Risk Factors and Contemporary Management Options for Pain and Discomfort Experienced During a Prostate Biopsy.

PURPOSE OF REVIEW: Prostate fusion biopsy, an innovative imaging modality for diagnosing prostate cancer, presents certain challenges for patients including discomfort and emotional distress, leading to nonadherence to treatment and follow-ups. To inform clinicians and offer pain relief alternatives to patients, this review delves into the risk factors for increased pain and modern management options to alleviate pain during prostate biopsy. RECENT FINDINGS: Individual responses to pain vary, and the overall experience of pain during a prostate biopsy has been contributed to numerous factors such as patient age, prostate volume, previous biopsy experience, and more. As a result, several strategies aim to mitigate pain during in-office procedures. Notably, techniques including pharmacological analgesics, hand holding, heating pads, entertainment/virtual reality, and distraction have shown significant efficacy. Existing studies explore risk factors influencing pain intensity during prostate biopsy and effective pain management strategies. This review consolidates available information to guide clinicians in enhancing patient comfort and thus, encourage surveillance adherence.

Cytologic evaluation of upper urinary tract specimens: An institutional retrospective study using The Paris System for Reporting Urine Cytology second edition with histopathologic follow-up.

OBJECTIVE: Cytologic evaluation of the upper urinary tract (UUT) can be challenging due to instrumentation artefacts. This study retrospectively reviewed UUT specimens using The Paris System for Reporting Urinary Cytopathology, second edition (TPS 2.0), compared it with the original reporting system (ORS) and correlated it with histopathologic follow-up. METHODS: An institutional database was reviewed for the UUT biopsy/resection histopathologic specimens, and we included 52 UUT cytology specimens pertinent to these cases in the study. These specimens were blindly reviewed and reclassified using TPS 2.0. The correlation between TPS 2.0, ORS and histopathologic follow-up was assessed. RESULTS: The UUT cytology specimens corresponded to 21 (40.4%) high-grade urothelial carcinoma (HGUC), 27 (51.9%) low-grade urothelial carcinoma (LGUC) and 4 (7.7%) benign cases on follow-up. For HGGC cases, the associated TPS categories included unsatisfactory (n = 1, 4.8%), negative for HGUC (NHGUC; n = 3, 14.3%), atypical urothelial cells (AUC; n = 6, 28.6%), suspicious for HGUC (SHGUC; n = 3, 14.3%) and HGUC (n = 8, 38.1%), while ORS categorised the specimens as unsatisfactory (n = 1, 4.8%), negative for malignant cells (NFMC; n = 3, 14.3%), AUC (n = 5, 23.8%), low-grade urothelial carcinoma (LGUC; n = 0, 0%), SHGUC (n = 5, 23.8%) and HGUC (n = 7, 33.3%). The risks of high-grade malignancy among cytologic categories were similar between ORS and TPS (p > 0.05). The majority of LGUC were classified as AUC similarly by ORS and TPS (55.6% vs. 59.3%). CONCLUSIONS: Our study demonstrated comparable performance between TPS 2.0 and ORS for UUT cytology specimens. Cytological diagnosis of UUT specimens remains challenging, especially for LGUC.

NCCN Guidelines® Insights: Prostate Cancer Early Detection, Version 1.2023.

The NCCN Guidelines for Prostate Cancer Early Detection provide recommendations for individuals with a prostate who opt to participate in an early detection program after receiving the appropriate counseling on the pros and cons. These NCCN Guidelines Insights provide a summary of recent updates to the NCCN Guidelines with regard to the testing protocol, use of multiparametric MRI, and management of negative biopsy results to optimize the detection of clinically significant prostate cancer and minimize the detection of indolent disease.

Multi-institutional analysis of clinical and imaging risk factors for detecting clinically significant prostate cancer in men with PI-RADS 3 lesions.

