Adaption and National Validation of a Tool for Predicting Mortality from Other Causes Among Men with Nonmetastatic Prostate Cancer

Plos Medicine

Background Estimating the medical complexity of people aging with HIV can inform clinical programs and policy to meet future healthcare needs. The objective of our study was to forecast the prevalence of comorbidities and multimorbidity among people with HIV (PWH) using antiretroviral therapy (ART) in the United States (US) through 2030. Methods and findings Using the PEARL model—an agent-based simulation of PWH who have initiated ART in the US—the prevalence of anxiety, depression, stage ≥3 chronic kidney disease (CKD), dyslipidemia, diabetes, hypertension, cancer, end-stage liver disease (ESLD), myocardial infarction (MI), and multimorbidity (≥2 mental or physical comorbidities, other than HIV) were forecasted through 2030. Simulations were informed by the US CDC HIV surveillance data of new HIV diagnosis and the longitudinal North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) data on risk of comorbidities from 2009 to 2017. The simulated population represented 15 subgroups of PWH including Hispanic, non-Hispanic White (White), and non-Hispanic Black/African American (Black/AA) men who have sex with men (MSM), men and women with history of injection drug use and heterosexual men and women. Simulations were replicated for 200 runs and forecasted outcomes are presented as median values (95% uncertainty ranges are presented in the Supporting information). In 2020, PEARL forecasted a median population of 670,000 individuals receiving ART in the US, of whom 9% men and 4% women with history of injection drug use, 60% MSM, 8% heterosexual men, and 19 …

Cancer Research

Purpose: The Veterans Health Administration (VA) created National TeleOncology (NTO) service in 2019 to provide telehealth cancer care to Veterans and to augment care provided at VA facilities through a hub and spoke model. More recently, VA established a Decentralized Clinical Trials (DCTs) infrastructure to support clinical trials (CTs) that rely on telehealth, where research staff are at different locations, and/or where a single IRB provides oversight even when subjects are at different locations. Brief Description: Research support and infrastructure is variable across VA facilities resulting in uneven access to cancer CTs in the VA system. Veterans often live in rural areas or have transportation challenges, which are barriers to participate in CTs. The COVID-19 pandemic resulted in increased telehealth use in clinical care and in CTs, providing the rationale for a focused effort in DCTs. DCTs have the potential to …

Annals of Surgery

Objective:Examine the association between prior SARS-CoV-2 infection, interval from infection to surgery, and adverse surgical outcomes.Summary Background Data:Earlier series have reported worse outcomes for surgery after COVID-19 illness, and these findings have led to routinely deferring surgery seven weeks after infection.Methods:We created a retrospective cohort of patients from US Veterans Health Administration facilities nationwide, April 2020-September 2022, undergoing surgical procedures. Primary outcomes were 90-day all-cause mortality and 30-day complications. Within surgical procedure groupings, SARS-CoV-2 infected and uninfected patients were matched in a 1: 4 ratio. We categorized patients by two-week intervals from SARS-CoV-2 positive test to surgery. Hierarchical multilevel multivariable logistic regression models were used to estimate the association between infection to surgery …

arXiv preprint arXiv:2401.10733

Electronic health records (EHRs) house crucial patient data in clinical notes. As these notes grow in volume and complexity, manual extraction becomes challenging. This work introduces a natural language interface using large language models (LLMs) for dynamic question-answering on clinical notes. Our chatbot, powered by Langchain and transformer-based LLMs, allows users to query in natural language, receiving relevant answers from clinical notes. Experiments, utilizing various embedding models and advanced LLMs, show Wizard Vicuna's superior accuracy, albeit with high compute demands. Model optimization, including weight quantization, improves latency by approximately 48 times. Promising results indicate potential, yet challenges such as model hallucinations and limited diverse medical case evaluations remain. Addressing these gaps is crucial for unlocking the value in clinical notes and advancing AI-driven clinical decision-making.

