Targeting genomic receptors in voided urine for confirmation of benign prostatic hyperplasia.

Objectives: The objective of this study is to validate a hypothesis that a non-invasive optical imaging assay targeting genomic VPAC receptors on malignant cells shed in voided urine will represent either benign prostatic hyperplasia (BPH) or prostatic cancer (PCa). Risk for BPH in men 50-70 years old is 50-70% and PCa is 17%. BPH and PCa can coexist in 20% of men with BPH. Most commonly practiced methods to diagnose BPH do not distinguish BPH from PCa. Patients or Materials and Methods: Males with BPH (N = 97, 60.8 ± 6.3 years, prostate-specific antigen 0.7 ± 0.4 ng/mL) and without oncologic disease (N = 35, 63.4 ± 5.8 years, prostate-specific antigen < 1.5 ng/mL) signed informed consent form and provided voided urine. Urine was cytocentrifuged, cells collected on glass slide, fixed, treated with VPAC specific fluorophore TP4303 (Kd 3.1 × 10-8M), washed, incubated with DAPI and observed using a fluorescence microscope. Cells with no VPAC did not fluoresce (BPH) and those with VPAC had red-orange fluorescence (PCa). Real-time polymerase chain reaction analyses for VPAC and NKX3.1 assay for cell origin were performed. Results: Eighty-seven subjects were negative for VPAC expression. Positive VPAC expression was noted in 10 subjects. Patient chart review for clinical data on these 10 VPAC positive subjects showed five had nephrolithiasis, three had renal cysts, one had prostatitis and one was being treated with finasteride. Real-time polymerase chain reaction analysis-VPAC expressions for 7 normal and 12 BPH subjects were 1.31 ± 1.26 and 0.94 ± 0.89, respectively (P = 0.46). NKX3.1 showed cells of prostate origin for finasteride-treated patient. Specificity for VPAC urine assay for excluding prostate cancer in this BPH cohort was 88.5%, positive predictive value 0.00% and negative predictive value 100%. Conclusion: VPAC assay may contribute extensively for BPH diagnosis and warrant continued investigation.

Urine Biopsy as Dynamic Biomarker to Enhance Clinical Staging of Bladder Cancer in Radical Cystectomy Candidates.

PURPOSE: There is significant interest in identifying complete responders to neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) to potentially avoid removal of a pathologically benign bladder. However, clinical restaging after NAC is highly inaccurate. The objective of this study was to develop a next-generation sequencing-based molecular assay using urine to enhance clinical staging of patients with bladder cancer. METHODS: Urine samples from 20 and 44 patients with bladder cancer undergoing RC were prospectively collected for retrospective analysis for molecular correlate analysis from two clinical trials, respectively. The first cohort was used to benchmark the assay, and the second was used to determine the performance characteristics of the test as it correlates to responder status as measured by pathologic examination. RESULTS: First, to benchmark the assay, known mutations identified in the tissue (MT) of patients from the Accelerated Methotrexate, Vinblastine, Doxorubicin, Cisplatin trial (ClinicalTrials.gov identifier: NCT01611662, n = 16) and a cohort from University of California-San Francisco (n = 4) were cross referenced against mutation profiles from urine (MU). We then determined the correlation between MU persistence and residual disease in pre-RC urine samples from a second prospective clinical trial (The pT0 trial; ClinicalTrials.gov identifier: NCT02968732). Residual MU status correlated strongly with residual disease status (pT0 trial; n = 44; P = .0092) when MU from urine supernatant and urine pellet were assessed separately and analyzed in tandem. The sensitivity, specificity, PPV, and NPV were 91%, 50%, 86%, and 63% respectively, with an overall accuracy of 82% for this second cohort. CONCLUSION: MU are representative of MT and thus can be used to enhance clinical staging of urothelial carcinoma. Urine biopsy may be used as a reliable tool that can be further developed to identify complete response to NAC in anticipation of safe RC avoidance.

Risk of Secondary Malignancies After Pelvic Radiation: A Population-based Analysis.

