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Background:Several treatment options for clinically localized prostate cancer currently exist under the established guidelines. We aim to assess nationally representative trends in treatment over time and determine potential geographic variation using two large national claims registries.Methods:Men with prostate cancer insured by Medicare (1998-2006) or a private insurer (Ingenix database, 2002-2006) were identified using International Classification of Diseases-9 and Current Procedural Terminology-4 codes. Geographic variation and trends in the type of treatment utilized over time were assessed. Geographic data were mapped using the GeoCommons online mapping platform. Predictors of any treatment were determined using a hierarchical generalized linear mixed model using the logit link function.Results:The use of radical prostatectomy increased, 33-48%, in the privately insured i3 database while remaining stable at 12% in the Medicare population. There was a rapid uptake in the use of newer technologies over time in both the Medicare and i3 cohorts. The use of laparoscopic-assisted prostatectomy increased from 1% in 2002 to 41% in 2006 in i3 patients, whereas the incidence increased from 3% in 2002 to 35% in 2006 for Medicare patients. The use of neoadjuvant/adjuvant androgen deprivation therapy was lower in the i3 cohort and has decreased over time in both i3 and Medicare. Physician density had an impact on the type of primary treatment received in the New England region; however, this trend was not seen in the western or southern regions of the United States.Conclusions:Using two large national claims registries, we have demonstrated trends over time and substantial geographic variation in the type of primary treatment used for localized prostate cancer. Specifically, there has been a large increase in the use of newer technologies (that is, laparoscopic-assisted prostatectomy and intensity-modulated radiation therapy). These results elucidate the need for improved data collection on prostate cancer treatment outcomes to reduce unwarranted variation in care.

Purpose Data are limited on imaging after primary treatment of localized prostate cancer. Materials and Methods We identified 8,435 men newly diagnosed with nonmetastatic prostate cancer in 1995 to 2012 who were enrolled in CaPSURE™. Patients were followed after primary treatment with radical prostatectomy, cryosurgery, brachytherapy, external beam radiation therapy or androgen deprivation therapy. We assessed the use of bone scan, computerized tomography and magnetic resonance imaging after primary treatment. Factors associated with posttreatment outcomes (number of imaging tests, and time to first imaging and salvage treatment) were evaluated with multivariate Poisson regression and Cox proportional hazards regression. Results The incidence of posttreatment bone scan, computerized tomography and magnetic resonance imaging was 20% or less. Last posttreatment log(prostate specific antigen) was associated with multiple posttreatment imaging. Management by radical prostatectomy, cryosurgery, external beam radiation therapy or brachytherapy vs androgen deprivation therapy was associated with a lower likelihood of posttreatment imaging. Of patients who were imaged after treatment 25% with radical prostatectomy and 9% with radiation underwent imaging before prostate specific antigen failure. The 5-year salvage treatment-free survival rate was 81%. Positive findings on posttreatment imaging were associated with a higher risk of salvage treatment. Conclusions Patients treated with androgen deprivation therapy for localized disease were most likely to be imaged, primarily by bone scan. Men treated with other therapies were less likely to be imaged and tended to undergo computerized tomography. Imaging may add value to posttreatment prostate specific antigen monitoring to identify disease recurrence and progression. Further studies are needed to establish guidelines for the optimal frequency and imaging type to monitor the treatment response.

Abstract Background An observed decrease of physician scientists in medical practice has generated much recent interest in increasing the exposure of research programs in medical school. The aim of this study was to review the experience and attitudes regarding research by medical students in Canada. Methods An anonymous, cross-sectional, self-report questionnaire was administered to second and fourth year students in three medical schools in Ontario between February and May of 2005. Questions were primarily closed-ended and consisted of Likert scales. Descriptive and correlative statistics were used to analyze the responses between students of different years and previous research experience. Results There was a 47% (327/699) overall response rate to the questionnaire. Despite 87% of respondents reporting that they had been involved in some degree of research prior to medical school, 43% report that they have not been significantly involved in research activity during medical school and 24% had no interest in any participation. There were significant differences in the attitudes towards research endeavors during medical school between students in their fourth year compared to second year. The greatest barriers to involvement in research in medical school appear to be time, availability of research mentors, formal teaching of research methodology and the perception that the student would not receive appropriate acknowledgement for work put towards a research project. Conclusion The results of this self-report survey outline the significant differences in attitudes towards mandatory research as a component of critical inquiry and scholarship in the undergraduate curriculum in Ontario medical schools.