Digestive Diseases and Sciences

BackgroundSurvival in pancreatic ductal adenocarcinoma (PDAC) remains poor due to late diagnosis. Electronic Health Records (EHRs) can be used to study this rare disease, but validated algorithms to identify PDAC in the United States EHRs do not currently exist.AimsTo develop and validate an algorithm using Veterans Health Administration (VHA) EHR data for the identification of patients with PDAC.MethodsWe developed two algorithms to identify patients with PDAC in the VHA from 2002 to 2023. The algorithms required diagnosis of exocrine pancreatic cancer in either ≥ 1 or ≥ 2 of the following domains: (i) the VA national cancer registry, (ii) an inpatient encounter, or (iii) an outpatient encounter in an oncology setting. Among individuals identified with ≥ 1 of the above criteria, a random sample of 100 were reviewed by three gastroenterologists to adjudicate PDAC status. We also adjudicated fifty …

Urology Practice

IntroductionThe AUA convened a 2021-2022 Quality Improvement Summit to bring together interdisciplinary providers to inform the current state and to discuss potential strategies for integrating primary palliative care into urology practice. We hypothesized that the Summit findings would inform a scalable primary palliative care model for urology.MethodsThe 3-part summit reached a total of 160 interdisciplinary health care professionals. Webinar 1, “Building a Primary Palliative Care Model for Urology,” focused on a urologist’s role in palliative care. Webinar 2, “Perspectives on Increasing the Use of Palliative Care in Advanced Urologic Disease,” addressed barriers to possible implementation of a primary palliative care model. The in-person Summit, “Laying the Foundation for Primary Palliative Care in Urology,” focused on operationalization of primary palliative care, clinical innovations needed, and relevant metrics …

The Journal of Urology

INTRODUCTION AND OBJECTIVEBladder cancer is one of most common cancers, with an estimated 82,290 new cases in 2023 in the U.S. alone. However, there is significant geographic variability in the incidence of bladder cancer that could be due to environmental exposures, including drinking water constituents. We sought to evaluate the potential county-level associations between municipal drinking water constituents and bladder cancer incidence.METHODSWe conducted a large-scale Water-Wide Association Study (WWAS) to systematically explore the relationships between 171 drinking water constituents and bladder cancer incidence across California’s 58 counties. This WWAS extracted the observed cancer cases for each county and also calculated the expected case counts based on population counts and cancer rates for specific age groups (<50, 50-64, 65-74, and 75+) for 2011-2015 and 2016 …

The Pharmacogenomics Journal

The objective of this study was to discover clinical and pharmacogenetic factors associated with bevacizumab-related gastrointestinal hemorrhage in Cancer and Leukemia Group B (Alliance) 90401. Patients with metastatic castration-resistant prostate cancer received docetaxel and prednisone±bevacizumab. Patients were genotyped using Illumina HumanHap610-Quad and assessed using cause-specific risk for association between single nucleotide polymorphisms (SNPs) and gastrointestinal hemorrhage. In 1008 patients, grade 2 or higher gastrointestinal hemorrhage occurred in 9.5% and 3.8% of bevacizumab (n= 503) and placebo (n= 505) treated patients, respectively. Bevacizumab (P< 0.001) and age (P= 0.002) were associated with gastrointestinal hemorrhage. In 616 genetically estimated Europeans (n= 314 bevacizumab and n= 302 placebo treated patients), grade 2 or higher gastrointestinal …

Open Forum Infectious Diseases

Existing outpatient parenteral antibiotic therapy (OPAT) registries are resource intensive, and OPAT programs struggle to produce objective data to show the value of their work. We describe the building and validation of an automated OPAT registry within our electronic medical record and provide objective data on the value of the program. Variables and outcomes include age, sex, race, ethnicity, primary insurance payor, antibiotic names, infection syndromes treated, discharge disposition, 30-day all-cause readmission and death rates, complications, and an estimate of the hospital days saved. Records for 146 OPAT episodes were reviewed manually to validate the registry. Data were displayed in a dashboard within the electronic medical record. Over the 4-year time frame, our registry collected 3956 unique patients who completed 4710 episodes (approximately 1200 episodes per year). A total of 400 …

