4583 Background: For cis-ineligible pts with MIBC undergoing radical cystectomy and pelvic lymph node dissection (RC+PLND), no neoadjuvant treatment options have been shown to improve survival, highlighting a clinical need. EV previously demonstrated encouraging antitumor activity in cis-ineligible pts with MIBC as neoadjuvant treatment in EV-103 Cohort H. We present updated 3-year efficacy results. Methods: EV-103 Cohort H enrolled cis-ineligible pts with MIBC (cT2-T4aN0M0) and ECOG PS ≤2 who were eligible for RC+PLND. Pts received neoadjuvant EV monotherapy (1.25 mg/kg) on Days 1 and 8 every 21 days for 3 cycles before undergoing RC+PLND. Primary endpoint was pathological complete response (pCR) rate by central pathology review. Secondary endpoints included event-free survival (EFS) per investigator assessment (INV), OS, and safety. A genAI tool (01/09/25; Pfizer; GPT-4o) developed the 1 st draft; authors assume content responsibility. Results: Overall, 22 pts were enrolled. 86.4% of pts completed all 3 cycles of neoadjuvant EV treatment. Three pts (13.6%) discontinued neoadjuvant EV due to AEs. All pts underwent RC+PLND; 13 (59.1%) were in long-term follow-up at data cutoff (Nov 20, 2024). Median follow-up was 49.7 mo (range, 3.1-53.6). pCR rate was 36.4% (8/22; 95% CI, 17.2-59.3). Median EFS by INV was 40.1 mo (95% CI, 14.5-NE) for all pts, NR (95% CI, 6.5-NE) for pts with pCR, and 18.8 mo (95% CI, 6.7-NE) for pts without pCR. Estimated EFS rate by INV at 24 and 36 months was 62.0% (95% CI, 38.2-78.9) and 56.9% (95% CI, 33.4-74.8), respectively, and improved in pts with pCR. Median OS was NR (95% CI, 33.4-NE) in all pts. Estimated OS rate at 24 and 36 months was 77.3% (95% CI, 53.7-89.9) and 68.2% (95% CI, 44.6-83.4), respectively. Key updated 3-year efficacy data are shown in the Table. The safety profile was consistent with prior reports, and no new safety concerns were seen. Conclusions: Based on 3-year efficacy results, neoadjuvant EV monotherapy treatment continued to show encouraging antitumor activity in cis-ineligible pts with MIBC, including median EFS and OS exceeding historical real-world data in cis-ineligible patients following RC alone (Li Eur Urol Oncol 2024; Rose SESAUA 2023). The safety profile was generally manageable and consistent with the known AE profile of EV in other settings. Phase 3 trials evaluating perioperative EV + pembrolizumab in cis-eligible and -ineligible pts with MIBC (KN-905/EV-303, KN-B15/EV-304) are ongoing. Clinical trial information: NCT03288545 . Median EFS by INV (95% CI), monthsAll ptspCRNon-pCR 40.1 (14.5-NE)NR (6.5-NE)18.8 (6.7-NE) 3-year EFS rate by INV (95% CI), %All ptspCRNon-pCR 56.9 (33.4-74.8)72.9 (27.6-92.5)46.4 (19.3-69.9) Median OS (95% CI), months NR (33.4-NE) 3-year OS rate (95% CI), % 68.2 (44.6-83.4) n=22. Median values should be interpreted with caution due to small sample size.

Prior studies evaluating the genetic predisposition to chemotherapy induced peripheral neuropathy (CIPN) have been limited by small populations due to difficulty with real-world data extraction. This genome-wide association study (GWAS) evaluates the genetic differences between patients who developed CIPN against those unaffected, using an electronic health record (EHR) definition of CIPN. This study included all patients who received chemotherapy associated with CIPN and had germline genetic data within the biobank at the Colorado Center for Personalized Medicine. CIPN was defined by a new neuropathic pain medication or an ICD-diagnosis of neuropathy after specified chemotherapy initiation. GWAS were stratified by (1) total population, (2) platinum chemotherapy, (3) taxane chemotherapy, and (4) vinca alkaloid chemotherapy. Genes previously associated with CIPN were analyzed within each GWAS. Nine hundred fifteen patients received chemotherapy associated with CIPN, with 528 patients (57