Background: The recommendation to perform biopsy of PIRADS 3 lesions has not been adopted with strength as compared to higher scored lesions on multiparametric MRI. This represents a challenging scenario and an unmet need for clinicians to apply a risk adapted approach in these cases. In the present study, we examined clinical and radiologic characteristics in men with PI-RADS 3 index lesions that can predict csPCa on mpMRI-target biopsy., Methods: Revision of a prospective database with patients who underwent targeted and systematic biopsies from 2015 to 2023 for PI-RADS 3 lesions identified on mpMRI. Baseline variables were collected, such as PSA density (PSAd), 4Kscore, prostate size, and the apparent diffusion coefficient (ADC) value of the lesion on mpMRI. Logistic regression, receiver operating characteristic (ROC) and decision curve analyses (DCA) assessing the association between clinic-radiologic factors and csPCa were performed., Results: Overall, 230 patients were included in the study and the median age was 65 years. The median prostate size and PSA were 50 g and 6.26 ng/mL, respectively. 17.4% of patients had csPCa, while 27.5% had Gleason group 1. In univariable logistic analyses, we found that age, BMI, prostate size, PSAd, ADC, and 4Kscore were significant csPCa predictors (P < 0.05). PSAd showed the best prediction performance in terms of AUC (= 0.679). On multivariable analysis, PSAd and 4Kscore were associated with csPCa. The net benefit of PSAd combined with clinical features was superior to those of other parameters. Within patients with PSAd < 0.15, 4Kscore was a statistically significant predictor of csPCa (OR = 3.25, P = 0.032)., Conclusion: PSAd and 4Kscore are better predictors of csPCa in patients with PIRADS 3 lesions compared to ADC. The predictive role of 4Kscore is higher in patients with low PSAd. These results can assist practitioners in the risk stratification of patients with equivocal lesions to determine the need of biopsy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Recent advancements in screening, prostate MRI, robotic surgery, and active surveillance have influenced the profile of patients undergoing radical prostatectomy (RP). We sought to examine their impact on trends in clinicodemographic, risk classification, and adverse pathology in men undergoing surgery., Methods: We queried the National Cancer Database for clinicodemographic, risk group, and pathology data in men undergoing upfront RP between 2006 and 2020. Patients were categorized by NCCN risk groups, and trends were assessed among 2006-2010, 2011-2015, and 2016-2020 periods. Endpoints included rates of pT3, positive surgical margins (PSM), pathologic upstaging, and Gleason grade group (GG) upgrading., Results: 610,762 patients were included. There were significant increases in African Americans (9.8-14.1%), comorbidities (2.1-5.2% with Charlson scores > 1), and robot-assisted RP (78-84%). Over the three time periods, high-risk cases increased from 15 to 20 to 27%, and intermediate-risk from 54 to 51 to 60%. Overall rates of pT3 rose from 20 to 38%, and PSM from 20 to 27% (p < 0.001). Pathologic upstaging increased in low (6-15%), intermediate (20-33%), and high-risk groups (42-58%) -p < 0.001. Gleason upgrading rose in low-risk (45-59%, p < 0.001), with slight reductions in the intermediate and high-risk groups., Conclusions: Recent trends in RP indicate a shift towards more advanced disease, evidenced by increasing rates of pT3, PSM, and pathologic upstaging across all NCCN risk groups. These findings emphasize the need for a careful balance in applying fascia and nerve-sparing techniques to avoid compromising oncological safety., (© 2024. The Author(s).)

