233 Background: In oligometastatic prostate cancer (OMPC), delaying time to initiation of androgen deprivation therapy (ADT) may have oncologic and quality of life benefits. Additionally, there is an emerging role for metastatic/primary tumor site-directed therapy for patients with OMPC. Prostate apoptosis response-4 (PAR-4) is a potent tumor suppressor, facilitating apoptosis in prostate cancer cells. Hydroxychloroquine (HCQ) has been identified to be a potent inducer of PAR-4 secretion and downstream tumor inhibition in preclinical models and Phase I trials. We present a single institution Phase II trial assessing induction of PAR-4 levels in the plasma of patients in response to HCQ administration in combination with radiation therapy (RT) for OMPC. Methods: Men with OMPC (≤5 synchronous metastatic lesions) following primary tumor treatment were eligible. Patients received 400 mg HCQ daily for 2 weeks prior to metastatic site-directed RT and 400 mg HCQ daily for 90 days post-radiation. Plasma samples were collected on Day 0, 14, 30, 60, and 90. The primary endpoint was induction of ≥50% serum PAR-4 expression above baseline level within 90 days of treatment initiation. We hypothesized that over half of patients would exhibit ≥50% induction of serum PAR-4 expression. Results: Nineteen participants met inclusion criteria and were treated with 90 days of HCQ and RT to oligometastatic lesions. Median age was 68 years (range 55-77), the majority of patients were Caucasian (94%) and the median baseline PSA was 6.30 ng/ml (range 0.99 to 27.80). Prior primary tumor treatment included radiation therapy in 26%, radical prostatectomy in 32%, and radical prostatectomy with radiation in 42%. Eleven patients (58%) showed ≥50% increase in plasma PAR-4 above baseline levels (p=0.0006). This was associated with a concomitant PSA decline at 6-months (mean -0.98 ng/ml, 95% CI -6.61 to 4.65) and 12-months (mean -7.21 ng/ml, 95% CI -12.45 to -1.97). At 12-month follow-up, seven patients (37%) were free from ADT and median progression-free survival was 9.3 months (95% CI 6.4 to N/A). Twelve patients (63%) reported at least one adverse event, with 2 patients (11%) experiencing grade 3 toxicity. Conclusions: Oral administration of HCQ is well tolerated and effectively induces plasma expression of the potent tumor suppressor PAR-4 in patients with OMPC. Given the promising findings, further investigation into possible radiosensitizing and anti-tumor benefits of HQC in a larger cohort of OMPC is necessary. Clinical trial information: NCT04011410 .

816 Background: The recommended treatment for high-grade upper tract urothelial carcinoma (UTUC) includes radical nephroureterectomy with regional lymph node dissection for clinically organ-confined disease. The timing of peri-operative systemic therapy is multifactorial, with extrapolation of data from muscle-invasive bladder cancer in the neoadjuvant setting, and level 1 data for UTUC in the adjuvant setting. The timing of peri-operative systemic therapy and need for surgical consolidation in the clinically node positive setting is even more unclear. The goal of this study is to compare survival in cN+ patients managed with neoadjuvant, adjuvant, and systemic therapy alone approaches. Methods: Patients with cT0-4 N1-3 M0 UTUC who received chemotherapy with or without nephroureterectomy (NU) between 2018 and 2021 in the National Cancer Database (NCDB) were included. Patients were stratified into three treatment groups: chemotherapy only (CO), neoadjuvant chemotherapy followed by nephroureterectomy (NAC-NU), and nephroureterectomy followed by adjuvant chemotherapy (NU-AC). OS was analyzed using Kaplan-Meier analysis and log rank tests. Cox proportional hazard models were employed to adjust for potential confounders. Results: A total of 1193 patients were included (CO, NAC-NU, and NU-AC treatment groups consisted of 495, 287, and 411 patients, respectively). Patients in the CO group were older (P<0.001), more commonly males (P<0.001) compared with NAC-NU and NU-AC cohorts. There was no significant difference in Charlson comorbidity index between the three groups. The pathologic complete response rate (ypT0N0) in the NAC-NU was 6.5%. Patients managed with NAC-NU exhibited the most favorable OS compared to NU-AC and CO (P<0.0001), with 3-year OS 65.4% (95% CI 58.4%-73.3%), 53.5% (47.9%-59.6%), and 20.8% (15.7%-27.6%) in these groups, respectively. On multivariate analysis controlling for age, sex, and clinical stage using NAC-NU as a referent, NU-AC and CO exhibited inferior OS (HR 1.48, 95% CI 1.06-2.06, P=0.021 and HR 2.92, 2.14-4.00, P<0.001, respectively). Conclusions: The use of neoadjuvant chemotherapy followed by nephroureterectomy provides optimal survival outcomes in patients with cN+ high-grade UTUC. These data suggest that, when feasible, surgical consolidation is an important treatment component in patients with cN+ disease, likely owing to low rates of pathologic complete response. Estimated overall survival at 1- and 3-year endpoints. Treatment Sample Size 1 Year Survival (95% CI) 3 Year Survival (95% CI) Chemo Alone 348 57.6% (52.5% - 63.2%) 20.8% (15.7% - 27.6%) Chemo before Surgery 202 80.8% (75.4% - 86.6%) 65.4% (58.4% - 73.3%) Surgery before Chemo 329 72.8% (68.1% - 77.8%) 53.5% (47.9% - 59.6

