Diffuse intrinsic pontine glioma (DIPG) is a fatal central nervous system (CNS) tumor that confers a median survival of 11 months. As B7-H3 is expressed on pediatric CNS tumors, we conducted BrainChild-03, a single-center, dose-escalation phase 1 clinical trial of repetitive intracerebroventricular (ICV) dosing of B7-H3-targeting chimeric antigen receptor T cells (B7-H3 CAR T cells) for children with recurrent or refractory CNS tumors and DIPG. Here we report results from Arm C, restricted to patients with DIPG. The primary objectives were to assess feasibility and tolerability, which were both met. Secondary objectives included assessments of CAR T cell distribution and survival. A total of 23 patients with DIPG enrolled, and 21 were treated with repeated doses of ICV B7-H3 CAR T cells using intra-patient dose-escalation regimens without previous lymphodepletion. Concurrent tumor-directed therapy, including re-irradiation, was not allowed while on protocol therapy. We delivered a total of 253 ICV doses and established the highest planned dose regimen, DR4, which escalated up to 10 × 107 cells per dose, as the maximally tolerated dose regimen. Common adverse events included headache, fatigue and fever. There was one dose-limiting toxicity (intratumoral hemorrhage) during DR2. For all treated patients (n = 21), the median survival from their initial CAR T cell infusion was 10.7 months and the median survival from diagnosis was 19.8 months with 3 patients still alive at 44, 45 and 52 months from diagnosis. Ultimately, this completed first-in-human trial shows that repetitive ICV dosing of B7-H3 CAR T cells in pediatric and young adult patients with DIPG is tolerable, including multiyear repeated dosing, and may have clinical efficacy that warrants further investigation on a multisite phase 2 trial. ClinicalTrials.gov registration: NCT04185038 . In the final report of a phase 1 trial evaluating intracerebroventricular B7-H3-targeting CAR T cells in children and young adults with diffuse intrinsic pontine glioma, repeated intracranial infusions were feasible and well tolerated with a median overall survival of 19.8 months and 3 patients surviving over 40 months from diagnosis.

e14626 Background: B7-H3 expression by a broad range of pediatric solid tumors has led to development of B7-H3-directed chimeric antigen receptor (B7-H3-CAR) T cells. However, early phase clinical trials of B7-H3-CAR T cells in recurrent/refractory solid tumors demonstrated inconsistent CAR T cell expansion and limited anti-tumor activity. We subsequently developed a dual transduced CAR product expressing B7-H3-CAR and CD19-CAR (CARB7H3x19) to enhance CAR T cell expansion with antigenic stimulation by normal B cells (STRIvE-02 Arm B). Augmented expansion was observed but CAR T cell persistence was variable, leading to a hypothesis that concurrent use of pembrolizumab (pembro), a PD1-inhibitor, would help prolong persistence, leading to improved anti-tumor activity. Methods: Patients up to age 26 years with recurrent/refractory solid tumors (excluding primary CNS) enrolled onto Arm C of STRIvE-02 to examine safety and feasibility of CARB7H3x19 at a dose of 0.5 x 106 CD19-CAR T/kg followed by pembro 2 mg/kg (max 200 mg) either 7- (Dose regimen (DR) 1) or 21-days (DR 2) post-CAR T cell using a 3+3 statistical design. All subjects received lymphodepletion with fludarabine and cyclophosphamide prior to CAR T cells. CTCAEv5 was used for toxicity grading. Results: Of six patients (pts) enrolled (age range 11–25 yrs, median 20 yrs, four received CAR T cell+pembro; three received DR1 pembro (day (D)+7), and one received DR2 (D+21). A pt on DR2 with nonseminomatous germ cell tumor developed grade (gr) 5 immune effector cell-associated hyperinflammatory syndrome (IEC-HS) on D+17 prior to pembro, resulting in trial suspension. One pt did not receive CAR T cells and is unevaluable. Adverse effects occurring in pts who received pembro included gr 3 fever in setting of neutropenia (n=1), and gr 2 hyperthyroidism (n=1), with no dose limiting toxicity attributed to CAR T cell+pembro. Maximum circulating CAR T expansion for Arm C was 192.18 cells/uL (range 6.86 – 192.18 cells/uL) with median persistence of 28 days (range 28 - 84), compared to a maximum circulating CAR T expansion of 740.95 cells/uL (range 8.29 – 740.95 cells/uL) and median persistence of 65 days (range 21 - 274) in pts treated on Arm B receiving the same CAR dose level (n=8). D+28 disease restaging in the four Arm C pts who received CAR T cells+pembro demonstrated stable disease (n=1) and disease progression (n=3). Conclusions: Although we observed tolerable toxicity among patients who received CAR T cell+pembro, the small number of patients limit full toxicity assessment. T cell expansion and persistence was observed, but the effects of pembro on CAR T cell fitness are unclear. Phenotypic characterization of circulating CAR T cells is underway to further assess impact of pembro. Of note, this is the first reported death attributed to IEC-HS in a patient after receiving B7-H3-CAR T cells. Investigations into etiology are ongoing. Clinical trial information: NCT04483778 .

