CD8+ T cell targeting of tumor antigens presented by HLA-E.

The nonpolymorphic major histocompatibility complex E (MHC-E) molecule is up-regulated on many cancer cells, thus contributing to immune evasion by engaging inhibitory NKG2A/CD94 receptors on NK cells and tumor-infiltrating T cells. To investigate whether MHC-E expression by cancer cells can be targeted for MHC-E-restricted T cell control, we immunized rhesus macaques (RM) with rhesus cytomegalovirus (RhCMV) vectors genetically programmed to elicit MHC-E-restricted CD8+ T cells and to express established tumor-associated antigens (TAAs) including prostatic acidic phosphatase (PAP), Wilms tumor-1 protein, or Mesothelin. T cell responses to all three tumor antigens were comparable to viral antigen-specific responses with respect to frequency, duration, phenotype, epitope density, and MHC restriction. Thus, CMV-vectored cancer vaccines can bypass central tolerance by eliciting T cells to noncanonical epitopes. We further demonstrate that PAP-specific, MHC-E-restricted CD8+ T cells from RhCMV/PAP-immunized RM respond to PAP-expressing HLA-E+ prostate cancer cells, suggesting that the HLA-E/NKG2A immune checkpoint can be exploited for CD8+ T cell-based immunotherapies.

Link between circadian rhythm and benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS).

BACKGROUND: Benign prostatic hyperplasia (BPH) is the most common urologic disease in aging males, affecting 50% of men over 50 and up to 80% of men over 80 years old. Its negative impact on health-related quality of life implores further investigation into its risk factors and strategies for effective management. Although the exact molecular mechanisms underlying pathophysiological onset of BPH are poorly defined, the current hypothesized contributors to BPH and lower urinary tract symptoms (LUTS) include aging, inflammation, metabolic syndrome, and hormonal changes. These processes are indirectly influenced by circadian rhythm disruption. In this article, we review the recent evidence on the potential association of light changes/circadian rhythm disruption and the onset of BPH and impact on treatment. METHODS: A narrative literature review was conducted using PubMed and Google Scholar to identify supporting evidence. The articles referenced ranged from 1975 to 2023. RESULTS: A clear relationship between BPH/LUTS and circadian rhythm disruption is yet to be established. However, common mediators influence both diseases, including proinflammatory states, metabolic syndrome, and hormonal regulation that can be asserted to circadian disruption. Some studies have identified a possible relationship between general LUTS and sleep disturbance, but little research has been done on the medical management of these diseases and how circadian rhythm disruption further affects treatment outcomes. CONCLUSIONS: There is evidence to implicate a relationship between BPH/LUTS and circadian rhythm disruptions. However, there is scarce literature on potential specific link in medical management of the disease and treatment outcomes with circadian rhythm disruption. Further study is warranted to provide BPH patients with insights into circadian rhythm directed appropriate interventions.

Validation of a Zero-shot Learning Natural Language Processing Tool to Facilitate Data Abstraction for Urologic Research.

BACKGROUND: Urologic research often requires data abstraction from unstructured text contained within the electronic health record. A number of natural language processing (NLP) tools have been developed to aid with this time-consuming task; however, the generalizability of these tools is typically limited by the need for task-specific training. OBJECTIVE: To describe the development and validation of a zero-shot learning NLP tool to facilitate data abstraction from unstructured text for use in downstream urologic research. DESIGN, SETTING, AND PARTICIPANTS: An NLP tool based on the GPT-3.5 model from OpenAI was developed and compared with three physicians for time to task completion and accuracy for abstracting 14 unique variables from a set of 199 deidentified radical prostatectomy pathology reports. The reports were processed in vectorized and scanned formats to establish the impact of optical character recognition on data abstraction. INTERVENTION: A zero-shot learning NLP tool for data abstraction. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The tool was compared with the human abstractors in terms of superiority for data abstraction speed and noninferiority for accuracy. RESULTS AND LIMITATIONS: The human abstractors required a median (interquartile range) of 93 s (72-122 s) per report for data abstraction, whereas the software required a median of 12 s (10-15 s) for the vectorized reports and 15 s (13-17 s) for the scanned reports (p < 0.001 for all paired comparisons). The accuracies of the three human abstractors were 94.7% (95% confidence interval [CI], 93.8-95.5%), 97.8% (95% CI, 97.2-98.3%), and 96.4% (95% CI, 95.6-97%) for the combined set of 2786 data points. The tool had accuracy of 94.2% (95% CI, 93.3-94.9%) for the vectorized reports and was noninferior to the human abstractors at a margin of -10% (α = 0.025). The tool had slightly lower accuracy of 88.7% (95% CI 87.5-89.9%) for the scanned reports, making it noninferior to two of three human abstractors. CONCLUSIONS: The developed zero-shot learning NLP tool offers urologic researchers a highly generalizable and accurate method for data abstraction from unstructured text. An open access version of the tool is available for immediate use by the urologic community. PATIENT SUMMARY: In this report, we describe the design and validation of an artificial intelligence tool for abstracting discrete data from unstructured notes contained within the electronic medical record. This freely available tool, which is based on the GPT-3.5 technology from OpenAI, is intended to facilitate research and scientific discovery by the urologic community.