INTRODUCTION:Patients with histologic subtypes (HS) of urothelial cancers are often excluded from neoadjuvant chemotherapy (NAC) trials for muscle-invasive bladder cancer (MIBC). Additionally, there exist conflicting data regarding the inherent chemotherapeutic sensitivity of individual HS. Herein, we assess the prognostic significance of pathologic response to NAC, a common surrogate endpoint of success in NAC trials, in patients with HS versus pure urothelial carcinoma (PUC). METHODS:The National Cancer Database (NCDB) was queried for patients with cT2-4N0M0 MIBC who received NAC and radical cystectomy (RC) between 2004 and 2020. Pathologic response to NAC was defined as complete (ypT0N0), partial (<ypT2N0), and no response (≥ypT2 or ypN+). Kaplan-Meier analysis and log-rank tests were performed for overall survival (OS) and Cox proportional hazard regressions were performed to test relationships between NAC response and the presence of a HS in predicting OS. RESULTS:5,372 patients were included, with 345 (6.4%) having HS. Nonresponse rates to NAC in HS patients were significantly higher than those with PUC (65.2% vs. 55.8%, P = 0.003). Patients with squamous and glandular differentiation exhibited the highest rates of nonresponse (79% and 72.2%, respectively). In unstratified analysis, patients with HS exhibited shorter OS (P < 0.0001). Patients with HS had uniformly worse OS even after controlling for pathologic response (P = 0.013), with the most notable discrepancy in partial responders (HR = 4.88, 95% CI 2.29-10.38, P < 0.001; 3-year OS 91% vs. 66% for partial response in PUC vs. HS, respectively). CONCLUSIONS:Patients with HS MIBC exhibit poor survival when treated with NAC followed by RC compared with PUC, even when controlling for pathologic response. These data suggest that pathologic response is a less accurate surrogate endpoint in patients with HS relative to PUC, and may suggest a role for therapeutic intensification in the adjuvant setting for patients with HS.

You have accessJournal of UrologyDiversity, Equity & Inclusion: Health Equity & Outcomes I (PD05)1 May 2024PD05-04 INVESTIGATING THE ROLE OF ACCESS TO QUALITY CARE FOR MUSCLE-INVASIVE BLADDER CANCER IN THE DISPARATE OUTCOMES FOR SOCIODEMOGRAPHICALLY DISADVANTAGED PATIENTS IN THE STATE OF KENTUCKY Joon Kyung Kim, Feitong Lei, Seth Teplitsky, Eric Wahlstedt, Jate Bernard, Derek Allison, Zin Myint, Stephen Strup, Bin Huang, and Patrick Hensley Joon Kyung KimJoon Kyung Kim , Feitong LeiFeitong Lei , Seth TeplitskySeth Teplitsky , Eric WahlstedtEric Wahlstedt , Jate BernardJate Bernard , Derek AllisonDerek Allison , Zin MyintZin Myint , Stephen StrupStephen Strup , Bin HuangBin Huang , and Patrick HensleyPatrick Hensley View All Author Informationhttps://doi.org/10.1097/01.JU.0001008624.07191.ab.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The reference standard of care (SOC) for non-metastatic muscle-invasive bladder cancer (MIBC) is neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) or trimodal therapy (TMT) with maximal transurethral resection of bladder tumor followed by chemoradiation. However, half of MIBC patients do not receive potential curative therapy for MIBC. Socioeconomic disparities are an increasingly recognized factors in receipt of quality bladder cancer care. The state of Kentucky has the 15th highest age-adjusted incidence rate for bladder cancer but 3rd highest death rate, which is disproportionately seen in the Appalachian region. We sought to investigate how social, demographic, and clinical factors influence receipt of SOC for MIBC, and how substandard care influences survival outcomes within the state of Kentucky. METHODS: Patients diagnosed with cT2-4 N0-2 M0 MIBC from 2004-2020 were identified from the Kentucky Cancer Registry population-based database. Sociodemographic and clinical variables were examined as predictors of receiving SOC management, defined as either NAC/RC or TMT. Kaplan-Meier, log-rank, and Cox regression analysis was performed for survival, and univariate and multivariable logistic regression analysis was performed for receipt of SOC. RESULTS: Of the 1846 patients included, 28% received SOC (NAC/RC in 340 patients and TMT in 177 patients). The most common substandard treated regimen was RC alone (271 patients, 15%). Factors associated with poor survival include sub-SOC management (p<0.001), old age (p<0.001), low income (p=0.046), Appalachian status (p=0.02), lack of insurance (p<0.001), and advanced TNM stage (p<0.001). On multivariate analysis, age (p=0.003) and insurance status (p<0.001) were associated with receipt of sub-SOC. Notably, income, and Appalachian residency were not independent predictors of receipt of SOC, nor were they associated with delays to definitive treatment, type of urinary diversion, or receipt of adjuvant chemotherapy. CONCLUSIONS: In the state of Kentucky, less than a third of patients with MIBC received SOC management. While sociodemographic factors such as Appalachian status and low income did not impact receipt of SOC therapy, they were each independent predictors of poor survival. These data suggest that disparate outcomes in these underserved patient populations are not primarily driven by receipt of quality or timely care and may reflect unmeasured confounders which need further investigation. Source of Funding: None © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e90 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Joon Kyung Kim More articles by this author Feitong Lei More articles by this author Seth Teplitsky More articles by this author Eric Wahlstedt More articles by this author Jate Bernard More articles by this author Derek Allison More articles by this author Zin Myint More articles by this author Stephen Strup More articles by this author Bin Huang More articles by this author Patrick Hensley More articles by this author Expand All Advertisement PDF downloadLoading ...

