Supplementary legends Supplementary Tables 1-3 Supplementary Figures 1-8

Are ChatGPT 3.5's responses to patient inquiries about urologic health conditions (1) supported by the American Urological Association's guidelines and (2) readable and accessible to patients? Artificial intelligence technology continues to increase in popularity, but it still must be heavily vetted to ensure safety and accuracy prior to clinical implementation. ChatGPT has varying success when it comes to accurately answering medical questions. We wanted to see if the chatbot's responses to urologic inquiries were conveyed in a patient-friendly manner and supported by the American Urological Association's guidelines. Our results were compared to those of prior studies looking at ChatGPT's performance on the United States Medical Licensing Examination and American Urological Association Self-Assessment Study Programme. ChatGPT's responses to inquiries were compared to guideline statements set forth by the American Urological Association on its website. In this qualitative experiment, 30 prompts were written from a patient's perspective covering multiple urologic domains. The prompts were posed to ChatGPT 3.5 with responses recorded verbatim and graded with a Support Score and Quality Score by eight evaluators consisting of five board-certified urologists and three current urology residents. Readability of the responses was assessed with Flesch-Kincaid Readability Grade Level scores and statistical analysis was performed with Stata version 15.1. 20/30 (66%) of ChatGPT's responses were supported by the American Urological Association's guidelines (median SS of 4, IQR 3-5), although responses to oncology questions were less supported (5/12 supported). 11/30 (37%) of responses were deemed high quality (median QS of 4, IQR 3-5) with responses related to infertility having the highest quality (3/4). The average Flesch-Kincaid Readability Grade Level score across all domains was 18, equivalent to a college graduate reading level. Most responses from ChatGPT 3.5 to urologic inquiries were supported by current American Urological Association guidelines, but the majority were of overall low quality. Responses were at a college graduate reading level, making them inaccessible to most patients. ChatGPT 3.5 has limitations in its ability to answer urologic health questions in a patient-friendly manner, but future versions may improve its utility.

Background and objective: Decipher is a tissue-based genomic classifier (GC) developed and validated in the post-radical prostatectomy (RP) setting as a predictor of metastasis. We conducted a prospective randomized controlled cluster-crossover trial assessing the use of Decipher to determine its impact on adjuvant treatment after RP. Methods: Eligible patients had undergone RP within 9 mo of enrollment, had pT3-4 disease and/or positive surgical margins, and prostate-specific antigen <0.1 ng/ml. Centers were randomized to a sequence of 3-mo periods of either GC-informed care or usual care (UC). Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) recurrence risk scores were provided to treating physicians and patients in all periods. Key findings and limitations: Impact of GC test results on adjuvant treatment were compared with UC alone. Longitudinal patient-reported urinary and sexual function was assessed. A total of 175 patients were enrolled in 27 periods with GC and 163 in 28 periods with UC. At 18 mo after RP, an average patient in the GC arm received adjuvant treatment 9.7% of the time compared with 8.7% for an average individual in the UC arm (0.99% mean difference, 95% confidence interval [CI] -7.6%, 9.6%, p = 0.8). While controlling for CAPRA-S score, higher GC scores tended to result in an increased likelihood of adjuvant treatment that was not statistically significant (odds ratio [OR] = 1.35 per 0.1 increase in GC score, 95% CI 0.98-1.85, p = 0.066). Using the GC risk groups, reflecting clinical use, a high GC risk was associated with significantly higher odds of receiving adjuvant treatment (OR = 6.9, 95% CI 1.8, 26, p = 0.005) compared with a low GC score, adjusted for CAPRA-S score. There were no differences in patient-reported urinary and sexual function between the study arms. As oncologic outcomes are immature, the present data cannot address whether GC testing provides any cancer control benefit. Conclusions and clinical implications: GC testing impacts adjuvant therapy administration when viewed through the risk categories presented in the patient report; however, these data do not provide specific support for GC testing in the adjuvant treatment setting. (c) 2024 European Association of Urology. Published by Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Genetic alterations play a pivotal role in various human diseases, particularly cancer. The androgen receptor (AR) is a crucial transcription factor driving prostate cancer progression across all stages. Current AR-targeting therapies utilize competitive AR antagonists or pathway suppressors. However, therapy resistance often emerges due to AR mutations and AR splice variants, such as AR-v7. To overcome this, we developed ATC-324, an AR degrader using the innovative protein degradation technology platform AUTOphagy-TArgeting Chimera (AUTOTAC). ATC-324 was designed to comprise enzalutamide, an AR inhibitor, as a target-binding ligand and YT 6-2, a ligand of the autophagy receptor p62/SQSTM1, as an autophagy-targeting ligand. ATC-324 induces the formation of the AR/p62 complex, leading to autophagy-lysosomal degradation of AR. Importantly, ATC-324 effectively degrades AR mutants frequently detected in prostate cancer and codegrades AR-v7 as a heterodimer with full-length AR. ATC-324 reduces nuclear AR levels and downregulates the target gene expression of AR and AR-v7, leading to cytotoxicity in AR-positive prostate cancer cells. We also provide evidence of the therapeutic potential of ATC-324 in vivo as well as ex vivo bone organ culture. Moreover, ATC-324 remains potent in enzalutamide-resistant prostate cancer cells. These results demonstrate the potential of the AUTOTAC platform to target previously considered undruggable proteins and overcome certain drug resistance mechanisms. Significance: The characterization of an AUTOTAC-based degrader capable of inducing autophagic degradation of wild-type and mutated androgen receptors demonstrates the potential of this approach for targeting castration-resistant prostate cancer and overcoming drug resistance.