BACKGROUND: Most Prostate Imaging-Reporting and Data System (PI-RADS) 3 lesions do not contain clinically significant prostate cancer (CSPCa; grade group ≥2). This study was aimed at identifying clinical and magnetic resonance imaging (MRI)-derived risk fac- tors that predict CSPCa in men with PI-RADS 3 lesions. METHODS: This study analyzed the detection of CSPCa in men who underwent MRI-targeted biopsy for PI-RADS 3 lesions. Multivariable logistic regression models with goodness-of-fit testing were used to identify variables associated with CSPCa. Receiver operating curves and decision curve analyses were used to estimate the clinical utility of a predictive model. RESULTS: Of the 1784 men reviewed, 1537 were included in the training cohort, and 247 were included in the validation cohort. The 309 men with CSPCa (17.3%) were older, had a higher prostate-specific antigen (PSA) density, and had a greater likelihood of an anteriorly located lesion than men without CSPCa (p < .01). Multivariable analysis revealed that PSA density (odds ratio [OR], 1.36; 95% confidence interval [CI], 1.05-1.85; p < .01), age (OR, 1.05; 95% CI, 1.02-1.07; p < .01), and a biopsy-naive status (OR, 1.83; 95% CI, 1.38-2.44) were independently associated with CSPCa. A prior negative biopsy was negatively associated (OR, 0.35; 95% CI, 0.24-0.50; p < .01). The application of the model to the validation cohort resulted in an area under the curve of 0.78. A predicted risk threshold of 12% could have prevented 25% of biopsies while detecting almost 95% of CSPCas with a sensitivity of 94% and a specificity of 34%. CONCLUSIONS: For PI-RADS 3 lesions, an elevated PSA density, older age, and a biopsy-naive status were associated with CSPCa, whereas a prior negative biopsy was negatively associated. A predictive model could prevent PI-RADS 3 biopsies while missing few CSPCas. LAY SUMMARY: Among men with an equivocal lesion (Prostate Imaging-Reporting and Data System 3) on multiparametric magnetic resonance imaging (mpMRI), those who are older, those who have a higher prostate-specific antigen density, and those who have never had a biopsy before are at higher risk for having clinically significant prostate cancer (CSPCa) on subsequent biopsy. However, men with at least one negative biopsy have a lower risk of CSPCa. A new predictive model can greatly reduce the need to biopsy equivocal lesions noted on mpMRI while missing only a few cases of CSPCa.

Optimal Use of Tumor-Based Molecular Assays for Localized Prostate Cancer.

PURPOSEOF REVIEW: The use of genomic testing for prostate cancer continues to grow; however, utilization remains institutionally dependent. Herein, we review current tissue-based markers and comment on current use with active surveillance and prostate MRI. RECENT FINDINGS: While data continues to emerge, several studies have shown a role for genomic testing for treatment selection. Novel testing options include ConfirmMDx, ProMark, Prolaris, and Decipher, which have shown utility in select patients. The current body of literature on this specific topic remains very limited; prospective trials with long-term follow-up are needed to improve our understanding on how these genomic tests fit when combined with our current clinical tools. As the literature matures, it is likely that newer risk calculators that combine our classic clinical variables with genomic and imaging data will be developed to bring about standard protocols for prostate cancer decision-making.

Targeting prostate cancer with Clostridium perfringens enterotoxin functionalized nanoparticles co-encapsulating imaging cargo enhances magnetic resonance imaging specificity.

Magnetic resonance is a key imaging tool for the detection of prostate cancer; however, better tools focusing on cancer specificity are required to distinguish benign from cancerous regions. We found higher expression of claudin-3 (CLDN-3) and -4 (CLDN-4) in higher grade than lower-grade human prostate cancer biopsies (n = 174), leading to the design of functionalized nanoparticles (NPs) with a non-toxic truncated version of the natural ligand Clostridium perfringens enterotoxin (C-CPE) that has a strong binding affinity to Cldn-3 and Cldn-4 receptors. We developed a first-of-its-type, C-CPE-NP-based MRI detection tool in a prostate tumor-bearing mouse model. NPs with an average diameter of 152.9 ±â€¯15.7 nm (RS1) had a 2-fold enhancement of tumor specificity compared to larger (421.2 ±â€¯33.8 nm) NPs (RS4). There was a 1.8-fold (P < 0.01) and 1.6-fold (P < 0.01) upregulation of the tumor-to-liver signal intensities of C-RS1 and C-RS4 (functionalized NPs) compared to controls, respectively. Also, tumor specificity was 3.1-fold higher (P < 0.001) when comparing C-RS1 to C-RS4. This detection tool improved tumor localization of contrast-enhanced MRI, supporting potential clinical applicability.