TPS350 Background: The optimal timing for initiating androgen deprivation therapy (ADT) in biochemical recurrent (BCR) prostate cancer (PC) patients, specifically those with PSA doubling time > 10 months, remains uncertain. Therefore, there is a compelling need for clinical trials exploring alternatives to ADT. Artesunate, derived from Artemisinin which is extracted from Artemisia annua (Aa), shows anti-cancer effects. Aa comprises several active constituents including dihydroartemisinic acid, artemisinic acid, and artemisinin. Our research group assessed the sensitivity of prostate cancer cells to Artesunate using established PC cell lines such as LNCaP, C4-2, CWR-22Rv1 and PC-3. Two cell lines, LNCaP (PSA and AR positive, hormone naïve) with an IC50 of 3.30 µM (95% CI 2.28-4.79) and C4-2 (PSA and AR positive, castration resistant) with an IC50 of 3.99 µM (3.13-5.10 µM) demonstrated sensitivity to Artesunate. Wang et. al (2017) reported that Artesunate, administered at varying doses, effectively suppressed tumor growth, inhibited cell viability and enhanced apoptosis in a mouse xenograft model using the 22rv1 PC cell line. Based on these promising preclinical findings, we hypothesize that Aa decaf coffee has the potential to decrease rising PSA levels in patients with BCR PC. Our research group previously conducted a phase I dose escalation of ArtemiCoffee in ovarian cancer (NCT04805333) and preliminary results indicated no grade ≥3 toxicities at the proposed dose (unpublished data). In this study, we aim to conduct a phase II study of Aa decaf coffee in men with BCR PC. Methods: An open-label, single center, phase II study targets men with BCR PC following primary definitive local therapy and a PSA doubling time > 10 months. Commercially available Aa decaf coffee pods supplied by ArtemiLife Inc. will be utilized. These decaf coffee pods adhere to FDA food-grade quality standards and Aa plants used for ArtemiLife coffee are cultivated in Kentucky, USA. Aa decaf coffee will be self-administered three times daily (total of 1,350mg Aa) on an outpatient basis for 24 weeks. The primary endpoint is to determine the proportion of patients achieving a ≥50% decline in PSA levels within 24 weeks of Aa decaf coffee treatment in BCR population. A total of 30 patients will be enrolled in this study, ensuring a maximum margin of error of approximately 16% in the 95% confidence interval for the primary endpoint. Secondary endpoints include safety and tolerability. Correlative endpoints include 1) changes in downstream biomarkers of the NRF2/KEAP1 signaling pathway and 2) changes in plasma concentrations of artemisinin and dihydroartemisinin by comparing pre- and post-treatment with Aa decaf coffee using non-parametric paired test. The study commenced accrual in August 2023. Clinical trial information: NCT05478239 .

INTRODUCTION:Previous studies noted varied adherence to clinical practice guidelines (CPGs), but studies are yet to quantify adherence to American Urological Association BPH guidelines. We studied guideline adherence in the context of a new quality improvement collaborative (QIC).METHODS:Data were collected as part of a statewide QIC. Medical records for patients undergoing select CPT codes from January 2020 to May 2022 were retrospectively reviewed for adherence to selected BPH guidelines.RESULTS:Most men were treated with transurethral resection of the prostate. Notably, 53.3% of men completed an IPSS and 52.3% had a urinalysis. 4.7% were counseled on behavioral modifications, 15.0% on medical therapy, and 100% on procedural options. For management, 79.4% were taking alpha-blockers and 59.8% were taking a 5-ARI. For evaluation, 57% had a PVR, 63.6% had prostate size measurement, 37.4% had uroflowmetry, and 12.3% were counseled about treatment failure. Postoperatively, 51.6% completed an IPSS, 57% had a PVR, 6.50% had uroflowmetry, 50.6% stopped their alpha-blocker, and 75.0% stopped their 5-ARI.CONCLUSIONS:There was adherence to preoperative testing recommendations, but patient counseling was lacking in the initial work-up and preoperative evaluation. We will convey the data to key stakeholders, expand data collection to other institutions, and devise an improvement implementation plan.