Applications of artificial intelligence in prostate cancer histopathology.

The diagnosis of prostate cancer (PCa) depends on the evaluation of core needle biopsies by trained pathologists. Artificial intelligence (AI) derived models have been created to address the challenges posed by pathologists' increasing workload, workforce shortages, and variability in histopathology assessment. These models with histopathological parameters integrated into sophisticated neural networks demonstrate remarkable ability to identify, grade, and predict outcomes for PCa. Though the fully autonomous diagnosis of PCa remains elusive, recently published data suggests that AI has begun to serve as an initial screening tool, an assistant in the form of a real-time interactive interface during histological analysis, and as a second read system to detect false negative diagnoses. Our article aims to describe recent advances and future opportunities for AI in PCa histopathology.

Saline-assisted fascial exposure (SAFE) technique to improve nerve-sparing in robot-assisted laparoscopic radical prostatectomy.

OBJECTIVE: To provide a summary of our initial experience and assess the impact of the Saline-Assisted Fascial Exposure (SAFE) technique on erectile function (EF), urinary continence, and oncological outcomes after Robot-Assisted Laparoscopic Radical Prostatectomy (RALP). PATIENTS AND METHODS: From January 2021 to July 2022, we included patients with a baseline Sexual Health Inventory for Men (SHIM) score of ≥17 and a high probability of extracapsular extension (ECE), ranging from 21% to 73%, as per the Martini et al. nomogram. A propensity score matching was carried out at a ratio of 1:2 between patients who underwent RALP + SAFE (33) and RALP alone (66). The descriptive statistical analysis is presented. The SAFE technique was performed using two approaches, transrectal guided by micro-ultrasound or transperitoneal. Its principle entails a low-pressure injection of saline solution in the periprostatic fascia to achieve an atraumatic dissection of the neural hammock. Potency was defined as a SHIM score of ≥17 and continence as no pads per day. RESULTS: At follow-up intervals of 6, 13, 26, and 52 weeks, the SHIM score differed significantly between the two groups, favouring the RALP + SAFE (P = 0.01, P < 0.001, P < 0.001, and P = 0.01, respectively). These results remained significant when the mean SHIM score was assessed. As shown by the cumulative incidence curve, EF rates were higher in the RALP + SAFE compared to the RALP alone group (log-rank P < 0.001). The baseline SHIM and use of the SAFE technique were independent predictors of EF recovery. CONCLUSIONS: The use of the SAFE technique led to better SHIM scores at 6, 13, 26, and 52 weeks after RALP in patients at high risk of ECE who underwent a partial NS procedure.

Intraoperative Fluorescent Image Guidance for Nerve-Sparing Prostatectomy: A Review of Historical Context and Current Research.