Abstract BACKGROUND BrainChild-04 is a first-in-human clinical trial of quad-chimeric antigen receptor (CAR) T cell therapy for children and young adults with central nervous system (CNS) tumors. This trial administers repeated locoregional CAR T cells targeting B7-H3, EGFR, HER2, and IL-13Ralpha2 (“quad-CAR T cells”), leveraging multi-antigen targeting to address the tumor heterogeneity of high-grade CNS tumors. METHODS The primary endpoints are feasibility and safety, and secondary endpoints are disease response and correlative studies of CAR T cell activity. The trial utilized a Bayesian Optimal Interval (BOIN) statistical design with three planned dose regimens(DR). There are 2 arms with weekly delivery for 3 weeks of a 4-week cycle:(A) –diffuse intrinsic pontine glioma (DIPG), (B) –non-pontine diffuse midline glioma (DMG) or other relapsed CNS tumors. RESULTS Enrolled patients include DMG N=6, DIPG N=5, other CNS tumors N=4. Of the 15 enrolled patients, 7 have been infused with 8 awaiting infusions. A total of 33 intracranial CAR T doses have been delivered, including Arm A DR 1 (N=1), Arm B DR 1 (N=3), DR2 (N=3). The most common adverse events have been grade 1-2 fever (7/7 patients), grade 1-3 headache (6/7), and grade 1-2 nausea/vomiting (6/7). There have been no DLTs and no cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity (ICANS). CTCAE and tumor inflammation-associated neurotoxicity are both being captured. All treated patients are alive with median follow up time post-initial infusion of 93(14-198) days. CAR T cells were detected by flow cytometric analysis of CSF post-infusion in 14/24 CSF samples. Radiographic response, CSF circulating tumor DNA, targeted mass spectrometry, and cytokine analysis will be presented. CONCLUSIONS Our preliminary experience suggests tolerability of locoregional delivery of quad-CAR T cells at doses currently evaluated. The trial remains ongoing and these data support continued evaluation of this product to better assess anti-tumor activity in patients with CNS tumors, including DIPG/DMG.

Diffuse intrinsic pontine glioma (DIPG) is a fatal central nervous system (CNS) tumor with a median survival of 11 months. Chimeric antigen receptor (CAR) T cells are clinically effective against hematologic malignancies, but there are limited data on their utility against CNS tumors. As B7-H3 is expressed on pediatric CNS tumors, we conducted BrainChild-03 (NCT04185038), a single-center, dose-escalation phase 1 study of repetitive intracerebroventricular (ICV) B7-H3 CAR T cells for children with recurrent/refractory CNS tumors and DIPG. Here, we report on Arm C restricted to patients with DIPG. The primary objectives were to assess feasibility and tolerability. The secondary objectives were to assess CAR T cell distribution and overall survival. Twenty-three patients with DIPG enrolled and 21 were treated with ICV B7-H3 CAR T cells using intra-patient dose escalation dose regimens (DR) beginning at 1x107 CAR T cells/dose. We established the DR4, the highest planned DR that escalated to 10x107 cells/dose, as the maximally tolerated dose regimen (MTDR). Common adverse events included fever and headache. There was 1 DLT (intratumoral hemorrhage). An intent-to-treat analysis of median overall survival of enrolled patients (n = 23) from study enrollment was 11.4 months (range: 2.7–36.8) and the median time from initial diagnosis to death (or last contact for survivors) was 18.6 months (range: 6.5–40.5) with 4 patients still alive at 18.6, 37.2, 38.3, 40.5 months from diagnosis. Ultimately, the report of this completed first-in-human trial demonstrates that repetitive ICV B7-H3 CAR T cells in pediatric and young adult patients with DIPG is tolerable, even over repeated multi-year dosing, and may improve overall survival. Main Text