PURPOSE Abiraterone use for prostate cancer can cause mineralocorticoid excess syndrome (MES; eg, hypertension and hypokalemia). Prednisone mitigates these effects; however, the optimal dose level is unclear. This study examines MES effects from abiraterone with 5 mg of prednisone once daily versus 5 mg twice daily. METHODS Data for 1,410 abiraterone-treated patients from 2011 to 2022 were identified from a large academic/community hospital system. Three hundred and fifty-three patients were excluded for missing medication data and use of an alternative steroid; 1,057 patients remained (5 mg once daily, n = 550, 5 mg twice daily, n = 507). Prednisone dose was treated as a time-varying covariate. Hypokalemia and hypertension incidence over 24 weeks after abiraterone initiation was analyzed via Cox proportional hazard models using Common Terminology Criteria for Adverse Events (v5.0) grading via direct clinical measurements and International Classification of Diseases (ICD)-10 code outcomes. RESULTS Patients receiving 5 mg of prednisone twice daily had a statistically significant decrease in cumulative hazard for experiencing at least one MES event (hypertension and/or hypokalemia) via direct clinical measurement (hazard ratio [HR], 0.79 [CI, 0.68 to 0.91]; P = .002) and by ICD-10 code (HR, 0.65 [CI, 0.54 to 0.79]; P < .001) analysis. This finding was durable with individual end point analysis of hypertension and hypokalemia. There were no changes to BMI or hyperglycemia (>140 mg/dL) between the cohorts. CONCLUSION This retrospective analysis shows a decrease in risk for the development of at least one episode of hypertension or hypokalemia with abiraterone using 5 mg twice-daily prednisone in the study population. Assessments of metabolic impacts (BMI, hyperglycemia) did not show differences with prednisone dosing. These findings may merit consideration when determining an optimal prednisone dosing regimen.

Building accurate prediction models and identifying predictive biomarkers for treatment response in Muscle-Invasive Bladder Cancer (MIBC) are essential for improving patient survival but remain challenging due to tumor heterogeneity, despite numerous related studies. To address this unmet need, we developed an interpretable Graph-based Multimodal Late Fusion (GMLF) deep learning framework. Integrating histopathology and cell type data from standard H&E images with gene expression profiles derived from RNA sequencing from the SWOG S1314-COXEN clinical trial (ClinicalTrials.gov NCT02177695 2014-06-25), GMLF uncovered new histopathological, cellular, and molecular determinants of response to neoadjuvant chemotherapy. Specifically, we identified key gene signatures that drive the predictive power of our model, including alterations in TP63, CCL5, and DCN. Our discovery can optimize treatment strategies for patients with MIBC, e.g., improving clinical outcomes, avoiding unnecessary treatment, and ultimately, bladder preservation. Additionally, our approach could be used to uncover predictors for other cancers.

Several clinical trials in bladder cancer have resulted in FDA approvals and subsequent revisions to the NCCN Guidelines for Bladder Cancer. Cystectomy remains the primary treatment approach for bacillus Calmette-Guérin—unresponsive non–muscle-invasive bladder cancer (MIBC); however, in patients for whom such surgical intervention is not feasible, several bladder-sparing approaches are now available. In addition to neoadjuvant chemotherapy followed by resection as an established standard for MIBC, perioperative or sandwich therapy with gemcitabine plus cisplatin plus durvalumab is now also an option. The systemic treatment landscape for MIBC and metastatic disease is expanding to further incorporate antibody–drug conjugates, immune checkpoint inhibitors, and targeted therapies.