Background and objective: Radiation therapy has increasingly been used in the management of pelvic malignancies. However, the use of radiation continues to pose a risk of a secondary malignancy to its recipients. This study investigates the risk of secondary malignancy development following radiation for primary pelvic malignancies. Methods: A retrospective cohort review of the Surveillance, Epidemiology, and End Results database from 1975 to 2016 was performed. Primary pelvic malignancies were subdivided based on the receipt of radiation, and secondary malignancies were stratified as pelvic or nonpelvic to investigate the local effect of radiation. Key findings and limitations: A total of 2 102 192 patients were analyzed (1 189 108 with prostate, 315 026 with bladder, 88 809 with cervical, 249 535 with uterine, and 259 714 with rectal/anal cancer). The incidence rate (defined as cases per 1000 person years) of any secondary malignancies (including but not limited to secondary pelvic malignancies) was higher in radiation patients than in nonradiation patients (incidence rate ratio [IRR] 1.04, confidence interval [CI] 1.03-1.05), with significantly greater rates noted in radiation patients with prostate (IRR 1.22, CI 1.21-1.24), uterine (IRR 1.34), and cervical (IRR 1.80, CI 1.72-1.88) cancer. While the overall incidence rate of any secondary pelvic malignancy was lower in radiation patients (IRR 0.79, CI 0.78-0.81), a greater incidence was still noted in the same cohorts including radiation patients with prostate (IRR 1.42, CI 1.39-1.45), uterine (IRR 1.15, CI 1.08-1.21), and cervical (IRR 1.72, CI 1.59-1.86) cancer. Conclusions and clinical implications: Except for localized cervical cancer, when put in the context of median overall survival, the impact of radiation likely does not carry enough weight to change practice patterns. Radiation for pelvic malignancies increases the risk for several secondary malignancies, and more specifically, secondary pelvic malignancies, but with a relatively low absolute risk of secondary malignancies, the benefits of radiation warrant continued use for most pelvic malignancies. Practice changes should be considered for radiation utilization in malignancies with excellent cancer-specific survival such as cervical cancer. Patient summary: The use of radiation for the management of pelvic malignancies induces a risk of secondary malignancies to its recipients. However, the absolute risk being low, the benefits of radiation warrant its continued use, and a change in practice patterns is unlikely.

Model risk scores may underestimate rate of biochemical recurrence in African American men with localized prostate cancer: a cohort analysis of over 3000 men.

INTRODUCTION: This study aims to determine if there is a difference in prostate cancer nomogram-adjusted risk of biochemical recurrence (BCR) and/or adverse pathology (AP) between African American (AAM) and Caucasian men (CM) undergoing radical prostatectomy (RP). METHODS: A retrospective review was performed of men undergoing RP in the Pennsylvania Urologic Regional Collaborative between 2015 and 2021. Cox proportional hazard regression models were used to compare the rate of BCR after RP, and logistic regression models were used to compare rates of AP after RP between CM and AAM, adjusting for the CAPRA, CAPRA-S, and MSKCC pre- and post-operative nomogram scores. RESULTS: Rates of BCR and AP after RP were analyzed from 3190 and 5029 men meeting inclusion criteria, respectively. The 2-year BCR-free survival was lower in AAM (72.5%) compared to CM (79.0%), with a hazard ratio (HR) of 1.38 (95% CI 1.16-1.63, p < 0.001). The rate of BCR was significantly greater in AAM compared to CM after adjustment for MSKCC pre-op (HR 1.29; 95% CI 1.08-1.53; p = 0.004), and post-op nomograms (HR 1.26; 95% CI 1.05-1.49; p < 0.001). There was a trend toward higher BCR rates among AAM after adjustment for CAPRA (HR 1.13; 95% CI 0.95-1.35; p = 0.17) and CAPRA-S nomograms (HR 1.11; 95% 0.93-1.32; p = 0.25), which did not reach statistical significance. The rate of AP was significantly greater in AAM compared to CM after adjusting for CAPRA (OR 1.28; 95% CI 1.10-1.50; p = 0.001) and MSKCC nomograms (OR 1.23; 95% CI 1.06-1.43; p = 0.007). CONCLUSION: This analysis of a large multicenter cohort provides further evidence that AAM may have higher rates of BCR and AP after RP than is predicted by CAPRA and MSKCC nomograms. Accordingly, AAM may benefit with closer post-operative surveillance and may be more likely to require salvage therapies.

Enhancing bladder cancer care through the multidisciplinary clinic approach.