Abstract BACKGROUND BrainChild-03 is a first-in-human clinical trial that completed the phase 1 component of repeatedly dosed intraventricular B7-H3 CAR T cells to children with diffuse intrinsic pontine glioma (DIPG) without lymphodepleting chemotherapy. METHODS We report on BrainChild-03 Arm C, patients with DIPG receiving up to 10x10^7 B7-H3CAR T cells/dose. Primary endpoints were feasibility and safety. Secondary endpoints were disease response and correlatives of CAR T activity. RESULTS 23 patients enrolled. All had successful CAR T manufacturing. 21 patients were treated; 17 received sufficient doses for safety evaluation (4 doses/8 weeks) without a dose limiting toxicity (DLT). 4 other treated patients include: 1 patient DLT (pontine hemorrhage 8 days post-initial dose) and 3 unevaluable patients (2 discontinued protocol therapy for rapid progression; 1 did not meet eligibility to begin treatment). Overall, patients received 224 doses (median: 7, range: 1-60). Common adverse events included headache, nausea/vomiting, and fever. Of 21 treated patients, 11 enrolled after progression and survived 9.7 months (range: 6-16.9) after initial CAR T cell infusion. Of the 10 patients enrolled prior to progression, the overall survival is 16.9 months (range: 7.6-40.5) with 5/10 patients still alive. Three patients are alive 3 years from diagnosis, including 2 patients still on protocol therapy. Patients were not allowed to receive other anti-tumor agents, radiation, or surgical debulking while on protocol therapy. Circulating CSF CAR T cells were identified in 18/21 (85.7%) of patients and elevations in chemokine/cytokines associated with T cell activation and migration, including CXCL10 and IFNy. CONCLUSIONS Repeated intraventricular B7-H3 CAR T cell dosing is feasible and tolerable for children with DIPG, even after progression, with evidence of local immune activation. Early signals of survival extension underscore the potential for clinical benefit and the consideration to advance to phase 2 multi-site clinical trials.

Abstract BACKGROUND BrainChild-04 is a first-in-human clinical trial of quad-chimeric antigen receptor (CAR) T cell therapy for children and young adults with central nervous system (CNS) tumors. This trial administers repeated locoregional CAR T cells targeting B7-H3, EGFR, HER2, and IL-13Ralpha2 (“quad-CAR T cells”), leveraging multi-antigen targeting to address the tumor heterogeneity of high-grade CNS tumors. METHODS The primary endpoints are feasibility and safety, and secondary endpoints are disease response and correlative studies of CAR T cell activity. The trial utilized a Bayesian Optimal Interval (BOIN) design with three dose regimens (DR). There are 2 arms with weekly delivery for 3 weeks of a 4-week cycle:(A) –diffuse intrinsic pontine glioma (DIPG), (B) –non-pontine diffuse midline glioma (DMG) or other relapsed CNS tumors. RESULTS Enrolled patients include DMG N=6, DIPG N=5, other CNS tumors N=4. Of the 15 enrolled patients, 7 have been infused with 8 awaiting infusions. A total of 33 intracranial CAR T doses have been delivered, including Arm A DR 1 (N=1), Arm B DR 1 (N=3), DR2 (N=3). The most common adverse events have been grade 1-2 fever (7/7 patients), grade 1-3 headache (6/7), and grade 1-2 nausea/vomiting (6/7). There have been no DLTs and no cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity(ICANS). CTCAE and tumor inflammation-associated neurotoxicity are both being captured. All treated patients are alive with median follow up time post-initial infusion of 93(14-198) days. CAR T cells were detected by flow cytometric analysis of CSF post-infusion in 14/24 CSF samples. Radiographic response, CSF ct-DNA, targeted mass spectrometry, and cytokine analysis will be presented. CONCLUSIONS Our preliminary experience suggests tolerability of locoregional quad-CAR T therapy at doses evaluated. The trial remains ongoing and these data support continued evaluation of this product to better assess anti-tumor activity in patients with CNS tumors, including DIPG/DMG.

