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Yale Urology Research [Q2: April-June 2022]

August 25, 2022

The following is a comprehensive list of Yale Urology faculty’s contributions to the field, as represented in their published work/research for the 2nd quarter of this year. The listing is in ascending published date order and includes cite details and at least portions of each abstract/summary.



A 71-year-old woman presented with an intravesical bladder mass found to be a clear cell adenocarcinoma of Müllerian origin with positive PAX-8 staining after transurethral resection. Partial cystectomy along with total hysterectomy were performed, and final pathology revealed no residual tumour and extensive endometriosis. She declined adjuvant therapy and was dispositioned to surveillance.



  • van der Heijden MS, Powles T, Petrylak D, de Wit R, Necchi A, Sternberg CN, Matsubara N, Nishiyama H, Castellano D, Hussain SA, Bamias A, Gakis G, Lee JL, Tagawa ST, Vaishampayan U, Aragon-Ching JB, Eigl BJ, Hozak RR, Rasmussen ER, Xia MS, Rhodes R, Wijayawardana S, Bell-McGuinn KM, Aggarwal A, Drakaki A. Predictive biomarkers for survival benefit with ramucirumab in urothelial cancer in the RANGE trial. Nat Commun. 2022 Apr 6;13(1):1878. doi: 10.1038/s41467-022-29441-y. PMID: 35388003; PMCID: PMC8987042.

The RANGE study (NCT02426125) evaluated ramucirumab (an anti-VEGFR2 monoclonal antibody) in patients with platinum-refractory advanced urothelial carcinoma (UC). Here, we use programmed cell death-ligand 1 (PD-L1) immunohistochemistry (IHC) and transcriptome analysis to evaluate the association of immune and angiogenesis pathways, and molecular subtypes, with overall survival (OS) in UC.



The literature regarding urologic complications from prolonged prone positioning in patients with COVID-19 ARDS is currently limited to a single case report describing Fournier’s gangrene in a proned patient with ARDS []. We describe the first reported instance of a patient with COVID-19 ARDS who developed penile glans necrosis and erosion of an inflatable penile prosthetic cylinder secondary to prolonged prone positioning.



Prostate cancer (PCa) is the second most common cause of cancer death in males. Targeting MRI-visible lesions has led to an overall increase in the detection of clinically significant PCa compared to the prior practice of random ultrasound-guided biopsy of the prostate. Additionally, advances in MRI-guided minimally invasive focal treatments are providing new options for patients with PCa. This review summarizes the currently utilized real-time MRI-guided interventions for PCa diagnosis and treatment.



The goal of this manuscript is to review the current literature on bladder health education, summarize Prevention of Lower Urinary Tract Symptoms (PLUS) findings on environmental factors that influence knowledge and beliefs about toileting and bladder function, and describe how PLUS work will contribute to improved understanding of women’s bladder-related knowledge and inform prevention intervention strategies.



Researchers found that people treated with avelumab maintenance treatment plus best supportive care lived, on average, 7 months longer than people who received best supportive care alone. People treated with avelumab had more side effects than those not treated with avelumab, but most were not severe. Common side effects with avelumab included persistent tiredness, itchy skin, urinary tract infection, and diarrhea.



Conclusion: ePLND is associated with a significantly greater risk of perioperative complication compared to sPLND, but not when comparing these templates performed via a robotic approach. Additional studies comparing the complication rates of sPLND and ePLND when utilizing a robotic approach should be conducted.



Conclusions: Although multifocal HCC clearly indicates a more aggressive phenotype even in early-stage disease, the continuity of an enhancing capsule and a higher radiomic signature may add value as MR imaging biomarkers for poor PFS in HCC treated with RF ablation.



Patient Summary: Our findings highlight that selected patients with high-risk nonmetastatic prostate cancer benefit from intensification of systemic therapy beyond hormonal treatment.



Purpose: In an era of rapid expansion of FDA approvals for oral anticancer agents (OAAs), it is important to understand the factors associated with survival among real-world populations, which include groups not well-represented in pivotal clinical trials of OAAs, such as the elderly, racial minorities, and medically complex patients. Our objective was to evaluate patient- and provider-level characteristics' associations with mortality among a multi-payer cohort of metastatic renal cell carcinoma (mRCC) patients who initiated OAAs.



Uroflowmetry is a noninvasive method used to assess for possible obstruction after hypospadias surgery. While numerous publications on this topic are available, few compare flows to age matched normals or to pediatric nomograms and most have small numbers of cases. Our aim is to establish normal flow values in patients after repair of varying degrees of hypospadias and to identify if there are reliable differences between those with complications and those without.