PURPOSE:In QUILT-3.032, the efficacy of interleukin-15 receptor agonist, nogapendekin alfa inbakicept (NAI), in combination with bacillus Calmette-Guérin (BCG) for BCG-unresponsive high-grade papillary-only nonmuscle-invasive bladder cancer was assessed. In this study, we report the 36-month follow-up among participants with BCG-unresponsive papillary disease (cohort B). MATERIALS AND METHODS:NCT03022825 is an open-label, multicenter study of patients with BCG-unresponsive high-grade Ta/T1 papillary nonmuscle-invasive bladder cancer who received 400 μg NAI plus 50 mg BCG intravesically weekly for 6 consecutive weeks. The primary end point is disease-free survival (DFS) at 12 months. Progression-free survival (PFS), disease-specific survival (DSS), and cystectomy avoidance were assessed. Treatment-related adverse events were assessed. RESULTS:At July 15, 2024, data cutoff, the DFS rates at 12, 24, and 36 months were 58.2% (95% CI: 46.6, 68.2), 52.1% (95% CI: 40.3, 62.7), and 38.2% (95% CI: 25.6, 50.6), respectively. The PFS rates at 12 and 36 months were 94.9% (95% CI: 86.9, 98.0) and 83.1% (95% CI: 69.5, 91.0). The DSS rates at 12 and 36 months were 98.7% (95% CI: 91.4, 99.8) and 96.0% (95% CI: 88.2, 98.7). The median DSS has not been reached. Cystectomy avoidance rates at 12 and 36 months were 92.2% (95% CI: 83.4, 96.4) and 81.8% (95% CI: 68.1, 90.1), with median time to cystectomy not reached. Most treatment-related adverse events were grade 1 to 2 (61%) with 3% grade 3 and no grade 4 to 5. CONCLUSIONS:The 12-month and 36-month DFS, PFS, DSS, and cystectomy avoidance rates demonstrate the effectiveness and safety of NAI plus BCG in the management of BCG-unresponsive papillary disease. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT03022825.