Nature Medicine

Chronic pain is a common problem, with more than one-fifth of adult Americans reporting pain daily or on most days. It adversely affects the quality of life and imposes substantial personal and economic costs. Efforts to treat chronic pain using opioids had a central role in precipitating the opioid crisis. Despite an estimated heritability of 25–50%, the genetic architecture of chronic pain is not well-characterized, in part because studies have largely been limited to samples of European ancestry. To help address this knowledge gap, we conducted a cross-ancestry meta-analysis of pain intensity in 598,339 participants in the Million Veteran Program, which identified 126 independent genetic loci, 69 of which are new. Pain intensity was genetically correlated with other pain phenotypes, level of substance use and substance use disorders, other psychiatric traits, education level and cognitive traits. Integration of the …

Clinical Journal of the American Society of Nephrology

Does your paper include study group (s)? If yes, please provide a list of study group (s) and members that have contributed to or participated in the submitted work in some way. This list may contain either a collaboration of individuals (eg, investigators) and/or the name of an organization (eg, a laboratory, educational institution, corporation, or department) and its

The Journal of Urology

INTRODUCTION AND OBJECTIVEReduced kidney function is associated with cardiovascular (CV) events and mortality. In patients undergoing kidney cancer surgery, partial nephrectomy preserves more kidney function than radical nephrectomy after surgery, but it remains unknown whether a nephron sparing approach is associated with a reduced risk of CV events.METHODSWe used national data from the Veterans Health Administration (VHA) to emulate a randomized trial of adult patients with a new diagnosis of T1a kidney cancer undergoing either radical nephrectomy (RN) or partial nephrectomy (PN) between January 1, 2010 and December 31, 2017. We excluded patients with an eGFR<30 in the 3 months before surgery. Follow-up began once participants were assigned to their respective treatment strategy and ended with one of the following: 1) the first major adverse cardiovascular event (MACE); 2 …

BMC cancer

Therapies for metastatic castration-resistant prostate cancer (mCRPC) include targeting the androgen receptor (AR) with androgen receptor inhibitors (ARIs) and prostate-specific membrane antigen (PSMA). Having the ability to detect AR, AR splice variant 7 (AR-V7), or PSMA in circulating tumor cells (CTCs) or circulating exosomal cell-free RNA (cfRNA) could be helpful to guide selection of the appropriate therapy for each individual patient. The Vortex Biosciences VTX-1 system is a label-free CTC isolation system that enables the detection of the expression of multiple genes in both CTCs and exosomal cfRNA from the same blood sample in patients with mCRPC. Detection of both AR-V7 and PSMA gene expression in both CTCs and cfRNA simultaneously has not yet been reported. To characterize the combined VTX-1-AdnaDetect workflow, 22Rv1 cancer cells were spiked into blood from healthy donors and processed with the VTX-1 to mimic patient samples and assess performances (capture efficiency, purity, AR and AR-V7 expression). Then, we collected 19 blood samples from 16 patients with mCRPC and therapeutic resistance to androgen receptor inhibitors (ARIs). Plasma was separated and the plasma-depleted blood was processed further with the VTX-1 to collect CTCs. Both plasma exosomal cfRNA and CTCs were subsequently analyzed for AR, AR-V7, PSMA, and prostate-specific antigen (PSA) mRNA expression using the AdnaTest ProstateCancerPanel AR-V7 assay. AR-V7 expression could be detected in 22Rv1 cells spiked into blood from healthy volunteers as well as in CTCs and plasma-derived exosomal cfRNA from …