Most kidney stones are composed of calcium oxalate (CO), calcium phosphate (CP), uric acid (UA), or a mix. Age, gender, and urine pH are known to be associated with stone type, but factors related to conversion of one stone type to another have not been established. We examined the association between demographics and medical history of recurrent stone formers (RSFs) with conversion between CO, CP, and UA compositions.



Conclusions: Long-term follow-up from the JAVELIN Bladder 100 trial continues to show prolonged OS with avelumab+BSC vs BSC alone. These results further support the standard-of-care role for avelumab as 1L maintenance in pts with advanced UC that has not progressed with 1L platinum-containing chemotherapy.



In primary analysis, enzalutamide plus androgen deprivation therapy (ADT) improved radiographic progression-free survival (rPFS) in patients with metastatic hormone-sensitive prostate cancer (mHSPC); however, overall survival data were immature. In the phase III, double-blind, global ARCHES trial (ClinicalTrials.gov identifier: NCT02677896), 1,150 patients with mHSPC were randomly assigned 1:1 to enzalutamide (160 mg once daily) plus ADT or placebo plus ADT, stratified by disease volume and prior docetaxel use.



While, it is standard to biopsy Prostate Imaging Reporting and Data System (PIRADS) 3 lesions, most do not contain clinically significant prostate cancer (CSPCa, Grade Group ≥2). We aim to identify clinical and magnetic resonance imaging (MRI) risk factors that predict CSPCa in men with PIRADS 3 lesions.



Prostate-specific antigen (PSA) isoforms, including a panel of four kallikrein markers, improve the prediction of high-grade prostate cancer in clinical studies and may potentially mitigate biopsy after prostate cancer screening. We evaluated determinants of real-world use of a commercially available four kallikrein marker panel (4Kscore®), and subsequent use of prostate biopsy among tested patients.



The predictive value of Decipher test in Grade Group (GG) 3-5, pT3b-T4, or lymph node involvement at radical prostatectomy (RP) is well established. However, little is known about its prognostic significance in other pathological surrogates for metastatic potential, including extraprostatic extension (EPE) and surgical margin, as well as pathologic concordance between biopsy and RP. Therefore, we sought to determine if Decipher score was associated with the presence of those pathological features at RP and biopsy-RP pathological discordance.



A very small proportion of patients undergoing MRI-ultrasound fusion biopsy will be classified as “very-low risk” by the NCCN definition, and the majority of patients managed appropriately with active surveillance do not meet these criteria. These findings imply a need to broaden support for active surveillance outside of “very-low risk” criteria to promote greater uptake.



Treatment decisions regarding elderly patients with upper tract urothelial carcinoma (UTUC) can be challenging given competing risks associated with age and comorbidities. Herein we assess survival outcomes among patients 80+ years diagnosed with clinically localized UTUC managed with definitive surgery versus expectant management.



Healthcare is a major contributor to global pollution. Reducing the over-use of clinical care is one solution to lowering environmental emissions and improving care value. We aimed to estimate the environmental impact of transrectal ultrasound (TRUS) prostate biopsy, a procedure that is commonly performed in excess of recommended guidelines based on patient age or life-expectancy.



Importance: Racial disparity in the use of prostate magnetic resonance imaging (MRI) presents obstacles to closing gaps in prostate cancer diagnosis, treatment, and outcome. Objective: To identify clinical, sociodemographic, and structural processes underlying racial disparity in the use of prostate MRI among men with a new diagnosis of prostate cancer.



The possibility of adverse surgical pathology among patients with low-risk prostate cancer is often used as a surrogate to determine the suitability of active surveillance (AS) versus definitive local treatment. We aimed to understand the association between adverse pathology and overall survival (OS) among ostensible candidates for AS who were treated with radical prostatectomy.



Discussion: This is the first study in urology to demonstrate that use of structured data elements can support multi-center research. Limitations include: inclusion of only academic sites with the Epic EHR and lack of data on utilization and sustainability at sites without a prior history of structured template use. Conclusions: Multi-center research collaboration using EHR-based data collection tools is feasible with generally high accuracy compared to manual chart review. Additionally, sites with a long history of template adoption have high levels of provider utilization.



  • Nie J, Breyer BN, Leapman MS. AUTHOR REPLY. Urology. 2022 Jun;164:117. doi: 10.1016/j.urology.2022.01.060. PMID: 35710166.