Purpose Transrectal ultrasound (US) imaging is paramount to the successful completion of prostate biopsies. Certain US features have been associated with prostate cancer (PCa), but their utility remains controversial. We explored the role of multiparametric US (mpUS) in the detection of clinically significant PCa. Methods We performed a retrospective cohort study to contrast the findings of prostate MRI and mpUS. Patients who underwent MRI, US and biopsy between 2015 and 2021 were included. Biopsies were performed using a systematic approach (12 cores), as well as with MRI (4 cores/lesion) and US (1 core/lesion) targeting. The US features analyzed consisted of: calcifications, hypoechoic lesions and power or color Doppler positivity. Gleason 3 + 4 or higher was used as to define true positives. Measures of diagnostic accuracy were calculated for the different imaging modalities. Results The final cohort included 74 patients, of which 24 (32.4%) had clinically significant PCa. The concordance between MRI and US was 63.5%. Seven individuals with discordant results had clinically significant PCa. MRI alone was more sensitive (87.5% vs 75%) but less specific (28% vs 32%) than US alone. An all-inclusive approach considering any suspicious US or MRI finding had a sensitivity of 95.8%. A more restrictive approach, targeting lesions noted in both US and MRI, yielded the highest specificity (50.0%) and accuracy (55.4%). Conclusion Biopsy targeting based on US findings can provide additional diagnostic information that may increase sensitivity or specificity. Additional research into this topic could open the door to a more personalized approach to prostate biopsy.

Background: Academic and community urology centers participating in a pragmatic clinical trial in non-muscle-invasive bladder cancer completed monthly surveys assessing restrictions in aspects of bladder cancer care due to the COVID-19 Public Health Emergency. Our objective was to describe pandemic-related restrictions on bladder cancer care. Methods: We invited 32 sites participating in a multicenter pragmatic bladder cancer trial to complete monthly surveys distributed through REDCap beginning in May 2020. These surveys queried sites on whether they were experiencing restrictions in the use of elective surgery, transurethral resection of bladder tumors (TURBT), radical cystectomy, office cystoscopy, and intravesical bacillus Calmette-Guerin (BCG) availability. Responses were collated with descriptive statistics. Results: Of 32 eligible sites, 21 sites had at least a 50% monthly response rate over the study period and were included in the analysis. Elective surgery was paused at 76% of sites in May 2020, 48% of sites in January 2021, and 52% of sites in January 2022. Over those same periods, coinciding with COVID-19 incidence waves, TURBT was restricted at 10%, 14%, and 14% of sites, respectively, radical cystectomy was restricted at 10%, 14%, and 19% of sites, respectively, and cystoscopy was restricted at 33%, 0%, and 10% of sites, respectively. Conclusions: Bladder cancer care was minimally restricted compared with more pronounced restrictions seen in general elective surgeries during the COVID-19 pandemic. (c) 2023 Elsevier Inc. All rights reserved.

4536 Background: Current guidelines recommend neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC) for muscle invasive bladder cancer (MIBC). NAC has been shown to confer a survival benefit across all ages. Yet, many elderly patients are not offered NAC due to concern regarding physiologic reserve and postoperative complications. Our objective was to evaluate age-based disparity in treatment and outcomes of MIBC. Methods: Using the National Cancer Database, we identified patients with MIBC from 2006-2017. First, use of different treatments, RC, RC and adjuvant chemotherapy, RC with NAC (“optimal treatment”), chemo-radiation, and no treatment, was compared between age groups. A second analysis was performed in the cohort of elderly patients, ≥70, undergoing cystectomy. Propensity weighting was used to compare peri-operative and mortality outcomes in those who received NAC vs. no NAC. Results: In 70,911 patients with non-metastatic MIBC, use of RC with NAC was lower in patients ≥70, 7.2 vs. 20.9%, p<0.001 (Table). Patients receiving RC with NAC were younger, had private insurance, higher high school completion rate and median income, shorter distance to hospital, lower CCI, diagnosis in recent years, and higher stage disease. NAC use was also associated with pelvic lymph node dissection (OR 4.55, p<0.001). In patients ≥70 undergoing RC, NAC was associated with shorter length of stay (LOS) (8.5 vs 9.6 days, p<0.001), decreased 30-day readmission (8.6 vs 10.6%, p=0.003), lower 30- and 90-day mortality (1.9 vs 3.6%, p=0.01 and 4.9 vs 7.7%, p=0.004, respectively), and better overall survival (OS) (43.8% vs. 37.5%, p<0.001). Multivariate logistic regression found NAC as an independent predictor of shorter LOS, lower 30-and 90-day mortality, and improved OS. Conclusions: Despite increased omission of NAC in patients ≥70, NAC is not associated with worse peri-operative outcomes or mortality in elderly patients. Advanced age in properly selected patients should not preclude offering NAC prior to radical cystectomy.[Table: see text]