Background The practice patterns and efficacy of ddMVAC administered with split-dose cisplatin for patients with muscle-invasive bladder cancer (MIBC) remains largely undefined. Objective To characterize the application and overall survival (OS) in patients with MIBC receiving conventional ddMVAC versus split-dosed ddMVAC and to examine the predictive variables in those receiving split-dosed cisplatin. Methods Using data from the CancerLinQ Discovery database, we identified 626 patients with bladder cancer between 2000–2023 with receipt of ddMVAC. The primary outcome was OS by receipt of split-dose versus conventional ddMVAC. A secondary outcome of interest assessed predictors of receipt of split-dose ddMVAC. Use of split-dose versus conventional ddMVAC was compared using chi-square tests. Univariate and multivariable OS were estimated using Cox proportional hazards models. Predictors of receipt of split dose versus conventional ddMVAC were estimated using logistic regression models. Results Most patients with MIBC are treated with standard dose ddMVAC. In multivariate analysis, no statistically significant difference in OS was observed between split-dose and conventional ddMVAC (HR 1.3, CI 0.78–2.18, p = 0.316). We demonstrate a notable decline in the use of split-dose cisplatin over time. Baseline GFR and performance status were not predictors of split-dosing in this cohort. Conclusions Most patients with MIBC received conventional ddMVAC with decreasing frequency of split-dose cisplatin use over time. We did not observe a difference in OS between patients with MIBC who received standard versus split-dose cisplatin.

TPS4617 Background: UC is 2nd most common genitourinary cancer. Enfortumab vedotin (EV) + pembrolizumab became a SOC in 2023 in frontline mUC setting. In previously treated mUC setting, erdafitinib is approved for pts with FGFR alterations, while all pts have the option of sacituzumab govitecan (SG) with objective response rate (ORR) of 27% (N=113). A phase I/II CTEP study of eribulin (E) for mUC established the activity of E with ORR of 37.5% and a median progression free survival (PFS) of 4.1 months (mo) and median overall survival (OS) of 9.5 mo (N=150). A phase II CTEP study of gemcitabine-eribulin (GE) in cisplatin ineligible mUC showed ORR of 50%, median OS of 11.9 mo and median PFS of 5.3 mo (N=24). The most common Grade 3-4 toxicities included: neutropenia 63%, anemia and fatigue 29%. Pts with liver metastases benefited from therapy with 71% ORR (n=7) for GE vs 24% for E (n=49). This trial has now been amended to account for first-line treatment changes and to include SG as a control arm option. Methods: This is an updated phase III, randomized trial comparing GE vs. SOC (SG, docetaxel, paclitaxel, or G monotherapy). E is given at 1.4mg/m2 on day (D) 1 and 8 of a 21 D cycle and G is given at 1000 mg/m2 on D1 and D8. SOC follows approved dosing. There is no limit to the number/sequence of prior regimens. In brief, all pts must have: received systemic therapy with EV; received PD1/PDL1 Ab or be deemed ineligible for PD1/PDL1 Ab. The study seeks to find at least a 50% increase in the primary endpoint of OS (Hazard Ratio (HR) = 0.667). The secondary endpoints include ORR, and progression free survival (PFS). One-sided 0.05 type I error to account and 80% power to detect a 50% improvement in OS. We require 92 eligible pts in each arm for a total of 184. The amended and restructured study was approved in January of 2024. Funding: National Institutes of Health/National Cancer Institute grants U10CA180888, U10CA180819. Eribulin is provided by Eisai. Clinical trial information: NCT04579224 .

