two IRFs, and D) three IRFs. The addition of ADT to dose-escalated external beam RT (DE-EBRT, ≥ 75.6 Gy), brachytherapy (BT), or combination EBRT+BT on OS was assessed within each subgroup using Kaplan-Meier and log-rank tests in propensity score-matched cohorts in all men and subsequently only in those with Charlson-Deyo comorbidity index (CDI) of zero. Results: There was no OS benefit with the addition of ADT to DE-EBRT, BT, or EBRT+BT in groups A, B, and C, even after limiting the cohort to men with CDI = 0. However, in group D, the addition of ADT to DE-EBRT was associated with a trend for OS improvement in patients with CDI = 0 only (8-year OS with and without ADT 68.3% and 62.4%, respectively, log-rank P= .07). Conversely, there was a trend for OS decrement with the addition of ADT to DE-EBRT in men with CDI ≥ 1 (8-year OS with and without ADT 61.8% and 67.5%, respectively, log-rank P= .06). There was no OS benefit of ADT in group D treated with BT or EBRT+BT, regardless of comorbidity status. Conclusions: The OS benefit of ADT in men with intermediate risk PCa may be limited to those with 3 IRFs and minimal comorbidities treated with DE-EBRT. If prospectively validated, extreme dose escalation achieved with BT (alone or in combination with EBRT) may obviate the addition of ADT in all men with intermediate risk disease, especially in an era of advanced molecular imaging.

Objectives To report outcomes for breast-conserving therapy using adjuvant accelerated partial breast irradiation (APBI) with interstitial multicatheter brachytherapy in node-positive compared with node-negative patients. Materials and methods From 1992 to 2013, 1351 patients (1369 breast cancers) were treated with breast-conserving surgery and adjuvant APBI using interstitial multicatheter brachytherapy. A total of 907 patients (835 node negative, 59 N1a, and 13 N1mic) had >1 year of data available and nodal status information and are the subject of this analysis. Median age (range) was 59 years old (22 to 90 y). T stage was 90% T1 and ER/PR/Her2 was positive in 87%, 71%, and 7%. Mean number of axillary nodes removed was 12 (SD, 6). Cox multivariate analysis for local/regional control was performed using age, nodal stage, ER/PR/Her2 receptor status, tumor size, grade, margin, and adjuvant chemotherapy/antiestrogen therapy. Results The mean (SD) follow-up was 7.5 years (4.6). The 5-year actuarial local control (95% confidence interval) in node-negative versus node-positive patients was 96.3% (94.5-97.5) versus 95.8% (87.6-98.6) (P=0.62). The 5-year actuarial regional control in node-negative versus node-positive patients was 98.5% (97.3-99.2) versus 96.7% (87.4-99.2) (P=0.33). The 5-year actuarial freedom from distant metastasis and cause-specific survival were significantly lower in node-positive versus node-negative patients at 92.3% (82.4-96.7) versus 97.8% (96.3-98.7) (P=0.006) and 91.3% (80.2-96.3) versus 98.7% (97.3-99.3) (P=0.0001). Overall survival was not significantly different. On multivariate analysis age 50 years and below, Her2 positive, positive margin status, and not receiving chemotherapy or antiestrogen therapy were associated with a higher risk of local/regional recurrence. Conclusions Patients who have had an axillary lymph node dissection and limited node-positive disease may be candidates for treatment with APBI. Further research is ultimately needed to better define specific criteria for APBI in node-positive patients.

