Optimizing outcomes in men with prostate cancer: the cardiovascular event lowering (CaELo) pathways.

INTRODUCTION: Risk of cardiovascular disease is higher among men with prostate cancer than men without, and prostate cancer treatments (especially those that are hormonally based) are associated with increased cardiovascular risk. MATERIALS AND METHODS: An 11-member panel of urologic, medical, and radiation oncologists (along with a men's health specialist and an endocrinologist/preventive cardiologist) met to discuss current practices and challenges in the management of cardiovascular risk in prostate cancer patients who are taking androgen deprivation therapies (ADT) including LHRH analogues, alone and in combination with androgen-targeted therapies (ATTs). RESULTS: The panel developed an assessment algorithm to categorize patients by risk and deploy a risk-adapted management strategy, in collaboration with other healthcare providers (the patient's healthcare "village"), with the goal of preventing as well as reducing cardiovascular events. The panel also developed a patient questionnaire for cardiovascular risk as well as a checklist to ensure that all aspects of cardiovascular disease risk reduction are completed and monitored. CONCLUSIONS: Prostate cancer patients receiving ADT with or without ATT need to be more zealously assessed for prevention and aggressively managed to reduce cardiovascular events. This can and should include participation from the entire multidisciplinary healthcare team.

Telemedicine Utilization in the COVID-19 Era: Patterns of Care in Community Urology Practice.

INTRODUCTION: The acute phase of the COVID-19 pandemic disrupted ambulatory care in the US, and in response telemedicine was adopted rapidly but unevenly across specialties and time. This study examines the utilization of telemedicine in the specialty of urology across a 3-year period (before, during, and after the onset of the pandemic) with the objective of describing patterns, costs, and trends in telemedicine utilization in the specialty. METHODS: The study data were drawn from the adjudicated claims of 1726 providers in 41 independent (privately owned) practices across the US from March 2019 to February 2022. Encounters were indexed to providers to allow for comparisons of utilization across time. Telehealth adoption was defined as the percentage of encounters eligible for reimbursement by telehealth actually conducted by telehealth. RESULTS: A total of 3,630,474 individual patients and 16,130,444 unique encounters were included in our analysis. Telehealth-eligible (evaluation and management) encounters declined sharply from a prepandemic baseline of 262 per provider per month (pppm) to a nadir of 164 pppm in April 2020 (acute phase), but quickly rebounded to 264 pppm by June 2020 (postacute phase). Telehealth adoption among urology providers in this study was 0% prior to March 2020, peaked at 46% in April 2020, and then declined rapidly in the months afterward. CONCLUSIONS: Telehealth adoption in urology spiked abruptly during the acute phase of the pandemic before declining to a low but stable level above prepandemic baseline. These findings may have implications for the broader role of telemedicine in the delivery of urologic care.

Clinical applications of robotic surgery platforms: a comprehensive review.

Robotic surgery has expanded globally across various medical specialties since its inception more than 20 years ago. Accompanying this expansion were significant technological improvements, providing tremendous benefits to patients and allowing the surgeon to perform with more precision and accuracy. This review lists some of the different types of platforms available for use in various clinical applications. We performed a literature review of PubMed and Web of Science databases in May 2023, searching for all available articles describing surgical robotic platforms from January 2000 (the year of the first approved surgical robot, da Vinci® System, by Intuitive Surgical) until May 1st, 2023. All retrieved robotic platforms were then divided according to their clinical application into four distinct groups: soft tissue robotic platforms, orthopedic robotic platforms, neurosurgery and spine platforms, and endoluminal robotic platforms. Robotic surgical technology has undergone a rapid expansion over the last few years. Currently, multiple robotic platforms with specialty-specific applications are entering the market. Many of the fields of surgery are now embracing robotic surgical technology. We review some of the most important systems in clinical practice at this time.

Technical and ethical considerations in telesurgery.

Telesurgery, a cutting-edge field at the intersection of medicine and technology, holds immense promise for enhancing surgical capabilities, extending medical care, and improving patient outcomes. In this scenario, this article explores the landscape of technical and ethical considerations that highlight the advancement and adoption of telesurgery. Network considerations are crucial for ensuring seamless and low-latency communication between remote surgeons and robotic systems, while technical challenges encompass system reliability, latency reduction, and the integration of emerging technologies like artificial intelligence and 5G networks. Therefore, this article also explores the critical role of network infrastructure, highlighting the necessity for low-latency, high-bandwidth, secure and private connections to ensure patient safety and surgical precision. Moreover, ethical considerations in telesurgery include patient consent, data security, and the potential for remote surgical interventions to distance surgeons from their patients. Legal and regulatory frameworks require refinement to accommodate the unique aspects of telesurgery, including liability, licensure, and reimbursement. Our article presents a comprehensive analysis of the current state of telesurgery technology and its potential while critically examining the challenges that must be navigated for its widespread adoption.

