Search

The Phoenix definition for biochemical failure (BCF) after radiotherapy uses nadir PSA (nPSA) + 2 ng/mL to classify a BCF and was derived from conventionally fractionated radiotherapy, which produces significantly higher nPSAs than stereotactic body radiotherapy (SBRT). We investigated whether an alternative nPSA-based threshold could be used to define post-SBRT BCFs.PSA kinetics data on 2038 patients from 9 institutions were retrospectively analyzed for low- and intermediate-risk PCa patients treated with SBRT without ADT. We evaluated the performance of various nPSA-based definitions. We also investigated the relationship of relative PSA decline (rPSA, PSAMedian follow-up was 71.9 months. BCF occurred in 6.9% of patients. Median nPSA was 0.16 ng/mL. False positivity of nPSA + 2 was 30.2%, compared to 40.9%, 57.8%, and 71.0% for nPSA + 1.5, nPSA + 1.0, and nPSA + 0.5, respectively. Among patients with BCF, the median lead time gained from an earlier nPSA + threshold definition over the Phoenix definition was minimal. Patients with BCF had significantly lower rates of early PSA decline (mean rPSA 1.19 vs. 0.39, p 0.0001) and were significantly more likely to reach nPSA + 2 ≥ 18 months (83.3% vs. 21.1%, p 0.0001). The proposed criterion (rPSA ≥ 2.6 or nPSA + 2 ≥ 18 months) had a sensitivity and specificity of 92.4% and 81.5%, respectively, for predicting BCF in patients meeting the Phoenix definition and decreased its false positivity to 6.4%.The Phoenix definition remains an excellent definition for BCF post-SBRT. Its high false positivity can be mitigated by applying additional criteria (rPSA ≥ 2.6 or time to nPSA + 2 ≥ 18 months).

In its current form, the Radiation Oncology Model (RO Model) prioritizes payment cuts over true value-based payment transformation. With significant modifications to the payment methodology, the reporting requirements, and recognition of the unique challenges faced by disadvantaged populations, the RO Model can protect patient access to care, preserve the physician-patient decision-making process, and ensure the delivery of high-quality, efficient radiation therapy treatment. The American Society for Radiation Oncology has spent several years advocating for a meaningful alternative payment model for radiation oncology and continues to push The Center for Medicare and Medicaid Innovation for changes to the RO Model that will recognize these key outcomes.

Background and purposeThe optimal dose for prostate stereotactic body radiotherapy (SBRT) is still unknown. This study evaluated the dose-response relationships for prostate-specific antigen (PSA) decay and biochemical recurrence (BCR) among 4 SBRT dose regimens.Materials and methodsIn 1908 men with low-risk (50.0%), favorable intermediate-risk (30.9%), and unfavorable intermediate-risk (19.1%) prostate cancer treated with prostate SBRT across 8 institutions from 2003 to 2018, we examined 4 regimens (35Gy/5 fractions [35/5, n=265, 13.4%], 36.25Gy/5 fractions [36.25/5, n=711, 37.3%], 40Gy/5 fractions [40/5, n=684, 35.8%], and 38Gy/4 fractions [38/4, n=257, 13.5%]). Between dose groups, we compared PSA decay slope, nadir PSA (nPSA), achievement of nPSA ≤0.2 and ≤0.5ng/mL, and BCR-free survival (BCRFS).ResultsMedian follow-up was 72.3months. Median nPSA was 0.01ng/mL for 38/4, and 0.17-0.20ng/mL for 5-fraction regimens (p&nbsp

Previously a phase III trial of a hydrogel rectal spacer during prostate radiation therapy found decreased toxicity and a clinically significant improvement in bowel quality of life (QOL) at 3 years by the Expanded Prostate Cancer Index. We performed a secondary analysis to identify men less likely to benefit.Clinical and dosimetric data for the 222 patients enrolled on the SpaceOAR phase III trial were analyzed. The volume of rectum treated to 70 Gy (V70) and the quantitative analysis of normal tissue effects in the clinic (QUANTEC) rectal dose goals were used as surrogates for clinical benefit and plan quality. Mean bowel QOL was assessed at 15 and 36 months posttreatment and the likelihood of 1× (5 points) or 2× (10 points) minimally important difference changes were assessed.Rectal V70 was correlated with physician scored toxicity (P = .033) and was used as a surrogate for plan quality. There was no correlation between prostate volume and rectal V70 (r = 0.077). Rectal V70 pre- and post-hydrogel was 13% and 3% for the smallest prostates (40 mL) and 12% and 2% for the largest (80 mL). The relative reduction in rectal V70 of 78% did not vary by prespacer V70, but the absolute reduction was greater for a higher V70. All spacer plans met the 5 QUANTEC rectal dose constraints, although 92% of control plans met all constraints. At 3 years, those not meeting all QUANTEC goals had a 15.0-point (standard deviation 15.1) decline, control patients meeting QUANTEC goals had a 4.0-point (9.5) decline, and spacer had0.5 (7.6; P.01). Previous surgery was not correlated with QOL (P = .8). Across prognostic groups, including age, body mass index, previous surgery, target volume, or quality of radiation plans, there was no statistically significant heterogeneity in the relative benefit of spacer in decreasing the risk of 1× or 2× the minimally important difference declines.There was little heterogeneity in the likelihood of spacer reducing the risk of declines in bowel QOL across clinical and dosimetric variables. Even for the95% of plans meeting QUANTEC rectal criteria, hydrogel spacer provided potentially meaningful benefits.

Purpose: To evaluate the safety of stereotactic body radiation therapy (SBRT) for prostate cancer in men with inflammatory bowel disease (IBD). Methods and Materials: We queried a consortium database for patients with IBD receiving SBRT for prostate cancer between 2006 and 2012. Identified patients were matched with patients without a history of IBD in a 3:1 fashion based on dose, fractionation, use of androgen deprivation therapy, and age distribution. Logistic regression was used to evaluate the association between having IBD and experiencing acute and late gastrointestinal (GI) and genitourinary (GU) toxicities as scored on the Common Terminology Criteria for Adverse Events scale. Time to late toxicity was evaluated using proportional hazard Cox models. Our study was limited by absence of data on prostate size, baseline International Prostate Symptom Score, and rectal dose-volume histogram parameters. Results: Thirty-nine patients with flare-free IBD at time of treatment (median follow-up 83.9 months) and 117 matched controls (median follow-up 88.7 months) were identified. A diagnosis of IBD was associated with increased odds of developing any late grade GI toxicity (odds ratio [OR] 6.11, P

PURPOSE: The Radiation Oncology Alternative Payment Model (APM) is a Medicare demonstration project that will test whether prospective bundled payments to a randomly selected group of physician practices, hospital outpatient departments, and freestanding radiation therapy centers reduce overall expenditures while preserving or enhancing the quality of care for beneficiaries. The Model follows a complicated pricing methodology that blends historical reimbursements for a defined set of services made to professional and technical providers to create a weighted payment average for each of 16 cancer types. These averages are then adjusted by various factors to determine APM payments specific to each participating provider. METHODS: This impact study segregates APM participants into rural and urban groups and analyzes the effect of the Radiation Oncology Alternative Payment Model on their fee-for-service reimbursements. RESULTS: The main findings of this study are (1) the greater net-negative revenue impact on rural facilities versus urban facilities that would have participated in the Model this year and (2) the relative lack of high-value treatment services (ie, stereotactic radiotherapy and brachytherapy) delivered by rural facilities that exacerbates their negative impact. CONCLUSION: As such, rural providers participating in the Model in its current form may face greater risk to their economic viability and greater difficulty in funding technology improvements necessary for the achievement of high-quality care compared with their urban counterparts.