… We would like to emphasize that the findings in the present study do not imply that private equity acquisition has led to lower access for patients with Medicaid. A more plausible explanation is that private equity firms target higher revenue practices which also have more restrictive Medicaid policies. Our work also highlights the challenges that still exist in increasing healthcare access for the large number of Americans who are now insured through Medicaid.



A phase I/II CTEP study of eribulin (E) for metastic UC (mUC) established the activity of E in UC with objective response rate (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 an ORR of 50%, median OS of 11.9 mo and median PFS of 5.3 mo (N = 24).



Neoadjuvant chemotherapy prior to radical cystectomy and pelvic lymph node dissection (RC+PLND) has been shown to prolong overall survival for patients who are cisplatin (cis) eligible. The standard of care for cis-ineligible pts undergoing surgery does not include neoadjuvant therapy. Therefore, safe and effective neoadjuvant therapies are an unmet need for cis-ineligible pts with muscle invasive bladder cancer (MIBC). Enfortumab vedotin (EV) is an antibody-drug conjugate directed to Nectin-4, which is highly expressed in urothelial cancer, and has been shown to benefit previously treated locally advanced or metastatic urothelial cancer pts in phase 2 and 3 trials, including cis-ineligible pts.



Background: Enfortumab vedotin (EV), an antibody-drug conjugate directed against Nectin-4, demonstrated longer overall survival (OS) and progression-free survival (PFS) in the confirmatory phase 3, randomized, open-label EV-301 trial at the prespecified interim analysis. The longer-term clinical profile of EV is unknown. Data from 12 additional months of follow-up in EV-301 are presented.



Background: Neoadjuvant chemotherapy is the standard of care in muscle-invasive bladder cancer patients. However, treatment is intense, the overall benefit is small, and there is no established marker to identify patients who benefit most. The aim of the study is to characterize cell-free DNA (cfDNA) methylation from patients receiving neoadjuvant chemotherapy in SWOG S1314, a prospective cooperative group trial, and to correlate the methylation signatures with pathologic response.



Background: Severe shortages in clinical trial staffing across the United States and internationally has been anecdotally noted, but data are lacking. To better assess the scope and impact of staffing shortages, SWOG conducted a Cooperative Group-wide survey of Oncology Research Professionals (ORP).



Given rapid changes within certain healthcare markets, we sought to understand whether PE acquisition of urology practices has been associated with increases in volume and change of focus towards higher revenue services in the Medicare population.



Objective: To investigate if peri-tumor and/or intra-tumor vasculature is associated with high grade tumor histology for renal cell carcinoma. Methods A retrospective review at a tertiary care facility was performed of patients who underwent radical nephrectomy or partial nephrectomy for a renal tumor between January 2015 to December 2020. Data of tumor characteristics was collected from final pathology reports. A single radiologist specializing in genitourinary imaging reviewed all pre-operative cross-sectional imaging for peri-tumor vessels and intra-tumor vessels. Single and multivariable logistic regression was utilized to identify variables associated with high grade tumor histology.



Conclusions: We identified access disparities and predictive factors for telehealth availability for colorectal cancer care during the COVID-19 pandemic. These factors should be considered when constructing telehealth policies.



The initial generation of nanoparticles relied on an enhanced permeability and retention effect, associated with an increased penetrability of tumor related blood vessels. With increasing knowledge of biomarkers and molecular targets, active targeting of circulating tumor cells by nanoparticles provides an exciting area for application. The selective targeting of prostate cancer cells using a nanotechnology-based mechanism has the potential to optimize the delivery of therapeutic payloads directly to prostate cancer cells while minimizing systemic toxicities … In this review, we present the molecular biomarkers that have been targeted by ligands conjugated to the surface of nanoparticles for prostate cancer imaging and therapy.



Importance: There are few published studies prospectively assessing pharmacological interventions that may delay prostate cancer progression in patients undergoing active surveillance (AS). Objective: To compare the efficacy and safety of enzalutamide monotherapy plus AS vs AS alone in patients with low-risk or intermediate-risk prostate cancer.



Purpose: The authors aimed to chronicle the evolution of the medical community's study of physician and surgeon pregnancy by investigating thematic trends in the literature in the context of pertinent sociopolitical events.



Conclusions: Although the underlying reasons are not clear, the USPSTF's 2012 PSA screening recommendation may have hindered insured patients from being regularly screened for prostate cancer and selectively led to worse outcomes for insured patients without affecting the survival of uninsured patients.



In this review, we found that use of prostate magnetic resonance imaging (MRI) scans and genetic testing differed by region, and race, with less prostate MRI use among Black versus White patients. These findings can help raise awareness about gaps in access to new prostate cancer tools.