The Prognostic Association of Prostate MRI PI-RADS™ v2 Assessment Category and Risk of Biochemical Recurrence after Definitive Local Therapy for Prostate Cancer: A Systematic Review and Meta-Analysis.

PURPOSE: Although the Prostate Imaging-Reporting and Data System™ version 2 (PI-RADS™ v2) is a reliable diagnostic tool for significant prostate cancer, less is known about the prognostic significance of the structured reporting scheme for estimating oncologic outcomes after treatment. We aimed to synthesize the available evidence regarding the association of PI-RADS v2 score and risk of biochemical recurrence (BCR) among patients undergoing primary definitive treatment for prostate cancer. MATERIALS AND METHODS: We systematically queried the PubMed® and Web of Science™ databases to identify studies addressing the association between the PI-RADS v2 and treatment outcomes. We included studies through November 2020 that assessed the independent prognostic significance of PI-RADS v2. After assessing risk of bias and quality, we conducted a formal meta-analysis to estimate the pooled effects of prostate magnetic resonance imaging (MRI) classification on the risk of BCR. RESULTS: We identified 9 and 7 eligible studies including 2,274 and 1,215 patients for the systematic review and meta-analysis, respectively. Eight were conducted in the context of radical prostatectomy and 1 post-radiation. Among patients treated with radical prostatectomy, higher PI-RADS v2 scores were significantly associated with risk of BCR (pooled HR 3.06, 95% CI 2.16-4.33; p <0.01). There was no significant heterogeneity among studies. For all studies, PI-RADS v2 score remained significantly associated with BCR (pooled HR 3.19, 95% CI 2.28-4.45; p <0.01). CONCLUSIONS: Prostate MRI findings assessed with the PI-RADS v2 classification were independently associated with risk of BCR after definitive local therapy, primarily based on data from radical prostatectomy. These findings support the prognostic significance of MRI, in addition to its role in prostate cancer diagnosis.

National trends in the management of patients with positive surgical margins at radical prostatectomy.

PURPOSE: To evaluate practice patterns of planned post-operative radiation therapy (RT) among men with positive surgical margins (PSM) at radical prostatectomy. METHODS: We identified 43,806 men within the National Cancer Database with pathologic node-negative prostate cancer diagnosed in 2010 through 2014 with PSM. The primary endpoint was receipt of planned (RT) within a patient's initial course of treatment. We examined post-RP androgen deprivation therapy (ADT) with RT as a secondary endpoint. We evaluated patterns of post-operative management and characteristics associated with planned post-prostatectomy RT. RESULTS: Within 12 months of RP, 87.0% received no planned RT, 8.5% RT alone, 1.3% ADT alone, and 3.1% RT with ADT. In a multivariable logistic regression model, planned RT use was associated with clinical and pathologic characteristics as estimated by surgical Cancer of the Prostate Risk Assessment (CAPRA-S) category (intermediate versus low, OR = 2.87, 95% CI 2.19-3.75, P < 0.001; high versus low, OR = 10.23, 95% CI 7.79-13.43, P < 0.001), treatment at community versus academic centers (OR = 1.24, 95% CI 1.15-1.34, P < 0.001), shorter distance to a treatment facility (OR = 0.97 for each 10-mile, 95% CI 0.96-0.98, P < 0.001), and uninsured status (OR = 1.39, 95% CI 1.10-1.77, P = 0.005). The odds of receiving planned RT were lower in 2014 versus 2010 (OR = 0.76, 95% CI 0.68-0.85, P < 0.001). There was no significant change in the use of ADT with RT. High versus low CAPRA-S category was associated with the use of ADT in addition to RT (OR = 5.13, 95% CI 1.57-16.80, P = 0.007). CONCLUSION: The use of planned post-prostatectomy RT remained stable among patients with PSM and appears driven primarily by the presence of other adverse pathologic features.