Introduction The prevalence of pulmonary impairments in older adults is increasing, especially in those living with multiple chronic conditions, and is associated with mortality. We examined whether the addition of pulmonary measures improves all-cause mortality prediction of the Veterans Aging Cohort Study (VACS) Index 2.0 and the updated VACS index with Charlson Comorbidity Index (VACS-CCI) among Veterans. Methods We included patients in care in the Veterans Affairs Health System with pulmonary function tests (PFTs) in 2013 (baseline), determined using CPT codes. We used a previously developed Structured Query Language (SQL) algorithm to extract diffusion capacity for carbon monoxide (% DLCO) and forced expiratory volume in one second (% FEV1) from clinical notes of patients with PFTs. Numeric percent predicted values immediately following the key terms were extracted if they were within …

medRxiv

Opioid addiction constitutes a public health crisis in the United States and opioids cause the most drug overdose deaths in Americans. Yet, opioid addiction treatments have limited efficacy. To help address this problem, we used network-based machine learning techniques to integrate results from genome-wide association studies (GWAS) of opioid use disorder and problematic prescription opioid misuse with transcriptomic, proteomic, and epigenetic data from the dorsolateral prefrontal cortex (dlPFC) in opioid overdose victims. We identified 211 highly interrelated genes identified by GWAS or dysregulation in the dlPFC of individuals with opioid overdose victims that implicated the Akt, BDNF, and ERK pathways, identifying 414 drugs targeting 48 of these opioid addiction-associated genes. This included drugs used to treat other substance use disorders and antidepressant drugs. Our synthesis of multi-omics using a systems biology approach revealed key gene targets that could contribute to drug repurposing, genetics-informed addiction treatment, and future discovery.

Frontiers in Medicine

Introduction As people age with HIV (PWH), many comorbid diseases are more common than among age matched comparators without HIV (PWoH). While the Veterans Aging Cohort (VACS) Index 2.0 accurately predicts mortality in PWH using age and clinical biomarkers, the only included comorbidity is hepatitis C. We asked whether adding comorbid disease groupings from the Charlson Comorbidity Index (CCI) improves the accuracy of VACS Index. Methods To maximize our ability to model mortality among older age groups, we began with PWoH in Veterans Health Administration (VA) from 2007–2017, divided into development and validation samples. Baseline predictors included age, and components of CCI and VACS Index (excluding CD4 count and HIV RNA). Patients were followed until December 31, 2021. We used Cox models to develop the VACS-CCI score and estimated mortality using a parametric (gamma) survival model. We compared accuracy using C-statistics and calibration curves in validation overall and within subgroups (gender, age Results The analytic sample consisted of 6,588,688 PWoH and 30,539 PWH. Among PWoH/PWH, median age was 65/55 years; 6%/3% were women; 15%/48% were Black and 5%/7% Hispanic. VACS-CCI provided the best discrimination (C-statistic = 0.81) with excellent calibration (predicted and observed mortality largely overlapped) overall and within subgroups. When VACS-CCI was applied to PWH it demonstrated similar discrimination as VACS Index 2.0 (C-statistic = 0.77 for both) but superior calibration among those with CD4 < 200. Discrimination was improved when CD4 …

European Urology Oncology

BackgroundAn electronic health record–based tool could improve accuracy and eliminate bias in provider estimation of the risk of death from other causes among men with nonmetastatic cancer.ObjectiveTo recalibrate and validate the Veterans Aging Cohort Study Charlson Comorbidity Index (VACS-CCI) to predict non–prostate cancer mortality (non-PCM) and to compare it with a tool predicting prostate cancer mortality (PCM).Design, setting, and participantsAn observational cohort of men with biopsy-confirmed nonmetastatic prostate cancer, enrolled from 2001 to 2018 in the national US Veterans Health Administration (VA), was divided by the year of diagnosis into the development (2001–2006 and 2008–2018) and validation (2007) sets.Outcome measurements and statistical analysisMortality (all cause, non-PCM, and PCM) was evaluated. Accuracy was assessed using calibration curves and C statistic in the …