INTRODUCTION AND OBJECTIVE: The COVID-19 pandemic has impacted various clinical and research processes in urologic care. As part of a pragmatic clinical trial in bladder cancer, we collected information regarding the impact of COVID-19 at participating sites, which provides insight into how the pandemic has imposed constraints on clinical bladder cancer care and research. METHODS: Starting in May 2020, we distributed a monthly survey to sites participating in CISTO (Comparison of Intravesical Therapy and Surgery as Treatment Options for Bladder Cancer, NCT0393382). The survey included questions about interruptions in routine clinical bladder cancer care, specifically assessing elective surgery restrictions, impact on radical cystectomy, TURBT, office cystoscopies, intravesical therapy, and intravesical bacillus Calmette- Guerin (BCG) supply. We report survey responses for sites that responded to > 50% of the monthly surveys from May 2020 to October 2021. RESULTS: From May 2020 through October 2021, 21 sites (66%) had > 50% monthly response rate. The time periods of greatest limitations on bladder cancer procedures (Figure 1) were May-July 2020, Dec-Jan 2020/2021, and Sept-Oct 2021, corresponding to the peak waves of COVID-19 infections. Elective surgery was most affected, with limitations or holds in those time periods at up to 76%, 38%, and 28% of CISTO sites, respectively. Most of the restrictions involved surgeries that required inpatient stays, potential intensive care unit admission, and staffing shortages. 9 sites (28%) experienced transient BCG shortages during the survey period. CONCLUSIONS: Clinical activity was most limited during the initial COVID-19 surge in Spring/Summer 2020. Despite higher COVID- 19 infection rates in subsequent waves, bladder cancer clinical activity has been maintained at CISTO sites throughout the COVID pandemic. Periodic BCG shortages continue to affect bladder cancer care across the US. (Figure Presented).

You have accessJournal of UrologyCME1 May 2022PD13-04 TRENDS IN DIAGNOSIS AND TREATMENT OF T1A, T1B PROSTATE CANCER IN THE UNITED STATES, 2010-2017 Eyal Kord, Hannah Koenig, On Ho, John Paul Flores, and Christopher Porter Eyal KordEyal Kord More articles by this author , Hannah KoenigHannah Koenig More articles by this author , On HoOn Ho More articles by this author , John Paul FloresJohn Paul Flores More articles by this author , and Christopher PorterChristopher Porter More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002545.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Currently, there is no consensus regarding optimal treatment for incidental prostate cancer (PCa) finding after surgical treatment for benign prostate obstruction. In addition, changing recommendations regarding PCa screening in the US during the last decade, have led to changes in incidence patterns of PCa. We aimed to assess recent trends in diagnosis and treatment of T1a, T1b PCa in the US. METHODS: Using the National Cancer Database, we identified patients diagnosed with T1a, T1b, and T1c PCa between 2010-2017. We described rates of diagnosis, change in clinically significant disease, and patients risk stratification over the time-period studied. Use of treatment modalities was compared between the risk stratified groups. We used the two-way ANOVA and Tukey post Hoc Tests to examine significant changes in incidence and treatment. RESULTS: We identified 24,679 patients diagnosed with T1a (15,186) or T1b (9,493) PCa between 2010-2017. Newly diagnosed T1a/b cases represented an average of 3.54% of all PCa cases without a significant change in incidence over the years. The chance of T1a/b being clinically significant (CS) increased steadily and significantly over time representing 38.7% in 2010 and 44.1% in 2017 (p <0.001). Low, intermediate, and high-risk disease comprised 72.3%,20.9%, and 6.8% of T1a, and 27.3%,33.5%, and 39.2% of T1b diagnosis, respectively. In comparison to T1c, patients diagnosed with T1a/b disease were older (62.2 Vs 70.3 for Low, 64.4 Vs 72.3 for intermediate, and 67.1 Vs 76.4 for high risk, p <0.001) and had a higher comorbidity score across all risk groups. (0.18 Vs 0.42 for Low, 0.23 Vs 0.46 for intermediate, and 0.27 Vs 0.45 for high risk, p <0.001) Across all risk groups, patients diagnosed with T1a/b disease were significantly less likely to be treated definitively with surgery or radiation, and more likely to be treated with active surveillance/watchful waiting or androgen deprivation therapy in comparison to T1c patients (Table 1). CONCLUSIONS: Although the incidence of T1a/b PCa remained stable, the chance of CS disease diagnosis increased between 2010-2017. In comparison to T1c, men diagnosed incidentally with T1a/b disease are less likely to receive definitive treatment by surgery or radiation. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e252 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Eyal Kord More articles by this author Hannah Koenig More articles by this author On Ho More articles by this author John Paul Flores More articles by this author Christopher Porter More articles by this author Expand All Advertisement PDF DownloadLoading ...