TPS351 Background: Definitive radiation therapy (DRT) combined with androgen deprivation therapy (ADT) remains the standard of care in patients with high-risk prostate cancer (HRPC) who do not want surgery. However, up to 50% experience biochemical recurrence (BCR) within 5 years. A phase 3 NCIC group reported the 10-year biochemical recurrence free survival was 63% in ADT plus DRT vs. 27% in ADT alone. There is an urgent need for effective novel combination strategies. We hypothesize combined immune sensitizing effects of PARPi and radiation will result in significant activity of immunotherapy in men with HRPC. Methods: This is a multicenter phase II randomized study to assess biochemical response rates, safety and tolerability of combined therapy in pts with localized HRPC who elected for concurrent DRT. A total of 64 pts will be randomized 1:1 to receive either pembrolizumab (P) combined with olaparib or single agent P in addition to the standard of care ADT with DRT. Hypofractionated IMRT (2.4 to 4 Gy per fraction over 4-6 weeks) will be delivered and all pts will receive adjuvant P for one year and ADT for at least 18 months. All pts will undergo germline testing. Key eligible criteria include biopsy confirmed prostate adenocarcinoma who meets at least one of the four high-risk features: 1) clinical T3a, T3b or T4, 2) N1, 3) Gleason grade group 4 or 5, and 4) PSA >20 ng/ml. Patients with less than 2 cm pelvic nodes and received ADT therapy within 3months prior to study enrollment are allowed. PSA >150 ng/ml and patients with distant metastases will be excluded. The primary endpoint is to assess the proportion of patients who achieve a PSA nadir level of ≤ 0.06 ng/ml within six months after completion of radiation therapy in each arm. The secondary objectives include safety/tolerability, BCR and metastasis-free survival at 3 years. BCR is defined by the Phoenix definition. The study is designed to detect a 15% improvement in PSA nadir ≤ 0.06 ng/mL within 6 months after completion of the combined therapy versus historical control group data Geara FB et al., 2017. Enrollment began in August 2023. Clinical trial information: NCT05568550 .

You have accessJournal of UrologyBladder Cancer: Epidemiology & Evaluation I (MP08)1 May 2024MP08-14 PROGNOSTIC SIGNIFICANT OF PATHOLOGIC RESPONSE TO PREOPERATIVE CHEMOTHERAPY IN MUSCLE-INVASIVE UROTHELIAL CARCINOMA OF THE BLADDER WITH SUBTYPE HISTOLOGY Seth Teplitsky, Will Cranford, Spencer Bell, Joon Kyung Kim, Syndey Strup, Derek Allison, Amanda Saltzman, Zin Myint, Stephen Strup, Akshay Sood, Ashish M. Kamat, Christopher McLouth, and Patrick J. Hensley Seth TeplitskySeth Teplitsky , Will CranfordWill Cranford , Spencer BellSpencer Bell , Joon Kyung KimJoon Kyung Kim , Syndey StrupSyndey Strup , Derek AllisonDerek Allison , Amanda SaltzmanAmanda Saltzman , Zin MyintZin Myint , Stephen StrupStephen Strup , Akshay SoodAkshay Sood , Ashish M. KamatAshish M. Kamat , Christopher McLouthChristopher McLouth , and Patrick J. HensleyPatrick J. Hensley View All Author Informationhttps://doi.org/10.1097/01.JU.0001008780.87855.57.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Bladder cancer with subtype histology (SH) is often treatment refractory, associated with atypical metastases, and has higher cancer-specific mortality than pure urothelial cancers (PUC). Patients with SH are often excluded or underrepresented in preoperative chemotherapy (PC) clinical trials for muscle invasive bladder cancer (MIBC). Additionally, data regarding PC sensitivity for each histologic subtype is conflicting. Herein, we assess prognostic significance of pathologic response to PC in MIBC patients with SH and PUC. METHODS: The National Cancer Database was queried for patients with cT2-4 N0 M0 MIBC who received POC followed by radical cystectomy (RC) between 2018-2020. Patients were stratified into PUC or SH, including squamous, glandular, micropapillary, small cell/neuroendocrine, and sarcomatoid subtypes. Pure squamous and adenocarcinoma were excluded. Pathologic response to PC was codified as complete (ypT0N0), partial (

Objective: CD47 is an antiphagocytic molecule that plays a critical role in immune surveillance. A variety of malignancies have been shown to evade the immune system by increasing the expression of CD47 on the cell surface. As a result, anti-CD47 therapy is under clinical investigation for a subset of these tumors. Interestingly, CD47 overexpression is associated with negative clinical outcomes in lung and gastric cancers; however, the expression and functional significance of CD47 in bladder cancer is not fully understood. Materials and Methods: We retrospectively studied patients with muscle invasion bladder cancer (MIBC) who underwent a transurethral resection of bladder tumor (TURBT) and subsequently underwent radical cystectomy (RC) with or without neoadjuvant chemotherapy (NAC). CD47 expression was examined by IHC in both TURBT and matched RC specimens. The difference in CD47 expression levels between TURBT and RC was also compared. The association of CD47 levels (TURBT) with clinicopathological parameters and survival outcomes was evaluated by Pearson’s chi-squared tests and the Kaplan–Meier method, respectively. Results: A total of 87 MIBC patients were included. The median age was 66 (39–84) years. Most patients were Caucasian (95%), male (79%), and aged >60 (63%) and most often (75%) underwent NAC prior to RC. Of those who received NAC, 35.6% were responders and 64.4% were non-responders. The final reported stages as per AJCC for all patients were as follows: stage 0 (32%), stage 1 (1%), stage 2 (20%), stage 3 (43%), and stage 4a (5%). A total of 60% of patients were alive; of those, 30% had disease recurrence and 40% died from bladder cancer at a median follow-up of 3.1 (0.2–14.2) years. CD47 levels were detectable in 38 (44%) TURBT samples. There was no association between CD47 levels and clinicopathological parameters such as age, gender, race, NAC, final stage, disease recurrence, and overall survival (OS). Patients aged >60 (p = 0.006), non-responders (p = 0.002), and at stage ≥ 3 (p < 0.001) were associated with worse OS by a univariate analysis and stage ≥ 3 remained significant even after a multivariate analysis. In patients managed with NAC, there were decreased CD47 levels in RC specimens compared to the TURBT specimens, but this did not reach statistical significance. Conclusion: CD47 expression was not a predictive nor prognostic marker for MIBC patients. However, expression of CD47 was detected in nearly half of MIBCs, and future studies are needed to explore the potential role of anti-CD47 therapy in these patients. Furthermore, there was a slight positive trend in decreased CD47 levels (from TURBT to RC) in patients receiving NAC. As a result, more research is needed to understand how NAC may modify immune surveillance mechanisms in MIBC.