Fluorescent probes in the near-infrared (NIR) range have immense potential to improve observation of positive margins, lymph nodes, and nerves in prostatectomy. Development of fluorescent dyes and mechanisms of cellular uptake paved the way for the current emerging technologies. However, intracellular transport of fluorophores proved to be logistically challenging with respect to intraoperative deployment. Peptide-based probes with high specificity for nerves enabled broader and more rapid labeling. Key features of the ideal probe include selectivity, minimal background noise, safety, and low cost. Human neuropeptide 401 (HNP401) and oxazine-based probes perform well in these categories. As for tumor-specific labeling, prostate specific membrane antigen is relatively selective for the prostate and can be conjugated to a fluorophore. NIR spectrum emission is an ideal range for clinical imaging use, as fluorescence occurs outside the field of visible light, and tissue optical properties diverge significantly at the visible-NIR transition. Indocyanine, carbocyanine, and fluorescein derivatives are common fluorophore conjugates for the probes. Finally, to harness the power of fluorescence intraoperatively, the surgeon must look through a specialized lens. Multiphoton microscopy, optical coherence tomography, and confocal laser endomicroscopy have emerged as frontrunners in this arena. As with any evolving technology, ongoing research is expanding the applications of fluorescent intraoperative imaging in prostate surgery. Innovations in camera technology, dye selection, and image processing are refining the technique's capabilities. A core challenge of these technologies translating into the operating room relates to size and the ability to view objects at vastly different magnifications. Dual modality zoom settings are promising solutions. Furthermore, interdisciplinary collaboration between surgeons, imaging specialists, and researchers continues to drive advancements. In conclusion, fluorescent intraoperative imaging has the potential to usher in a new era of precision and safety in prostate surgery.

Metaverse Surgical Planning with Three-dimensional Virtual Models for Minimally Invasive Partial Nephrectomy.

The recent integration of new virtual visualization modalities with artificial intelligence and high-speed internet connection has opened the door to the advent of the metaverse in medicine. In this totally virtual environment, three-dimensional virtual models (3DVMs) of the patient's anatomy can be visualized and discussed via digital avatars. Here we present for the first time a metaverse preoperative clinical case discussion before minimally invasive partial nephrectomy. The surgeons' digital avatars met in a virtual room and participated in a virtual consultation on the surgical strategy and clamping approach before the procedure. Robotic or laparoscopic procedures are then carried out according to the simulated surgical strategy. We demonstrate how this immersive virtual reality experience overcomes the barriers of distance and how the quality of surgical planning is enriched by a great sense of "being there", even if virtually. Further investigation will improve the quality of interaction with the models and among the avatars.

Defining the Role of Large Language Models in Urologic Care and Research.

Large language models such as ChatGPT are poised to transform health care. We envision them being used in the future in urology, albeit with appropriate supervision, to educate patients, guide clinicians and scientists, and automate complex tasks.

AI-powered real-time annotations during urologic surgery: The future of training and quality metrics.

INTRODUCTION AND OBJECTIVE: Real-time artificial intelligence (AI) annotation of the surgical field has the potential to automatically extract information from surgical videos, helping to create a robust surgical atlas. This content can be used for surgical education and qualitative initiatives. We demonstrate the first use of AI in urologic robotic surgery to capture live surgical video and annotate key surgical steps and safety milestones in real-time. SUMMARY BACKGROUND DATA: While AI models possess the capability to generate automated annotations based on a collection of video images, the real-time implementation of such technology in urological robotic surgery to aid surgeon and training staff it is still pending to be studied. METHODS: We conducted an educational symposium, which broadcasted 2 live procedures, a robotic-assisted radical prostatectomy (RARP) and a robotic-assisted partial nephrectomy (RAPN). A surgical AI platform system (Theator, Palo Alto, CA) generated real-time annotations and identified operative safety milestones. This was achieved through trained algorithms, conventional video recognition, and novel Video Transfer Network technology which captures clips in full context, enabling automatic recognition and surgical mapping in real-time. RESULTS: Real-time AI annotations for procedure #1, RARP, are found in Table 1. The safety milestone annotations included the apical safety maneuver and deliberate views of structures such as the external iliac vessels and the obturator nerve. Real-time AI annotations for procedure #2, RAPN, are found in Table 1. Safety milestones included deliberate views of structures such as the gonadal vessels and the ureter. AI annotated surgical events included intraoperative ultrasound, temporary clip application and removal, hemostatic powder application, and notable hemorrhage. CONCLUSIONS: For the first time, surgical intelligence successfully showcased real-time AI annotations of 2 separate urologic robotic procedures during a live telecast. These annotations may provide the technological framework for send automatic notifications to clinical or operational stakeholders. This technology is a first step in real-time intraoperative decision support, leveraging big data to improve the quality of surgical care, potentially improve surgical outcomes, and support training and education.