INTRODUCTION: To report the impact of our 25-year multidisciplinary care delivery model experience on patients with muscle invasive bladder cancer treated at our National Cancer Institute (NCI)-designated Sidney Kimmel Cancer Center at Jefferson University. To our knowledge, our multidisciplinary genitourinary cancer clinic (MDC) is the longest continuously operating center of its kind at an NCI Cancer Center in the United States. MATERIALS AND METHODS: We selected a recent group of patients with cT2-4 N0-1 M0 bladder cancer seen in the Sidney Kimmel Cancer Center Genitourinary Oncology MDC from January 2016 to September 2019. These patients were identified retrospectively. SEER-18 (Surveillance, Epidemiology, and End Results) database, November 2019 submission was queried to obtain patients with similarly staged disease diagnosed between 2015 and 2017. Completion rates of radical cystectomy, use of neoadjuvant therapies, and survival outcomes were compared between the two cohorts. RESULTS: Ninety-one patients from the MDC form this time period were identified; 65.9% underwent radical cystectomy and 71.8% received neoadjuvant therapy in the form of chemotherapy, immune checkpoint inhibition or a combination of the two - higher than reported national trends for neoadjuvant therapies. Progression of disease was seen in 24.2% of patients. A total of 8675 patients met inclusion criteria in the SEER database. Rates of radical cystectomy were significantly higher in MCD patients when compared to SEER derived data (65.9% vs. 37.7%, p =< 0.001). MCD patients had significantly better cancer-specific survival (mean 20.4 vs. 18.3 months p = 0.028, median survival not reached). CONCLUSION: Our long term experience caring for patients with genitourinary malignancies such as bladder cancer in a uniform multidisciplinary team results in a high utilization of neoadjuvant therapies. When compared to a contemporary SEER-derived cohort, multidisciplinary patients were more likely to undergo radical cystectomy and had longer cancer-specific survival.

Multiparametric MRI is not sufficient for prostate cancer staging: A single institutional experience validated by a multi-institutional regional collaborative.

OBJECTIVE: Multiparametric magnetic resonance imaging (mpMRI) has been increasingly utilized in prostate cancer (CaP) diagnosis and staging. While Level 1 data supports MRI utility in CaP diagnosis, there is less data on staging utility. We sought to evaluate the real-world accuracy of mpMRI in staging localized CaP. MATERIALS AND METHODS: Men who underwent radical prostatectomy (RP) for CaP in 2021 at our institution were identified. Sensitivity, specificity, positive predictive value and negative predictive value of mpMRI in predicting pT2N0 organ confined disease , extracapsular extension , seminal vesicle invasion , lymph node involvement, and bladder neck invasion were evaluated. Associations between MRI accuracy and AUA risk stratification (AUA RS), MRI institution (MRI-I), MRI strength (1.5 vs. 3T) (MRI-S), and MRI timing (MRI-T) were assessed. These analyses were repeated using Pennsylvania Urologic Regional Collaborative (PURC) data. RESULTS: Institutional and community mpMRI CaP staging data demonstrated poor sensitivity (2.9%-49.2%% vs. 16.8%-24.4%), positive predictive value (40%-100% vs. 35.8%-68.2%), and negative predictive value (56.3%-94.3% vs. 68.4%-96.2%) in predicting surgical pathologic features - in contrast, specificity (89.1%-100% vs. 93.9%-98.6%) was adequate. mpMRI accuracy for extracapsular extension, seminal vesicle invasion, and lymph node involvement was significantly (p < 0.001) associated with AUA RS. There was no association between mpMRI accuracy and MRI-I, MRI-S, and MRI-T. CONCLUSION: Despite enthusiasm for its use, in a real-world setting, mpMRI appears to be a poor staging study for localized CaP and is unreliable as the sole means of staging patients prior to prostatectomy. mpMRI should be used cautiously as a staging tool for CaP, and should be interpreted considering individual patient risk strata.

The use of individualized 3D-printed models on trainee and patient education, and surgical planning for robotic partial nephrectomies.

3D printing is a growing tool in surgical education to visualize and teach complex procedures. Previous studies demonstrating the usefulness of 3D models as teaching tools for partial nephrectomy used highly detailed models costing between $250 and 1000. We aimed to create thorough, inexpensive 3D models to accelerate learning for trainees and increase health literacy in patients. Patient-specific, cost-effective ($30-50) 3D models of the affected urologic structures were created using pre-operative imaging of 40 patients undergoing partial nephrectomy at Thomas Jefferson University Hospital (TJUH) between July 2020 and May 2021. Patients undergoing surgery filled out a survey before and after seeing the model to assess patient understanding of their kidney, pathophysiology, surgical procedure, and risks of surgery. Three urological residents, one fellow, and six attendings filled out separate surveys to assess their surgical plan and confidence before and after seeing the model. In a third survey, they ranked how much the model helped their comprehension and confidence during surgery. Patient understanding of all four subjects significantly improved after seeing the 3D model (P < 0.001). The urology residents (P < 0.001) and fellow (P < 0.001) reported significantly increased self-confidence after interacting with the model. Attending surgeon confidence increased significantly after seeing the 3D model (P < 0.01) as well. Cost-effective 3D models are effective learning tools and assist with the evaluation of patients presenting with renal masses, and increase patient, resident, and fellow understanding in partial nephrectomies. Further research should continue to explore the utility of inexpensive models in other urologic procedures.