Abstract Prostate cancer (PCa) progression is largely driven by the androgen receptor (AR), making it a prime target for therapy. However, therapy resistance often arises due to AR mutations and splice variants, such as AR-v7. AUTOTAC (AUTOphagy-TArgeting Chimera) is a novel protein degradation platform that utilizes the autophagy-lysosomal pathway to selectively degrade disease-causing proteins. In this study, we characterize ATC-324, an AUTOTAC-based AR degrader designed for the treatment of PCa. ATC-324 comprises enzalutamide linked to YT 6-2, a small molecule activator of the autophagy receptor p62/SQSTM1. ATC-324 induces the formation of the AR/p62 complex while activating autophagic flux, leading to the autophagy-lysosomal degradation of AR. To characterize ATC-324, we employed various AR-dependent, AR-null, and enzalutamide-resistant PCa cell lines. Given that bone metastasis is a major clinical complication of castrate-resistant PCa associated with greater morbidity and mortality, we utilized the bone-in-culture array (BICA) assay, an ex vivo bones culture model, to investigate the impact of ATC-324 on PCa cell survival and growth in the bone microenvironment. We demonstrated that ATC-324 effectively degrades wild-type, mutant, and splice variants of AR. In addition, ATC-324 induces AR-dependent apoptosis and cytotoxicity. Importantly, ATC-324 maintains its potency in enzalutamide-resistant PCa cells. Utilizing the BICA assay, we showed that ATC-324 exhibits cytotoxicity against 22Rv1 bone micrometastases at even lower concentrations than in 2D cell culture. In conclusion, our study demonstrates the successful development and characterization of ATC-324 as a potent and selective degrader of various forms of AR. Furthermore, its effectiveness against enzalutamide-resistant cells indicates its capability to overcome therapy resistance. The observed cytotoxicity against bone micrometastases suggests a therapeutic potential for combating bone metastasis, a major complication of castration-resistant PCa. Our study underscores the potential of the AUTOTAC platform to selectively degrade disease-causing proteins Citation Format: Tri Pham, Tae Hyun Bae, Ki Woon Sung, Abdo Najy, Alaleh Zamiri, Hyejeong Jang, Su Ran Mun, Seongho Kim, Dongping Shi, Steven Kregel, Elizabeth Heath, Michael Cher, Yong Tae Kwon, Hyeong-Reh Kim. Development and characterization of ATC-324: An AUTOTAC-based androgen receptor degrader for prostate cancer treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6045.

Purpose: We investigated the association of MRI findings in men with a previous diagnosis of atypical small acinar proliferation (ASAP) or multifocal high-grade intraepithelial neoplasia (HGPIN) with pathologic findings on repeat biopsy.Materials and methods: We retrospectively reviewed patients with ASAP/multifocal HGPIN undergoing a repeat biopsy in the Michigan Urological Surgery Improvement Collaborative registry. We included men with and without an MRI after the index biopsy demonstrating ASAP/multifocal HGPIN but before the repeat biopsy. Men with an MRI prior to the index biopsy were excluded. We compared the proportion of men with >= GG2 CaP (Grade Group 2 prostate cancer) on repeat biopsy among the following groups with the chi(2) test: no MRI, PIRADS (Prostate Imaging-Reporting and Data System) >= 4, and PIRADS <= 3. Multivariable models were used to estimate the adjusted association between MRI findings and >= GG2 CaP on repeat biopsy.Results: Among the 207 men with a previous diagnosis of ASAP/multifocal HGPIN that underwent a repeat biopsy, men with a PIRADS >= 4 lesion had a higher proportion of >= GG2 CaP (56%) compared with men without an MRI (12%, P < .001). A lower proportion of men with PIRADS <= 3 lesions had >= GG2 CaP (3.0%) compared with men without an MRI (12%, P = .13). In the adjusted model, men with a PIRADS 4 to 5 lesion had higher odds (OR: 11.4, P < .001) of >= GG2 CaP on repeat biopsy.Conclusions: MRI is a valuable diagnostic tool to triage which men with a history of ASAP or multifocal HGPIN on initial biopsy should undergo or avoid repeat biopsy without missing clinically significant CaP.