Risk of Clinically Significant Prostate Cancer Associated With Prostate Imaging Reporting and Data System Category 3 (Equivocal) Lesions Identified on Multiparametric Prostate MRI.

OBJECTIVE: The objective of this study is to determine the frequency of clinically significant cancer (CSC) in Prostate Imaging Reporting and Data System (PI-RADS) category 3 (equivocal) lesions prospectively identified on multiparametric prostate MRI and to identify risk factors (RFs) for CSC that may aid in decision making. MATERIALS AND METHODS: Between January 2015 and July 2016, a total of 977 consecutively seen men underwent multiparametric prostate MRI, and 342 underwent MRI-ultrasound (US) fusion targeted biopsy. A total of 474 lesions were retrospectively reviewed, and 111 were scored as PI-RADS category 3 and were visualized using a 3-T MRI scanner. Multiparametric prostate MR images were prospectively interpreted by body subspecialty radiologists trained to use PI-RADS version 2. CSC was defined as a Gleason score of at least 7 on targeted biopsy. A multivariate logistic regression model was constructed to identify the RFs associated with CSC. RESULTS: Of the 111 PI-RADS category 3 lesions, 81 (73.0%) were benign, 11 (9.9%) were clinically insignificant (Gleason score, 6), and 19 (17.1%) were clinically significant. On multivariate analysis, three RFs were identified as significant predictors of CSC: older patient age (odds ratio [OR], 1.13; p = 0.002), smaller prostate volume (OR, 0.94; p = 0.008), and abnormal digital rectal examination (DRE) findings (OR, 3.92; p = 0.03). For PI-RADS category 3 lesions associated with zero, one, two, or three RFs, the risk of CSC was 4%, 16%, 62%, and 100%, respectively. PI-RADS category 3 lesions for which two or more RFs were noted (e.g., age ≥ 70 years, gland size ≤ 36 mL, or abnormal DRE findings) had a CSC detection rate of 67% with a sensitivity of 53%, a specificity of 95%, a positive predictive value of 67%, and a negative predictive value of 91%. CONCLUSION: Incorporating clinical parameters into risk stratification algorithms may improve the ability to detect clinically significant disease among PI-RADS category 3 lesions and may aid in the decision to perform biopsy.

MRI-Ultrasound Fusion Targeted Biopsy of Prostate Imaging Reporting and Data System Version 2 Category 5 Lesions Found False-Positive at Multiparametric Prostate MRI.

OBJECTIVE: The purpose of this study was to determine imaging and clinical features associated with Prostate Imaging Reporting and Data System (PI-RADS) category 5 lesions identified prospectively at multiparametric MRI (mpMRI) that were found benign at MRI-ultrasound fusion targeted biopsy. MATERIALS AND METHODS: Between January 2015 and July 2016, 325 men underwent prostate mpMRI followed by MRI-ultrasound fusion targeted biopsy of 420 lesions prospectively identified and assessed with PI-RADS version 2. The frequency of clinically significant prostate cancer (defined as Gleason score ≥ 7) among PI-RADS 5 lesions was determined. Lesions with benign pathologic results were retrospectively reassessed by three abdominal radiologists and categorized as concordant or discordant between mpMRI and biopsy results. Multivariate logistic regression was used to identify factors associated with benign disease. Bonferroni correction was used. RESULTS: Of the 98 PI-RADS 5 lesions identified in 89 patients, 18% (18/98) were benign, 10% (10/98) were Gleason 6 disease, and 71% (70/98) were clinically significant prostate cancer. Factors associated with benign disease at multivariate analysis were lower prostate-specific antigen density (odds ratio [OR], 0.88; p < 0.001) and apex (OR, 3.54; p = 0.001) or base (OR, 7.11; p = 0.012) location. On secondary review of the 18 lesions with benign pathologic results, 39% (7/18) were scored as benign prostatic hyperplasia nodules, 28% (5/18) as inflammatory changes, 5% (1/18) as normal anatomic structures, and 28% (5/18) as discordant with imaging findings. CONCLUSION: PI-RADS 5 lesions identified during routine clinical interpretation are associated with a high risk of clinically significant prostate cancer. A benign pathologic result was significantly correlated with lower prostate-specific antigen density and apex or base location and most commonly attributed to a benign prostatic hyperplasia nodule. Integration of these clinical features may improve the interpretation of high-risk lesions identified with mpMRI.