Volumetric Quantitative Contrast-enhanced Ultrasonography Evaluation of Complex Renal Cysts: An Adjunctive Metric to the Bosniak Classification System to Predict Malignancy.

BACKGROUND: Management of complex renal cysts is guided by the Bosniak classification system, which may be inadequate for risk stratification of patients for intervention. Fractional tumor vascularity (FV) calculated from volumetric contrast-enhanced ultrasound (CEUS) images may provide additional useful information. OBJECTIVE: To evaluate CEUS and FV calculation for risk stratification of patients with complex renal cysts. DESIGN, SETTING, AND PARTICIPANTS: This was a pilot prospective study with institutional review board approval involving patients undergoing surgery for Bosniak IIF-IV complex renal cysts. CEUS was performed preoperatively on the day of surgery with two-dimensional (2D) and three-dimensional (3D) imaging and sulfur hexafluoride lipid-type A microspheres as the ultrasound contrast agent. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A custom MATLAB program was used to select regions of interest on CEUS scans. FV was calculated according to FV = 1 - (total nonenhancing area/total lesion area). We assessed the ability of 2D- and 3D-derived percentage FV (2DFV%, and 3DFV%) and Bosniak classification schemes (pre-2019 [P2019B] and post-2019 [B2019]) to predict malignancy, aggressive histology, and upstaging on surgical pathology. Performance was assessed as area under the receiver operating characteristic curve (AUC). RESULTS AND LIMITATIONS: Twenty eligible patients were included in final analysis, of whom 85% (n = 17) had Bosniak IV cysts and 85% (n = 17) had malignant disease on final pathology. Four (24%) of the malignant lesions were International Society of Urological Pathology grade 3-4. The AUC for predicting malignancy was 0.980, 0.824, 0.863, and 0.824 with P2019B, B2019, 2DFV%, and 3DFV%, respectively. When the Bosniak classification was combined with FV%, three models had an AUC of 1, while the combined 2DFV% + B2019 model had AUC of 0.980. CONCLUSIONS: FV is a novel metric for evaluating complex cystic renal masses and enhances the ability of the Bosniak classification system to predict malignancy. This metric may serve as an adjunct in risk stratification for surgical intervention. Further prospective evaluation is warranted. PATIENT SUMMARY: Cysts in the kidney are currently classified using a scheme called the Bosniak system. We assessed measurement of the percentage of vascular tissue (called fractional vascularity) in cysts on a special type of ultrasound scan. This promising test adds information when combined with the Bosniak system and can help in guiding appropriate treatment.

The evolving role of contrast-enhanced ultrasound in urology: a review.

PURPOSE: Ultrasound's versatility and ease of use has expanded its application in many clinical settings. Technological advancements with contrast-enhanced ultrasound (CEUS) have allowed high quality imaging similar to CT or MRI with lower risk of contrast toxicity and radiation exposure. In this review article we examine the development of CEUS and its vast applications in the field of urology. METHODS: A PubMed literature search was performed using keywords: contrast enhanced ultrasound, prostate cancer, renal cancer, and multiparametric ultrasound. RESULTS: The development of CEUS has improved transrectal ultrasound imaging with increased detection of prostate cancer (PCa). Further enhancements of CEUS such as subharmonic imaging (SHI), flash replenishment imaging (FRI) and contrast ultrasound dispersion imaging (CUDI) allow improved PCa diagnosis. CEUS has also emerged as an important tool in characterizing suspicious renal mass without compromising renal function with contrast imaging. CONCLUSION: CEUS has modernized imaging and diagnosis of prostate and renal cancer. Future advancements and utilization of CEUS will allow its expansion into other urological subspecialties.

IL-15 Superagonist NAI in BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer.