Prostate cancer (PCa) is the second leading cause of cancer-related death in American men. Androgen deprivation therapy (ADT) is often used for patients with rising prostate specific antigen (PSA) levels after local treatment but is associated with morbidity and decreased quality of life. Patients with non-metastatic PSA progression after local therapy and a long PSA doubling time (PSADT) may have an extended observation period when monitoring PSA levels prior to starting ADT and other systemic therapies. This observation period provides an opportunity to investigate low-impact interventions. Grape seed extract (GSE) is a phytochemical which has shown promise given its tolerability and potential effect on PCa growth and progression. Herein, we report the results of a completed Phase II clinical trial (CT.gov-NCT03087903) which investigated the effect of oral GSE in patients with PSA-only recurrence after maximum local therapy for PCa. GSE was administered as a Leucoselect Phytosome-Indena S.p.A. formulation which contained ∼100% proanthocyanidins, enriched in lower procyanidin oligomers complexed with soy phospholipids, in the ratio 1:2.6 w/w (to increase GSE bioavailability). Eligible patients had a PSA ≥ 0.2 ng/mL and evidence of rising PSA, on 2 separate occasions, at least one week apart. Study endpoints included PSA response (defined as a ≥ 30% increase in PSADT) and change in PSA velocity. PSA levels were checked at baseline, 6 weeks and 3, 6, 9, and 12 months after starting GSE. Forty-one patients were given 150mg of GSE orally twice daily for 12 months or until PSADT ≤3 months. PSADT increased with GSE intervention from 5.71 months at screening to 6.86 months post treatment (p <0.001). Notably, 32 patients of 41 (78%) had an increase in their PSADT, with 15 (37%) of those patients meeting the primary endpoint of a ≥ 30% increase. Nine (22%) patients showed a decrease in PSADT. Interestingly, patients with increased PSADT had higher baseline PSA (average ∼1.9 vs. 0.7 ng/mL) and testosterone levels (average ∼3.73 vs. 2.28 ng/mL), at screening, compared to patients in the decreased PSADT response group. GSE was well tolerated with only one patient discontinuing treatment due to hypertension and rash. In conclusion, GSE may delay progression of prostate cancer based on impact of PSADT; PCa patients with increased baseline PSA and testosterone levels may be more responsive to GSE intervention. Confirmation of its benefits are necessary in larger patient cohorts (placebo-controlled trials). This work was supported by NCI P30 CA046934 Cancer Center Support Grant, Cancer League of Colorado, the Diane D. Writer Foundation, and the Barbara and Richard Gardner Fund for Prostate Cancer Research. Paul Maroni, Tad Manalo, Elizabeth R. Kessler, Andrew Nicklawsky, Victor Trevisanut, Thomas W. Flaig, Elaine T. Lam, Dexiang Gao, Komal Raina, Rajesh Agarwal. Phase II trial of grape seed extract for localized prostate cancer with PSA progression after local therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT219.

Bladder cancer is a leading cause of cancer-related mortality, yet current intravesical drug delivery methods often suffer from poor retention times in the bladder. Gecko feet-like nanomaterials offer the potential to overcome this challenge, however, conventional methods to fabricate high surface area nanomaterials for drug delivery involve complex and expensive manufacturing processes. In this work, a simple fluid flow templating method is reported for manufacturing soft dendritic particles (SDPs) composed of poly(lactic-co-glycolic acid) (PLGA) with a chitosan coating for enhanced adhesion to epithelial tissues via van der Waals interactions. The biodegradable SDPs encapsulate chemotherapeutic agents and are administered using an alginate hydrogel, enabling precise deposition by extrusion for sustained drug release. The results demonstrate that SDPs adhere to mouse and human cancer cells for several days. The SDPs effectively encapsulate and release several clinically utilized chemotherapeutic drugs such as gemcitabine, docetaxel, and methotrexate, exhibiting superior cancer cell killing in vitro. In murine models, gemcitabine-loaded SDPs instilled into tumor-bearing bladders elicited stronger CD45+ immune cell responses than control groups while maintaining minimal toxicity. This work presents a simple, biomimetic drug delivery platform with prolonged retention and controlled drug release, offering a versatile approach for enhancing therapeutic delivery in epithelial cancer models.

The use of supraphysiologic testosterone, particularly when alternated with an anti-androgen agent in men with metastatic castration-resistant prostate cancer (CRPC), has demonstrated promising results in clinical trials. As the use of this therapy in clinical practice is more widely adopted, there will be a growing need to understand the mechanisms of resistance. To that end, we independently derived three separate cell models of testosterone-sensitive CRPC. From each CRPC line, high dose testosterone-resistance (HTR) lines were selected. We demonstrated the differential response of the three CRPC lines to a high dose of testosterone in vitro and in vivo. We subsequently demonstrated the resistance of the HTR lines to testosterone and varying responses to testosterone withdrawal in vivo. The heterogeneity in responses to hormonal manipulation is correlated with varying levels of androgen receptor expression within the population. Overall, we show that we have developed three models of HTR that can be used to study the mechanisms of high dose testosterone resistance and identify potential therapeutic targets.