Purpose Understanding prostate-specific antigen (PSA) kinetics after radiation therapy plays a large role in the management of patients with prostate cancer (PCa). This is particularly true in establishing expectations regarding PSA nadir (nPSA) and PSA bounces, which can be disconcerting. As increasingly more patients are being treated with stereotactic body radiation therapy (SBRT) for low- and intermediate-risk PCa, it is imperative to understand the PSA response to SBRT. Methods and Materials PSA data from 5 institutions were retrospectively analyzed for patients with localized PCa treated definitively with SBRT alone from 2004 to 2016. Patients received 35 to 40 Gy in 5 fractions, per institutional standards. Patients who had less than 12 months of PSA data or received androgen deprivation therapy were excluded from this study. Linear and logistic multivariable analysis were performed to identify predictors of nPSA, bounce, and biochemical recurrence, and joint latent class models were developed to identify significant predictors of time to biochemical failure. Results A total of 1062 patients were included in this study. Median follow-up was 66 months (interquartile range [IQR], 36.4-89.9 months). Biochemical failure per the Phoenix criteria occurred in 4% of patients. Median nPSA was 0.2 ng/mL, median time to nPSA was 40 months, 84% of patients had an nPSA ≤0.5 ng/mL, and 54% of patients had an nPSA ≤0.2 ng/mL. On multivariable analysis, nPSA was a significant predictor of biochemical failure. Benign PSA bounce was noted in 26% of patients. The median magnitude of PSA bounce was 0.52 ng/mL (IQR, 0.3-1.0 ng/mL). Median time to PSA bounce was 18.1 months (IQR, 12.0-31.1 months). On multivariable analysis, age and radiation dose were significantly associated with a lower incidence of bounce. Joint latent class models modeling found that nPSA and radiation dose were significantly associated with longer time to biochemical failure. Conclusions In this multi-institutional cohort of patients with long-term follow-up, we found that SBRT led to low nPSAs. In turn, lower nPSAs are associated with reduced incidence of, and longer time to, biochemical failure. Benign PSA bounces occurred in a quarter of patients, as late as several years after treatment. Further studies are needed to directly compare the PSA response of patients who receive SBRT versus other treatment modalities.

Purpose: To establish the safety and efficacy of gantry-mounted linear accelerator-based stereotactic body radiation therapy (SBRT) for low- and intermediate-risk prostate cancer. Methods: We pooled 921 patients enrolled on 7 single-institution prospective phase II trials of gantry-based SBRT from 2006 to 2017. The cumulative incidences of biochemical recurrence (defined by the Phoenix definition) and physician-scored genitourinary (GU) and gastrointestinal (GI) toxicities (defined per the original trials using Common Terminology Criteria for Adverse Events) were estimated using a competing risk framework. Multivariable logistic regression was used to evaluate the relationship between late toxicity and prespecified covariates: biologically effective dose, every other day versus weekly fractionation, intrafractional motion monitoring, and acute toxicity. Results: Median follow-up was 3.1 years (range, 0.5-10.8 years). In addition, 505 (54.8%) patients had low-risk disease, 236 (25.6%) had favorable intermediate-risk disease, and 180 (19.5%) had unfavorable intermediate-risk disease. Intrafractional motion monitoring was performed in 78.0% of patients. The 3-year cumulative incidence of biochemical recurrence was 0.8% (95% confidence interval [CI], 0-1.7%), 2.2% (95% CI, 0-4.3%), and 5.1% (95% CI, 1.0-9.2%) for low-, favorable intermediate-, and unfavorable intermediate-risk disease. Acute grade ≥2 GU and GI toxicity occurred in 14.5% and 4.6% of patients, respectively. Three-year cumulative incidence estimates of late grade 2 GU and GI toxicity were 4.1% (95% CI, 2.6-5.5%) and 1.3% (95% CI, 0.5-2.1%), respectively, with late grade ≥3 GU and GI toxicity estimates of 0.7% (95% CI, 0.1-1.3%) and 0.4% (95% CI, 0-0.8%), respectively. The only identified significant predictors of late grade ≥2 toxicity were acute grade ≥2 toxicity (P < .001) and weekly fractionation (P < .01), although only 12.4% of patients were treated weekly. Conclusions: Gantry-based SBRT for prostate cancer is associated with a favorable safety and efficacy profile, despite variable intrafractional motion management techniques. These findings suggest that multiple treatment platforms can be used to safely deliver prostate SBRT.

For inoperable endometrial cancer (ECA) patients, definitive chemoradiation with stereotactic body radiotherapy (SBRT) boost may be an option. SBRT schedules and dose distributions approximate brachytherapy boost (BB) radiobiologic dosing, while eliminating the need for applicator placement and thus anesthesia. We report toxicity, disease control, and quality-of-life outcomes of a multi-institutional series of SBRT for ECA. Twenty-three patients met the following eligibility criteria: (1) primary ECA, (2) contraindication or refusal of BB, and (3) need for definitive radiation (RT). Prior to SBRT, patients received pelvic RT +/− nodal boost concurrent with cisplatin. SBRT dose of 25.0–35.0 Gy was prescribed to a high-risk clinical target volume (HR-CTV) in 4–5 fractions. Assessments included (1) post-treatment disease surveillance, (2) toxicity using the U.S. National Cancer Institute’s CTCAE scales, and (3) quality-of-life using FACT-G. Median follow-up was 31 months. BB was infeasible due to medical comorbidities, patient refusal, and technical contraindications (73.9%, 21.7%, and 4.3%, respectively). Most patients were FIGO stage I (60.8%). Mean cumulative dose to high-risk clinical target volume (HR-CTV) was 88.94 Gy (range 75.50–93.83 Gy). Mean SBRT dose to 95% of the planning target volume (PTV) was 32.55 Gy (range 25.00–35.77 Gy), and mean PTV receiving 100% of the dose was 95.29% (range 91.48–99.01%). No patients had grade 2+ long-term gastrointestinal or genitourinary toxicity. Locoregional and distant control was 91.6% at 1 year and 85.4% at 2 year. Only one patient died due to ECA at 6 months. Overall survival was 95.0% at 1 year, 74.0% at 2 year, and 59.2% at 5 year. Patient-reported physical and emotional well-being worsened but improved after the acute phase of treatment. Functional and social/family well-being worsened after 1 month. Definitive chemoradiation with SBRT boost is safe and effective alternative when BB is not possible.