Objectives To investigate impact of age and race on health-related quality of life (HRQoL) in men undergoing radical prostatectomy (RP) using a prospectively maintained, racially diverse cohort. Methods The Center for Prostate Disease Research Multicenter National Database was used to identify patients receiving RP from 2007-2017. The Expanded PCa Index Composite and 36 Item Short-Form Health Survey were completed at baseline and regular intervals. Groups were stratified based on age: <60, 60-70, >70. Longitudinal patterns in HRQoL were assessed using linear regression models, adjusting for baseline HRQoL, demographics, and clinical characteristics. Results In 626 patients undergoing RP, 278 (44.4%) were <60, 291 (46.5%) were 60-70, 57 (9.1%) were >70. Older men had worse baseline urinary bother (P<.01) and sexual HRQoL (P<.01). Baseline urinary function was similar for older and younger men. Post-RP urinary and sexual HRQoL was significantly lower in men >70. However, when adjusting for baseline HRQoL, race, NCCN risk, and comorbidities, no difference was found between age groups in urinary function or bother, or sexual function. Sexual bother was worse in older men until 48 months post-operatively but subsequently improved to levels similar to younger patients. Race independently affected HRQoL outcomes with older African American men reporting worse urinary function and sexual bother. Conclusions When accounting for baseline HRQoL, age does not independently predict worse HRQoL outcomes. Older and younger men experience similar declines in urinary and sexual domain scores after RP. Our findings may be used to better inform patients regarding their expected post RP HRQoL and guide treatment decision-making.

Abstract Background Changing recommendations regarding prostate cancer (PCa) screening in the US during the last decade, have led to changes in incidence patterns of PCa. We aimed to assess recent trends in diagnosis and treatment of T1a, T1b PCa in the US. Materials and Methods Using the National Cancer Database, we identified patients diagnosed with T1a, T1b, and T1c PCa between 2010–2017. We described rates of diagnosis, change in clinically significant (CS) disease, patients risk stratification and primary treatment modalities over the time-period studied. Treatment modality proportions were compared between the risk stratified groups. We used the one-way ANOVA and proportional z tests to examine significant changes in incidence and treatment rates. Results We identified 24,679 patients diagnosed with T1a (15,186) or T1b (9,493) PCa between 2010–2017. T1a/b cases represented an average of 3.5% of all PCa cases without a significant change in incidence over time. The chance of T1a/b being CS increased over time representing 38.7% in 2010 and 44.1% in 2017 (p < 0.001). Across all risk groups, patients diagnosed with T1a/b disease were significantly less likely to be treated definitively with surgery or radiation, and more likely to enter active surveillance/watchful waiting in comparison to T1c patients. These findings were consistent even after controlling for age and comorbidity status. Conclusions Although the incidence of T1a/b PCa remained stable, CS T1a/b disease increased between 2010–2017. In comparison to T1c, men diagnosed incidentally with T1a/b PCa are significantly less likely to receive definitive treatment regardless of their risk group, age, and comorbidity status.