PURPOSE:In urothelial carcinoma, prior studies have indicated that the basal/squamous molecular subtype and the presence of select DNA damage response (DDR) gene alterations are associated with improved benefit from cisplatin-based chemotherapy. We sought to evaluate these biomarkers in specimens from the phase III Cancer and Leukemia Group B (CALGB) 90601 trial. METHODS:We performed whole-transcriptome sequencing (n = 188) and exon capture DNA sequencing (n = 208) on pretreatment tumors from the CALGB 90601 randomized trial of gemcitabine/cisplatin plus bevacizumab or placebo in patients with treatment-naïve metastatic bladder cancer. Whole-exome sequencing (WES) was performed on tumors from 22 patients who exhibited rapid progression or durable response. Tumors were assigned to molecular subtypes using three different classifiers. Proportional hazards model was used to correlate molecular subtype with overall survival (OS) and progression-free survival (PFS), adjusting for stratification factors and treatment arm (for PFS). RESULTS:Patients with basal tumors had the shortest PFS and OS in the entire cohort. PFS was numerically longer in patients with basal tumors receiving bevacizumab. DDR gene alterations were not associated with improved outcomes. FRY, a candidate predictive biomarker of chemosensitivity identified by WES, did not confer sensitivity to cisplatin or gemcitabine in functional studies. CONCLUSION:Molecular subtype and DDR alterations did not correlate with improved outcomes in CALGB 90601. Possible explanations for these results include the small cohort size, lack of strong therapeutic effects of the treatments, genomic heterogeneity between profiled specimens and the metastatic lesions under treatment pressure, and differences in biology associated with different disease states (muscle-invasive v metastatic disease).

Three-way classifier comparison for n=155 patients

You have accessJournal of UrologyProstate Cancer: Detection & Screening III (MP31)1 May 2024MP31-17 VARIATION IN GENOMIC TESTING AMONGST LOCALIZED PROSTATE CANCER PATIENTS UNDERGOING RADICAL PROSTATECTOMY OR RADIATION THERAPY: RESULTS FROM A POPULATION-BASED COHORT Brett Wiesen, Justin Achua, Adam Warren, Badrinath Konety, Tyler Robin, Boris Gershman, Thomas Flaig, Corbin Eule, and Simon Kim Brett WiesenBrett Wiesen , Justin AchuaJustin Achua , Adam WarrenAdam Warren , Badrinath KonetyBadrinath Konety , Tyler RobinTyler Robin , Boris GershmanBoris Gershman , Thomas FlaigThomas Flaig , Corbin EuleCorbin Eule , and Simon KimSimon Kim View All Author Informationhttps://doi.org/10.1097/01.JU.0001008936.35187.0b.17AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Genetic testing for prostate cancer is an emerging technology to aid individualized clinical decision-making. Currently, several genetic tests exist with little guidance from clinical practice guidelines. Herein, we sought to assess the use of genetic testing amongst patients with localized prostate cancer and underwent surgery or radiation therapy from a population-based cohort in the U.S. METHODS: Using the CancerLinQ database, which captures medical oncology practices across the U.S., we identified all men who received intervention via a radical prostatectomy or radiation therapy for localized prostate cancer (clinical T1-3NxMx and Gleason 6 – 10) from 2015-2023. The primary outcome was use of genetic testing either in the pre-treatment (one year prior to treatment) or post-treatment setting (6 months post-treatment). Multivariable logistic regression analyses were utilized to identify patient and clinical covariates associated with genomic testing utilization. RESULTS: Amongst the 10,367 patients diagnosed with localized prostate cancer and underwent surgery or radiation therapy, only 247 patients received genetic testing (2.3%) during the study interval. Compared to patients age<50 years, lower odds ratios were observed for patients 50 – 59 years (OR: 0.03; p=0.001), 60 – 69 years (OR: 0.06; p=0.003), 70 – 79 years (OR: 0.01; p<0.001) and>80 years (OR 0.09; p=0.02) on multivariable analysis. Compared to white patients, black patients also had lower odds ratio for genetic testing (OR: 0.09; p=0.03). There were no differences in using genomic testing for surgery versus radiation therapy (OR 1.76; p=0.36). CONCLUSIONS: Over the last decade, the use of genomic testing at the time surgery or radiation therapy for localized prostate cancer remains low and underutilized. Older and black patients were far less likely to receive genetic testing at the time of primary therapy to help inform treatment decisions. Further study is needed to analyze genomic testing use and its role in clinical decision making as it pertains to prostate cancer. Source of Funding: Schramm Foundation © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e511 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Brett Wiesen More articles by this author Justin Achua More articles by this author Adam Warren More articles by this author Badrinath Konety More articles by this author Tyler Robin More articles by this author Boris Gershman More articles by this author Thomas Flaig More articles by this author Corbin Eule More articles by this author Simon Kim More articles by this author Expand All Advertisement PDF downloadLoading ...