Novel signatures of prostate cancer progression and therapeutic resistance.

INTRODUCTION: The extensive heterogeneity of prostate cancer (PCa) and multilayered complexity of progression to castration-resistant prostate cancer (CRPC) have contributed to the challenges of accurately monitoring advanced disease. Profiling of the tumor microenvironment with large-scale transcriptomic studies have identified gene signatures that predict biochemical recurrence, lymph node invasion, metastases, and development of therapeutic resistance through critical determinants driving CRPC. AREAS COVERED: This review encompasses understanding of the role of different molecular determinants of PCa progression to lethal disease including the phenotypic dynamic of cell plasticity, EMT-MET interconversion, and signaling-pathways driving PCa cells to advance and metastasize. The value of liquid biopsies encompassing circulating tumor cells and extracellular vesicles to detect disease progression and emergence of therapeutic resistance in patients progressing to lethal disease is discussed. Relevant literature was added from PubMed portal. EXPERT OPINION: Despite progress in the tumor-targeted therapeutics and biomarker discovery, distant metastasis and therapeutic resistance remain the major cause of mortality in patients with advanced CRPC. No single signature can encompass the tremendous phenotypic and genomic heterogeneity of PCa, but rather multi-threaded omics-derived and phenotypic markers tailored and validated into a multimodal signature.

Biopsy and Erectile Functional Outcomes of Partial Prostate Ablation: A Systematic Review and Meta-analysis of Prospective Studies.

OBJECTIVE: To provide a systematic summary of prospectively performed studies evaluating ablative therapies for the treatment of prostate cancer (PCa) that included protocol-mandated assessment of (1) residual disease by post-treatment biopsy and/or (2) erectile functional outcomes. MATERIALS AND METHODS: We performed a comprehensive literature search in September 2022. Studies were evaluated according to a predefined and registered plan in PROSPERO (CRD42022302777). Only prospective trials with protocol-mandated post-treatment prostate biopsies or functional assessments were included. Targeted focal therapy was the only ablation pattern with sufficient data to perform meta-analyses (29 studies, 1079 patients). RESULTS: At baseline, 65.0% of patients treated with targeted focal therapy harbored grade group (GG) ≥2 PCa. One year after treatment, in-field treatment failure with ≥GG1 and ≥GG2 PCa occurred in 25.7% (range 11.1%-66.7%) and 8.8% (range 0%-27.8%) of men, respectively. In patients that received whole-gland biopsies 1year after ablation, residual ≥GG1 and ≥GG2 PCa was detected anywhere in the prostate in 43.7% (range 19.4%-71.7%) and 13.0% (range 0%-35.9%) of men. Erectile function was negatively affected by treatment, but 78.7% were potent 1year after targeted focal therapy (7 studies, 197 patients), and the average decrease in erectile function scores was 8.8% at 1year (21 studies, 760 patients). CONCLUSION: Though long-term data after targeted focal therapy are limited, oncologic and treatment failure occurred in 13% and 9% (≥GG2 at 6-12months after treatment). Most men were able to maintain potency. This work can help benchmark new techniques and power future trials.

Genitourinary cancer neoadjuvant therapies: current and future approaches.

Neoadjuvant therapies can improve tolerability, reduce tumor volume to facilitate surgery, and assess subsequent treatment response. Therefore, there is much enthusiasm for expanding the benefits of cancer therapies to the neoadjuvant setting to reduce recurrence and improve survival in patients with localized or locally advanced genitourinary (GU) cancer. This approach is clinically pertinent because these treatments are administered primarily to treatment-naive patients and can elicit the greatest drug response. In addition, the results are not impacted by other anticancer treatments. While neoadjuvant therapies have been the standard treatment for bladder cancer in the past, they are presently restricted to clinical trials for renal and prostate cancer (PCa); however, changes are imminent. Precision neoadjuvant therapies will be ushered in by biomarker-stratified neoadjuvant trials with appropriate survival endpoints and comprehensive correlative and imaging studies. This review discusses neoadjuvant studies in GU malignancies and how they inform future study design considerations.

Optimum threshold of the 4Kscore for biopsy in men with negative or indeterminate multiparametric magnetic resonance imaging.