Current Management Strategy for Active Surveillance in Prostate Cancer.

PURPOSE OF REVIEW: Active surveillance has been increasingly utilized as a strategy for the management of favorable-risk, localized prostate cancer. In this review, we describe contemporary management strategies of active surveillance, with a focus on traditional stratification schemes, new prognostic tools, and patient outcomes. RECENT FINDINGS: Patient selection, follow-up strategy, and indication for delayed intervention for active surveillance remain centered around PSA, digital rectal exam, and biopsy findings. Novel tools which include imaging, biomarkers, and genetic assays have been investigated as potential prognostic adjuncts; however, their role in active surveillance remains institutionally dependent. Although 30-50% of patients on active surveillance ultimately undergo delayed treatment, the vast majority will remain free of metastasis with a low risk of dying from prostate cancer. The optimal method for patient selection into active surveillance is unknown; however, cancer-specific mortality rates remain excellent. New prognostication tools are promising, and long-term prospective, randomized data regarding their use in active surveillance will be beneficial.

NCCN Guidelines Insights: Prostate Cancer Early Detection, Version 2.2016.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prostate Cancer Early Detection provide recommendations for prostate cancer screening in healthy men who have elected to participate in an early detection program. The NCCN Guidelines focus on minimizing unnecessary procedures and limiting the detection of indolent disease. These NCCN Guidelines Insights summarize the NCCN Prostate Cancer Early Detection Panel's most significant discussions for the 2016 guideline update, which included issues surrounding screening in high-risk populations (ie, African Americans, BRCA1/2 mutation carriers), approaches to refine patient selection for initial and repeat biopsies, and approaches to improve biopsy specificity.

Gleason 6 Prostate Cancer: Translating Biology into Population Health.

PURPOSE: Gleason 6 (3+3) is the most commonly diagnosed prostate cancer among men with prostate specific antigen screening, the most histologically well differentiated and is associated with the most favorable prognosis. Despite its prevalence, considerable debate exists regarding the genetic features, clinical significance, natural history, metastatic potential and optimal management. MATERIALS AND METHODS: Members of the Young Urologic Oncologists in the Society of Urologic Oncology cooperated in a comprehensive search of the peer reviewed English medical literature on Gleason 6 prostate cancer, specifically focusing on the history of the Gleason scoring system, histological features, clinical characteristics, practice patterns and outcomes. RESULTS: The Gleason scoring system was devised in the early 1960s, widely adopted by 1987 and revised in 2005 with a more restrictive definition of Gleason 6 disease. There is near consensus that Gleason 6 meets pathological definitions of cancer, but controversy about whether it meets commonly accepted molecular and genetic criteria of cancer. Multiple clinical series suggest that the metastatic potential of contemporary Gleason 6 disease is negligible but not zero. Population based studies in the U.S. suggest that more than 90% of men newly diagnosed with prostate cancer undergo treatment and are exposed to the risk of morbidity for a cancer unlikely to cause symptoms or decrease life expectancy. Efforts have been proposed to minimize the number of men diagnosed with or treated for Gleason 6 prostate cancer. These include modifications to prostate specific antigen based screening strategies such as targeting high risk populations, decreasing the frequency of screening, recommending screening cessation, incorporating remaining life expectancy estimates, using shared decision making and novel biomarkers, and eliminating prostate specific antigen screening entirely. Large nonrandomized and randomized studies have shown that active surveillance is an effective management strategy for men with Gleason 6 disease. Active surveillance dramatically reduces the number of men undergoing treatment without apparent compromise of cancer related outcomes. CONCLUSIONS: The definition and clinical relevance of Gleason 6 prostate cancer have changed substantially since its introduction nearly 50 years ago. A high proportion of screen detected cancers are Gleason 6 and the metastatic potential is negligible. Dramatically reducing the diagnosis and treatment of Gleason 6 disease is likely to have a favorable impact on the net benefit of prostate cancer screening.