BackgroundActive surveillance (AS) is the preferred strategy for low-risk prostate cancer (LRPC); however, limited data on determinants of AS adoption exist, particularly among Black men.MethodsBlack and White newly diagnosed (from January 2014 through June 2017) patients with LRPC <= 75 years of age were identified through metro-Detroit and Georgia population-based cancer registries and completed a survey evaluating factors influencing AS uptake.ResultsAmong 1688 study participants, 57% chose AS (51% of Black participants, 61% of White) over definitive treatment. In the unadjusted analysis, patient factors associated with initial AS uptake included older age, White race, and higher education. However, after adjusting for covariates, none of these factors was significant predictors of AS uptake. The strongest determinant of AS uptake was the AS recommendation by a urologist (adjusted prevalence ratio, 6.59, 95% CI, 4.84-8.97). Other factors associated with the decision to undergo AS included a shared patient-physician treatment decision, greater prostate cancer knowledge, and residence in metro-Detroit compared with Georgia. Conversely, men whose decision was strongly influenced by the desire to achieve "cure" or "live longer" with treatment and those who perceived their LRPC diagnosis as more serious were less likely to choose AS.ConclusionsIn this contemporary sample, the majority of patients with newly diagnosed LRPC chose AS. Although the input from their urologists was highly influential, several patient decisional and psychological factors were independently associated with AS uptake. These data shed new light on potentially modifiable factors that can help further increase AS uptake among patients with LRPC. We found that urologists' recommendation had a strong influence on the patient's decision to initiate active surveillance, whereas patients' perception regarding the seriousness of their cancer and the benefits of treatment were associated with treatment. Education and interventions targeting patients and urologists regarding these factors may help further increase the use of active surveillance in men with low-risk prostate cancer.

The chemokine receptor, CXCR4 signaling regulates cell growth, invasion, and metastasis to the bone-marrow niche in prostate cancer (PCa). Previously, we established that CXCR4 interacts with phosphatidylinositol 4-kinase IIIα (PI4KIIIα encoded by PI4KA) through its adaptor proteins and PI4KA overexpressed in the PCa metastasis. To further characterize how the CXCR4-PI4KIIIα axis promotes PCa metastasis, here we identify CXCR4 binds to PI4KIIIα adaptor proteins TTC7 and this interaction induce plasma membrane PI4P production in prostate cancer cells. Inhibiting PI4KIIIα or TTC7 reduces plasma membrane PI4P production, cellular invasion, and bone tumor growth. Using metastatic biopsy sequencing, we found PI4KA expression in tumors correlated with overall survival and contributes to immunosuppressive bone tumor microenvironment through preferentially enriching non-activated and immunosuppressive macrophage populations. Altogether we have characterized the chemokine signaling axis through CXCR4-PI4KIIIα interaction contributing to the growth of prostate cancer bone metastasis.

Supplementary Figure Legends - PDF file 86K, Description of supplementary figures

Active surveillance (AS) for prostate cancer (CaP) or small renal masses (SRMs) helps in limiting the overtreatment of indolent malignancies. Implementation of AS for these conditions varies substantially across individual urologists. We examined the Michigan Urological Surgery Improvement Collaborative (MUSIC) registry to assess for correlation of AS between patients with low-risk CaP and patients with SRM managed by individual urologists. We identified 27 urologists who treated at least ten patients with National Comprehensive Cancer Network low-risk CaP and ten patients with SRMs between 2017 and 2021. For surgeons in the lowest quartile of AS use for low-risk CaP (<74%), 21% of their patients with SRMs were managed with AS, in comparison to 74% of patients of surgeons in the highest quartile (>90%). There was a modest positive correlation between the surgeon-level risk-adjusted proportions of patients managed with AS for low-risk CaP and for SRMs (Pearson correlation coefficient 0.48). A surgeon's tendency to use AS to manage one low-risk malignancy corresponds to their use of AS for a second low-risk condition. By identifying and correcting structural issues associated with underutilization of AS, interventions aimed at increasing AS use may have effects that influence clinical tendencies across a variety of urologic conditions. PATIENT SUMMARY: The use of active surveillance (AS) for patients with low-risk prostate cancer or small kidney masses varies greatly among individual urologists. Urologists who use AS for low-risk prostate cancer were more likely to use AS for patients with small kidney masses, but there is room to improve the use of AS for both of these conditions.