BACKGROUND: Patients with Bacillus Calmette­Guérin (BCG)­unresponsive non­muscle-invasive bladder cancer (NMIBC) have limited treatment options. The immune cell­activating interleukin-15 (IL-15) superagonist Nogapendekin alfa inbakicept (NAI), also known as N-803, may act synergistically with BCG to elicit durable complete responses (CRs) in this patient population. METHODS: In this open-label, multicenter study, patients with BCG-unresponsive bladder carcinoma in situ (CIS) with or without Ta/T1 papillary disease were treated with intravesical NAI plus BCG (cohort A) or NAI alone (cohort C). Patients with BCG-unresponsive high-grade Ta/T1 papillary NMIBC also received NAI plus BCG (cohort B). The primary end point was the incidence of CR at the 3- or 6-month assessment visit for cohorts A and C, and the disease-free survival (DFS) rate at 12 months for cohort B. Durability, cystectomy avoidance, progression-free survival, disease-specific survival (DSS), and overall survival were secondary end points for cohort A. RESULTS: In cohort A, CR was achieved in 58 (71%) of 82 patients (95% confidence interval [CI]=59.6 to 80.3; median follow-up, 23.9 months), with a median duration of 26.6 months (95% CI=9.9 months to [upper bound not reached]). At 24 months in patients with CR, the Kaplan­Meier estimated probability of avoiding cystectomy and of DSS was 89.2% and 100%, respectively. In cohort B (n=72), the Kaplan­Meier estimated DFS rate was 55.4% (95% CI=42.0% to 66.8%) at 12 months, with median DFS of 19.3 months (95% CI=7.4 months to [upper bound not reached]). Most treatment-emergent adverse events for patients receiving BCG plus NAI were grade 1 to 2 (86%); three grade 3 immune-related treatment-emergent adverse events occurred. CONCLUSIONS: In patients with BCG-unresponsive bladder carcinoma in situ and papillary NMIBC treated with BCG and the novel agent NAI, CRs were achieved with a persistence of effect, cystectomy avoidance, and 100% bladder cancer­specific survival at 24 months. The study is ongoing, with an estimated target enrollment of 200 participants (Funded by ImmunityBio.)

Does antithrombotic use enable earlier diagnosis of bladder cancer? A brief institutional assessment.

INTRODUCTION: Wallis et al (JAMA 2017) demonstrated use of antithrombotic medications (ATMs) is associated with increased prevalence of hematuria-related complications and subsequent bladder cancer diagnosis within 6 months. Stage of diagnosis was lacking in this highly publicized study. This study examined the association of ATM use on bladder cancer stage at the time of diagnosis. MATERIALS AND METHODS: We completed a retrospective chart review of patients with a bladder cancer diagnosis at our institution. Patient demographics and bladder cancer work up information were assessed. Patients were stratified based on use of ATMs at time diagnosis. Descriptive statistics were completed to identify association between ATM use and stage of bladder cancer diagnosis, as stratified by non-muscle invasive bladder cancer (NMIBC) versus muscle invasive bladder cancer (MIBC). RESULTS: A total of 1052 patient charts were reviewed. Eight hundred and forty-four were included and 208 excluded due to unavailability of diagnosis history. At diagnosis, 357 (42.3%) patients were taking ATMs. Patients on ATMs presented with NMIBC at similar rates as patients not taking ATMs (81.2% vs. 77.8%, p = 0.23). Subgroup analysis by ATM class similarly demonstrated no statistically significant differences in staging. CONCLUSION: While Wallis et al established that patients on blood thinners who present with hematuria are more likely to be diagnosed with genitourinary pathology, this factor does not appear to enable an earlier diagnosis of bladder cancer. Future study may assess hematuria at presentation (gross, microscopic), type of blood thinners, and low versus high risk NMIBC presentation.

Non-infectious complications following transrectal prostate needle biopsy - Outcomes from over 8000 procedures.

Background: Prostate needle biopsy (PNB) remains the referent standard for diagnosing prostate cancer. Contemporary data highlight an increase in PNB-related infections particularly when performed transrectally. Non-infectious complications, however, may similarly contribute to biopsy-related morbidity. We review the incidence and predictors of non-infectious complications following transrectal PNB in a large statewide quality registry. Methods: Transrectal ultrasound-guided prostate needle biopsies performed between 2015 and 2018 were retrospectively reviewed. The incidence and distribution of non-infectious complications were annotated. Clinical, demographic, and biopsy variables of interest were evaluated by logistic regression for potential association with specific types of non-infectious complications. Results: Of 8,102 biopsies, 277 (3.4%) biopsies had reported post-procedure complications including 199 (2.5%) non-infectious and 78 (0.9%) infectious. Among the non-infectious complications, the most common events included urinary or rectal bleeding (74; 0.9%), urinary retention (70, 0.9%), vasovagal syncope (13, 0.2%), and severe post-operative pain (10, 0.1%). Approximately 56% of these non-infectious complications required an Emergency Department visit (111/199) and 27% (54/199) hospital admission for monitoring. Increasing transrectal ultrasound prostate volume was associated with post-procedure urinary retention (Odds ratio (OR) 1.07, 1.02-1.11, p = 0.002). No specific variables noted association with post-biopsy bleeding. Conclusion: Non-infectious complications occurred 2.5 times more often than infectious complications following transrectal ultrasound prostate needle biopsies. Larger prostate size was associated with a greater risk of post-procedure urinary retention. These data originating from experience from over 100 urologists across different health systems provide an important framework in counseling patients regarding expectations following transrectal prostate biopsy.