European Urology Oncology

BackgroundProstate cancers featuring an expansile cribriform (EC) pattern are associated with worse clinical outcomes following radical prostatectomy (RP). However, studies of the genomic characteristics of Gleason pattern 4 subtypes are limited.ObjectiveTo explore transcriptomic characteristics and heterogeneity within Gleason pattern 4 subtypes (fused/poorly formed, glomeruloid, small cribriform, EC/intraductal carcinoma [IDC]) and the association with biochemical recurrence (BCR)-free survival.Design, setting, and participantsThis was a retrospective cohort study including 165 men with grade group 2–4 prostate cancer who underwent RP at a single academic institution (2016–2020) and Decipher testing of the RP specimen. Patients with Gleason pattern 5 were excluded. IDC and EC patterns were grouped. Median follow-up was 2.5 yr after RP for patients without BCR.Outcomes measurements and …

European Urology Oncology

BackgroundPrognostic models have been developed using data from a multicentre noncomparative study to forecast the likelihood of a 50% reduction in prostate-specific antigen (PSA50), longer prostate-specific antigen (PSA) progression-free survival (PFS), and longer overall survival (OS) in patients with metastatic castration-resistant prostate cancer receiving [177Lu]Lu-PSMA radioligand therapy. The predictive utility of the models to identify patients likely to benefit most from [177Lu]Lu-PSMA compared with standard chemotherapy has not been established.ObjectiveTo determine the predictive value of the models using data from the randomised, open-label, phase 2, TheraP trial (primary objective) and to evaluate the clinical net benefit of the PSA50 model (secondary objective).Design, setting, and participantsAll 200 patients were randomised in the TheraP trial to receive [177Lu]Lu-PSMA-617 (n = 99) or …

European Urology Oncology

Stereotactic magnetic resonance (MR)-guided adaptive radiotherapy (SMART) for renal cell carcinoma may result in more precise treatment delivery through the capabilities for improved image quality, daily adaptive planning, and accounting for respiratory motion during treatment with real-time MR tracking. In this study, we aimed to characterize the safety and feasibility of SMART for localized kidney cancer. Twenty patients with localized kidney cancer (ten treated in a prospective phase 1 trial and ten in the supplemental cohort) were treated to 40 Gy in five fractions on a 0.35 T MR-guided linear accelerator with daily adaptive planning and a cine MR-guided inspiratory breath hold technique. The median follow-up time was 17 mo (interquartile range: 13–20 months). A single patient developed local failure at 30 mo. No grade ≥3 adverse events were reported. The mean decrease in estimated glomerular filtration …

European Urology Oncology

BackgroundAccurate risk stratification is critical to guide management decisions in localized prostate cancer (PCa). Previously, we had developed and validated a multimodal artificial intelligence (MMAI) model generated from digital histopathology and clinical features. Here, we externally validate this model on men with high-risk or locally advanced PCa treated and followed as part of a phase 3 randomized control trial.ObjectiveTo externally validate the MMAI model on men with high-risk or locally advanced PCa treated and followed as part of a phase 3 randomized control trial.Design, setting, and participantsOur validation cohort included 318 localized high-risk PCa patients from NRG/RTOG 9902 with available histopathology (337 [85%] of the 397 patients enrolled into the trial had available slides, of which 19 [5.6%] failed due to poor image quality).Outcome measurements and statistical analysisTwo previously …

European Urology Oncology

BackgroundAccurate risk stratification is critical to guide management decisions in localized prostate cancer (PCa). Previously, we had developed and validated a multimodal artificial intelligence (MMAI) model generated from digital histopathology and clinical features. Here, we externally validate this model on men with high-risk or locally advanced PCa treated and followed as part of a phase 3 randomized control trial.ObjectiveTo externally validate the MMAI model on men with high-risk or locally advanced PCa treated and followed as part of a phase 3 randomized control trial.Design, setting, and participantsOur validation cohort included 318 localized high-risk PCa patients from NRG/RTOG 9902 with available histopathology (337 [85%] of the 397 patients enrolled into the trial had available slides, of which 19 [5.6%] failed due to poor image quality).Outcome measurements and statistical analysisTwo previously …