Supplementary Figure S2. BALB/c mice were inoculated with TUBO 3d before adoptive serum transfer of 25 µg equivalent α-neu Ab from mice previously treated with cryo + CpG or pNeuE2 vaccination, naïve control serum, or 25 µg monoclonal Ab4 (n=3-5) as a single tail vein injection in a total volume of 200 µL with PBS. TUBO tumor volume 30 days after inoculation. **P<0.01

You have accessJournal of UrologyCME1 Apr 2023MP44-09 CAN MRI REPLACE REPEAT BIOPSY IN MEN WITH MULTIFOCAL HIGH GRADE PROSTATIC INTRAEPITHELIAL NEOPLASIA OR ATYPICAL SMALL ACINAR PROLIFERATION? Michael Sessine, Codrut Radoiu, Ji Qi, Frank Burks, Arvin George, Brian Lane, Kenneth Lim, Ali Dabaja, Michael Cher, Alice Semerjian, Kevin Ginsburg, and For the Michigan Urological Surgery Improvement Collaborative Michael SessineMichael Sessine More articles by this author , Codrut RadoiuCodrut Radoiu More articles by this author , Ji QiJi Qi More articles by this author , Frank BurksFrank Burks More articles by this author , Arvin GeorgeArvin George More articles by this author , Brian LaneBrian Lane More articles by this author , Kenneth LimKenneth Lim More articles by this author , Ali DabajaAli Dabaja More articles by this author , Michael CherMichael Cher More articles by this author , Alice SemerjianAlice Semerjian More articles by this author , Kevin GinsburgKevin Ginsburg More articles by this author , and For the Michigan Urological Surgery Improvement Collaborative More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003290.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: High-grade prostatic intraepithelial neoplasia (HGPIN) and atypical small acinar proliferation (ASAP) are associated with an increased risk of clinically significant prostate cancer (CaP) on subsequent prostate biopsy. We investigated the association of multiparametric MRI (mpMRI) findings in men with a previous diagnosis of HGPIN or ASAP with findings on repeat biopsy. METHODS: We retrospectively reviewed patients with multifocal HGPIN or ASAP undergoing a repeat biopsy in the Michigan Urological Surgery Improvement Collaborative (MUSIC) registry. We compared the proportion of men with a benign biopsy, GG1, and ≥GG2 CaP on repeat biopsy within 24 months of the initial biopsy with HGPIN/ASAP. Men were placed into three groups: 1) without a mpMRI, 2) with a mpMRI demonstrating a PIRADS 1-3 lesion, 4) and PIRADS 4-5 lesion. Men with a mpMRI performed before or after the initial biopsy that demonstrated HGPIN/ASAP were analyzed separately. RESULTS: There were 219 men in the MUSIC registry with a diagnosis of HGPIN or ASAP on their initial biopsy that underwent a repeat biopsy, of which 86 had a mpMRI before (n=12) or after (n=74) the initial biopsy. Among men with a mpMRI after the initial biopsy (Figure 1), we noted that a lower proportion of men with PIRADS 1-3 lesions had GG1 (15%) or ≥GG2 (3.0%) CaP and a higher proportion had benign biopsies (82%) compared with men without a mpMRI (19%, 12%, and 70%, respectively, p=0.237). Men with a PIRADS 4-5 lesion after the initial biopsy had a higher proportion of ≥GG2 (56%) and GG1 (17%) CaP and a lower proportion of benign biopsies (27%) on repeat biopsy compared with men without a mpMRI (19%, 12%, and 70%, respectively, p<0.001). Among patients with a mpMRI prior to the initial biopsy, 0/12 patients were diagnosed with ≥GG2 CaP on repeat biopsy. CONCLUSIONS: Men with PIRADS 1-3 lesions on MRI after a diagnosis of HGPIN/ASAP had a low risk of clinically significant CaP on repeat biopsy while men with PIRADS 4-5 lesions were less likely to have benign biopsies and more likely to have clinically significant CaP compared with men without an MRI prior to repeat biopsy. MRI is a valuable tool to triage which men with HGPIN or ASAP on initial biopsy should undergo or avoid repeat biopsy without missing clinically significant CaP. Source of Funding: Blue Cross Blue Shield of Michigan, Rogel Cancer Center © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e614 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Michael Sessine More articles by this author Codrut Radoiu More articles by this author Ji Qi More articles by this author Frank Burks More articles by this author Arvin George More articles by this author Brian Lane More articles by this author Kenneth Lim More articles by this author Ali Dabaja More articles by this author Michael Cher More articles by this author Alice Semerjian More articles by this author Kevin Ginsburg More articles by this author For the Michigan Urological Surgery Improvement Collaborative More articles by this author Expand All Advertisement PDF downloadLoading ...