Background: 4Kscore is used to aid the decision for prostate biopsy, however its role in active surveillance (AS) has not been investigated in a magnetic resonance imaging (MRI)-based protocol. Our objective was to assess the association between 4Kscore and progression in men undergoing AS on a prospective MRI-based protocol., Methods: This was a single-institution, single-arm, non-therapeutic, interventional trial of 166 men with biopsy-confirmed prostate cancer enrolled between 2014-2020. Patients were placed on a trial-mandated AS protocol including yearly multiparametric (mp)MRI, prostate biopsy, and 4Kscore followed for 48 months after diagnosis. We analyzed protocol-defined and grade progression at confirmatory and subsequent surveillance biopsies., Results: Out of 166 patients, 83 (50%) men progressed per protocol and of them 41 (24.7% of whole cohort) progressed by grade. At confirmatory biopsy, men with a baseline 4Kscore ≥ 20% had a higher risk of grade progression compared to those with 4Kscore < 20% (OR = 4.04, 95% CI: 1.05-15.59, p = 0.043) after adjusting for National Comprehensive Cancer Network (NCCN) risk and baseline PIRADS score. At surveillance biopsies, most recent 4Kscore ≥ 20% significantly predicted per protocol (OR = 2.61, 95% CI: 1.03-6.63, p = 0.044) and grade progression (OR = 5.13, 95% CI: 1.63-16.11, p = 0.005)., Conclusions: For patients on AS, baseline 4Kscore predicted grade progression at confirmatory biopsy, and most recent 4Kscore predicted per-protocol and grade progression at surveillance biopsy., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: Alterations in forkhead box A1 (FOXA1), a pioneer transcription factor, are associated with poor prognosis in breast cancer (BC) and prostate cancer (PC). We characterized FOXA1 genomic alterations and their clinical impacts in a large pan-cancer cohort from the AACR GENIE database., Methods: FOXA1 alterations were characterized across >87,000 samples from >30 cancer types for primary and metastatic tumors alongside patient characteristics and clinical outcomes. FOXA1 alterations were queried in the MSK-MET cohort (a GENIE subset), allowing definition of hazard ratios (HRs) and survival estimates based on Cox proportional hazard models., Results: FOXA1 was altered in 1,869 samples (2.1%), with distinct patterns across different cancers: PC enriched with indel-inframe alterations, BC with missense mutations, and lung cancers with copy number (CN) amplifications.Of 74,715 samples with FOXA1 CN profiles, amplification was detected in 834 (1.1%). Amplification was most common in non-small cell lung cancer (NSCLC, 3% in primary; 6% in metastatic) and small cell lung cancer (4.1% primary; 3.5% metastatic), followed by BC (2% primary; 1.6% metastatic) and PC (2.2% primary; 1.6% metastatic).CN amplifications were associated with decreased overall survival in NSCLC (HR: 1.45, 95%CI: 1.06-1.99, p = .02), BC (HR: 3.04, 95%CI: 1.89-4.89, p = 4e-6), and PC (HR: 1.94, 95%CI: 1.03-3.68, p = .04). Amplifications were associated with wide-spread metastases in NSCLC, BC, and PC., Conclusions: FOXA1 demonstrates distinct alteration profiles across cancer sites. Our findings suggest an association between FOXA1 amplification and both enhanced metastatic potential and decreased survival, highlighting prognostic and therapeutic potential in breast cancer, prostate cancer, and NSCLC., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Context.—: Retraction artifact, paradoxic maturation/differentiation, desmoplasia, and complex irregular growth are morphologic criteria of invasion in urothelial carcinoma., Objective.—: To describe changes mimicking invasion in noninvasive papillary urothelial carcinoma (NPUC)., Design.—: We reviewed 159 consecutive in-house patients with NPUC for either the presence of pseudoinvasion (irregular carcinoma nests within dense hyalinized stroma in the absence of other criteria of invasion) or precursor findings (stromal hyalinization not yet associated with epithelial architectural alteration). We assessed the correlation of these findings with age, sex, evidence of peripheral vascular disease, tumor grade, tumor infarction, and tumor size. We then followed up the patients clinically for tumor recurrence or progression., Results.—: We identified 233 separate NPUCs (136 high grade and 97 low grade) in 125 men and 34 women. Of the 233 tumors, 26 (11.2%) had pseudoinvasion and 24 of 233 tumors (10.3%) had precursor findings. Except for complex irregular growth, no other criteria for invasion were seen. Pseudoinvasion and precursor findings were more common in men (47 of 183 [26%] versus 3 of 50 [6%]; P = .003), larger tumors (mean size, 2.6 versus 1.2 cm; P < .001), and tumors with infarction (33 of 50 [66%] versus 29 of 183 [15.8%]; P < .001). In multivariable analysis, tumor size (odds ratio, 1.49; P =.006), male sex (odds ratio, 6.48; P = .007), and the presence of infarction (odds ratio, 6.59; P < .001) were significant variables. Recurrence rates did not differ between patients with and those without pseudoinvasion (31% [5 of 16] versus 42% [45 of 107], respectively; P = .41). None of the tumors with pseudoinvasion progressed to invasive carcinoma., Conclusions.—: Given the correlation with size and presence of infarcted papillae, we suggest the possibility of tumor ischemia/infarction as a plausible etiology of pseudoinvasion. Awareness of this phenomenon is important for the accurate diagnosis of invasion in papillary urothelial carcinoma., Competing Interests: The authors have no relevant financial interest in the products or companies described in this article., (© 2024 College of American Pathologists.)