Surgical Stone Treatment: Patterns May Predict Performance on Episode-based Cost Measure in the Quality Payment Program.

INTRODUCTION: The Renal or Ureteral Stone Surgical Treatment Episode-based Measure in the Quality Payment Program evaluates clinicians' cost to Medicare for beneficiaries who receive surgical treatment for stones. The measure score is calculated from Medicare claims according to a complex methodology. This paper seeks to describe the stone treatment patterns of urologists and establish benchmarks for 2 surrogate measures-preoperative stenting and postoperative infection-which may predict clinician performance on the episode cost-based measure. METHODS: The study data were drawn from the adjudicated claims of 960 providers who performed at least 30 surgical stone treatments between January 1, 2020, and June 30, 2022. To allow for the correlation of procedures performed by the same providers, generalized estimating equations logistic regression models were used to evaluate the rate of preoperative stenting and postoperative infection. RESULTS: A total of 185,076 surgical episodes (113,799 [61.5%] ureteroscopy, 63,931 [34.5%] extracorporeal shock wave lithotripsy, and 7,346 [4.0%] percutaneous nephrolithotripsy) were identified over the study period. Preoperative stenting was performed in 35,550 episodes (19.2%) and postoperative infection was documented in 13,114 episodes (7.1%). Preoperative stenting and postoperative infection were significantly more common in patients who were female (adjusted OR 1.42, 1.38), in those undergoing ureteroscopy vs extracorporeal shock wave lithotripsy (adjusted OR 3.24, 1.66), and in patients on Medicare vs commercial insurance (adjusted OR 1.19, 1.17). CONCLUSIONS: This large study of surgical stone treatments documents rates of events and associated attributes of patients that may increase episode cost and be relevant to urologists participating in the Quality Payment Program.

Testosterone therapy in prostate cancer: is it still a controversy?

PURPOSE OF REVIEW: The benefits of testosterone therapy (TTh) in the hypogonadal male can be dramatic. Historically, TTh has been contraindicated in prostate cancer (PCa). Current evidence has redefined our understanding of the influence serum testosterone has on prostatic androgen activity. Increasing numbers of hypogonadal men with coexisting PCa emphasizes the importance of describing those who may safely receive TTh. This review aims to present literature that evaluates the efficacy and safety of TTh in men with coexisting PCa. RECENT FINDINGS: Our study, a comprehensive review of published literature regarding TTh in men with a history of PCa, consisted of studies conducted from the 1940s to 2022. Our review discusses evidence in accordance with previous studies that TTh has a role in patients with localized PCa as it has not been reported to increase rates of recurrence or progression of PCa. SUMMARY: The use of TTh in hypongonadal men with a localized PCa has been shown to have positive clinical outcomes without increasing the rate of disease progression or recurrence. Further research, in a randomized controlled setting, is warranted.

Are robots the future? A case for robotic pyeloplasty as the gold standard treatment in ureteropelvic junction obstruction.

PURPOSE OF REVIEW: Robotic pyeloplasty is still a relatively novel procedure. Clinically, early studies have shown high success rates, decreased complication rates, decreased length of hospital stay, and better cosmetic results. This goal of this article is to argue for the use of robotic pyeloplasty as the gold standard of ureteropelvic junction obstruction (UPJO) treatment. Results of studies that have compared robotic pyeloplasty with other procedures currently used are reviewed. RECENT FINDINGS: Our study, a comprehensive review of published outcomes of robotic pyeloplasty and alternative therapies, consisted of 666 pediatric patients and 653 adult patients. Our review coincided with the previously established studies that robotic pyeloplasty shows equivalent surgical success rates as previous standard of care treatments. Open pyeloplasty has fallen out of favor as standard of care due to the increased length of hospital stay, increased adverse events, and the undesirable aesthetics. SUMMARY: The use of robotic pyeloplasty has shown to have clinical outcomes that are consistent with other intervention for UPJO, with a potential decrease in length of stay and morbidity. More work has to be done to develop ways to decrease cost of the robot to help establish it as the gold standard for UPJO treatment.

Optimizing the role of androgen deprivation therapy in advanced prostate cancer: Challenges beyond the guidelines.