Apoptosis induced by vitamin A signaling is crucial for connecting the ureters to the bladder.

Removal of toxic substances from the blood depends on patent connections between the kidney, ureters and bladder that are established when the ureter is transposed from its original insertion site in the male genital tract to the bladder. This transposition is thought to occur as the trigone forms from the common nephric duct and incorporates into the bladder. Here we re-examine this model in the context of normal and abnormal development. We show that the common nephric duct does not differentiate into the trigone but instead undergoes apoptosis, a crucial step for ureter transposition controlled by vitamin A-induced signals from the primitive bladder. Ureter abnormalities occur in 1-2% of the human population and can cause obstruction and end-stage renal disease. These studies provide an explanation for ureter defects underlying some forms of obstruction in humans and redefine the current model of ureter maturation.

Reliable Prostate Cancer Risk Mapping From MRI Using Targeted and Systematic Core Needle Biopsy Histopathology.

OBJECTIVE: To compute a dense prostate cancer risk map for the individual patient post-biopsy from magnetic resonance imaging (MRI) and to provide a more reliable evaluation of its fitness in prostate regions that were not identified as suspicious for cancer by a human-reader in pre- and intra-biopsy imaging analysis. METHODS: Low-level pre-biopsy MRI biomarkers from targeted and non-targeted biopsy locations were extracted and statistically tested for representativeness against biomarkers from non-biopsied prostate regions. A probabilistic machine learning classifier was optimized to map biomarkers to their core-level pathology, followed by extrapolation of pathology scores to non-biopsied prostate regions. Goodness-of-fit was assessed at targeted and non-targeted biopsy locations for the post-biopsy individual patient. RESULTS: Our experiments showed high predictability of imaging biomarkers in differentiating histopathology scores in thousands of non-targeted core-biopsy locations (ROC-AUCs: 0.85-0.88), but also high variability between patients (Median ROC-AUC [IQR]: 0.81-0.89 [0.29-0.40]). CONCLUSION: The sparseness of prostate biopsy data makes the validation of a whole gland risk mapping a non-trivial task. Previous studies i) focused on targeted-biopsy locations although biopsy-specimens drawn from systematically scattered locations across the prostate constitute a more representative sample to non-biopsied regions, and ii) estimated prediction-power across predicted instances (e.g., biopsy specimens) with no patient distinction, which may lead to unreliable estimation of model fitness to the individual patient due to variation between patients in instance count, imaging characteristics, and pathologies. SIGNIFICANCE: This study proposes a personalized whole-gland prostate cancer risk mapping post-biopsy to allow clinicians to better stage and personalize focal therapy treatment plans.

Association between pelvic lymph node dissection and survival among patients with prostate cancer treated with radical prostatectomy.

Introduction: Although the clinical benefits of pelvic lymph node dissection (PLND) at the time of radical prostatectomy for prostate cancer remain uncertain, major guidelines recommend PLND based on risk profile. Thus, the objective of this study was to examine the association between PLND and survival among patients undergoing RP stratified by Gleason grade group (GG) with the aim of allowing patients and physicians to make more informed care decisions about the potential risks and benefits of PLND. Materials and methods: From the SEER-17 database, we examined overall (OS) and prostate cancer-specific (PCSS) survival of prostate cancer patients who underwent RP from 2010 to 2015 stratified by GG. We applied propensity score matching to balance pre-operative characteristics including race, age, PSA, household income, and housing status (urban/rural) between patients who did and did not undergo PLND for each GG. Statistical analyses included log-rank test and Kaplan-Meier curves. Results: We extracted a matched cohort from 80,287 patients with GG1-5 who underwent RP. The median PSA value was 6.0 ng/mL, and the median age was 62-years-old. 49,453 patients underwent PLND (61.60%), while 30,834 (38.40%) did not. There was no difference in OS and PCSS between patients who received PLND and those who did not for all Gleason GG (OS-GG1: P = 0.20, GG2: P = 0.34, GG3: P > 0.05, GG4: P = 0.55, GG5: P = 0.47; PCSS-GG1: P = 0.11, GG2: P = 0.96, GG3: P = 0.81, GG4: P = 0.22, GG5: P = 0.14). Conclusions: In this observational study, PLND at the time of RP was not associated with improved OS or PCSS among patients with cGS of 3 + 3, 3 + 4, 4 + 3, 4 + 4, 4 + 5, and 5 + 4. These findings suggest that until definitive clinical trials are completed, prostate cancer patients who have elected RP should be appropriately counseled on the potential risks and lack of proven survival benefit of PLND.