AIMS There is a lack of early predictive measures of outcome for patients with intermediate-risk prostate cancer (PCa) treated with stereotactic body radiotherapy (SBRT). The aim of the present study was to explore 4-year prostate-specific antigen response rate (4yPSARR) as an early predictive measure. MATERIALS AND METHODS Individual patient data from six institutions for patients with intermediate-risk PCa treated with SBRT between 2006 and 2016 with a 4-year (42-54 months) PSA available were analysed. Cumulative incidences of biochemical failure and metastasis were calculated using Nelson-Aalen estimates and overall survival was calculated using the Kaplan-Meier method. Biochemical failure-free survival was analysed according to 4yPSARR, with groups dichotomised based on PSA

PURPOSE/OBJECTIVE(S) There is a lack of early predictive measures of outcome for patients with intermediate-risk prostate cancer (PCa) treated with stereotactic body radiotherapy (SBRT). We aim to explore 4-year PSA response rate (4yPSARR) as an early predictive measure. MATERIALS/METHODS Individual patient data from 6 institutions for patients with intermediate-risk PCa treated with SBRT between 2006 and 2016 with a 4-year (42-54 months) PSA available were analyzed. Cumulative incidences of biochemical failure and metastasis were calculated using Nelson-Aalen estimates and overall survival was calculated using the Kaplan-Meier method. Biochemical failure-free survival was analyzed according to 4yPSARR with groups dichotomized based on PSA < 0.4 ng/mL or ≥ 0.4 ng/mL and compared using the log-rank test. Multivariable competing risk analysis was performed to predict for biochemical failure and development of metastasis. RESULTS Six-hundred thirty-seven patients were included, including 424 (67%) with favorable and 213 (33%) with unfavorable intermediate-risk disease. Median follow-up was 6.2 years (IQR 4.9-7.9). The cumulative incidence of biochemical failure and metastasis, and overall survival at 6 years was 7%, 0.6% and 97%, respectively. The cumulative incidence of biochemical failure at 6 years if 4yPSARR < 0.4ng/mL was 1.7%, compared to 27% if 4yPSARR ≥ 0.4 ng/mL (P < 0.0001). On multivariable competing risk analysis, 4yPSARR was a statistically significant predictor of biochemical failure-free survival (sHR 15.3, 95% CI 7.5-31.3, P < 0.001) and metastasis-free survival (sHR 31.2, 95% CI 3.1-311.6, P = 0.003). CONCLUSION 4yPSARR is an encouraging early predictor of outcome in patients with intermediate-risk PCa treated with SBRT. Validation in prospective trials is warranted.

PURPOSE/OBJECTIVE(S) Stereotactic body radiation therapy (SBRT) has emerged as a promising modality for the treatment of prostate cancer (PCa) and involves the delivery of ablative doses of radiation to the prostate. The patterns of failure at the time of biochemical recurrence (BCR) after SBRT remain unknown. The purpose of this study is to explore the development of distant metastasis (DM) following the diagnosis of BCR. MATERIALS/METHODS We queried a multi-institutional database of 2,430 patients who were prospectively treated with SBRT on single institution phase II trials or registries to identify patients who developed a BCR by the Phoenix criteria or by initiation of salvage therapy for PSA rise at a lower threshold. Patterns of distant failure were obtained for patients who had BCR, including presence and sites of DM. Multivariable analysis (MVA) using logistic regression was used to evaluate the association between multiple clinicopathologic and treatment variables and DM. RESULTS 150 patients with BCR were identified (6.2% of total). Of these, 19% presented with low-risk, 42% with intermediate-risk, and 39% with high-risk disease. The median PSA at BCR was 4.56, median time to BCR was 36 months, and median follow-up after BCR was 15.5 months. Sixty-seven patients (44.7%) had DM identified at or after the time of BCR. Among those with DM, 13 had M1a disease, 50 had M1b disease, 3 had M1c disease, and 1 had an unknown distribution of disease. Time to BCR was significantly shorter in patients with DM compared to those who did not have DM (28.1 vs. 41.4 months, P = 0.002) and initial PSA (iPSA) was significantly greater (11.0 vs. 8.0, P = 0.03). On MVA, Gleason Grade Group (GG) 4 (vs. GG 1, OR 3.76, P = 0.047) and higher SBRT dose (36.25 Gy vs. 35 Gy: OR 4.03, P = 0.02; 40 Gy vs. 35 Gy: OR 3.73, P = 0.03) were significantly associated with DM. CONCLUSION A substantial proportion of patients with BCR after SBRT for localized PCa ultimately develop DM, particularly those with higher iPSA and shorter time to BCR. The association with SBRT dose is likely reflective of the use of higher doses in more modern cohorts with higher-risk disease, while the association with GG likely reflects the more aggressive biology of these tumors at presentation. Further research into patterns of failure after SBRT is needed, especially in the context of more sensitive nuclear imaging. Early predictors of treatment failure are needed to facilitate timely treatment intensification.

PURPOSE The clinical cell-cycle risk (CCR) score, which combines the University of California, San Francisco's Cancer of the Prostate Risk Assessment (CAPRA) and the cell cycle progression (CCP) molecular score, has been validated to be prognostic of disease progression for men with prostate cancer. This study evaluated the ability of the CCR score to prognosticate the risk of metastasis in men receiving dose-escalated radiation therapy (RT) with or without androgen deprivation therapy (ADT). METHODS AND MATERIALS This retrospective, multi-institutional cohort study included men with localized National Comprehensive Cancer Network (NCCN) intermediate-, high-, and very high-risk prostate cancer (N = 741). Patients were treated with dose-escalated RT with or without ADT. The primary outcome was time to metastasis. RESULTS The CCR score prognosticated metastasis with a hazard ratio (HR) per unit score of 2.22 (95% confidence interval [CI], 1.71-2.89; P < .001). The CCR score better prognosticated metastasis than NCCN risk group (CCR, P < .001; NCCN, P = .46), CAPRA score (CCR, P = .002; CAPRA, P = .59), or CCP score (CCR, P < .001; CCP, P = .59) alone. In bivariable analyses, CCR score remained highly prognostic when accounting for ADT versus no ADT (HR, 2.18; 95% CI, 1.61-2.96; P < .001), ADT duration as a continuous variable (HR, 2.11; 95% CI, 1.59-2.79; P < .001), or ADT given at or below the recommended duration for each NCCN risk group (HR, 2.19; 95% CI, 1.69-2.86; P < .001). Men with CCR scores below or above the multimodality threshold (CCR score, 2.112) had a 10-year risk of metastasis of 3.7% and 21.24%, respectively. Men with below-threshold scores receiving RT alone had a 10-year risk of metastasis of 3.7%, and for men receiving RT plus ADT, the 10-year risk of metastasis was also 3.7%. CONCLUSIONS The CCR score accurately and precisely prognosticates metastasis and adds clinically actionable information relative to guideline-recommended therapies based on NCCN risk in men undergoing dose-escalated RT with or without ADT. For men with scores below the multimodality threshold, adding ADT may not significantly reduce their 10-year risk of metastasis.