European Urology Oncology

Background and objectiveThere exists ongoing debate about the benefits and harms of prostate-specific antigen (PSA) screening for prostate cancer. This study sought to evaluate the association of county-level PSA screening rates with county-level incidence of metastatic prostate cancer and prostate cancer mortality in the USA.MethodsThis ecological study used data from the 2004–2012 Behavioral Risk Factor Surveillance System (BRFSS) to build a multilevel mixed-effect model with poststratification using US Census data to estimate county-level PSA screening rates for all 3143 US counties adjusted for age, race, ethnicity, and county-level poverty rates. The exposure of interest was average county-level PSA screening rate from 2004 to 2012, defined as the proportion of men aged 40–79 yr who underwent PSA screening within the prior 2 yr. The primary outcomes were county-level age-adjusted incidence of …

European Urology Oncology

BackgroundThe PROpel study (NCT03732820) demonstrated a statistically significant progression-free survival benefit with olaparib plus abiraterone versus placebo plus abiraterone in the first-line metastatic castration-resistant prostate cancer (mCRPC) setting, irrespective of homologous recombination repair mutation status.ObjectiveWe report additional safety analyses from PROpel to increase clinical understanding of the adverse-event (AE) profiles of olaparib plus abiraterone versus placebo plus abiraterone.Design, setting, and participantsA randomised (1:1), double-blind, placebo-controlled trial was conducted at 126 centres in 17 countries (October 2018–January 2020). Patients had mCRPC and no prior systemic mCRPC treatment.InterventionOlaparib (300 mg bid) or placebo with abiraterone (1000 mg od) plus prednisone/prednisolone (5 mg bid).Outcome measurements and statistical analysisThe data …

European Urology Oncology

BackgroundFurther stratification of the risk of recurrence of clear-cell renal cell carcinoma (ccRCC) with venous tumor thrombus (VTT) will facilitate selection of candidates for adjuvant therapy.ObjectiveTo assess the impact of tumor grade discrepancy (GD) between the primary tumor (PT) and VTT in nonmetastatic ccRCC on disease-free survival (DFS), overall survival (OS), and cancer-specific survival (CSS).Design, setting, and participantsThis was a retrospective analysis of a multi-institutional nationwide data set for patients with pT3N0M0 ccRCC who underwent radical nephrectomy and thrombectomy.Outcomes measurements and statistical analysisPathology slides were centrally reviewed. GD, a bidirectional variable (upgrading or downgrading), was numerically defined as the VTT grade minus the PT grade. Multivariable models were built to predict DFS, OS, and CSS.Results and limitationsWe analyzed data …

European Urology Oncology

BackgroundRenal c carcinoma (RCC) is one of the most common urinary cancers worldwide, with a predicted increase in incidence in the coming years. Immunotherapy, as a single agent, in doublets, or in combination with anti–vascular endothelial growth factor receptor tyrosine kinase inhibitors (TKIs), has rapidly become a cornerstone of the RCC therapeutic scenario, but no head-to-head comparisons have been made. In this setting, real-world evidence emerges as a cornerstone to guide clinical decisions.ObjectiveThe objective of this retrospective study was to assess the outcome of patients treated with first-line immune combinations or immune oncology (IO)-TKIs for advanced RCC.Design, setting, and participantsData from 930 patients, 654 intermediate risk and 276 poor risk, were collected retrospectively from 58 centers in 20 countries. Special data such as sarcomatoid differentiation, body mass index …