102 Background: Patients with Gleason score (GS) 9-10 prostate cancer (PCa) have a high risk of early biochemical recurrence (BCR). Salvage therapy options differ depending on the upfront management strategy. Patients who received upfront surgery (RP) may be curable with salvage external beam radiation therapy (EBRT). However those who underwent EBRT or EBRT with a brachytherapy boost (EBRT+BT) are less likely to receive local salvage therapy and are commonly treated with androgen deprivation therapy (ADT). In this study, we examine the risk of distant metastases (DM) and prostate-cancer specific mortality (PCSM) among patients with GS 9-10 PCa who had BCR following RP, EBRT, or EBRT+BT. Methods: 712 patients with GS 9-10 PCa treated between 2000-2013 at 12 institutions who had BCR were included (346 RP, 282 EBRT, 84 EBRT+BT). Time to DM and PCSM were compared between groups using Cox proportional hazards models with propensity score adjustment. Propensity scores were calculated using age, T-stage, PSA, and GS. Results: In patients who had a BCR, incidence rates of DM and PCSM after RP were 40% and 28%. Rates after EBRT were 60% and 46% and after EBRT+BT were 49% and 31%. Median times to DM and PCSM were 3.5 and 4.9 years after RP, 3.7 and 5.1 years after EBRT, and 3.3 and 6.8 years after EBRT+BT. The rates of local salvage RT and systemic salvage therapy among RP patients were 38% and 59%, respectively. Local and systemic salvage rates were 5% and 31% for EBRT patients and 5% and 28% for EBRT+BT patients. EBRT patients had a shorter time interval to DM compared with RP (HR 1.4, p = .02) and EBRT+BT (HR 1.9, p < .01). EBRT patients also had a shorter time interval to PCSM compared with RP (HR 1.5, p = .02). Conclusions: Among patients with GS 9-10 PCa who experience BCR after definitive management, those treated with EBRT have a shorter time interval to DM and PCSM compared with RP and EBRT+BT. While this analysis is confounded by the differential thresholds for diagnosing a BCR after different modalities, it does suggest that outcomes following BCR after EBRT+BT and RP are similar. It also suggests that extreme dose escalation delays the onset of DM and PCSM even after BCR, when compared with conventionally-dosed EBRT alone.

53 Background: The costs of treating localized, Gleason score 9 and 10 prostate cancer remain poorly described, especially when the particularly aggressive nature of the disease often requires a multimodal approach. We report the results of time-driven activity-based costing to assess the long-term costs of treating this subset of patients with either RALP, high-dose EBRT, or EBRT with a high-dose rate brachytherapy (BT) boost. Methods: Based on a multi-institutional cohort of 487 patients with Gleason score 9-10 prostate cancer, we generated process maps for each phase of care from the initial urologic visit through a median follow-up of 3.76 years, incorporating all prostate cancer treatment over this horizon. Costs were calculated per unit time, and the proportion of capacity for each step was determined. TDABC was defined as the sum of its resources. Results: Substantial cost variation was demonstrated between treatment modalities with an estimated median cost of $49,681 for EBRT, $35,140 for RALP, and $31,647 for EBRT + BT at 3.76 years. The primary driver in cost variation was the use of ADT. RALP (170 pts) ranged from $18,896 (29.5%) for no postoperative therapy to $63,270 for immediate long-term ADT (5.3%). EBRT (230 pts) had the greatest cost variation [Table 1]. Finally, EBRT + BT (336 pts) ranged from $26,522 for EBRT + BT alone (12.6%) to $37,834 for EBRT + BT + salvage ADT + HIFU (1.2%). Conclusions: Characterizing the costs associated with the distribution of treatments for men with high-risk prostate cancer is essential as we move towards health care accountability. There is substantial long-term cost variation between treatments in this subset of patients, and understanding these differences may affect treatment implications as we shift toward accountable payment models.[Table: see text]

Purpose/Objective(s): To compare the outcomes of a modern cohort of patients with Gleason Score (GS) 9-10 prostate adenocarcinoma (PCa) following treatment with external beam radiotherapy (EBRT), extremely dose-escalated radiotherapy (exemplified by EBRT with a brachytherapy boost [EBRT+BT]), and radical prostatectomy (RP). Materials/Methods: One thousand four hundred three patients with biopsy GS 9-10 PCa who received definitive treatment between 2000 and 2013 were included (506 treated with EBRT, 392 with EBRT+BT, and 505 with RP). Distant metastasis-free survival (DMFS) and prostate cancer-specific mortality (PCSM) were compared across the three cohorts with four cause-specific Cox regression models: (a) unadjusted, (b) covariate-adjusted for age, ln(iPSA), cT stage, and GS, (c) propensity score adjusted for the same covariates, and (d) in a doubly robust analysis (i.e., propensity score and covariate adjusted). Four analogous Fine and Gray competing risk models were developed to compare cumulative PCSM incidence. Results: The median follow-up period was 5.1 years (5.1, 6.4, and 4.3 years in the EBRT, EBRT + BT, and RP cohorts, respectively). The median doses among EBRT and EBRT+BT patients were isoeffective to 81 Gy and 96 Gy in 1.8 Gy fractions, respectively. Over 90% of patients treated with EBRT or EBRT+BT received ADT (median durations of 23 months and 12 months, respectively). Nearly 40% of RP patients received postoperative RT; 78% of postoperative RT was delivered in the salvage setting. PCSM was significantly lower among EBRT+BT patients than among either EBRT or RP patients in all cause-specific hazard models and Fine and Gray competing risk models, including unadjusted models (P