BACKGROUND: For specific clinical indications, androgen deprivation therapy (ADT) will induce disease prostate cancer (PC) regression, relieve symptoms and prolong survival; however, ADT has a well-described range of side effects, which may have a detrimental effect on the patient's quality of life, necessitating additional interventions or changes in PC treatment. The risk-benefit analysis for initiating ADT in PC patients throughout the PC disease continuum warrants review. METHODS: A 14-member panel comprised of urologic and medical oncologists were chosen for an expert review panel, to provide guidance on a more judicious use of ADT in advanced PC patients. Panel members were chosen based upon their academic and community experience and expertise in the management of PC patients. Four academic members of the panel served as group leaders; the remaining eight panel members were from Large Urology Group Practice Association practices with proven experience in leading their advanced PC clinics. The panel members were assigned to four separate working groups, and were tasked with addressing the role of ADT in specific PC settings. RESULTS: This article describes the practical recommendations of an expert panel for the use of ADT throughout the PC disease continuum, as well as an algorithm summarizing the key recommendations. The target for this publication is all providers (urologists, medical oncologists, radiation oncologists, or advanced practice providers) who evaluate and manage advanced PC patients, regardless of their practice setting. CONCLUSION: The panel has provided recommendations for monitoring PC patients while on ADT, recognizing that PC patients will progress despite testosterone suppression and, therefore, early identification of conversion from castrate-sensitive to castration resistance is critical. Also, the requirement to both identify and mitigate side effects of ADT as well as the importance of quality of life maintenance are essential to the optimization of patient care, especially as more combinatorial therapeutic strategies with ADT continue to emerge.

The ongoing dilemma in pelvic lymph node dissection during radical prostatectomy: who should decide and in which patients?

Pelvic lymph node dissection (pLND) is considered the most reliable method for the detection of lymph node metastases in prostate cancer. Current clinical guidelines recommend performing pLND in intermediate- and high-risk patients that are defined using different clinical nomograms and different cut-off values. Although the detection of lymph node metastatic disease can identify patients who could benefit from adjuvant therapies and potentially improve prostate cancer-related survival outcomes, so far there has been no level 1 evidence to support this survival benefit. Available retrospective data that suggest oncological benefits are subject to various forms of bias. Furthermore, pLND is not feasible or may be risky in some patient-related conditions, such as morbid obesity and previous history of intraabdominal surgery including organ transplants. In this review, we discuss the current controversies surrounding pLND during robotic-assisted prostatectomy in prostate cancer, specifically the pitfalls in interpretation of restricted evidence suggesting its oncological benefits, and examine the potential influence of patient- and surgeon-related factors that may determine the decision to perform pLND.

Application of Artificial Intelligence/Machine Vision & Learning for the Development of a Live Single-cell Phenotypic Biomarker Test to Predict Prostate Cancer Tumor Aggressiveness.

To assess the usefulness and applications of machine vision (MV) and machine learning (ML) techniques that have been used to develop a single cell-based phenotypic (live and fixed biomarkers) platform that correlates with tumor biological aggressiveness and risk stratification, 100 fresh prostate samples were acquired, and areas of prostate cancer were determined by post-surgery pathology reports logged by an independent pathologist. The prostate samples were dissociated into single-cell suspensions in the presence of an extracellular matrix formulation. These samples were analyzed via live-cell microscopy. Dynamic and fixed phenotypic biomarkers per cell were quantified using objective MV software and ML algorithms. The predictive nature of the ML algorithms was developed in two stages. First, random forest (RF) algorithms were developed using 70% of the samples. The developed algorithms were then tested for their predictive performance using the blinded test dataset that contained 30% of the samples in the second stage. Based on the ROC (receiver operating characteristic) curve analysis, thresholds were set to maximize both sensitivity and specificity. We determined the sensitivity and specificity of the assay by comparing the algorithm-generated predictions with adverse pathologic features in the radical prostatectomy (RP) specimens. Using MV and ML algorithms, the biomarkers predictive of adverse pathology at RP were ranked and a prostate cancer patient risk stratification test was developed that distinguishes patients based on surgical adverse pathology features. The ability to identify and track large numbers of individual cells over the length of the microscopy experimental monitoring cycles, in an automated way, created a large biomarker dataset of primary biomarkers. This biomarker dataset was then interrogated with ML algorithms used to correlate with post-surgical adverse pathology findings. Algorithms were generated that predicted adverse pathology with >0.85 sensitivity and specificity and an AUC (area under the curve) of >0.85. Phenotypic biomarkers provide cellular and molecular details that are informative for predicting post-surgical adverse pathologies when considering tumor biopsy samples. Artificial intelligence ML-based approaches for cancer risk stratification are emerging as important and powerful tools to compliment current measures of risk stratification. These techniques have capabilities to address tumor heterogeneity and the molecular complexity of prostate cancer. Specifically, the phenotypic test is a novel example of leveraging biomarkers and advances in MV and ML for developing a powerful prognostic and risk-stratification tool for prostate cancer patients.