European Urology Oncology

PROpel (NCT03732820) was a positive phase 3 trial that demonstrated a clinically significant improvement in radiographic progression-free survival with olaparib plus abiraterone versus placebo plus abiraterone in first-line metastatic castration-resistant prostate cancer. For a subset of PROpel patients, steady-state concentrations of olaparib, abiraterone, and Δ4-abiraterone were measured in blood samples collected before and at several time points after dose administration. The pharmacokinetics (PK) for each drug and metabolite were evaluated to determine whether any clinically relevant drug-drug interactions between olaparib and abiraterone occurred. The results demonstrate that steady-state PK parameters for olaparib and abiraterone in PROpel were comparable with those in monotherapy trials. Abiraterone steady-state exposures were similar between treatment arms. Δ4-Abiraterone had slightly lower …

European Urology Oncology

Chemoradiation therapy (CRT) is a treatment for muscle-invasive bladder cancer (MIBC). Using a novel transcriptomic profiling panel, we validated prognostic immune biomarkers to CRT using 70 pretreatment tumor samples from prospective trials of MIBC (NRG/RTOG 0524 and 0712). Disease-free survival (DFS) and overall survival (OS) were estimated via the Kaplan-Meier method and stratified by genes correlated with immune cell activation. Cox proportional-hazards models were used to assess group differences. Clustering of gene expression profiles revealed that the cluster with high immune cell content was associated with longer DFS (hazard ratio [HR] 0.53, 95% confidence interval [CI] 0.26–1.10; p = 0.071) and OS (HR 0.48, 95% CI 0.24–0.97; p = 0.040) than the cluster with low immune cell content. Higher expression of T-cell infiltration genes (CD8A and ICOS) was associated with longer DFS (HR 0.40 …

European Urology Oncology

Over the past two decades, careful patient selection has been emphasized for cytoreductive nephrectomy (CN). However, which patients are ideal for CN remains unclear, especially for patients treated with upfront CN in combination with modern systemic therapies [

European Urology Oncology

BackgroundStandard of care management for synchronous metastatic castration-sensitive prostate cancer (mCSPC) includes androgen deprivation therapy with a second-generation antiandrogen therapy and/or docetaxel. Recently, randomized data have demonstrated that prostate-directed therapy (PDT) is associated with an improvement in overall survival (OS) among patients with low-volume metastatic disease. Tumor genomics represents an additional dimension to define the clinical trajectory of patients with mCSPC.ObjectiveTo evaluate a high-risk (HiRi) genomic signature to predict the benefit from PDT.Design, setting, and participantsWe performed a single-institution retrospective review of men with synchronous low-volume mCSPC who underwent DNA panel sequencing of their tumor. Patients were classified according to the presence of HiRi mutation including pathogenic mutations in TP53, ATM …

European Urology Oncology

Stereotactic magnetic resonance (MR)-guided adaptive radiotherapy (SMART) for renal cell carcinoma may result in more precise treatment delivery through the capabilities for improved image quality, daily adaptive planning, and accounting for respiratory motion during treatment with real-time MR tracking. In this study, we aimed to characterize the safety and feasibility of SMART for localized kidney cancer. Twenty patients with localized kidney cancer (ten treated in a prospective phase 1 trial and ten in the supplemental cohort) were treated to 40 Gy in five fractions on a 0.35 T MR-guided linear accelerator with daily adaptive planning and a cine MR-guided inspiratory breath hold technique. The median follow-up time was 17 mo (interquartile range: 13–20 months). A single patient developed local failure at 30 mo. No grade ≥3 adverse events were reported. The mean decrease in estimated glomerular filtration …