Purpose/Objective(s) To assess the effect on clinical outcomes of the addition of whole pelvis radiation (WPRT) to definitive prostate external beam radiation therapy (EBRT) or external beam radiation therapy plus brachytherapy boost (EBRT-BT) for patients with Gleason Score (GS) 9-10 prostate cancer (PCa), who are at high risk of having occult nodal metastases. Materials/Methods Nine-hundred-forty-two patients with biopsy-proven GS 9-10 PCa treated between 2000 and 2013 at 10 institutions (506 with EBRT and 436 with EBRT+BT) were included. 299 EBRT patients (59%) and 320 EBRT+BT patients (73.4%) received WPRT. A cohort of surgically-treated patients from the same multi-institutional database had a pathologic node positivity rate of 17%. Biochemical recurrence-free survival (bRFS), distant metastasis-free survival (DMFS), and prostate cancer-specific mortality (PCSM) were compared between groups using Cox proportional hazards models with propensity score adjustment. Propensity scores were calculated as the conditional probability of receiving WPRT given age, tumor stage, GS, and initial PSA. Results The median follow-up was 5.6 years. The median doses were isoeffective to 81 Gy and 96 Gy in 1.8 Gy fractions in the EBRT and EBRT-BT groups, respectively. The median WPRT dose was isoeffective to 50.4 Gy in 1.8 Gy fractions. In the EBRT group 94% of patients receiving WPRT and 96% of patients not receiving WPRT received ADT (median duration 23 months), and in the EBRT-BT group, 80% of patients receiving WPRT received ADT, and 98% not receiving WPRT received ADT (median duration 12 months). WPRT did not significantly improve PCSM in the EBRT group (HR = 0.76, 95% CI 0.45-1.3, p = .3), though it trended towards improvement in the EBRT-BT group (HR 0.46, 0.19-1.11, p = .08). Similar results were seen in a competing risks regression model, treating other cause mortality as a competing risk. WPRT improved bRFS among patients treated with EBRT-BT (HR = 0.4, 95% CI 0.29-0.54, p < .001) but not in those treated with EBRT (HR 1.1, 95% CI 0.67-1.68, p = 0.8). There was borderline improvement in DMFS in the EBRT-BT group (HR 0.64, 95% CI .40-1.03, p = .065), but not the EBRT group (HR = 1.21, 95% CI 0.76-1.93, p= .4). Conclusion WPRT offered a trend towards improved DMFS and PCSM in this large cohort of patients with biopsy GS 9-10 PCa, but only in those treated with EBRT+BT. This trend did not reach statistical significance. WPRT did significantly improve bRFS, but again only in patients treated with EBRT+BT. These results are hypothesis-generating in suggesting that a long-term clinical benefit to WPRT, if present, might only be seen in the setting of extreme dose-escalation to the prostate itself.

Purpose: To determine predictors of distant metastases (DM) in prostate cancer patients treated with high dose rate brachytherapy boost (HDR-B) and external beam radiation therapy (EBRT). Material and methods: From 1991 to 2002, 768 men with localized prostate cancer were treated with HDR-B and EBRT. The mean EBRT dose was 37.5 Gy (range: 30.6-45 Gy), and the HDR-B was 22 or 24 Gy delivered in 4 fractions. Univariate and multivariate analyses using a Cox proportional hazards model including age at diagnosis, T stage, Gleason score (GS), pretreatment PSA, biologically equivalent dose (BED), and use of androgen deprivation therapy (ADT) was used to determine predictors of developing distant metastases. Results: The median follow-up time for the entire patient population was 4.2 years (range: 1-11.2 years). Distant metastases were identified in 22/768 (3%) of patients at amedian of 4.1 years. PSA failure according to the Phoenix definition developed in 3%, 5%, and 14% of men with low, intermediate, and high risk disease with amedian time to failure of 3.8 years. Prostate cancer specific mortality was observed in 2% of cases. T stage, GS, and use of ADT were significantly associated with developing DM on univariate analysis. GS, and use of ADT were the only factors significantly associated with developing DM on multivariate analysis (p < 0.01). Patients who received ADT had significantly higher risk features suggesting patient selection bias for higher DM in this group of patients rather than a negative interaction between HDR-B and EBRT. Conclusions: In men treated with HDR-B and EBRT, GS is a significant factor on multivariate analysis for developing distant metastasis.