Clinical Proof-of-concept of a Novel Platform Utilizing Biopsy-derived Live Single Cells, Phenotypic Biomarkers, and Machine Learning Toward a Precision Risk Stratification Test for Prostate Cancer Grade Groups 1 and 2 (Gleason 3 + 3 and 3 + 4).

OBJECTIVE: To examine the ability of a novel live primary-cell phenotypic (LPCP) test to predict postsurgical adverse pathology (P-SAP) features and risk stratify patients based on SAP features in a blinded study utilizing radical prostatectomy (RP) surgical specimens. METHODS: Two hundred fifty-one men undergoing RP were enrolled in a prospective, multicenter (10), and proof-of-concept study in the United States. Fresh prostate samples were taken from known areas of cancer in the operating room immediately after RP. Samples were shipped and tested at a central laboratory. Utilizing the LPCP test, a suite of phenotypic biomarkers was analyzed and quantified using objective machine vision software. Biomarkers were objectively ranked via machine learning-derived statistical algorithms (MLDSA) to predict postsurgical adverse pathological features. Sensitivity and specificity were determined by comparing blinded predictions and unblinded RP surgical pathology reports, training MLDSAs on 70% of biopsy cells and testing MLDSAs on the remaining 30% of biopsy cells across the tested patient population. RESULTS: The LPCP test predicted adverse pathologies post-RP with area under the curve (AUC) via receiver operating characteristics analysis of greater than 0.80 and distinguished between Prostate Cancer Grade Groups 1, 2, and 3/Gleason Scores 3 + 3, 3 + 4, and 4 + 3. Further, LPCP derived-biomarker scores predicted Gleason pattern, stage, and adverse pathology with high precision-AUCs>0.80. CONCLUSION: Using MLDSA-derived phenotypic biomarker scores, the LPCP test successfully risk stratified Prostate Cancer Grade Groups 1, 2, and 3 (Gleason 3 + 3 and 7) into distinct subgroups predicted to have surgical adverse pathologies or not with high performance (>0.85 AUC).

Live-cell phenotypic-biomarker microfluidic assay for the risk stratification of cancer patients via machine learning.

The risk stratification of prostate cancer and breast cancer tumours from patients relies on histopathology, selective genomic testing, or on other methods employing fixed formalin tissue samples. However, static biomarker measurements from bulk fixed-tissue samples provide limited accuracy and actionability. Here, we report the development of a live-primary-cell phenotypic-biomarker assay with single-cell resolution, and its validation with prostate cancer and breast cancer tissue samples for the prediction of post-surgical adverse pathology. The assay includes a collagen-I/fibronectin extracellular-matrix formulation, dynamic live-cell biomarkers, a microfluidic device, machine-vision analysis and machine-learning algorithms, and generates predictive scores of adverse pathology at the time of surgery. Predictive scores for the risk stratification of 59 prostate cancer patients and 47 breast cancer patients, with values for area under the curve in receiver-operating-characteristic curves surpassing 80%, support the validation of the assay and its potential clinical applicability for the risk stratification of cancer patients.

Rapid and Short-term Extracellular Matrix-mediated In Vitro Culturing of Tumor and Nontumor Human Primary Prostate Cells From Fresh Radical Prostatectomy Tissue.