BACKGROUND:Small cell prostate cancer (SCPC) is a rare, aggressive disease with limited clinical data to guide treatment. In this retrospective study, we evaluated clinical, treatment, and outcomes data for patients with SCPC. METHODS:Patients with SCPC were selected from CancerLinQ Discovery®, a United States-based de-identified clinical database derived from the electronic health records of over 60 medical oncology organizations. A diagnosis of SCPC was made based on a tumor histology code of small cell carcinoma. The primary outcome of this study was assessing first-line systemic therapy within 1 year of diagnosis of SCPC. RESULTS:74 patients with SCPC who received systemic therapy between 2010-2023 were identified. The majority had documented metastatic disease (45 patients, 60.8%) and a low PSA (median 2.8 ng/dL) at SCPC diagnosis. Platinum chemotherapy plus etoposide was the most common systemic treatment (62, 83.8%) and carboplatin plus etoposide was the most common regimen (42, 56.8%) used in the first line. Median overall survival (OS) was 8.3 months for patients with metastatic SCPC. Patients treated with cisplatin plus etoposide had improved survival versus those receiving carboplatin plus etoposide (odds ratio 3.15, 95% CI 1.57-6.30; p = 0.001). 45.9% of patients with SCPC received second-line systemic therapies, which were highly varied. CONCLUSIONS:This contemporary real-world data represent one of the largest descriptions of the treatment of SCPC. Clear consensus on the optimal systemic therapy for SCPC is lacking. While additional research is needed, real-world practice patterns can serve as a resource when considering a treatment approach for this rare disease.

PURPOSE:Locally advanced/metastatic urothelial cancer (la/mUC) affects patients' quality of life (QOL) and functioning. We describe the impact of first-line (1L) enfortumab vedotin (EV) alone or with pembrolizumab (P) on QOL/functioning/symptoms in patients with la/mUC who were cisplatin-ineligible from EV-103 Cohort K. METHODS:In this phase Ib/II trial, patients were randomly assigned 1:1 to EV + P or EV monotherapy (mono). Exploratory patient-reported outcomes (PROs) were assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questionnaire (EORTC QLQ-C30) and Brief Pain Inventory Short Form (BPI-SF) at baseline, once per week for cycles 1-3, and then in every cycle through the end of treatment. Changes in scores from baseline to week 24, reported as least squares mean (standard error), were assessed by mixed models for repeated measures. There were no formal statistical comparisons between treatment arms. RESULTS:Of 149 patients treated, 65 (EV + P) and 63 (EV mono) comprised the PRO analysis set. For EV + P, EORTC QLQ-C30 QOL was maintained through week 24 with improvements in emotional functioning, pain, and insomnia. Clinically meaningful improvements were seen in EORTC QLQ-C30 pain after EV + P at weeks 12 (-14.41 [3.14]) and 24 (-14.99 [3.56]) and BPI-SF worst pain at week 24 (-2.07 [0.37]). For EV mono, EORTC QLQ-C30 QOL remained stable with clinically meaningful improvements in EORTC QLQ-C30 pain (-12.55 [4.27]), insomnia (-14.46 [4.69]), and constipation (-10.09 [4.35]) at week 24. There were small-to-moderate improvements in BPI-SF worst pain at week 24. CONCLUSION:EV + P in patients with la/mUC who were cisplatin-ineligible was associated with preservation or improvement of QOL/functioning/symptoms. Improvement in pain was seen in both PRO instruments and treatment arms. These data complement clinical outcomes of 1L EV + P.