Objective: The study aims to identify the optimal 4Kscore thresholds to determine the need for a prostate biopsy when multiparametric magnetic resonance imaging (MRI) (mpMRI) is negative or indeterminate. Materials and methods: We analysed retrospective data from men in eight different institutions who underwent an mpMRI, 4Kscore and prostate biopsy for evaluation of prostate cancer. We selected men with a negative (PIRADS ≤2) or indeterminate (PIRADS 3) mpMRI. 4Kscore values were categorized into ranges of 1-7, 8-19, 20-32 and greater than 32. We evaluated the proportion of men with grade group 2 or higher (GG2+) cancer in groups defined by PIRADS and 4Kscore. We also evaluated the number of biopsies avoided and GG2+ cancer missed in each group reported depend on 4Kscore cutoff points. Results: Among 1111 men who had an mpMRI, 4Kscore and biopsy, 625 of them had PIRADS ≤3 on mpMRI: 374 negative (PIRADS ≤2) and 251 indeterminate (PIRADS 3). In men with a negative mpMRI, we found a 4Kscore cut-point of 33 resulted in an increased risk of GG2+ cancer on biopsy. In patients with an equivocal lesion on mpMRI, men with a 4Kscore cutoff ≥8 had a greater risk of GG2+ cancer on biopsy. Decision curve analysis supported the proposed cut-points in each mpMRI group. Conclusions: In men with negative and indeterminate mpMRI, we found the best 4Kscore threshold to determine the need for biopsy to be 33 and 8 respectively. Future prospective studies in independent populations are needed to confirm these findings.

A multi-institutional study of 1,111 men with 4K score, multiparametric magnetic resonance imaging, and prostate biopsy.

OBJECTIVE: Prostate magnetic resonance imaging (MRI) and biomarkers are often used in conjunction to enhance the selection process for prostate biopsy. However, the optimal sequence of ordering these tests has not been established. A comprehensive evaluation was conducted on a large multi-institutional cohort of patients who underwent MRI, 4K score, and biopsy of the prostate to examine the impact of utilizing both tests vs. either test alone and to determine if the order in which these tests are administered affects the ability to detect clinically significant prostate cancer (csCaP). METHODS AND MATERIALS: We evaluated men from 8 different institutions who were referred for prostate cancer evaluation and underwent MRI, 4K score test, and prostate biopsy. The primary outcome was the presence of csCaP, defined as grade group 2 or higher cancer on a biopsy of the prostate. We used logistic regression, calibration plots, and decision curve analysis to evaluate using a 4K score or MRI alone vs. both tests together for detecting csCaP. In addition, we evaluated several strategies using one or both tests for selecting men for biopsy and compared them based on the proportion of biopsies avoided and the csCaP's missed. RESULTS: Among the 1,111 men who formed the final cohort, 553 (49.8%) had prostate cancer, and 353 (31.8%) had csCaP. We found that using MRI and 4K score together had better discrimination, calibration, and a higher clinical utility on decision curve analysis compared to using either test individually. Using both tests together resulted in fewer biopsies avoided and missed cancers compared to using either test alone. Strategies that sequence MRI and 4K score tests resulted in the largest biopsy reduction, with no appreciable difference between starting with an MRI vs. a biomarker. CONCLUSIONS: We found that using both an MRI and 4K score together was superior to using either test alone but found no appreciable difference between starting with an MRI vs. starting with a 4K score. Prospective studies are needed to identify the best strategy to sequence MRI and biomarkers in the evaluation of csCaP.

Impact of exercise on continence in prostate cancer patients post robotic assisted radical prostatectomy: a systematic review.