OBJECTIVE: To culture prostate cells from fresh biopsy core samples from radical prostatectomy (RP) tissue. Further, given the genetic heterogeneity of prostate cells, the ability to culture single cells from primary prostate tissue may be of importance toward enabling single-cell characterization of primary prostate tissue via molecular and cellular phenotypic biomarkers. METHODS: A total of 260 consecutive tissue samples from RPs were collected between October 2014 and January 2016, transported at 4°C in serum-free media to an off-site central laboratory, dissociated, and cultured. A culture protocol, including a proprietary extracellular matrix formulation (ECMf), was developed that supports rapid and short-term single-cell culture of primary human prostate cells derived from fresh RP samples. RESULTS: A total of 251 samples, derived from RP samples, yielded primary human tumor and nontumor prostate cells. Cultured cells on ECMf exhibit (1) survival after transport from the operating room to the off-site centralized laboratory, (2) robust (>80%) adhesion and survival, and (3) expression of different cell-type-specific markers. Cells derived from samples of increasing Gleason score exhibited a greater number of focal adhesions and more focal adhesion activation as measured by phospho-focal adhesion kinase (Y397) immunofluorescence when patient-derived cells were cultured on ECMf. Increased Ki67 immunofluorescence levels were observed in cells derived from cancerous RP tissue when compared to noncancerous RP tissue. CONCLUSION: By utilizing a unique and defined extracellular matrix protein formulation, tumor and nontumor cells derived from primary human prostate tissue can be rapidly cultured and analyzed within 72 hours after harvesting from RP tissue.

Decision-making tools in prostate cancer: from risk grouping to nomograms.

INTRODUCTION: Prostate cancer (PCa) is the most common solid neoplasm and the second leading cause of cancer death in men. After the Partin tables were developed, a number of predictive and prognostic tools became available for risk stratification. These tools have allowed the urologist to better characterize this disease and lead to more confident treatment decisions for patients. The purpose of this study is to critically review the decision-making tools currently available to the urologist, from the moment when PCa is first diagnosed until patients experience metastatic progression and death. EVIDENCE ACQUISITION: A systematic and critical analysis through Medline, EMBASE, Scopus and Web of Science databases was carried out in February 2016 as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The search was conducted using the following key words: "prostate cancer," "prediction tools," "nomograms." EVIDENCE SYNTHESIS: Seventy-two studies were identified in the literature search. We summarized the results into six sections: Tools for prediction of life expectancy (before treatment), Tools for prediction of pathological stage (before treatment), Tools for prediction of survival and cancer-specific mortality (before/after treatment), Tools for prediction of biochemical recurrence (before/after treatment), Tools for prediction of metastatic progression (after treatment) and in the last section biomarkers and genomics. CONCLUSIONS: The management of PCa patients requires a tailored approach to deliver a truly personalized treatment. The currently available tools are of great help in helping the urologist in the decision-making process. These tests perform very well in high-grade and low-grade disease, while for intermediate-grade disease further research is needed. Newly discovered markers, genomic tests, and advances in imaging acquisition through mpMRI will help in instilling confidence that the appropriate treatments are being offered to patients with prostate cancer.

Live-single-cell phenotypic cancer biomarkers-future role in precision oncology?

The promise of precision and personalized medicine is rooted in accurate, highly sensitive, and specific disease biomarkers. This is particularly true for cancer-a disease characterized by marked tumor heterogeneity and diverse molecular signatures. Although thousands of biomarkers have been described, only a very small number have been successfully translated into clinical use. Undoubtedly, there is need for rapid, quantitative, and more cost effective biomarkers for tumor diagnosis and prognosis, to allow for better risk stratification and aid clinicians in making personalized treatment decisions. This is particularly true for cancers where specific biomarkers are either not available (e.g., renal cell carcinoma) or where current biomarkers tend to classify individuals into broad risk categories unable to accurately assess individual tumor aggressiveness and adverse pathology potential (e.g., prostate cancer), thereby leading to problems of over-diagnosis and over-treatment of indolent cancer and under-treatment of aggressive cancer. This perspective highlights an emerging class of cancer biomarkers-live-single-cell phenotypic biomarkers, as compared to genomic biomarkers, and their potential application for cancer diagnosis, risk-stratification, and prognosis.

A Head-to-Head Comparative Phase II Study of Standard Urine Culture and Sensitivity Versus DNA Next-generation Sequencing Testing for Urinary Tract Infections.

Many studies have discussed clinical practice guidelines for the treatment of cystitis and pyelonephritis. Treatment of uncomplicated urinary tract infections (UTIs) can be based on empiric antibiotic therapy. For complicated or recurrent UTIs, therapy can be based on laboratory-controlled culture and sensitivity (C&S) reports. The diagnosis of UTI by clinical criteria alone has an error rate of up to 33%. In addition, positive laboratory culture results do not always indicate a diagnosis of UTI. Comparison of urine in a conventional culture model versus DNA next-generation sequencing (NGS) to accurately identify and provide information on resistance factors (mobile genetic elements) is warranted. Our study was a head-to-head comparative phase II study of standard urine C&S versus DNA NGS testing for the diagnosis and treatment efficacy in patients with symptoms of acute cystitis based on short-term outcomes.