Purpose In 2019, the Centers for Medicare and Medicaid Services proposed a new radiation oncology alternative payment model aimed at reducing expenditures. We examined changes in aggregate physician Medicare charges allowed per specialty to provide contemporary context to proposed changes and hypothesize that radiation oncology charges remained stable through 2017. Methods and Materials Medicare physician/supplier utilization, program payments, and balance billing for original Medicare beneficiaries, by physician specialty, were analyzed from 2002 to 2017. Total allowed charges under the physician/supplier fee-for-service program, inflation-adjusted charges, and percent of total charges billed per specialty were examined. We adjusted for inflation using the consumer price index for medical care from the US Bureau of Labor Statistics. Results Total allowed charges increased from $83 billion in 2002 to $138 billion in 2017. The specialties accounting for the most charges billed to Medicare were internal medicine and ophthalmology. Radiation oncology charges accounted for 1.2%, 1.6%, and 1.4% of total charges allowed by Medicare in 2002, 2012, and 2017, respectively. Radiation oncology charges allowed increased 44% from 2002 to 2012 ($987.6 million to $1.42 billion) but decreased by 19% from 2012 to 2017 ($1.15 billion), adjusted for inflation. Total charges allowed by internal medicine decreased 2% from 2002 to 2012 ($8.53 to $8.36 billion), adjusted for inflation, and decreased 16% from 2012 to 2017 ($7.05 billion). When adjusting for inflation, ophthalmology charges increased 18% from 2002 to 2012 ($4.53 to $5.36 billion) and increased 3% from 2012 to 2017 ($5.5 billion). Conclusions Radiation oncology physician charges represent a small fraction of total Medicare expenses and are not a driver for Medicare spending. Aggregate inflation-adjusted charges by radiation oncology have dramatically declined in the past 5 years and represent a stable fraction of total Medicare charges. The need to target radiation oncology with cost-cutting measures may be overstated.

Stereotactic body radiation therapy (SBRT), low dose rate brachytherapy (LDR-BT) and high dose rate brachytherapy (HDR-BT) are ablative-intent radiotherapy options for prostate cancer (PCa). These vary considerably in dose delivery, which may impact post-treatment prostate-specific antigen (PSA) patterns and biochemical control. We compared PSA kinetics between SBRT, HDR-BT, and LDR-BT, and assessed their relationships to biochemical recurrence-free survival (BCRFS).Retrospective PSA data were analyzed for 3502 men with low-risk (n = 2223; 63.5%), favorable intermediate-risk (n = 869; 24.8%), and unfavorable intermediate-risk (n = 410; 11.7%) PCa treated with SBRT (n = 1716; 49.0%), HDR-BT (n = 512; 14.6%), or LDR-BT (n = 1274; 36.4%) without upfront androgen deprivation therapy at 10 institutions from 1990 to 2017. We compared nadir PSA (nPSA), time to nPSA, achievement of nPSA0.2 ng/mL and0.5 ng/mL, rates of nPSA0.4 ng/mL at 4 years, and BCRFS.Median follow-up was 72 months. Median nPSA and nPSA0.2 ng/mL were stratified by risk group (interaction p ≤ 0.001). Median nPSA and time to nPSA were 0.2 ng/mL at 44 months after SBRT, 0.1-0.2 ng/mL at 37 months after HDR-BT, and 0.01-0.2 ng/mL at 51 months after LDR-BT (mean log nPSA p ≤ 0.009 for LDR-BT vs. SBRT or HDR-BT for low/favorable intermediate-risk). There were no differences in nPSA0.4 ng/mL at 4 years (p ≥ 0.51). BCRFS was similar for all three modalities (p ≥ 0.27). Continued PSA decay beyond 4 years was predictive of durable biochemical control.LDR-BT led to lower nPSAs with longer continued decay compared to SBRT and HDR-BT, but no differences in BCRFS.

Purpose/Objective(s) Since the seminal Phoenix definition (nadir PSA+2) of biochemical failure (BCF) was published in 2006, increasingly more patients with low- and intermediate-risk prostate cancer (PCa) are being treated with stereotactic body radiation therapy (SBRT). Since SBRT leads to lower nadir PSA (nPSA) compared to conventionally fractionated RT, we investigated if an earlier nPSA+threshold can be used as an alternative definition of BCF. Materials/Methods PSA kinetics from 9 institutions were retrospectively analyzed for patients with localized PCa treated definitively with SBRT alone from 2003 to 2018. Patients received 35 to 40 Gy in 5 fractions, 38 Gy in 4 fractions or 26 Gy in 2 fractions (EQD23 Gy = 70-95 Gy) per institutional standards. Cox multivariable regression model was used to determine the adjusted association of relative change in PSA kinetics with biochemical relapse-free survival (BRFS) and association of BCF with time to nadir+2. Results A total of 2061 patients were included. Median follow-up was 71.9 months (interquartile range [IQR], 41.2-96.0). BCF occurred in 140 (6.8%) of patients. Median nPSA was 0.16 ng/mL, median time to nPSA was 48 months. Sensitivity of Phoenix definition for BCF was 93%, compared to 96%, 100%, and 100% for nPSA+1.5, nPSA+1.0 and nPSA+0.5, respectively. False positive rate of Phoenix definition was 30%, compared to 41%, 58%, and 71% for nPSA+1.5, nPSA+1.0 and nPSA+0.5, respectively. In patients who developed BCF, lead time gained from an earlier nPSA+threshold definition compared to Phoenix definition was 6 (IQR 0-15.3), 0 (IQR 0-11.3), 0 (IQR 0-0) months for nPSA+0.5, nPSA+1.0 and nPSA+1.5, respectively. Relative change in PSA between 6 months and 18 months after treatment was significantly associated with BRFS (hazard ratio [HR] 1.73, 95% confidence interval [CI] 1.28-2.34, P 18 months. In patients who had BCF, 27 (19.3%) reached nPSA+2 in ≤18 months, and 113 (80.7%) in > 18 months. Median time to nPSA+2 was significantly longer in patients with BCF (41 vs. 12 months, P Conclusion A lower nadir-based threshold provides minimal increase in sensitivity at the cost of a higher false positive rate and does not provide a clinically relevant lead time benefit for a pending BCF in patients with low- to intermediate-risk PCa undergoing SBRT. A rate-of-change based metric in the first 18 months post-SBRT is significantly associated with BRFS. Patients who have an early PSA bounce after SBRT rarely develop a true BCF and true BCF tends to happen later (> 18 months). Phoenix definition remains a valuable tool in the SBRT era. BCF should not be prematurely called which runs the risk of high rates of false positivity.