Utility of PSA density in patients with PI-RADS 3 lesions across a large multi-institutional collaborative.

INTRODUCTION: Prostate MRI detecting PI-RADs = 3 lesions has low diagnostic utility for prostate malignancy. Use of PSA density has been suggested to further risk-stratify these men, to potentially avoid biopsies in favor of monitoring. We evaluate the ability of PSA density (PSAd) to risk-stratify PIRADs 3 lesions across patients who underwent a prostate biopsy in a large multi-institutional collaborative. MATERIALS AND METHODS: Pennsylvania Urology Regional Collaborative (PURC) is a voluntary quality improvement collaborative of 11 academic and community urology practices in Pennsylvania and New Jersey. A retrospective analysis was performed on all patients in the PURC database that had a prostate MRI with PI-RADs 3 lesions only. PSA just before the MRI and prostate size reported on MRI were used to calculate the PSA. Clinicopathologic data were evaluated. Univariable analysis using Chi-Square and Kruskal Wallis tests and multivariable logistic regression were used to identify predictors of any PCa, and clinically significant prostate cancer (csPCa) was defined as ≥ Grade Group 2 (GG2.) RESULTS: Between May 2015 and March 2021, 349 patients with PIRADs 3 lesions only were identified and comprised the cohort of interest. Median PSA was 5.0 with a prostate volume of 58cc and a median PSA density of 0.11, 10.6% of the cohort was African American with 81.4% being Caucasian. Significant prostate cancer was detected in 70/349 (20.0%) men. Smaller prostate volume, abnormal DRE, and higher PSAd were significantly associated with clinically significant prostate cancer on univariable analysis. In men with PSAd <0.15, 31/228 (13.6%) harbored csPCa. Multivariable analysis confirmed that men with PSAd >0.15 were more likely to harbor clinically significant prostate cancer (P < 0.001). CONCLUSION: Across a large regional collaborative, patients with PIRADs 3 lesions on mpMRI were noted to have clinically significant cancer in 20% of biopsies. Using a PSA density cut-off of 0.15 may result in missing clinically significant prostate cancer in 13.6%. This information is useful for prebiopsy risk stratification and counseling.

Safety of repeat blue light cystoscopy with hexaminolevulinate (HAL) in the management of bladder cancer: Results from a phase III, comparative, multi-center study.

PURPOSE: The therapeutic benefit of intravesical instillation of hexaminolevulinate (HAL) at the time of transurethral resection of bladder tumor (TURBT) has been demonstrated in multiple studies. The purpose of this study was to prospectively assess the safety of repeated administration of HAL from a phase III pre-trial planned analysis. MATERIALS AND METHODS: All patients evaluated in the study received at least 1 dose of HAL at the time of office cystoscopy, and a subset of these patients (n = 103, 33.2%) received a second dose a few weeks later at the time of TURBT. Adverse events (AEs) were recorded, and the safety of repeat use of HAL was determined by comparing the proportion of patients with AEs considered causally related to HAL in the surveillance examination compared to the OR examination. Association between categorical variables was tested using Fisher's Exact Test, and a P < 0.05 was considered statistically significant. RESULTS: HAL-related AEs were experienced by 6 patients (2.2%) during surveillance cystoscopy and 3 patients (3.4%) following TURBT (P = 0.76); 181 patients (59.5%) had prior exposure to HAL before enrolling in the study with no difference in the number of AEs when comparing prior exposure to HAL to no prior exposure (P = 0.76). Of the patients who previously received intravesical therapy, 8 (2.9%) had at least 1 AE during surveillance compared to 3 (9.7%) who had no prior intravesical therapy (P = 0.09). CONCLUSIONS: Repeat use of HAL is safe even when administered within a few weeks of receiving a dose of intravesical therapy.

Technology-enhanced AcceleRation of Germline Evaluation for Therapy (TARGET): A randomized controlled trial of a pretest patient-driven webtool vs. genetic counseling for prostate cancer germline testing.