Prostate-specific antigen screening for prostate cancer: Diagnostic performance, clinical thresholds, and strategies for refinement.

Prostate specific antigen (PSA) has transformed the diagnosis and treatment of prostate cancer by enabling early detection at global scale. Due to expression in both benign and malignant cells, PSA-based prostate cancer screening using single cut-points yields imperfect diagnostic performance and has led to the detection and over-treatment of low-grade prostate cancer. Additional challenges in the interpretation of PSA include substantial inter and intrapersonal variation, differences with age and prostate volume, and selection of standardized PSA value cutoffs for clinical application. In response, refinements to PSA including risk and age-based thresholds, age and genetic adjustments, PSA density, percentage free PSA, and PSA velocity have been proposed and extensively studied. In this review, we focus on the clinical role of PSA as a screening biomarker with a particular emphasis on its test characteristics, clinically actionable thresholds, and strategies to refine its clinical interpretation.

Association between sociodemographic factors and diagnosis of lethal prostate cancer in early life.

OBJECTIVE: A subset of patients are diagnosed with lethal prostate cancer (CaP) early in life before prostate-specific antigen (PSA) screening is typically initiated. To identify opportunities for improved detection, we evaluated patient sociodemographic factors associated with advanced vs. localized (CaP) diagnosis across the age spectrum. METHODS: We conducted a retrospective cohort study using the National Cancer Database, identifying patients diagnosed with CaP from 2004 to 2020. We compared characteristics of patients diagnosed at the advanced (cN1 or M1) versus localized (cT1-4N0M0) stage. Using multivariable logistic regression, we evaluated the associations among patient clinical and sociodemographic factors and advanced diagnosis, stratifying patients by age as ≤55 (before screening is recommended for most patients), 56 to 65, 66 to 75, and ≥76 years. RESULTS: We identified 977,722 patients who met the inclusion criteria. The mean age at diagnosis was 65.3 years and 50,663 (5.1%) had advanced disease. Overall, uninsured (OR = 3.20, 95% CI 3.03-3.78) and Medicaid-insured (OR 2.58, 95% CI 2.48-2.69) vs. privately insured status was associated with higher odds of diagnosis with advanced disease and this effect was more pronounced for younger patients. Among patients ≤55 years, uninsured (OR 4.14, 95% CI 3.69-4.65) and Medicaid-insured (OR 3.39, 95% CI 3.10-3.72) vs. privately insured patients were associated with higher odds of advanced cancer at diagnosis. Similarly, residence in the lowest vs. highest income quartile was associated with increased odds of advanced CaP in patients ≤55 years (OR 1.15, 95% CI 1.02-1.30). Black vs. White race was associated with increased odds of advanced CaP at diagnosis later in life (OR 1.17, 95% CI 1.09-1.25); however, race was not significantly associated with advanced stage CaP in those ≤55 years (P = 0.635). CONCLUSIONS: Sociodemographic disparities in diagnosis at advanced stages of CaP were more pronounced in younger patients, particularly with respect to insurance status. These findings may support greater attention to differential use of early CaP screening based on patient health insurance.

Association of Crowd-Sourced Assessment of Technical Skills (CSATSTM) and Outcomes of Robotic Assisted Radical Prostatectomy.