INTRODUCTION: Urinary incontinence is one of the most common long term side effects after robotic prostatectomy (RALP), and significantly impacts patient quality of life. Pelvic floor muscle training (PFMT) has been a standard part of the urologist's armamentarium for maximizing continence outcomes post-op. Recently, aerobic and resistance exercises have been described as improving functional outcomes post RALP. We performed a systematic review to determine the influence of exercise, in the form of PFMT, aerobic exercise, and resistance training, on incontinence post-RALP. MATERIALS AND METHODS: This systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, with database searches performed on January 14, 2022 and again on August 10, 2022 to account for any new publications. The search identified 1675 papers. Of the 1675 papers, 1007 were found to be duplicates, leaving 668 total studies for screening. Of the 668 papers, nine met all inclusion criteria. Of the nine, four studies presented data from patients who had undergone RALP and were included in the final descriptive systematic review. RESULTS: Sayilan et al. and Milios et al. showed postoperative PFMT and physical activity resulted in significantly improved continence outcomes at 1 and 6 months and 2, 6, and 12 weeks postoperatively, respectively. Heydenreich et al. combined PFMT with an oscillating rod therapy, which was found to significantly improve both postoperative urinary continence and health related quality of life compared to PFMT and relaxation techniques alone. On the contrary, Goode et al. examined delivery of exercise information and demonstrated no difference in continence outcomes between focused telehealth PFMT program and generic prostate cancer education. CONCLUSION: Pelvic floor muscle training, with or without adjunct therapies, results in improved continence outcomes post RALP. Supervised training programs may or may not accelerate this finding. There is no recent literature to support or refute the benefit of aerobic exercise or resistance training on reducing post-prostatectomy incontinence after RALP.

Diagnostic Performance and Safety of Positron Emission Tomography with 18F-rhPSMA-7.3 in Patients with Newly Diagnosed Unfavourable Intermediate- to Very-high-risk Prostate Cancer: Results from a Phase 3, Prospective, Multicentre Study (LIGHTHOUSE).

BACKGROUND: Radiohybrid (rh) 18F-rhPSMA-7.3 is a novel high-affinity prostate-specific membrane antigen (PSMA)-targeting radiopharmaceutical for prostate cancer (PCa) imaging. OBJECTIVE: To evaluate the diagnostic performance and safety of 18F-rhPSMA-7.3 in newly diagnosed PCa patients planned for prostatectomy. DESIGN, SETTING, AND PARTICIPANTS: Data on 18F-rhPSMA-7.3 were reported from the phase 3 prospective, multicentre LIGHTHOUSE study (NCT04186819). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patients underwent positron emission tomography/computed tomography (PET/CT) 50-70 min after an injection of 296 MBq 18F-rhPSMA-7.3. Images were interpreted locally and by three blinded independent readers. The coprimary endpoints were patient-level sensitivity and specificity for the detection of pelvic lymph node (PLN) metastases, validated using histopathology at PLN dissection. Prespecified statistical thresholds (lower bounds of 95% confidence interval [CI]) were set at 22.5% for sensitivity and 82.5% for specificity. RESULTS AND LIMITATIONS: Of 372 patients screened, 352 had evaluable 18F-rhPSMA-7.3-PET/CT and 296 (99 [33%] with unfavourable intermediate-risk [UIR] and 197 [67%] with high-/very-high-risk [VHR] PCa) subsequently underwent surgery. As per the independent reads, 23-37 (7.8-13%) patients had 18F-rhPSMA-7.3-positive PLN. Seventy (24%) patients had one or more positive PLNs on histopathology. The sensitivity for PLN detection was 30% (95% CI, 19.6-42.1%) for reader 1, 27% (95% CI, 17.2-39.1%) for reader 2, and 23% (95% CI, 13.7-34.4%) for reader 3, not meeting the prespecified threshold. Specificity was 93% (95% CI, 88.8-95.9%), 94% (95% CI, 89.8-96.6%), and 97% (95% CI, 93.7-98.7%), respectively, exceeding the threshold for all readers. Specificity was high (≥92%) across both risk stratifications. Sensitivity was higher among high-risk/VHR (24-33%) than among UIR (16-21%) patients. Extrapelvic (M1) lesions were reported for 56-98/352 (16-28%) patients who underwent 18F-rhPSMA-7.3-PET/CT irrespective of surgery. Verification of these (predominantly by conventional imaging) gave a verified detection rate of 9.9-14% (positive predictive value, 51-63%). No serious adverse events were observed. CONCLUSIONS: Across all risk stratifications, 18F-rhPSMA-7.3-PET/CT had high specificity, meeting the specificity endpoint. The sensitivity endpoint was not met, although higher sensitivity was noted among high-risk/VHR than among UIR patients. Overall, 18F-rhPSMA-7.3-PET/CT was well tolerated, and identified N1 and M1 disease prior to surgery in newly diagnosed PCa patients. PATIENT SUMMARY: In order to select the most appropriate treatment for patients with prostate cancer, it is critical to diagnose the disease burden accurately at initial diagnosis. In this study, we investigated a new diagnostic imaging agent in a large population of men with primary prostate cancer. We found it to have an excellent safety profile and to provide clinically useful information regarding the presence of disease beyond the prostate.