BACKGROUND: Germline testing has an increasingly important role in prostate cancer care. However, a relative shortage of genetic counselors necessitates alternate strategies for delivery of pre-test education for germline testing. This study, funded by the Prostate Cancer Foundation, seeks to address the need for novel methods of delivery of pre-test germline education beyond traditional germline counseling to facilitate informed patient decision-making for germline testing. METHODS: This is a two-armed randomized controlled trial (RCT) with a target enrollment of 173 participants with prostate cancer per study arm (total anticipated n = 346). Patients who meet criteria for germline testing based on tumor features, family history or Ashkenazi Jewish ancestry are being recruited from 5 US sites including academic, private practice and Veterans healthcare settings. Consenting participants are randomized to the interactive pretest webtool or germline counseling with assessment of key patient-reported outcomes involved in informed decision-making for germline testing. RESULTS: Participants complete surveys at baseline, after pretest education/counseling, and following disclosure of germline results. The primary outcome of the study is decisional conflict for germline testing. Secondary outcomes include genetic knowledge, satisfaction, uptake of germline testing, and understanding of results. CONCLUSION: Our hypothesis is that the web-based genetic education tool is non-inferior to traditional genetic counseling regarding key patient-reported outcomes involved in informed decision-making for germline testing. If proven, the results would support deploying the webtool across various practice settings to facilitate pre-test genetic education for individuals with prostate cancer and developing collaborative care strategies with genetic counseling. CLINICALTRIALS: gov Identifier: NCT04447703.

Helix: A Digital Tool to Address Provider Needs for Prostate Cancer Genetic Testing in Clinical Practice.

BACKGROUND: Prostate cancer (PCA) germline testing (GT) is now standard-of-care for men with advanced PCA. Thousands of men may consider GT due to clinical and family history (FH) features. Identifying and consenting men for GT can be complex. Here we identified barriers and facilitators of GT across a spectrum of providers which informed the development of Helix - an educational and clinical/FH collection tool to facilitate GT in practice. MATERIALS AND METHODS: A 12-question survey assessing knowledge of genetics PCA risk and FH was administered December 2017 to March 2018 in the Philadelphia area and at the Mid-Atlantic AUA meeting (March 2018). Responses were analyzed using descriptive statistics. Semi-structured interviews were conducted with medical oncologists, radiation oncologists, and urologists across practice settings from March-October 2020 as part of a larger study based on the Tailored Implementation in Chronic Diseases framework. Helix was then developed followed by user testing. RESULTS: Fifty-six providers (50% urologists) responded to the survey. Multiple FH and genetic knowledge gaps were identified: only 66% collected maternal FH and 43% correctly identified BRCA2 and association to aggressive PCA. Genetic counseling gaps included low rates of discussing genetic discrimination laws (45%). Provider interviews (n = 14) identified barriers to FH intake including access to details and time needed. In user testing (n = 10), providers found Helix helpful for FH collection. All providers found Helix easy to use, suggesting expanded clinical use. CONCLUSION: Helix addressed multiple GT knowledge and practice gaps across a spectrum of providers. This tool will become publicly available soon to facilitate PCA GT in clinical practice.

Contrast-Enhanced Ultrasound and Shear Wave Elastography: Novel Methods for the Evaluation of Urethral Stricture Disease.

PURPOSE: Urologists will benefit from an imaging modality which can assess intra and extraluminal characteristics of urethral strictures. We conducted a prospective pilot study evaluating the utility of contrast-enhanced ultrasound and shear wave elastography for the evaluation of bulbar urethral stricture disease. MATERIALS AND METHODS: Patients with a single, bulbar urethral stricture were prospectively recruited. Contrast-enhanced ultrasound and shear wave elastography were performed at the time of surgical repair and at 4 months' followup using an Aplio i800 scanner (Canon Medical Systems, Tustin, California) with an i8CX1 transducer. Sulfur hexafluoride lipid-type A microsphere ultrasound contrast (Lumason®, Bracco Imaging, Princeton, New Jersey) was injected retrograde through the urethra. Stiffness of the corpus spongiosum was measured at and adjacent to the stricture site. Stricture lengths based on retrograde urethrogram, grayscale ultrasound and contrast-enhanced ultrasound were correlated with measured intraoperative stricture length. RESULTS: Thirty men were enrolled. Contrast-enhanced ultrasound (R2=0.709) showed the best correlation with intraoperative measured stricture length compared to retrograde urethrogram (R2=0.016) or grayscale ultrasound (R2=0.471). Stiffness of the spongiosum was greater at the site of the stricture (32.6±5.4 vs 27.3±5.8 kPa, p=0.044) and in narrower caliber strictures (p=0.044) but did not differ by stricture length (p=0.182). At followup (4.3±1.1 months) contrast-enhanced ultrasound detected stricture recurrence with 80% sensitivity, 100% specificity, and 93% accuracy compared to cystoscopy. CONCLUSIONS: This pilot study demonstrates the ability of contrast-enhanced ultrasound and shear wave elastography to become safe, accurate, and potentially efficacious modalities for assessing bulbar urethral strictures and spongiofibrosis.