INTRODUCTION:Racial differences in Health-Related Quality of Life (HRQoL) after treatment of prostate cancer (PCa) are not well studied. We compared treatment patterns and HRQoL in African American (AA) and non-AA men undergoing active surveillance (AS), radical prostatectomy (RP), or radiation (XRT).METHODS:Men diagnosed with PCa from 2007-2017 in the Center for Prostate Disease Research Database were identified. HRQoL was evaluated using Expanded PCa Index Composite and SF-36 Health Survey.RESULTS:In 1006 men with localized PCa, 223 (22.2%) were AA (mean follow up 5.2 yrs). AA men with low-risk disease were less likely to undergo AS (28.5 vs. 38.8%) and more likely to undergo XRT (22.3 vs. 10.6%) than non-AA men, p < 0.001. In intermediate-risk disease, AA received more XRT (43.0 vs. 26.9%) and less RP (50.5 vs 66.8%), p = 0.016. In all men, RP resulted in worse urinary function and sexual HRQoL compared to AS and XRT. Bowel HRQoL did not vary by treatment in AA men, however, in non-AA men, XRT resulted in worse bowel scores than AS and RP. HRQoL was then compared for each treatment modality. AA men had worse sexual bother (p = 0.024) after RP than non-AA men, No racial differences were found in urinary, bowel, hormonal, or SF-36 scores for men undergoing AS, RP or XRT.CONCLUSION:AA men are less often treated with AS for low-risk disease and are more likely to undergo XRT. AA men experience worse sexual bother after RP, however, the effect of XRT on bowel symptoms is worse in non-AA men.

To compare 5-year health-related quality of life (HRQoL) outcomes between prostate cancer (CaP) patients who underwent robotic-assisted laparoscopic radical prostatectomy (RALP) versus open radical retropubic prostatectomy (RRP) and assess for racial disparities between Caucasian American (CA) and African American (AA) men undergoing surgery. A prospective cohort study of HRQoL data was conducted on patients diagnosed with CaP from 2007 to 2017 and enrolled in the Center for Prostate Disease Research (CPDR) Multicenter National Database. Using the EPIC and SF-36 instruments, changes in urinary, sexual, bowel, and hormonal domains, as well as physical and mental component summary scores were compared across surgery type (RALP versus RRP) at pre-treatment (“baseline”), and annually for 5 years. We further compared HRQoL outcomes in CA and AA men undergoing surgery. Longitudinal HRQoL patterns were modeled using generalized estimating equations (GEE), adjusting for baseline HRQoL and other characteristics. 448 CaP patients (22% AA) met study inclusion criteria, 66% underwent RALP and 34% underwent RRP. At baseline, HRQoL domains were comparable across treatment group (RALP vs. RRP). In the adjusted low-risk cohort, there were only three time points that met a statistically significant HRQoL difference in EPIC scores between RALP and RRP. Urinary function score during year 4 of follow-up showed a 7.5 (95% CI 3.1–11.9, P = 0.01) points difference in favor of RRP. Bowel bother scores favored RRP in year 1 with a difference of 3.1 (95% CI 0.7–5.4, P = 0.04) points, and in year 5 with a difference of 3.8 (95% CI 1.1–6.4, P = 0.03) points. In the intermediate/high-risk cohort, there were no statistically significant differences in any of the domain scores between RALP and RRP during follow-up. The robotic and open approach to radical prostatectomy led to comparable HRQoL outcomes at a follow-up length of 60 months. No HRQoL racial disparities were found between AA and CA men during long-term follow-up.

BACKGROUND:Oncological outcomes after localized prostate cancer (CaP) treatment are excellent and generally considered equivalent across treatment modalities. Thus, short, and long-term patient health related quality of life (HRQoL) is an important factor in treatment discussions. The purpose of this review was to assess the impact of treatment modality for localized CaP on HRQoL as reflected by recent published trials.METHODS:We conducted a literature review using the PubMed database for studies published between January 2010 and January 2021. We included randomized control trials and observational cohort studies examining HRQoL in patients with localized CaP treated with active surveillance, radical prostatectomy, external beam radiotherapy or brachytherapy.RESULTS:Four randomized control trials and 15 prospective cohort studies were reviewed. Current evidence suggests that surgery has the largest short and long-term negative effect on sexual function and incontinence but advantages with regards to bowel function and irritative-obstructive urinary symptoms. Radiation therapy mainly impacts urinary irritative symptoms and bowel bother. Short-term HRQoL outcomes for active surveillance are most favorable, however, during long-term follow up, there is no significant difference in comparison to radiation. Long-term global quality of life impact regarding anxiety, mental, emotional well-being, and fatigue seem to be equivalent between treatment modalities.CONCLUSIONS:The choice of primary treatment modality for localized CaP results in a unique impact profile on cancer specific HRQoL in both the short and long-term periods. Understanding the different adverse events profiles can provide a basis for informing patients and clinicians regarding the impact of disease and treatments on quality of life and allow for a better patient centered discussion.