Purpose/Objective(s): To compare outcomes of patients with Gleason score (GS) 9-10 prostate adenocarcinoma (CaP) following external beam radiation therapy (EBRT), extremely dose-escalated radiation therapy (as exemplified by EBRT with a brachytherapy boost [EBRT+BT]), and radical prostatectomy (RP).

Purpose: To evaluate the dosimetric effect of catheter displacement on target coverage and doses to organs at risks (OARs) in high dose rate prostate brachytherapy. Methods: CT simulations from 21 prostate cancer patients treated with HDR monotherapy (7.25 Gy × 6 fractions) were used. The prostate CTV and OARs were contoured on the 3D‐CT. Treatment plans were optimized using an inverse planning simulated annealing algorithm and graphical optimization to ensure dosimetry objectives: target coverage (CTV D90=100–115%, V100 >97%, and V150

Table 1. Patient Characteristics (N=40) Median Follow-up (range in months) 35 (7-120) Median Age (range) 62 (38-79) Surgical Staging (# of pts) 39 Histology (# of pts) Endometrioid Adenocarcinoma 13 (32.5%) Papillary Serous 15 (37.5%) Clear Cell 11 (27.5%) Undifferentiated 1 (2.5%) Adjuvant Treatment (# of pts) Combined Chemotherapy and Radiation 23 EBRT+ VC 11 (3 extended field) EBRT only 8 (4 extended field) VC only 3 Chemotherapy or Radiation Alone (# of pts) 17 Chemotherapy alone (# of pts) 9 Radiation alone (# of pts) 8 EBRT+ VC 3 EBRT only 4 (2 extended field) VC only 1 Materials/Methods The optimal management of high-risk endometrial cancer has yet to be determined. A retrospective review was undertaken to determine whether adjuvant therapy with combined chemotherapy and radiation (CRT) versus either chemotherapy or radiation therapy alone (C/RT) impacts clinical outcomes. Figure 1 Local Failure (LF)

Purpose: The Strut‐Adjusted Volume Implant (SAVI) is a partial breast irradiation applicator. We developed a method to reconstruct the 3D device location using scout images to provide applicator position and proper expansion verification. We also used this technique to evaluate interfraction motion. Methods: The SAVI device was implanted in a lumpectomy cavity. The patient was aligned by CT lasers and skin tattoos to ensure reproducible setup. A post‐operative CT scan was performed for treatment planning. The patient was treated in 10 fractions over the course of 5 days. Daily CT scans and anterior and lateral scout scans were acquired prior to each fraction. Radio‐opaque markers located on three of the struts were localized using a peak detection filter. The location of each marker on the 2D scout image was backprojected towards the CT x‐ray source. Each 3D marker position was reconstructed at the backprojection intersection. The 3D marker position was compared to the location in the 3D CTimage. The interfractional displacement of the device was assessed from the reconstructed marker locations. Results: The average distance (standard deviation) between the marker positions reconstructed using the scout images and the CTimages was 0.76 (0.28) mm. Using the scout image data, the average interfractional device movement (standard deviation) in the SI, AP, and LR directions, and 3D was 0.51 (0.46) mm, 0.95 (0.81) mm, 0.73 (0.61) mm, and 1.56 (0.68) mm. Conclusion: SAVI interfraction motion can be accurately measured using scout images. The patient setup for partial breast brachytherapy can be improved by correcting the applicator displacement. This proposed technique eliminates the need for CT verifications, and therefore additional dose to the patient, while still accurately identifying applicator displacement.