Objective: To assess the efficacy and safety of combined High-Intensity Focused Ultrasound (HIFU) and Holmium Laser Enucleation of the Prostate (HoLEP) in treating patients with both localized prostate cancer (PCa) and prostate > 60 g., Methods: All patients who underwent HIFU for treatment of localized PCa were prospectively enrolled in our study. We reviewed records of patients undergoing procedures from January 2016 to January 2023. For patients with prostate sizes > 60 g, HoLEP was offered before HIFU to prevent worsened urinary symptoms post-treatment. Oncological outcomes-prostatic-specific (PSA) kinetics, recurrence rates, treatment failure - and functional results-Sexual Health Inventory for Men (SHIM), International Prostate Symptoms Score (IPSS), and urinary complications were compared between patients undergoing combined HoLEP and HIFU with those underwent HIFU-monotherapy., Results: Among 100 patients, 74 underwent HIFU-monotherapy and 26 underwent the combined HoLEP and HIFU. The majority had intermediate-risk PCa (67%). Pathologic assessment of HoLEP specimens showed no tumor evidence in 57% of cases. In comparison to the HIFU-only group, the combined group exhibited significantly lower PSA metrics across various intervals, however, no differences were found regarding overall and infield recurrences and treatment failure rates. While the combined treatment initially resulted in higher incontinence rates and shorter catheterization durations (P < 0.001), no significant difference in IPSS was observed during subsequent follow-ups., Conclusion: HoLEP and HIFU can be safely combined for the treatment of PCa in patients with >60 g prostate volume without compromising early oncological outcomes thereby expanding the therapeutic scope of HIFU in treating patients with localized PCa and large adenomas., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: There are 2 grading approaches to radical prostatectomy (RP) in multifocal cancer: Grade Group (GG) and percentage of Gleason pattern 4 (GP4%). We investigated whether RP GG and GP4% generated by global vs individual tumor grading correlate differently with biochemical recurrence., Methods: We reviewed 531 RP specimens with GG2 or GG3 cancer. Each tumor was scored separately with assessment of tumor volume and GP4%. Global grade and GP4% were assigned by combining Gleason pattern 3 and 4 volumes for all tumors. Correlation of GG and GP4% generated by 2 methods with biochemical recurrence was assessed by Cox proportional hazard regression and receiver operating characteristic curves, with optimism adjustment using a bootstrap analysis., Results: Median age was 63 (range, 42-79) years. Median prostate-specific antigen was 6.3 (range, 0.3-62.9) ng/mL. In total, the highest-grade tumor in 371 (36.9%) men was GG2 and in 160 (30.1%) men was GG3. Global grading was downgraded from GG3 to GG2 in 37 of 121 (30.6%) specimens with multifocal disease, and 145 of 404 (35.9%) specimens had GP4% decreased by at least 10%. Ninety-eight men experienced biochemical recurrence within a median of 13 (range, 3-119) months. Men without biochemical recurrence were followed up for a median of 47 (range, 12-205) months. Grade Group, GP4%, and margin status correlated with the risk of biochemical recurrence using highest-grade tumor and global grading, but the degrees of these correlations varied and were statistically significantly different between the 2 grading approaches., Conclusions: Grade Group, GP4%, and margin status derived by global vs individual tumor grading predict postoperative biochemical recurrence statistically significantly differently. This difference has important implications if results derived from cohorts graded using different methods are compared., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Surgical training traditionally took place at academic centres, but changed to incorporate community and rural hospitals. As little data exist comparing resident case volumes between these locations, the objective of this study was to determine variations in these volumes for routine general surgery procedures., Methods: We analyzed senior resident case logs from 2009 to 2019 from a general surgery residency program. We classified training centres as academic, community, and rural. Cases included appendectomy, cholecystectomy, hernia repair, bowel resection, adhesiolysis, and stoma formation or reversal. We matched procedures to blocks based on date of case and