SpaceOAR, a Food and Drug Administration-approved hydrogel intended to create a rectal-prostate space, was evaluated in a single-blind phase III trial of image guided intensity modulated radiation therapy. A total of 222 men were randomized 2:1 to the spacer or control group and received 79.2 Gy in 1.8-Gy fractions to the prostate with or without the seminal vesicles. The present study reports the final results with a median follow-up period of 3 years.Cumulative (Common Terminology Criteria for Adverse Events, version 4.0) toxicity was evaluated using the log-rank test. Quality of life (QOL) was examined using the Expanded Prostate Cancer Index Composite (EPIC), and the mean changes from baseline in the EPIC domains were tested using repeated measures models. The proportions of men with minimally important differences (MIDs) in each domain were tested using repeated measures logistic models with prespecified thresholds.The 3-year incidence of grade ≥1 (9.2% vs 2.0%; P=.028) and grade ≥2 (5.7% vs 0%; P=.012) rectal toxicity favored the spacer arm. Grade ≥1 urinary incontinence was also lower in the spacer arm (15% vs 4%; P=.046), with no difference in grade ≥2 urinary toxicity (7% vs 7%; P=0.7). From 6 months onward, bowel QOL consistently favored the spacer group (P=.002), with the difference at 3 years (5.8 points; P.05) meeting the threshold for a MID. The control group had a 3.9-point greater decline in urinary QOL compared with the spacer group at 3 years (P.05), but the difference did not meet the MID threshold. At 3 years, more men in the control group than in the spacer group had experienced a MID decline in bowel QOL (41% vs 14%; P=.002) and urinary QOL (30% vs 17%; P=.04). Furthermore, the control group were also more likely to have experienced large declines (twice the MID) in bowel QOL (21% vs 5%; P=.02) and urinary QOL (23% vs 8%; P=.02).The benefit of a hydrogel spacer in reducing the rectal dose, toxicity, and QOL declines after image guided intensity modulated radiation therapy for prostate cancer was maintained or increased with a longer follow-up period, providing stronger evidence for the benefit of hydrogel spacer use in prostate radiation therapy.

INTRODUCTION AND OBJECTIVES:PROCEED [NCT01306890], a large real-world study of sipuleucel-T in men with mCRPC, offers an opportunity to examine patients who experienced longer term (≥3 yr) survivals after receiving sipuleucel-T. The current analysis seeks insights regarding these patients, especially noting the timing of sipuleucel-T relative to the other FDA-approved treatments in the modern era.METHODS:Men with mCRPC receiving sipuleucel-T, given every 2 weeks x 3, were eligible for PROCEED. Follow-up continued until death, study withdrawal, or a minimum of 3 years. Long-term survivors were defined as those who survived ≥3 yr. Baseline characteristics and treatments received pre/post-sipuleucel-T are reported in this ad-hoc subgroup analysis.RESULTS:From 2011-2014, 1902 men received ≥1 sipuleucel-T infusion. Of these, an estimated 42.3% survived ≥3yr. At baseline, long-term survivors (OS ≥3 yr) and those who survived

Importance Stereotactic body radiotherapy harnesses improvements in technology to allow the completion of a course of external beam radiotherapy treatment for prostate cancer in the span of 4 to 5 treatment sessions. Although mounting short-term data support this approach, long-term outcomes have been sparsely reported. Objective To assess long-term outcomes after stereotactic body radiotherapy for low-risk and intermediate-risk prostate cancer. Design, Setting, and Participants This cohort study analyzed individual patient data from 2142 men enrolled in 10 single-institution phase 2 trials and 2 multi-institutional phase 2 trials of stereotactic body radiotherapy for low-risk and intermediate-risk prostate cancer between January 1, 2000, and December 31, 2012. Statistical analysis was performed based on follow-up from January 1, 2013, to May 1, 2018. Main Outcomes and Measures The cumulative incidence of biochemical recurrence was estimated using a competing risk framework. Physician-scored genitourinary and gastrointestinal toxic event outcomes were defined per each individual study, generally by Radiation Therapy Oncology Group or Common Terminology Criteria for Adverse Events scoring systems. After central review, cumulative incidences of late grade 3 or higher toxic events were estimated using a Kaplan-Meier method. Results A total of 2142 men (mean [SD] age, 67.9 [9.5] years) were eligible for analysis, of whom 1185 (55.3%) had low-risk disease, 692 (32.3%) had favorable intermediate-risk disease, and 265 (12.4%) had unfavorable intermediate-risk disease. The median follow-up period was 6.9 years (interquartile range, 4.9-8.1 years). Seven-year cumulative rates of biochemical recurrence were 4.5% (95% CI, 3.2%-5.8%) for low-risk disease, 8.6% (95% CI, 6.2%-11.0%) for favorable intermediate-risk disease, 14.9% (95% CI, 9.5%-20.2%) for unfavorable intermediate-risk disease, and 10.2% (95% CI, 8.0%-12.5%) for all intermediate-risk disease. The crude incidence of acute grade 3 or higher genitourinary toxic events was 0.60% (n = 13) and of gastrointestinal toxic events was 0.09% (n = 2), and the 7-year cumulative incidence of late grade 3 or higher genitourinary toxic events was 2.4% (95% CI, 1.8%-3.2%) and of late grade 3 or higher gastrointestinal toxic events was 0.4% (95% CI, 0.2%-0.8%). Conclusions and Relevance In this study, stereotactic body radiotherapy for low-risk and intermediate-risk disease was associated with low rates of severe toxic events and high rates of biochemical control. These data suggest that stereotactic body radiotherapy is an appropriate definitive treatment modality for low-risk and intermediate-risk prostate cancer., This cohort study of pooled individual patient data assesses long-term outcomes after stereotactic body radiotherapy for low-risk and intermediate-risk prostate cancer., Key Points Question Is stereotactic body radiotherapy safe and effective in the long term for low-risk and intermediate-risk prostate cancer? Findings In this pooled, individual patient data analysis of cohort studies with a total of 2142 patients with low-risk and intermediate-risk prostate cancer treated with stereotactic body radiotherapy across 10 institutional studies and 2 multi-institutional trials, the 7-year incidence of biochemical recurrence was 4.5% for those with low-risk disease and 10.2% for those with intermediate-risk disease. The 7-year cumulative incidence of severe genitourinary toxic events was 2.4% and of severe gastrointestinal toxic events was 0.4%. Meaning These findings suggest that stereotactic body radiotherapy is associated with a long-term clinical outcomes profile—both in terms of toxic events and disease control—that is comparable with other, more widely used treatments for low-risk and intermediate-risk prostate cancer.