Purpose Radiation management literature focused on optimizing care for patients with intellectual disability is sparse. We add our experience to the literature with the goal to improve care to this vulnerable patient population. To this end, we report three cases of prostate cancer in patients with limited cognition who were treated with low dose rate (LDR) prostate brachytherapy to highlight an effective strategy to deliver optimal care to this group of patients. Materials and Methods This is a case series of three adult male patients with limited cognition each of whom developed prostate cancer which was managed primarily with LDR brachytherapy. Results Patient #1: A 53-year-old male with favorable intermediate-risk prostate cancer (PSA 8.8 ng/ml, Grade Group 2), Patient #2: a 68-year-old male with unfavorable intermediate risk prostate cancer (PSA 12.6 ng/ml, Grade Group 3), and Patient #3: a 52-year-old male with high-risk prostate cancer (PSA 24 ng/ml, Grade Group 1), all of whom had intellectual disability, were evaluated for radiation therapy. A thorough discussion occurred with each patient and their legal guardian about prostate cancer therapy options including surgery versus radiation treatment with or without androgen deprivation therapy. Radiation therapy treatment strategies presented included low dose rate brachytherapy versus external beam radiation treatment including SBRT to a total dose of 3625 cGy in 5 fractions every other day or a moderately hypofractionated regimen to a total dose of 7000 cGy in 28 daily fractions Monday to Friday. In each case, a shared decision was made for each patient to undergo interstitial prostate seed implant. Of note, two out of the three patients lived more than an hour away from the radiation treatment center and relied on family support for transportation needs. Each patient initially underwent a prostate volume study with a transrectal ultrasound to 1) determine the dimensions of the prostate and 2) develop a plan for radiation dose coverage of the prostate with interstitial Cs-131 brachytherapy seeds. Each patient then underwent seed implantation under anesthesia followed by fluoroscopy and post-implant CT, to assess for appropriate seed placement as well as the post-implant dosimetry. Patient #1 received a total prescription dose of 110 Gy to the prostate D90 using 61 sources each with a strength of 1.6 U per seed for a total strength of 97.6 U and at 14 months follow up, his PSA had decreased to 1.7 ng/ml from 8.8 ng/ml. Patient #2 received a total prescription dose of 100 Gy to the prostate D90 using 59 sources each with a strength of 1.43 U per seed for a total strength of 84.37 U, and at 38 months follow up, his PSA had decreased to 0.018 ng/ml from 12.6 ng/ml. Patient #3 received 115 Gy to the prostate D90 using 90 sources each with a strength of 1.8 U per seed for a total of 162 U, and at 34 months follow up, his PSA had decreased to 0.8 ng/mL from 24 ng/ml. In all three cases, treatment was completed without complications and there was no CTCAE grade 3 or higher toxicity noted. Conclusions In patients with limited cognition with select non-metastatic prostate cancer, low dose rate brachytherapy is an excellent treatment modality. It provides adequate tumor control with acceptable radiation induced toxicities. It reduces the transportation burden associated with multiple treatment sessions by requiring only two visits to a radiation treatment center. The use of sedation reduces the challenge associated with patient immobilization encountered with external beam radiation treatments. And, it is less invasive than surgery. These advantages for LDR brachytherapy are extremely useful for patients with limited cognition. Thus, LDR brachytherapy should be strongly considered for this patient population when applicable. Radiation management literature focused on optimizing care for patients with intellectual disability is sparse. We add our experience to the literature with the goal to improve care to this vulnerable patient population. To this end, we report three cases of prostate cancer in patients with limited cognition who were treated with low dose rate (LDR) prostate brachytherapy to highlight an effective strategy to deliver optimal care to this group of patients. This is a case series of three adult male patients with limited cognition each of whom developed prostate cancer which was managed primarily with LDR brachytherapy. Patient #1: A 53-year-old male with favorable intermediate-risk prostate cancer (PSA 8.8 ng/ml, Grade Group 2), Patient #2: a 68-year-old male with unfavorable intermediate risk prostate cancer (PSA 12.6 ng/ml, Grade Group 3), and Patient #3: a 52-year-old male with high-risk prostate cancer (PSA 24 ng/ml, Grade Group 1), all of whom had intellectual disability, were evaluated for radiation therapy. A thorough discussion occurred with each patient and their legal guardian about prostate cancer therapy options including surgery versus radiation treatment with or without androgen deprivation therapy. Radiation therapy treatment strategies presented included low dose rate brachytherapy versus external beam radiation treatment including SBRT to a total dose of 3625 cGy in 5 fractions every other day or a moderately hypofractionated regimen to a total dose of 7000 cGy in 28 daily fractions Monday to Friday. In each case, a shared decision was made for each patient to undergo interstitial prostate seed implant. Of note, two out of the three patients lived more than an hour away from the radiation treatment center and relied on family support for transportation needs. Each patient initially underwent a prostate volume study with a transrectal ultrasound to 1) determine the dimensions of the prostate and 2) develop a plan for radiation dose coverage of the prostate with interstitial Cs-131 brachytherapy seeds. Each patient then underwent seed implantation under anesthesia followed by fluoroscopy and post-implant CT, to assess for appropriate seed placement as well as the post-implant dosimetry. Patient #1 received a total prescription dose of 110 Gy to the prostate D90 using 61 sources each with a strength of 1.6 U per seed for a total strength of 97.6 U and at 14 months follow up, his PSA had decreased to 1.7 ng/ml from 8.8 ng/ml. Patient #2 received a total prescription dose of 100 Gy to the prostate D90 using 59 sources each with a strength of 1.43 U per seed for a total strength of 84.37 U, and at 38 months follow up, his PSA had decreased to 0.018 ng/ml from 12.6 ng/ml. Patient #3 received 115 Gy to the prostate D90 using 90 sources each with a strength of 1.8 U per seed for a total of 162 U, and at 34 months follow up, his PSA had decreased to 0.8 ng/mL from 24 ng/ml. In all three cases, treatment was completed without complications and there was no CTCAE grade 3 or higher toxicity noted. In patients with limited cognition with select non-metastatic prostate cancer, low dose rate brachytherapy is an excellent treatment modality. It provides adequate tumor control with acceptable radiation induced toxicities. It reduces the transportation burden associated with multiple treatment sessions by requiring only two visits to a radiation treatment center. The use of sedation reduces the challenge associated with patient immobilization encountered with external beam radiation treatments. And, it is less invasive than surgery. These advantages for LDR brachytherapy are extremely useful for patients with limited cognition. Thus, LDR brachytherapy should be strongly considered for this patient population when applicable.