Exploring the positive aspects of caregiving among family caregivers of the older adults in India.

Background: Caregiving is a committed role that focuses on providing the required support and care to a care receiver who is either ill, disabled, or dependent to the extent that they are incapable of independent functioning. The topic of caregiving has been extensively studied worldwide, mainly focused on the negative aspects of caregiving, like caregiver stress, burden, role conflicts, and burnout among caregivers. However, limited efforts have been made to understand the positive aspects of caregiving among informal caregivers who spend most of their time in this unpaid role. The present study addresses this concern by exploring the positive aspects of caregiving among family caregivers of older persons in India. Methodology: This is a qualitative study, which was conducted, using the existential-phenomenological approach. In this study, a purposive sampling technique was used, and a total of a 100 family caregivers participated from four cities in India, namely Prayagraj, Pune, Visakhapatnam, and Guwahati. Twenty-five family caregivers between the age of 30-50 years participated from each of these four cities. The data was collected using six semi-structured interview questions on positive aspects of caregiving based on the lived experiences of caregivers. The interview schedule was developed based on the PERMA model and finalized after the pilot study. Each interview took 30-50 min and was recorded and transcribed. Results: The data was analyzed using thematic analysis. Some commonalities and differences were observed in the responses given by family caregivers from the four cities. Four major themes that emerged for the "Nature of positive caregiving" among participants from all four cities are "Caregiver's attitude," "Care and compassion," "Roles and responsibilities," and "Beliefs and values." Four significant themes for the "Factors contributing to positive caregiving" are "Meaningfulness in life," "Sense of belongingness," "Personal growth," and "Empathetic understanding." Conclusion: Based on the study's findings, it can be said that the themes were associated with the PERMA model. Positive caregiving is an important indicator of caregivers' and care receivers' well-being. The findings have implications for planning some action research, training, and counseling programs for promoting positive aspects of caregiving among informal caregivers.

15-year biochemical failure, metastasis, salvage therapy, and cancer-specific and overall survival rates in men treated with robotic radical prostatectomy for PSA-screen detected prostate cancer.

BACKGROUND: An informed decision regarding a treatment option requires data on its long-term efficacy and side-effect profile. While the side-effects of robotic radical prostatectomy have been well-quantified, the data on its long-term efficacy are lacking. We here provide 15-year oncological outcomes of clinically-localized prostate cancer (CLPCa) patients treated with robot-assisted laparoscopic prostatectomy (RALP). METHODS: We treated 1,807 men with CLPCa with RALP between 2001 and 2005 and prospectively collected follow-up data through 2020. We examined the rates of biochemical failure (BCF), metastatic progression, secondary therapy use, PCa-specific mortality (PCSM), and overall survival (OS) using Kaplan-Meier and competing-risk cumulative incidence methods as appropriate. RESULTS: The median follow-up was 14.1 years. Six hundred eight and 312 men had D'Amico intermediate- and high-risk disease, respectively. Overall, the 15-year rates of BCF, metastasis, secondary therapy use, PCSM, and OS were 28.1%, 4.0%, 16.3%, 2.5%, and 82.1%, respectively. The rates of oncologic failure increased with increasing D'Amico (preoperative) and Diaz (postoperative) risk scores - BCF, metastasis, and PCSM rates in D'Amico low-, intermediate-, and high-risk groups at 15-years were 15.2%, 38.3%, and 44.1% [BCF], 1.1%, 4.1%, and 13.0% [metastasis], and 0.5%, 3.4%, and 6.6% [PCSM], respectively, and in Diaz risk groups 1, 2, 3, 4, and 5 were 5.5%, 20.6%, 41.8%, 66.9%, and 89.2% [BCF], 0%, 0.5%, 3.2%, 20.5%, and 60.0% [metastasis], and 0%, 0.8%, 0.6%, 13.5%, and 37.5% [PCSM], respectively. The OS rates in D'Amico low-to-high and Diaz 1-to-5 risk groups at 15-years were 85.9%, 78.6%, and 75.2%, and 89.4%, 83.2%, 80.6%, 67.2%, and 23.4%, respectively. CONCLUSIONS: Men diagnosed with clinically-localized prostate cancer in the contemporaneous PSA-screening era and treated with RALP achieve durable long-term oncological control. The data reported here (in a risk-stratified manner) represent the longest follow-up after robotic radical prostatectomy, and as such, should be of value when counseling patients regarding expected oncologic outcomes from RALP.