OBJECTIVE: To investigate if use of the Crowd-Sourced Assessment of Technical Skills (CSATSTM) platform and video peer review with constructive feedback is associated with improvement in technical skill and patient outcomes for robotic-assisted laparoscopic prostatectomy (RALP). METHODS: Five fellowship-trained urologists voluntarily submitted RALP cases for CSATSTM Global Evaluative Assessment of Robotic Skills (GEARS) scoring and expert narrative review between April 15, 2022 - April 30, 2023. Surgeon-selected and randomly-selected cases were reviewed. Surgeons underwent local peer review of videos with constructive feedback. Change in GEARS scores and frequency of post-operative outcomes over the 12-month periods before and during the study were analyzed in logistic regression models. Bias was assessed with sensitivity analysis comparing surgeon-selected to randomly-selected cases. RESULTS: GEARS scores for randomly-selected versus surgeon-selected cases did not differ significantly. Overall GEARS score correlated positively with annual surgical RALP volume (r=0.39, p=0.003) and negatively with years in practice (r=-0.34, p=0.01). After adjusting for confounders, there was no significant improvement in overall GEARS Score (0.01±0.02/month, p=0.48); but likelihood of sepsis (Odds Ratio 0.07, 95% CI 0.01-1.00, p=0.05) and pelvic fluid collection (Odds Ratio 0.09, 95% CI 0.01-0.99, p=0.049) were significantly decreased during the intervention period (n=165) compared to the prior 12 months (n=144). No outcome increased in likelihood (p>0.05). CONCLUSIONS: Integration of CSATSTM and local video peer review is associated with significant improvement in patient outcomes after RALP, despite no significant change in surgeons' GEARS scores. This is the first study demonstrating improvement in patient RALP outcomes after implementation of such a paradigm in practicing surgeons.

Development of a Longitudinal Prostate Cancer Transcriptomic and Clinical Data Linkage.

Importance: Although tissue-based gene expression testing has become widely used for prostate cancer risk stratification, its prognostic performance in the setting of clinical care is not well understood. Objective: To develop a linkage between a prostate genomic classifier (GC) and clinical data across payers and sites of care in the US. Design, Setting, and Participants: In this cohort study, clinical and transcriptomic data from clinical use of a prostate GC between 2016 and 2022 were linked with data aggregated from insurance claims, pharmacy records, and electronic health record (EHR) data. Participants were anonymously linked between datasets by deterministic methods through a deidentification engine using encrypted tokens. Algorithms were developed and refined for identifying prostate cancer diagnoses, treatment timing, and clinical outcomes using diagnosis codes, Common Procedural Terminology codes, pharmacy codes, Systematized Medical Nomenclature for Medicine clinical terms, and unstructured text in the EHR. Data analysis was performed from January 2023 to January 2024. Exposure: Diagnosis of prostate cancer. Main Outcomes and Measures: The primary outcomes were biochemical recurrence and development of prostate cancer metastases after diagnosis or radical prostatectomy (RP). The sensitivity of the linkage and identification algorithms for clinical and administrative data were calculated relative to clinical and pathological information obtained during the GC testing process as the reference standard. Results: A total of 92 976 of 95 578 (97.2%) participants who underwent prostate GC testing were successfully linked to administrative and clinical data, including 53 871 who underwent biopsy testing and 39 105 who underwent RP testing. The median (IQR) age at GC testing was 66.4 (61.0-71.0) years. The sensitivity of the EHR linkage data for prostate cancer diagnoses was 85.0% (95% CI, 84.7%-85.2%), including 80.8% (95% CI, 80.4%-81.1%) for biopsy-tested participants and 90.8% (95% CI, 90.5%-91.0%) for RP-tested participants. Year of treatment was concordant in 97.9% (95% CI, 97.7%-98.1%) of those undergoing GC testing at RP, and 86.0% (95% CI, 85.6%-86.4%) among participants undergoing biopsy testing. The sensitivity of the linkage was 48.6% (95% CI, 48.1%-49.1%) for identifying RP and 50.1% (95% CI, 49.7%-50.5%) for identifying prostate biopsy. Conclusions and Relevance: This study established a national-scale linkage of transcriptomic and longitudinal clinical data yielding high accuracy for identifying key clinical junctures, including diagnosis, treatment, and early cancer outcome. This resource can be leveraged to enhance understandings of disease biology, patterns of care, and treatment effectiveness.