compared groups using a Poisson mixed-methods model and 95% confidence intervals (CIs)., Results: We included 85 residents and 28 532 cases. Postgraduate year (PGY) 3 residents at academic sites performed 10.9 (95% CI 10.1-11.6) cases per block, which was fewer than 14.7 (95% CI 13.6-15.9) at community and 15.3 (95% CI 14.2-16.5) at rural sites. Fourth-year residents (PGY4) showed a greater difference, with academic residents performing 8.7 (95% CI 8.0-9.3) cases per block compared with 23.7 (95% CI 22.1-25.4) in the community and 25.6 (95% CI 23.6-27.9) at rural sites. This difference continued in PGY5, with academic residents performing 8.3 (95% CI 7.3-9.3) cases per block, compared with 18.9 (95% CI 16.8-21.0) in the community and 14.5 (95% CI 7.0-21.9) at rural sites., Conclusion: Senior residents performed fewer routine cases at academic sites than in community and rural centres. Programs can use these data to optimize scheduling for struggling residents who require exposure to routine cases, and help residents complete the requirements of a Competence by Design curriculum., Competing Interests: Competing interests:: None declared., (© 2024 CMA Impact Inc. or its licensors.)

Introduction: In the realm of computational pathology, the scarcity and restricted diversity of genitourinary (GU) tissue datasets pose significant challenges for training robust diagnostic models. This study explores the potential of Generative Adversarial Networks (GANs) to mitigate these limitations by generating high-quality synthetic images of rare or underrepresented GU tissues. We hypothesized that augmenting the training data of computational pathology models with these GAN-generated images, validated through pathologist evaluation and quantitative similarity measures, would significantly enhance model performance in tasks such as tissue classification, segmentation, and disease detection., Methods: To test this hypothesis, we employed a GAN model to produce synthetic images of eight different GU tissues. The quality of these images was rigorously assessed using a Relative Inception Score (RIS) of 1.27 ± 0.15 and a Fréchet Inception Distance (FID) that stabilized at 120, metrics that reflect the visual and statistical fidelity of the generated images to real histopathological images. Additionally, the synthetic images received an 80% approval rating from board-certified pathologists, further validating their realism and diagnostic utility. We used an alternative Spatial Heterogeneous Recurrence Quantification Analysis (SHRQA) to assess the quality of prostate tissue. This allowed us to make a comparison between original and synthetic data in the context of features, which were further validated by the pathologist's evaluation. Future work will focus on implementing a deep learning model to evaluate the performance of the augmented datasets in tasks such as tissue classification, segmentation, and disease detection. This will provide a more comprehensive understanding of the utility of GAN-generated synthetic images in enhancing computational pathology workflows., Results: This study not only confirms the feasibility of using GANs for data augmentation in medical image analysis but also highlights the critical role of synthetic data in addressing the challenges of dataset scarcity and imbalance., Conclusions: Future work will focus on refining the generative models to produce even more diverse and complex tissue representations, potentially transforming the landscape of medical diagnostics with AI-driven solutions.

A subset of men with prostate cancer have elevated periprostatic androgens compared with levels in peripheral blood (termed the sneaky T phenomenon), which are associated with poor clinical outcomes after radical prostatectomy. These androgens are of testicular origin and reach the prostate, presumably through venous shunting. Varicocele physiology is accompanied by increased hydrostatic pressure within the pelvic venous system, providing a theoretical mechanistic explanation for the sneaky T phenomenon. These observations suggest a potential role for varicocele in contributing to prostate cancer pathophysiology through sneaky T, which if proved, could be a further indication for varicocele repair. Sneaky T can help to explain the differences in the natural history of benign or malignant prostatic diseases between individuals and could be a tool when deciding on the therapeutic course to take., (© 2024. Springer Nature Limited.)