European Urology Oncology

When data from the CLOCK randomized controlled trial (RCT) revealed no significant difference in new-baseline estimated glomerular filtration rate (at 6, 12, 18, and 24 mo) between on-clamp and off-clamp robotic partial nephrectomy (RPN)[1], most urologists wondered whether the off-clamp technique could finally be laid to rest. Interestingly, the possible end game for the off-clamp technique happened only once the bar of evidence was raised by suitably designed RCTs [2, 3]. Although RCTs revealed no benefit in renal function associated with avoidance of clamping of the renal artery, they did disprove the dogma that an off-clamp approach during RPN led to greater blood loss and higher risks of complications and positive surgical margins, at least in selected patients with specific tumor characteristics. Notably, a subgroup analysis of the CLOCK trial for cases with an unexpected change from a planned off …

European Urology Oncology

BackgroundFurther stratification of the risk of recurrence of clear-cell renal cell carcinoma (ccRCC) with venous tumor thrombus (VTT) will facilitate selection of candidates for adjuvant therapy.ObjectiveTo assess the impact of tumor grade discrepancy (GD) between the primary tumor (PT) and VTT in nonmetastatic ccRCC on disease-free survival (DFS), overall survival (OS), and cancer-specific survival (CSS).Design, setting, and participantsThis was a retrospective analysis of a multi-institutional nationwide data set for patients with pT3N0M0 ccRCC who underwent radical nephrectomy and thrombectomy.Outcomes measurements and statistical analysisPathology slides were centrally reviewed. GD, a bidirectional variable (upgrading or downgrading), was numerically defined as the VTT grade minus the PT grade. Multivariable models were built to predict DFS, OS, and CSS.Results and limitationsWe analyzed data …

European Urology Oncology

BackgroundStandard of care management for synchronous metastatic castration-sensitive prostate cancer (mCSPC) includes androgen deprivation therapy with a second-generation antiandrogen therapy and/or docetaxel. Recently, randomized data have demonstrated that prostate-directed therapy (PDT) is associated with an improvement in overall survival (OS) among patients with low-volume metastatic disease. Tumor genomics represents an additional dimension to define the clinical trajectory of patients with mCSPC.ObjectiveTo evaluate a high-risk (HiRi) genomic signature to predict the benefit from PDT.Design, setting, and participantsWe performed a single-institution retrospective review of men with synchronous low-volume mCSPC who underwent DNA panel sequencing of their tumor. Patients were classified according to the presence of HiRi mutation including pathogenic mutations in TP53, ATM …

European Urology Oncology

Background and objectiveGrowing evidence supports the use of neoadjuvant chemotherapy (NAC) for upper tract urothelial carcinoma (UTUC). However, the implications of residual UTUC at radical nephroureterectomy (RNU) after NAC are not well characterized. Our objective was to compare oncologic outcomes for pathologic risk–matched patients who underwent RNU for UTUC who either received NAC or were chemotherapy-naïve.MethodsWe retrospectively identified 1993 patients (including 112 NAC recipients) who underwent RNU for nonmetastatic, high-grade UTUC between 1985 and 2022 in a large, international, multicenter cohort. We divided the cohort into low-risk and high-risk groups defined according to pathologic findings of muscle invasion and lymph node involvement at RNU. Recurrence-free survival (RFS), overall survival (OS), and cancer-specific survival (CSS) estimates were calculated …

European Urology Oncology

BackgroundThe role of local therapies including radical prostatectomy (RP) in prostate cancer (PCa) patients with clinical lymphadenopathies on prostate-specific membrane antigen (PSMA) positron emission tomography/computerized tomography (PET/CT) has scarcely been explored. Limited data are available to identify men who would benefit from RP; on the contrary, those more likely to benefit already have systemic disease.ObjectiveWe aimed to assess the predictors of prostate-specific antigen (PSA) persistence in surgically managed PCa patients with lymphadenopathies on a PSMA PET/CT scan by integrating clinical, magnetic resonance imaging (MRI), and PSMA PET/CT parameters.Design, setting, and participantsWe identified 519 patients treated with RP and extended lymph node dissection, and who received preoperative PSMA PET between 2017 and 2022 in nine referral centers. Among them, we …