195 Background: This study evaluated the ability of the combined clinical cell-cycle risk score (CCR) to prognosticate the risk of prostate cancer metastasis in men receiving dose-escalated radiation therapy (RT) with or without androgen deprivation therapy (ADT). Methods: The CCR score is a validated model that combines the cell cycle progression score (CCP) with the UCSF Cancer of the Prostate Risk Assessment score (CAPRA). The CCR score and a CCR-based multimodality threshold score (2.112) were evaluated in a retrospective, multi-institutional cohort of men with National Comprehensive Cancer Center (NCCN) intermediate- or high-risk localized disease (N = 741) who received single (RT) or multimodality therapy (ADT with RT). Effects of prognostic variables were analyzed using Kaplan-Meier and Cox regression methods. Results: Median follow-up was 5.9 years. CCR predicted metastasis [hazard ratio (HR) 2.21, 95% Confidence Interval (CI) 1.70-2.87, p < 0.001]. The CCR score was a better prognosticator of metastasis (C-index 0.78) than either NCCN-risk group (C-index 0.70), CAPRA score (C-index 0.71), or CCP score (C-index 0.69) alone. In bivariate analyses, the CCR score remained highly prognostic for metastasis when comparing any ADT vs none (HR 2.19, 95% CI 1.62 to 2.97, p < 0.001), ADT duration as a continuous variable (HR 2.05, 95% CI 1.54-2.72, p < 0.001), or ADT use given as less than or at the recommended duration for each NCCN risk group (HR 2.22, 95% CI 1.71-2.88, p < 0.001). Men with CCR scores either below or above the threshold (2.112) had a 10-year risk of metastasis of 4.2% and 25.3%, respectively. For men below the threshold receiving RT alone versus RT+ADT, the 10-year risk of metastasis was 4.2% and 3.9%, respectively. Conclusions: CCR is a highly precise and accurate predictor of metastasis in men undergoing dose-escalated RT, with or without ADT. CCR adds clinically actionable information relative to guideline recommended therapies that are based on NCCN risk groups or CAPRA alone. Men with scores below the multimodality threshold may not significantly reduce their 10-year risk of metastasis with the addition of ADT.

214 Background: Multiple authorities including an NCI Taskforce have recommended routine evaluation of patient reported outcomes (PRO) in cancer care. The Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) is a single-page quality-of-life (QOL) tool which is easily integrated into routine clinical practice. The EPIC-CP has 5 domains (each scored 0-12). The present study evaluated whether early clinically significant changes in EPIC-CP were correlated with later changes in patients undergoing definitive radiotherapy (RT) for prostate cancer. Methods: A cohort of 979 patients including the PROSTQA study and 3 other institutions with prospective QOL data pooled for analysis were evaluated for patient-reported outcomes. Patients were treated with definitive low-dose rate brachytherapy (n=284), intensity-modulated RT (n=251), or stereotactic body RT (n=444). EPIC-CP scores were derived based upon responses to the EPIC-26. Data were evaluated using minimal clinically important difference (MCID) thresholds to compare QOL at 1-2 months and 24 months from baseline. Univariate analysis was used to assess the correlation between early and late MCID changes. Results: On univariate analysis, early ≥1 MCID change from baseline was strongly associated with a late ≥1 MCID across all 5 domains (urinary incontinence, urinary irritation/obstruction, bowel, sexual, and vitality/hormonal) within EPIC-CP and for the overall EPIC-CP score (Table). When MCID was instead defined as 1 or 3, early toxicity remained predictive of late toxicity for all domains and the overall EPIC-CP score. Conclusions: The EPIC-CP is an easy-to-use QOL assessment with clinically relevant outcomes. Early QOL decline was strongly associated with late QOL decline in patients undergoing definitive RT for prostate cancer across all EPIC-CP domains. Patients with early QOL decline may be candidates for early QOL-based interventions to alleviate their late toxicity burden from treatment. [Table: see text]

241 Background: Stereotactic body radiotherapy (SBRT) is increasingly used to treat patients with intermediate-risk prostate cancer (IR-PCa), but there is a lack of early surrogate measures in this patient population treated with SBRT to guide clinicians and patients. We aim to explore the outcomes of IR-PCa patients treated with SBRT and to assess the role of PSA response at 4 years (4yPSARR) as an early surrogate measure given its encouraging results in patients treated with brachytherapy. Methods: Individual patient data from 6 institutions for 820 patients with IR-PCa treated with SBRT between 2006 and 2014 were analyzed. Cumulative incidence of biochemical recurrence (defined by Phoenix criteria) was calculated using Nelson-Aalen estimates, and metastases-free survival and overall survival were calculated using the Kaplan-Meier method. Biochemical recurrence-free survival was analyzed according to 4yPSARR with groups dichotomized based on PSA < 0.4 ng/mL or >0.4 ng/mL and compared using Log-rank test. Results: 820 patients were included, including 549 (67%) with favorable intermediate and 271 (33%) with unfavorable intermediate risk disease defined by NCCN risk group classification. Median age at time of treatment was 70 years. The most common dose, fractionation and treatment schedule was 36.25 Gy in 5 fractions prescribed to the planning target volume delivered every other day. Androgen deprivation therapy was used in combination with SBRT in 9.2% of patients for a median duration of 3 months. Median follow-up was 5.9 years. The cumulative incidence of biochemical recurrence was 7.9% at 5 years. Metastases-free survival and overall survival rates at 5 years were 99.4% and 94.6%, respectively. Median 4yPSARR (n = 504) was 0.2 ng/mL. Biochemical recurrence-free survival in patients with 4yPSARR < 0.4 ng/mL (n = 387) was 99.2%, and in patients with 4yPSARR >0.4 ng/mL (n = 117) was 81.5% at 5 years (p < 0.0001). Conclusions: Prostate SBRT is an effective treatment modality in men with IR-PCa with at least comparable rates of biochemical failure and metastases compared to other standard treatment modalities in patients with IR-PCa. 4yPSARR may represent an early surrogate measure for use in this patient population treated with SBRT and should be included for further study in prospective SBRT trials.

Purpose The new short Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) patient-reported health-related quality of life (HRQOL) tool has removed the rectal bleeding question from the previous much longer version, EPIC-26. Herein, we assess the impact of losing the dedicated rectal bleeding question in 2 independent prospective multicenter cohorts. Methods and Materials In a prospective multicenter test cohort (n=865), EPIC-26 patient-reported HRQOL data were collected for 2 years after treatment from patients treated with prostate radiation therapy from 2003 to 2011. A second prospective multicenter cohort (n=442) was used for independent validation. A repeated-effects model was used to predict the change from baseline in bowel summary scores from longer EPIC instruments using the change in EPIC-CP bowel summary scores with and without rectal bleeding scores. Results Two years after radiation therapy, 91% of patients were free of bleeding, and only 2.6% reported bothersome bleeding problems. Correlations between EPIC-26 and EPIC-CP bowel scores were very high ( r 2 =0.90-0.96) and were statistically improved with the addition of rectal bleeding information ( r 2 =0.94-0.98). Considering all patients, only 0.2% of patients in the test cohort and 0.7% in the validation cohort reported bothersome bleeding and had clinically relevant HRQOL changes missed with EPIC-CP. However, of the 2.6% (n=17) of men with bothersome rectal bleeding in the test cohort, EPIC-CP failed to capture 1 patient (6%) as experiencing meaningful declines in bowel HRQOL. Conclusions Modern prostate radiation therapy results in exceptionally low rates of bothersome rectal bleeding, and