You have accessJournal of UrologyCME1 Apr 2023PD21-02 ASSESSING THE GENERALIZABILITY OF RANDOMIZED EVIDENCE BY COMPARING RESULTS FROM A CLINICAL TRIAL AND ESTABLISHED QUALITY IMPROVEMENT COLLABORATIVE: RESULTS FROM G-MINOR AND MUSIC Udit Singhal, Ralph Jiang, Daniel E. Spratt, Matthew Schipper, Simpa S. Salami, Stephanie Daignault-Newton, Rodney Dunn, Thomas J. Maatman, Brian R. Lane, Frank N. Burks, Paul Rodriguez, Eduardo Kleer, Richard Sarle, Felix Y. Feng, Michael L. Cher, Robert T. Dess, and Todd M. Morgan Udit SinghalUdit Singhal More articles by this author , Ralph JiangRalph Jiang More articles by this author , Daniel E. SprattDaniel E. Spratt More articles by this author , Matthew SchipperMatthew Schipper More articles by this author , Simpa S. SalamiSimpa S. Salami More articles by this author , Stephanie Daignault-NewtonStephanie Daignault-Newton More articles by this author , Rodney DunnRodney Dunn More articles by this author , Thomas J. MaatmanThomas J. Maatman More articles by this author , Brian R. LaneBrian R. Lane More articles by this author , Frank N. BurksFrank N. Burks More articles by this author , Paul RodriguezPaul Rodriguez More articles by this author , Eduardo KleerEduardo Kleer More articles by this author , Richard SarleRichard Sarle More articles by this author , Felix Y. FengFelix Y. Feng More articles by this author , Michael L. CherMichael L. Cher More articles by this author , Robert T. DessRobert T. Dess More articles by this author , and Todd M. MorganTodd M. Morgan More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003287.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Although randomized controlled trials (RCTs) represent the gold standard for clinical research, results from RCTs are often substantially less dramatic when implemented in practice. Previous studies have evaluated the congruence of observational studies with RCTs and shown conflicting results. However, minimal to no data exist comparing RCT populations with their non-RCT contemporaries. We aimed to assess the generalizability of RCT evidence by comparing results from an RCT with those from a prospectively collected, geographically equivalent, quality improvement collaborative. METHODS: The G-MINOR RCT randomized 356 men with localized prostate cancer at high-risk of recurrence after prostatectomy to clinical risk stratification with or without Decipher testing to assess its utility in clinical decision-making. Enrollment of patients occurred across 12 practices within the Michigan Urological Surgery Improvement Collaborative (MUSIC). Matching between MUSIC and G-MINOR was performed using 3:1 nearest neighbor matching on propensity scores. Differences between the matched populations were assessed via Kaplan-Meier estimates and multivariable Cox regression, with a primary endpoint of failure-free survival (FFS), which was defined as any biochemical recurrence or receipt of salvage treatment. Secondary endpoints were adjuvant treatment-free survival and cumulative incidence of salvage treatment. RESULTS: After matching, a total of 1352 men were included in the analysis (338 G-MINOR, 1014 MUSIC), with no differences in age, race, comorbidity, PSA, grade group, clinical T-stage, margin status, presence of extra-prostatic extension, or Decipher risk between the groups. Despite matching, FFS was greater at 48 months follow-up in the G-MINOR group compared to MUSIC (20.1% vs 19.9%, p=0.041). Men in MUSIC received significantly more adjuvant therapy (20.1% vs 9.2%, p<0.0001), but salvage treatment rates were similar between the groups (G-MINOR 11.2% vs MUSIC 8.6%, p=0.62). CONCLUSIONS: Despite similar geographic, practice-level, and disease-related characteristics, men enrolled in a RCT were less likely to have failure after initial treatment compared to matched patients in the same communities not enrolled in the RCT. These results suggest possible unmeasured differences between these populations or unmeasured benefits of trial participation that may result in improved outcomes for RCT participants. Source of Funding: U.S. is supported by an AUA/UCF Research Scholar Award © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e590 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Udit Singhal More articles by this author Ralph Jiang More articles by this author Daniel E. Spratt More articles by this author Matthew Schipper More articles by this author Simpa S. Salami More articles by this author Stephanie Daignault-Newton More articles by this author Rodney Dunn More articles by this author Thomas J. Maatman More articles by this author Brian R. Lane More articles by this author Frank N. Burks More articles by this author Paul Rodriguez More articles by this author Eduardo Kleer More articles by this author Richard Sarle More articles by this author Felix Y. Feng More articles by this author Michael L. Cher More articles by this author Robert T. Dess More articles by this author Todd M. Morgan More articles by this author Expand All Advertisement PDF downloadLoading ...