Objectives/Introduction Neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC) is associated with survival benefit across patients of all ages, yet it is not offered to many elderly patients. We aimed to evaluate age-based disparity in treatment and outcomes of MIBC. Methods Using the National Cancer Database, we identified patients with MIBC from 2006 to 2017. Use of treatment modalities was compared between age groups. A second analysis compared perioperative outcomes and overall survival (OS) in elderly patients (70 years or older) undergoing RC with NAC vs no NAC. Propensity score weighting (PSW) was used for each analysis. Results In 70,911 patients, use of NAC with RC was lower in patients 70 years or older (7.2% vs 20.9%; P < .001). In patients 70 years or older undergoing RC, NAC was associated with shorter inpatient stay (8.5 vs 9.6 days; P < .001), decreased 30-day readmission (8.6% vs 10.6%; P <.001), and lower 30- and 90-day mortality (1.5% vs 3.1%; P = .01; and 4.9% vs 7.7%; P = .003, respectively). On weighted multivariate regressions, NAC predicted shorter length of stay and lower 30-and 90-day mortality. Elderly patients receiving NAC had improved OS compared with RC alone (P = .0011, 2010-2013; P < .001, 2014-2016). Conclusions Despite increased omission of NAC in patients 70 years or older, elderly patients receiving NAC and RC had improved perioperative outcomes and OS compared with those undergoing RC alone. There may be selection bias unaccounted for with our PSW; however, our results provide compelling evidence that NAC does not compromise surgical outcomes in appropriately selected elderly patients. Patients of advanced age who are candidates for RC should be offered NAC.

e16530 Background: National Comprehensive Cancer Network (NCCN) guidelines state partial cystectomy (PC) may be offered in select patients with clinical T2 (cT2) muscle invasive bladder cancer (MIBC) utilizing neoadjuvant chemotherapy (NAC) and pelvic lymphadenectomy (PLND). Our objective was to investigate utilization and survival outcomes of PC in a large contemporary cohort. Methods: Propensity matching was used to compare pathological and surgical outcomes in non-metastatic MIBC patients in the National Cancer Database undergoing PC or radical cystectomy (RC). Multivariate logistic regression was used to determine predictors of NAC, LND, peri-operative morbidity and mortality outcomes. This analysis was repeated in the subset with cT2 MIBC. Results: Of 31,306 T2-T4N0M0 patients, 1543 (4.9%) underwent PC. PC use was higher in older patients and most often (85%) performed for cT2 disease. The PC group was less likely to receive standard of care including NAC (11.4 vs 27.9%, p<0.001) and PLND (58.7 vs 92.5%, p<0.001) than the RC group. Pathological ≥T3 disease (pT3) was found in 39.4% and pos. nodes in 6.9% of PCs. Positive margins were higher in PC, 15.7 vs 10.6%, p<0.001. PC patients had shorter inpatient stay (4.2 vs 8.7 days, p<0.001), lower 30-day readmission (6.7 vs 9.6%, p<0.001), and decreased 30- and 90-day mortality (1.3 vs 1.8%, p<0.001 & 4.8 vs 4.9%, p=0.04). PC was an independent predictor of lack of NAC (OR 0.49, p<0.001) and PLND (OR 0.11, p<0.001), shorter LOS (b -4.66, <0.001), readmission rate (OR 0.72, p<0.001), and improved 30- and 90- day mortality (OR 0.55 & 0.75, p<0.001). In cT2 patients only: PLND and NAC were less utilized in PC (p<0.001), 32% were ≥pT3 and 6.6% node pos. In both full cohort and cT2 subset, PC was associated with slight improvement in time to mortality (Table) and overall survival (OS) (OR 1.44, p<0.001). Conclusions: PC is rarely used in treatment of MIBC. Despite guidelines, NAC and PLND are underutilized in PC. Care is required in selecting patients for PC as up to one third of cT2 patients have ≥pT3. In these likely highly selected patients, PC had lower peri-operative mortality and comparable OS to RC. Selection bias may play a role in these results and further investigation is needed to determine optimal candidates for PC.[Table: see text]