Salvage Low-Dose-Rate Prostate Brachytherapy: Clinical Outcomes of a Phase 2 Trial for Local Recurrence after External Beam Radiation Therapy (NRG Oncology/RTOG 0526).

PURPOSE: We report efficacy of a prospective phase 2 trial (NCT00450411) of salvage low-dose-rate (LDR) prostate brachytherapy (BT) for local failure (LF) after prior external beam radiation therapy (EBRT) with minimum 5-years' follow-up. METHODS AND MATERIALS: Eligible patients had low/intermediate risk prostate cancer (PCa) before EBRT and biopsy-proven LF >30 months after EBRT, with prostate-specific antigen <10 ng/mL and no regional/distant disease. The primary endpoint, late gastrointestinal and genitourinary adverse events (Common Terminology Criteria for Adverse Events v3.0) grade ≥3 were 14%. With minimum 5-year follow-up after salvage BT, secondary clinical outcomes including disease-free survival (DFS; includes death from any cause), disease-specific survival, and overall survival (OS) were estimated using the Kaplan-Meier method and modelled using Cox proportional hazards regression. Local tumor progression (ie, LF), distant failure (DF), and biochemical failure (BF) were estimated using cumulative incidence. Time to LF, DF, and BF were modeled by cause-specific Cox proportional hazards regression. RESULTS: From May 2007 to January 2014, 20 centers registered 100 patients (92 analyzable). Median follow-up is 6.7 years (range, 0.3-11.2); median age 70 years (range, 55-82); median prior EBRT dose 74 Gy [interquartile range (IQR):70 - 76] at a median of 85 months prior (IQR 60-119 months). Androgen deprivation was combined with salvage BT in 16%. Ten-year OS is 70% [95% confidence interval (CI) 58% - 83%]. Nineteen patients died (5 PCa, 10 other, 4 unknown). Ten-year failure rates are local 5% (95% CI, 1-11), distant 19% (95% CI, 10-29), and biochemical 46% (95% CI, 34-57). DFS is 61% at 5 years and 33% at 10 years. No baseline characteristic was significantly associated with any clinical outcome. CONCLUSIONS: This is the first prospective multicenter trial reporting outcomes of salvage LDR BT for LF after EBRT. Five-year freedom from BF is 68%, comparable to other salvage modalities. Although further LF is rare (5%), BF climbs to 46% by 10 years.

Pretest Genetic Education Video Versus Genetic Counseling for Men Considering Prostate Cancer Germline Testing: A Patient-Choice Study to Address Urgent Practice Needs.

PURPOSE: Germline testing (GT) for prostate cancer (PCA) is now central to treatment and hereditary cancer assessment. With rising demand for and shortage of genetic counseling (GC), tools to deliver pretest informed consent across practice settings are needed to improve access to GT and precision care. Here, we report on Evaluation and Management for Prostate Oncology, Wellness, and Risk (EMPOWER), a patient-choice study for pretest video-based genetic education (VBGE) versus GC to inform urgent practice needs. PATIENTS AND METHODS: Men with PCA or at risk for PCA (family history of PCA) were eligible and could choose pretest VBGE or GC. Outcomes included decisional conflict for GT, change in genetics knowledge, satisfaction, and intention to share results with family and/or providers. Descriptive statistics summarized results with counts and percentages for categorical variables and mean ± standard deviation for continuous variables. Data were compared with Fisher's exact, chi-squared, or Wilcoxon two-sample tests. Mean change in genetics knowledge was compared with t tests. The significance level was set a priori at .05. RESULTS: Data on the first 127 participants were analyzed. Characteristics were White (85.8%), bachelor's degree (66.9%), and PCA diagnosis (90.6%). The majority chose VBGE (71%) versus GC (29%; P < .001). No differences were observed in decisional conflict for GT or satisfaction. Cancer genetics knowledge improved in both groups without significant difference (+0.9 VBGE, +1.8 GC, P = .056). Men who chose VBGE had higher intention to share GT results (96.4% VBGE v 86.4% GC, P = .02). Both groups had high rates of GT uptake (VBGE 94.4%, GC 92%). CONCLUSION: A substantial proportion of men opted for pretest VBGE, with comparable patient-reported outcomes and uptake of GT. The results support the use of pretest video to address the critical GC shortage in the precision era.