Solitary fibrous tumours (SFTs) are rare mesenchymal neoplasms composed of spindle cells, most often occurring in the pleura. SFTs arising from the prostate are exceptionally rare, with only around 40 cases reported in literature to date. We report a man in his 60s who was referred to our clinic for elevated prostate-specific antigen and presented with mild obstructive lower urinary tract and defecatory symptoms. Prostate needle-core biopsy revealed neoplastic spindle cells that strongly expressed CD34. Cross-sectional imaging demonstrated a 12 cm locally advanced heterogeneous prostate mass with intravesical extension and mass effect on the anterior rectum. Radical cystoprostatectomy with orthotopic neobladder reconstruction was performed, and the diagnosis of primary prostatic SFT was made based on histological characteristics and immunophenotyping. We present diagnostic, clinical management and prognostic considerations in patients with primary prostatic SFT.

257 Background: There is a need for a low toxicity option for men with prostate cancer with biochemical recurrence (BCR) following primary curative therapy. Cannabinoids (CBD) have anti-tumor activity in preclinical studies, but products may vary in activity without clear standardization. As epidiolex is a standardized FDA approved oral CBD solution for treatment of certain types of seizures, we studied epidiolex in patients with BCR of prostate cancer to determine safety and dosing of this therapy to support future studies. Methods: We present an open-label, single center, phase I dose escalation study followed by a dose expansion. Patients with BCR prostate cancer after primary definitive local therapy (prostatectomy +/- salvage radiotherapy or primary definitive radiotherapy) were eligible. Majority of our patients’ prostate-specific antigen (PSA) doubling time was ≤ 12 months. All patients were screened for urine tetrahydrocannabinol (THC) prior to enrollment. With use of a Bayesian optimal interval design, patients received escalating doses of epidiolex starting at 600mg daily and up to 800mg daily. All patients were treated for 90 days followed by a 10 day taper. The Primary endpoints were safety and tolerability. Patients were monitored for both acute (30 days) and chronic (90 days) treatment-related toxicities. Secondary endpoints included change in PSA levels and testosterone levels from baseline throughout the treatment period. Results: A total of 21 patients were enrolled but four withdrew from the study (one patient was hospitalized with COVID-19 and three patients requested to stop due to grade 2 adverse events (AEs). There were seven patients included in the dose escalation phase. Four patients received 600mg daily; two of the four in this phase did not finish the first 30 days (one with COVID-19 and one withdrew). The other three patients received 800 mg daily. No dose-limiting toxicities were observed at any dose level so an additional 14 patients were enrolled at the 800mg dose. Treatment-related chronic AEs occurring in >10% of patients were grade 1 or 2 diarrhea (47.6%), grade 1 or 2 nausea (23.8%) and grade 1 or 2 fatigue (19%). The mean PSA at baseline was 2.9 ng/ml. One patient developed oligo-metastasis disease, two patients progressed after the study period, and one patient died from a non-treatment or disease-related cause. Conclusions: Epidiolex at a dose of 800mg daily appears to be safe and tolerable in patients with BCR of prostate cancer, supporting a safe dose for future studies to determine if there is clinical activity to delay development of hormone refractory metastatic disease. Clinical trial information: NCT04428203.