Supplementary Data - PDF file 589K, S1. Mutations in putative Ets/ERG binding sites in CXCR4 promoter oigos diminishes oligo binding with either VCaP cell nuclear extracts or in vitro translated ERG protein. S2. ERG ChIP seq analysis of VCaP cells. S3. N-terminus deletion of ERG regulates CXCR4 promoter activation similar to full length ERG protein. S4. LNCaP cells were transfected with ARR2Pb-LUC as a vector control and ARR2Pb-ERG-LUC plasmid. S5. MS3 spectrum of trypsin-digested, TiO2 eluted ERG peptides from VCaP cells

Supplementary Figure S1. (A) Untreated TUBO - tumor volume (mm3) and α-neu IgG (Ab4 equivalent μg/mL) are plotted on the left and right y-axis respectively. (B) Experimental Scheme - BALB/c females were vaccinated with pNeuE2 on day 0 and 2 (n= 4). Data representative of three independent experiments.

BACKGROUND:Most prostate cancer (PC) active surveillance (AS) protocols recommend "Per Protocol" surveillance biopsy (PPSBx) every 1-3 years, even if clinical and imaging parameters remained stable. Herein, we compared the incidence of upgrading on biopsies that met criteria for "For Cause" surveillance biopsy (FCSBx) versus PPSBx. METHODS:We retrospectively reviewed men with GG1 PC on AS in the Michigan Urological Surgery Improvement Collaborative (MUSIC) registry. Surveillance prostate biopsies obtained 1 year after diagnosis were classified as either PPSBx or FCSBx. Biopsies were retrospectively deemed FCSBx if any of these criteria were met: PSA velocity > 0.75 ng/mL/year; rise in PSA > 3 ng from baseline; surveillance magnetic resonance imaging (MRI) (sMRI) with a PIRADS ≥ 4; change in DRE. Biopsies were classified PPSBx if none of these criteria were met. The primary outcome was upgrading to ≥GG2 or ≥GG3 on surveillance biopsy. The secondary objective was to assess for the association of reassuring (PIRADS ≤ 3) confirmatory or surveillance MRI findings and upgrading for patients undergoing PPSBx. Proportions were compared with the chi-squared test. RESULTS:We identified 1773 men with GG1 PC in MUSIC who underwent a surveillance biopsy. Men meeting criteria for FCSBx had more upgrading to ≥GG2 (45%) and ≥GG3 (12%) compared with those meeting criteria for PPSBx (26% and 4.9%, respectively, p < 0.001 and p < 0.001). Men with a reassuring confirmatory or surveillance MRI undergoing PPSBx had less upgrading to ≥GG2 (17% and 17%, respectively) and ≥GG3 (2.9% and 1.8%, respectively) disease compared with men without an MRI (31% and 7.4%, respectively). CONCLUSIONS:Patients undergoing PPSBx had significantly less upgrading compared with men undergoing FCSBx. Confirmatory and surveillance MRI seem to be valuable tools to stratify the intensity of surveillance biopsies for men on AS. These data may help inform the development of a risk-stratified, data driven AS protocol.