Purpose To develop multi-institutional consensus clinical target volumes (CTVs) and organs at risk (OARs) for male and female bladder cancer patients undergoing adjuvant radiation therapy (RT) in clinical trials. Methods and Materials We convened a multidisciplinary group of bladder cancer specialists from 15 centers and 5 countries. Six radiation oncologists and 7 urologists participated in the development of the initial contours. The group proposed initial language for the CTVs and OARs, and each radiation oncologist contoured them on computed tomography scans of a male and female cystectomy patient with input from ≥1 urologist. On the basis of the initial contouring, the group updated its CTV and OAR descriptions. The cystectomy bed, the area of greatest controversy, was contoured by another 6 radiation oncologists, and the cystectomy bed contouring language was again updated. To determine whether the revised language produced consistent contours, CTVs and OARs were redrawn by 6 additional radiation oncologists. We evaluated their contours for level of agreement using the Landis-Koch interpretation of the κ statistic. Results The group proposed that patients at elevated risk for local-regional failure with negative margins should be treated to the pelvic nodes alone (internal/external iliac, distal common iliac, obturator, and presacral), whereas patients with positive margins should be treated to the pelvic nodes and cystectomy bed. Proposed OARs included the rectum, bowel space, bone marrow, and urinary diversion. Consensus language describing the CTVs and OARs was developed and externally validated. The revised instructions were found to produce consistent contours. Conclusions Consensus descriptions of CTVs and OARs were successfully developed and can be used in clinical trials of adjuvant radiation therapy for bladder cancer.

We previously reported the results of a phase 3 trial evaluating a prostate/rectal hydrogel spacer during prostate intensity modulated radiation therapy, which resulted in decreased rectal dose and toxicity and less decline in bowel quality of life (QOL). A secondary analysis was performed to correlate penile bulb dose and sexual QOL.Sexual QOL was measured with the Expanded Prostate Cancer Index Composite (EPIC) by mean scores, the proportion of patients with a minimal clinically important difference (MID), and analyses of the different items composing the sexual domain.A total of 222 men enrolled with median follow-up of 37 months. Hydrogel reduced penile bulb mean dose, maximum dose, and percentage of penile bulb receiving 10 to 30 Gy (all P.05) with mean dose indirectly correlated with erections sufficient for intercourse at 15 months (P = .03). Baseline EPIC was low (53 [standard deviation ± 24]) with no difference between arms (P.1). A total of 41% (88/222) of men had adequate baseline sexual QOL (EPIC60 (mean, 77 [± 8.3]). This subgroup at 3 years had better sexual function (P = .03) with a spacer with a smaller difference in sexual bother (P = .1), which resulted in a higher EPIC summary on the spacer arm (58 [±24.1] vs control 45 [± 24.4]) meeting threshold for MID without statistical significance (P = .07). There were statistically nonsignificant differences favoring spacer for the proportion of men with MID and 2× MID declines in sexual QOL with 53% vs 75% having an 11-point decline (P = .064) and 41% vs 60% with a 22-point decline (P = .11). At 3 years, more men potent at baseline and treated with spacer had "erections sufficient for intercourse" (control 37.5% vs spacer 66.7%, P = .046) as well as statistically higher scores on 7 of 13 items in the sexual domain (all P.05).The use of a hydrogel spacer decreased dose to the penile bulb, which was associated with improved erectile function compared with the control group based on patient-reported sexual QOL.

Purpose/Objectives: The SAVI Collaborative Research Group (SCRG) is a coalition of 14 institutions who have retrospectively compiled a large database of APBI patients treated with a strut-based brachytherapy device (SAVI). This report details the findings of statistical correlations between numerous dosimetric variables and cosmetic outcome. Materials/Methods: The SCRG study enrolled 1005 patients. A subset of patients with complete dosimetry and more than 1 year of follow-up by a radiation oncologist were analyzed for toxicity, cosmesis and recurrence/survival. Dosimetric parameters were tabulated for patients, including: V90, V95, V100, V150, V200, skin spacing (skin-bridge), maximum skin dose, tumor size, PTV-Eval volume and applicator size (model). Toxicity (e.g., telangiectasia, fibrosis, fat necrosis, seroma) were graded by physicians for patients with at least 1 year of follow-up (up to 6 years) using the CTCAE v3 Scale and fat necrosis using a simplified CTCAE scale (Grade 1 asymptomatic but seen on imaging, grade 2 symptomatic without intervention, & grade 3 required intervention). Results: Median follow up in this cohort was 29.2 months (range 2.4 to 72.2 months). Follow up was >2 yr and >3 yr for 323 and 191 subjects, respectively. Overall, in 500 subjects the late toxicity (grade ≥2) rates were less than 5% during follow up: telangiectasia 1.0%, fibrosis 4.1%, seroma 2.9% and fat necrosis 0.6%. Cosmesis was reported at various post-APBI follow-up visits following treatment completion (6, 12, 24, 36, 48 & 60+ months). For the 6 and 12 month intervals, 98% (n = 122) and 97% (n = 262) were reported excellent or good (E/G), respectively. At 24, 36, 48 and 60 month intervals, the E/G rates were 93% (n = 184), 90% (n = 98), 100% (n = 41) and 94% (n = 15), respectively. The raw rates of ipsilateral breast tumor recurrence (IBTR) and TR/MM were 1.6% (n = 8) and 1.2% (n = 6), respectively, in 500 patients with >1 year of follow up. The 1- and 2-year actuarial rates of overall survival and disease-free survival were: 1-year, 99.6% & 99.4%, resp. and 2-year, 99.2% & 96.7%. Conclusions: APBI treatment with the strut-based applicators was well-tolerated, demonstrated low toxicity rates, favorable cosmetic outcomes and excellent local control over the follow-up to date. Patients with challenging breast anatomy were successfully treated with strut-based devices. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-14-06.

Purpose This registry trial studied the long-term outcomes of women receiving accelerated partial breast irradiation (APBI) using strut-based applicators and reports on the local control, toxicity, and survival for the first 250 patients treated with this device. Methods and Materials Patients were treated using the strut-based brachytherapy device with conventional dose and fractionation of 34 Gy in 10 twice-daily fractions. Planning goals for the planning target volume were V 90 > 90%, V 150 V 200 Results Median followup was 59.5 months for the 250 patients. Grade 2 or higher adverse events at any time for hyperpigmentation, induration, erythema, telangiectasia, breast pain, seroma, and fat necrosis were 0.4%, 3.0%, 3.0%, 3.0%, 3.9%, 4.8%, and 1.3%, respectively. The median V 90 was 97%, V 95 was 95.1%, V 150 was 28.7 cc, and V 200 was 14.2 cc. For those patients with a less than a 5-mm or 3-mm-skin bridge, the median skin max doses were 272 and 289 cGy, respectively. The 4-year actuarial recurrence rates for true recurrence/marginal miss and ipsilateral breast tumor recurrence were 2.3% and 3.6%, respectively. The 4-year actuarial rates for overall survival, cause-specific survival, and disease-free survival were 97%, 98%, and 92%, respectively. Conclusions The strut-based applicator was designed to simplify APBI compared to interstitial brachytherapy. This report confirms excellent tumor control and survival with low toxicity and supports the evidence that brachytherapy has less normal tissue toxicity than APBI with external beam irradiation.