Purpose: Cannabinoids (CBD) have anti-tumor activity against prostate cancer (PCa). Preclinical studies have demonstrated a significant decrease in prostate specific antigen (PSA) protein expression and reduced tumor growth in xenografts of LNCaP and DU-145 cells in athymic mice when treated with CBD. Over-the-counter CBD products may vary in activity without clear standardization, and Epidiolex is a standardized FDA-approved oral CBD solution for treatment of certain types of seizures. We aimed to assess the safety and preliminary anti-tumor activity of Epidiolex in patients with biochemically recurrent (BCR) PCa. Experimental design: This was an open-label, single center, phase I dose escalation study followed by a dose expansion in BCR patients after primary definitive local therapy (prostatectomy +/− salvage radiotherapy or primary definitive radiotherapy). Eligible patients were screened for urine tetrahydrocannabinol prior to enrollment. The starting dose level of Epidiolex was 600 mg by mouth once daily and escalated to 800 mg daily with the use of a Bayesian optimal interval design. All patients were treated for 90 days followed by a 10-day taper. The primary endpoints were safety and tolerability. Changes in PSA, testosterone levels, and patient-reported health-related quality of life were studied as secondary endpoints. Results: Seven patients were enrolled into the dose escalation cohort. There were no dose-limiting toxicities at the first two dose levels (600 mg and 800 mg). An additional 14 patients were enrolled at the 800 mg dose level into the dose expansion cohort. The most common adverse events were 55% diarrhea (grade 1–2), 25% nausea (grade 1–2), and 20% fatigue (grade 1–2). The mean PSA at baseline was 2.9 ng/mL. At the 12-week landmark time-point, 16 out of 18 (88%) had stable biochemical disease, one (5%) had partial biochemical response with the greatest measurable decline being 41%, and one (5%) had PSA progression. No statistically significant changes were observed in patient-reported outcomes (PROs), but PROs changed in the direction of supporting the tolerability of Epidiolex (e.g., emotional functioning improved). Conclusion: Epidiolex at a dose of 800 mg daily appears to be safe and tolerable in patients with BCR prostate cancer supporting a safe dose for future studies.

You have accessJournal of UrologyEducation Research III (MP20)1 Sep 2021MP20-11 UTILIZING A MULTIDISCIPLINARY APPROACH TO NEAR MISS EVENT ANALYSIS LEADS TO SUCCESSFUL IMPLEMENTATION OF ACTION ITEMS Christopher Hayden, Rohail Rashid Kazi, Jason Bylund, Alison Rasper, Stephen Strup, and Andrew Harris Christopher HaydenChristopher Hayden , Rohail Rashid KaziRohail Rashid Kazi , Jason BylundJason Bylund , Alison RasperAlison Rasper , Stephen StrupStephen Strup , and Andrew HarrisAndrew Harris View All Author Informationhttps://doi.org/10.1097/JU.0000000000002005.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Root cause analysis (RCA) is a valuable event analysis tool used to determine causes of patient safety (PS) events. In this study, we present six multidisciplinary meetings in which six near miss events were analyzed and action items were created and implemented in order to improve PS. METHODS: Near miss events were identified by resident teams and evaluated by the program director and PS champion. These events were analyzed in a multidisciplinary fashion with stakeholders including nurse managers, staff, residents, Urology faculty, information technology staff, Radiology staff, and Anesthesia providers. The involved stakeholders were tailored to the event being analyzed. Timelines were constructed for each case and RCA was done using 5-whys and fishbone analysis. Subsequently, actions items for each case were constructed and implemented. RESULTS: In total, six near miss events were identified and analyzed by the multidisciplinary teams. The near miss events addressed the following topics: (1) Continuous Bladder Irrigation, (2) miscommunication between the surgery and anesthesia teams concerning anticoagulation, (3) failure of ambulation on POD 0, (4) delayed recognition of sepsis, (5) delayed reporting of an obstructed, infected kidney stone, and (6) uncertainty concerning preoperative antibiotics. As a result of these meetings, action items were designed and implemented in response to the near miss events. The actions items were developed and executed by participating stakeholders. CONCLUSIONS: Analyzing near miss events using a multidisciplinary approach is an effective tool to efficiently create and implement action items in order to improve PS, as well as promote PS education in our department. The collaboration has been well received and this process is currently ongoing in our department. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e340-e341 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Christopher Hayden More articles by this author Rohail Rashid Kazi More articles by this author Jason Bylund More articles by this author Alison Rasper More articles by this author Stephen Strup More articles by this author Andrew Harris More articles by this author Expand All Advertisement PDF downloadLoading ...

High Glutaminase (GLS1) expression may have prognostic implications in colorectal and breast cancers; however, high quality data for expression in prostate cancer (PCa) are lacking. The purpose of this study is to investigate the status of GLS1 expression in PCa and correlated expression levels with clinicopathologic parameters. This study was conducted in two phases: an exploratory cohort analyzing RNA-Seq data for GLS1 from The Cancer Genome Atlas (TCGA) data portal (246 PCa samples) and a GLS1 immunohistochemical protein expression cohort utilizing a tissue microarray (TMA) (154 PCa samples; 41 benign samples) for correlation with clinicopathologic parameters. In the TCGA cohort, GLS1 mRNA expression did not show a statistically significant difference in disease-free survival (DFS) but did show a small significant difference in overall survival (OS). In the TMA cohort, there was no correlation between GLS1 expression and stage, Gleason score, DFS and OS. GLS1 expression did not significantly correlate with the clinical outcomes measured; however, GLS1 expression was higher in PCa cells compared to benign epithelium. Future studies are warranted to evaluate expression levels in greater numbers of high-grade and advanced PCa samples to investigate whether there is a rational basis for GLS1 targeted therapy in a subset of patients with prostate cancer.