554 Background: Trimodality therapy (TMT) consists of concurrent chemoradiation following maximal transurethral resection of the bladder tumor for muscle-invasive bladder cancer (MIBC). Current TMT treatment guidelines allow for several different radiosensitizing chemotherapy regimens, however there is limited data on existing use patterns. Methods: Using data from CancerLinQ Discovery, 71,499 patients with a bladder tumor diagnosed between 2000-2022 were included. Patients with documented radiation to “bladder” or “pelvis” with no known metastatic disease and a documented chemotherapy regimen started within a 30-day window of radiation, were included in the final analyses (n=233). Chemotherapy regimens included cisplatin, gemcitabine, 5FU+ mitomycin, taxanes, and other. Through bivariate analyses, patient characteristics and TMT treatment patterns were characterized. Results: The most commonly utilized TMT chemotherapy regimen was cisplatin alone (42.5%) followed by gemcitabine (19.3%), 5FU+ mitomycin (15.8%), taxanes (12.5%) and other (9.9%). These data demonstrated a significant relationship between age at diagnosis and chosen TMT regimen (p=0.017). Patients <65 were more likely to receive cisplatin (27.3%), 5FU mitomycin (29.7%) or other (30.4%) while patients 85+ were more likely to receive gemcitabine (28.9%). Patients more frequently received cisplatin alone prior to 2017 (before 2011: 28.3% vs. 2011-2016: 53.5% vs. 2017-2022:18.2%, p-value <.001), with a trend towards more gemcitabine use in the most recent period between 2017-2022 (51.1% vs. before 2011: 20.0% vs 2011-2016: 28.9%, p-value <.001). Additionally, there was less taxane use over time (before 2011: 37.9% vs. 2011-2016: 55.2% vs 2017-2022: 6.9%, p-value <.001). Finally, the association between TMT regimen and Charlson Comorbidity Index (CCI) trended toward significance—those treated with cisplatin alone were most likely to have a CCI of 0 (62.6%, p-value = 0.081) while patients receiving gemcitabine alone or 5FU + mitomycin were more likely to have a CCI of 1+ (gemcitabine alone: 51.1%, 5FU + mitomycin 51.4%, p-value = 0.081). Conclusions: There remains wide variation in the use of chemotherapy regimens in TMT with cisplatin monotherapy as the most utilized radiosensitizing agent overall. Since 2000, there has been a shift away from taxane therapy and increased gemcitabine use. Patients with lower CCI had a trend to more frequently receive cisplatin and older patients more frequently received gemcitabine. Further investigations are needed to better characterize patient characteristics as well as toxicity and survival by drug regimen to better help inform treatment guidelines.

Bladder cancer, the sixth most common cancer in the United States, is most commonly of the urothelial carcinoma histologic subtype. The clinical spectrum of bladder cancer is divided into 3 categories that differ in prognosis, management, and therapeutic aims: (1) non - muscle-invasive bladder cancer (NMIBC); (2) muscle invasive, nonmetastatic disease; and (3) metastatic bladder cancer. These NCCN Guidelines Insights detail recent updates to the NCCN Guidelines for Bladder Cancer, including changes in the fifth edition of the WHO Classification of Tumours: Urinary and Male Genital Tumours and how the NCCN Guidelines aligned with these updates; new and emerging treatment options for bacillus Calmette-Guerin (BCG) -unresponsive NMIBC; and updates to systemic therapy recommendations for advanced or metastatic disease.

We previously reported that tumors harboring any one of four gene mutations (ATM, ATM , RB1, FANCC, , or ERCC2) ) were likely to respond to neoadjuvant cisplatin-based chemotherapy (NAC), resulting in cancer-free surgical specimens at the time of cystectomy (pT0). Here, we report our validation of this finding. Using the CARIS 592 Gene Panel (Caris Life Sciences, Phoenix, AZ, USA), we analyzed 105 pre-NAC tumor specimens from a large multicenter trial (S1314) of either neoadjuvant gemcitabine and cisplatin (GC), or dose- dense methotrexate, vinblastine, Adriamycin, and cisplatin (DDMVAC). We found that a mutation in any one of these four genes predicted for pT0 at surgery (odds ratio = 5.36; 95% confidence interval [CI] 2.05, 14.02; two-sided p = 0.0006). The biomarker was better at predicting the presence of disease (negative predictive value for pT0 86%; 95% CI 73%, 94%) than the absence of disease (positive predictive value for pT0 48%; 95% CI 35%, 62%). There was no evidence of an interaction between the treatment arm (DDMVAC vs GC) and the genetic variant in terms of pT0. When combined with clinical assessment, these findings help inform patient selection for bladder preservation after cisplatinbased chemotherapy. (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.