233 Background: Ra-223, a targeted alpha therapy, extended survival and had a favorable safety profile at 3 years’ follow up in pts with mCRPC in the pivotal phase 3 ALSYMPCA trial. The maturing global, prospective, single-arm, observational REASSURE study, designed to evaluate long-term safety at 7 years’ follow up, enrolled pts with mCRPC with bone metastases planned to receive Ra-223. Methods: We performed a descriptive analysis of safety and BL characteristics of US pts according to prior or concomitant abiraterone/enzalutamide (abi/enza) or prior docetaxel/cabazitaxel (chemo) using data from the first planned interim analysis (pts receiving ≥1 Ra-223 dose; median follow up 8 mo). Results: 244 US pts were included; 80% had no prior chemo. Prior abi/enza and/or chemo pts had higher median BL PSA and were less likely to complete 5-6 doses (Table). Subgroups had similar median ALP, LDH and Hb. Overall, drug-related tx-emergent AEs occurred in 71 pts (29%) and serious AEs in 9 (3.7%). Most common AEs were diarrhea, fatigue and anemia. AE incidence was numerically higher in pts who received prior chemo and/or abi/enza. Clinical trial information: NCT02141438. Conclusions: To date, REASSURE has not revealed any new safety findings and most pts complete 5-6 Ra-223 doses in routine US clinical practice. Pts with prior tx lines had lower Ra-223 tx completion and higher AE incidence, likely reflecting greater disease burden, as evidenced by higher median BL PSA.[Table: see text]

84 Background: While a growing body of evidence supports the use of stereotactic body radiotherapy (SBRT) for the treatment of low- and intermediate-risk prostate adenocarcinoma (PCa), some trepidation exists regarding its long-term efficacy and safety. Methods: Men with low- and intermediate-risk PCa, as defined per the National Comprehensive Cancer Network guidelines, who were enrolled on various institutional phase II trials of SBRT between 2000-2012 were included in a multi-institutional consortium. Biochemical relapse (BCR) was defined as PSA > “nadir +2” or initiation of androgen deprivation therapy (ADT). Toxicity data were scored according to the CTCAE v 3.0 or Radiation Therapy Oncology Group scoring systems. Results: A total of 1644 men were eligible for analysis, with a median followup of 7.2 years. 297 patients (18.1%) had at least 9 years of followup. Fractionation schemes ranged from 33.50-40 Gy in 4-5 fractions. 892 patients had low-risk disease and 752 had intermediate-risk disease. 59 patients (3.6%) received short-term ADT. 100 patients (6.0%) experienced BCR, and 7 (0.4%) experienced distant metastases. No patients died of PCa. By Kaplan-Meier analysis, 5- and 10-year BCR-free survival rates were 98% and 94% in the low-risk group and 96% and 90% in the intermediate-risk group (p < 0.05 by log-rank test). 5- and 10-year overall survival rates were 93% and 86% in the low-risk group and 95% and 91% in the intermediate-risk group (p > 0.05 by log-rank test). Five patients (0.3%) experienced grade 3 acute genitourinary (GU) toxicities, including urinary retention, hematuria, and frequency. 30 (2%) experienced grade 3 late GU toxicity, including urinary strictures, hematuria, and retention. One late grade 4 GU toxicity (hemorrhagic urethritis) and one late grade 4 gastrointestinal toxicity (fistula-in-ano) were seen. Conclusions: To the best of our knowledge, this is the largest analysis of long-term outcomes following SBRT for PCa. The results indicate that SBRT has an efficacy and toxicity profile that compares favorably to more widespread forms of treatment, such as conventionally-fractionated external beam radiotherapy and brachytherapy.

PurposePerirectal spacing, whereby biomaterials are placed between the prostate and rectum, shows promise in reducing rectal dose during prostate cancer radiation therapy. A prospective multicenter randomized controlled pivotal trial was performed to assess outcomes following absorbable spacer (SpaceOAR system) implantation.Methods and MaterialsOverall, 222 patients with clinical stage T1 or T2 prostate cancer underwent computed tomography (CT) and magnetic resonance imaging (MRI) scans for treatment planning, followed with fiducial marker placement, and were randomized to receive spacer injection or no injection (control). Patients received postprocedure CT and MRI planning scans and underwent image guided intensity modulated radiation therapy (79.2 Gy in 1.8-Gy fractions). Spacer safety and impact on rectal irradiation, toxicity, and quality of life were assessed throughout 15 months.ResultsSpacer application was rated as “easy” or “very easy” 98.7% of the time, with a 99% hydrogel placement success rate. Perirectal spaces were 12.6 ± 3.9 mm and 1.6 ± 2.0 mm in the spacer and control groups, respectively. There were no device-related adverse events, rectal perforations, serious bleeding, or infections within either group. Pre-to postspacer plans had a significant reduction in mean rectal V70 (12.4% to 3.3%, P

Purpose External beam radiation therapy (EBRT) alone for early stage, medically inoperable non-small cell lung cancer (MILC) can produce local disease control and sometimes cure. We have previously reported that higher EBRT doses result in improved disease control and, for patients with tumors ≥3.0 cm, improved survival. This report describes the impact of dose escalation with endobronchial brachytherapy boost during or following EBRT upon local disease control. Methods and materials Medical records of 404 patients with MILC treated with radiotherapy alone were reviewed. Thirty-nine patients received a planned endobronchial brachytherapy boost during or following a course of EBRT. A matched-pair analysis of disease control and survival was performed by matching each brachytherapy patient to 2 EBRT patients from a reference group of the remaining patients. Results Endobronchial brachytherapy boost significantly improved local disease control over EBRT alone (58% vs. 32% at 5 years). The local control benefit for brachytherapy was found to be limited to patients with T 1–2 disease or tumors ≤5.0 cm. Among these patients treated with endobronchial boost, EBRT doses of ≥6500 cGy were necessary to optimize local disease control. No overall survival differences were observed at 3 years. Excess toxicity with brachytherapy was not observed. Conclusion Endobronchial brachytherapy boost enhances local disease control rates in MILC treated with EBRT. Local control outcome is optimized when radical EBRT doses are used in conjunction with brachytherapy.

Treatment of testicular, penile, and bladder cancer with surgery, radiation therapy, and chemotherapy may result in significant sexual morbidity. The pathophysiology of erectile dysfunction is reviewed. The incidence of posttreatment erectile dysfunction, infertility, loss of libido, retrograde ejaculation, loss of orgasm, and sexual dissatisfaction is estimated from the published literature. Morbidity resulting from different treatment options are compared and innovative approaches which hold promise for reducing sexual dysfunction in this patient population are highlighted.