Cone beam CT-guided prostate stereotactic body radiotherapy (SBRT) treatment on the recently installed novel O-ring coplanar geometry Halcyon Linac with a single energy 6MV-flattening filter free (FFF) beam and volumetric modulated arc therapy (VMAT) is a fast, safe, and feasible treatment modality for early stage low- and intermediate-risk prostate cancer patients. Following the RTOG-0938 compliance criteria and utilizing two-full arc geometry, VMAT prostate SBRT plans were generated for ten consecutive patients using advanced Acuros-based algorithm for heterogeneity corrections with Halcyon couch insert. Halcyon VMAT plans with the stacked and staggered multileaf collimators (MLC) produced highly conformal SBRT dose distributions to the prostate, lower intermediate dose spillage and similar dose to adjacent organs-at-risks (OARs) compared to SBRT-dedicated Truebeam VMAT plans. Due to lower monitor units per fraction and less MLC modulation through the target, the Halcyon VMAT plan can deliver prostate SBRT fractions in and overall treatment time of less than 10 minutes (for 36.25 Gy in five fractions), significantly improving patient compliance and clinic workflow. Pretreatment quality assurance results were similar to Truebeam VMAT plans. We have implemented Halcyon Linac for prostate SBRT treatment in our institution. We recommend that others use Halcyon for prostate SBRT treatments to expand the access of curative hypofractionated treatments to other clinics only equipped with a Halcyon Linac. Clinical follow-up results for patients who underwent prostate SBRT treatment on our Halcyon Linac is underway.

To analyze the use of alvimopan, a peripheral mu-opioid receptor antagonist, in expediting gastrointestinal recovery after benign abdominal urinary tract reconstruction. Alvimopan use has been well defined in the management of radical cystectomy and urinary diversion for oncologic indications. It has not been studied in benign abdominal genitourinary reconstruction. Patients who underwent urinary reconstruction utilizing harvested bowel segments for benign conditions from 12/2014–7/2019 were retrospectively reviewed. From 5/2018–7/2019 our institution approved the use of perioperative alvimopan in the aforementioned patients (N = 11), who were paired 1:2 with patients from a cohort of alvimopan-eligible patients who did not receive the drug (N = 22). Patients were paired by (1) type of reconstruction and (2) presence of neurogenic bowel-bladder (NBB). Of the 70 patients who underwent urinary reconstruction during the study period, 46 patients (66%) were eligible to receive alvimopan. Length of stay was shorter for the alvimopan group compared to the non-alvimopan group (median 5 days [IQR 4–5 days] vs. 8 days [IQR 6–11 days]; P = 0.002). Time to first bowel movement was shorter for the alvimopan group (median 4 days [IQR 3–4 days] vs. 6 days [IQR 4–7], P = 0.001). No patient treated with alvimopan required a nasogastric (NG) tube for post-operative ileus compared to 7 (32%) patients in the non-treatment group (P = 0.035). Post-operative complications and 30-day readmissions were similar between the two groups. The use of perioperative alvimopan in benign abdominal urinary tract reconstruction expedited return of bowel function and decreased length of stay compared to a matched cohort of untreated patients.

Recently published data from the American Cancer Society indicates that 233,000 estimated new cases of prostate cancer were diagnosed in 2014, with 29,480 estimated deaths from the disease [1]. Although several risk factors have been attributed to the development of prostate cancer, the pathogenesis of the disease is yet to be elucidated. Prostatic tissue uninvolved in the primary tumor may actively contribute to carcinogenic transformation. Recurrent or chronic inflammation in the uninvolved prostate has been identified as a potential contributor to prostate cancer tumorogenesis. Possible etiological factors in the genesis of chronic prostatic inflammation are an imbalanced diet, exposure to environmental pollutants, high circulating testosterone, bacterial and viral infection or genetic predisposition [2]. Inflammation, regardless of etiology, is thought to incite carcinogenesis by causing cell and genome damage, promoting cellular replacement and creating a tissue microenvironment rich in cytokines and growth factors that can enhance cell replication, angiogenesis and tissue repair [3]. Areas of chronic inflammation are commonly identified in radical prostatectomy specimens and prostate needle biopsies [4]. Gupta et al. analyzed the association between chronic inflammation and prostatic carcinoma in prostate biopsies specimens, showing that 20% of patients with chronic inflammation in initial biopsies were subsequently diagnosed with adenocarcinoma on follow-up biopsies during the next 5 years, suggesting a strong association between chronic prostatic inflammation and malignant changes [5]. Resnick et al. analyzed the prevalence of chronic inflammation in radical prostatectomy specimens, finding that chronic inflammation was associated with prostate cancer in 57.5 % of tissue specimens [6]. Multiple studies have examined the association between chronic inflammation and prostate cancer, but few existing studies correlate the prevalence of chronic inflammation to prostate tumor stage and grade. Karakiewicz et al. found chronic inflammation was more frequent in men diagnosed with low-grade Research article