Association between Expression of Connective Tissue Genes and Prostate Cancer Growth and Progression.

To find an association between genomic features of connective tissue and pejorative clinical outcomes on radical prostatectomy specimens. We performed a retrospective analysis of patients who underwent radical prostatectomy and underwent a Decipher transcriptomic test for localized prostate cancer in our institution (n = 695). The expression results of selected connective tissue genes were analyzed after multiple t tests, revealing significant differences in the transcriptomic expression (over- or under-expression). We investigated the association between transcript results and clinical features such as extra-capsular extension (ECE), clinically significant cancer, lymph node (LN) invasion and early biochemical recurrence (eBCR), defined as earlier than 3 years after surgery). The Cancer Genome Atlas (TCGA) was used to evaluate the prognostic role of genes on progression-free survival (PFS) and overall survival (OS). Out of 528 patients, we found that 189 had ECE and 27 had LN invasion. The Decipher score was higher in patients with ECE, LN invasion, and eBCR. Our gene selection microarray analysis showed an overexpression in both ECE and LN invasion, and in clinically significant cancer for COL1A1, COL1A2, COL3A1, LUM, VCAN, FN1, AEBP1, ASPN, TIMP1, TIMP3, BGN, and underexpression in FMOD and FLNA. In the TCGA population, overexpression of these genes was correlated with worse PFS. Significant co-occurrence of these genes was observed. When presenting overexpression of our gene selection, the 5-year PFS rate was 53% vs. 68% (p = 0.0315). Transcriptomic overexpression of connective tissue genes correlated to worse clinical features, such as ECE, clinically significant cancer and BCR, identifying the potential prognostic value of the gene signature of the connective tissue in prostate cancer. TCGAp cohort analysis showed a worse PFS in case of overexpression of the connective tissue genes.

Value of multiphoton microscopy in uro-oncology: a narrative review.

Background and Objective: Multi-photon microscopy (MPM) is a 3-dimension fluorescence imaging technique that combines the excitation of two low-energy photons, enabling less photo-bleaching and deeper penetration of the imaged tissue. Two signals are detected, autofluorescence (AF), from natural intracellular fluorophores [such as nicotinamide adenine dinucleotide phosphate (NADP) and flavine adenine dinucleotide (FAD) transformation], and second harmonic generation (SHG), a physical property of the laser enhancing non-centrosymmetric structures such as collagen fibers. MPM can give both visual and quantitative information of a fresh tissue (without the need of processing, cutting or staining the tissue), aiding in the progress towards optimizing a real-time imaging device. The objective of this review is to show the value and benefits of the use of MPM in uro-oncology. Methods: A structured literature review was performed using PubMed and Web of Sciences, including all articles with the following keywords: "multiphoton microscopy", "two-photon microscopy", "non-linear microscopy", "second harmonic generation", "urology", "prostate", "bladder", "kidney", "upper tract", "oncology", "surgical margins", "frozen section". Articles were reviewed to summarize the use of this tool in performing biopsies, assessing surgical margins, staging and grading complementary tool, and real-time imaging. Key Content and Findings: A total of 476 articles were identified with these keywords, and later screened for inclusion. We finally included 47 publications that were relevant to our topic. The advantages of this technique have led to its application in the management of several cancers, allowing cellular description as well as quantitative measurements of AF or SHG and their correlation with clinical outcomes. Conclusions: MPM has shown great improvement in providing a real time assessment of fresh tissue, giving oncologic diagnosis, performing in vivo imaging and quantitative analysis of the tissue as well as increasing precision of the diagnosis. This nonlinear optical technique has the potential of guiding both biopsy and surgery, as well as helping the surgeon with interesting additional tissue information intra-operatively.