Advantage of whole-mount histopathology in prostate cancer: current applications and future prospects.

BACKGROUND: Whole-mount histopathology (WMH) has been a powerful tool to investigate the characteristics of prostate cancer. However, the latest advancement of WMH was yet under summarization. In this review, we offer a comprehensive exposition of current research utilizing WMH in diagnosing and treating prostate cancer (PCa), and summarize the clinical advantages of WMH and outlines potential on future prospects. METHODS: An extensive PubMed search was conducted until February 26, 2023, with the search term "prostate", "whole-mount", "large format histology", which was limited to the last 4 years. Publications included were restricted to those in English. Other papers were also cited to contribute a better understanding. RESULTS: WMH exhibits an enhanced legibility for pathologists, which improved the efficacy of pathologic examination and provide educational value. It simplifies the histopathological registration with medical images, which serves as a convincing reference standard for imaging indicator investigation and medical image-based artificial intelligence (AI). Additionally, WMH provides comprehensive histopathological information for tumor volume estimation, post-treatment evaluation, and provides direct pathological data for AI readers. It also offers complete spatial context for the location estimation of both intraprostatic and extraprostatic cancerous region. CONCLUSIONS: WMH provides unique benefits in several aspects of clinical diagnosis and treatment of PCa. The utilization of WMH technique facilitates the development and refinement of various clinical technologies. We believe that WMH will play an important role in future clinical applications.

Evaluation of the effect of prostate diameters on erectile dysfunction in patients who underwent low-anterior resection.

OBJECTIVE: Male erectile dysfunction is an important complication of rectal surgery. In this research, the effect of prostate dimensions on the development of postoperative erectile dysfunction in patients diagnosed with mid-rectum adenocarcinoma who underwent low anterior resection (LAR) is examined. PATIENTS AND METHODS: Thirty-one male patients diagnosed as mid-rectal adenocancer were included. The International Index of Erectile Function (IIEF) questionnaire was used to determine the patients' pre and postoperative erectile dysfunction levels, and the level of relationship between the change in these IIEF scores and prostate measurements determined by computed tomography were evaluated. RESULTS: There were statistically significant differences between IIEF index score and anterior posterior (AP) and transverse (TR) measurements (p≤0.001; p≤0.001), but no statistically significant difference was found between craniocaudal (CC) measurement values (p=0.169). CONCLUSIONS: The risk of nerve injury will be higher in those with a small prostate transverse diameter. Intraoperative nerve monitoring should be recommended primarily in younger patient groups.

Prediction of false-positive PI-RADS 5 lesions on prostate multiparametric MRI: development and internal validation of a clinical-radiological characteristics based nomogram.

BACKGROUND: To develop a risk model including clinical and radiological characteristics to predict false-positive The Prostate Imaging Reporting and Data System (PI-RADS) 5 lesions. METHODS: Data of 612 biopsy-naïve patients who had undergone multiparametric magnetic resonance imaging (mpMRI) before prostate biopsy were collected. Clinical variables and radiological variables on mpMRI were adopted. Lesions were divided into the training and validation cohort randomly. Stepwise multivariate logistic regression analysis with backward elimination was performed to screen out variables with significant difference. A diagnostic nomogram was developed in the training cohort and further validated in the validation cohort. Calibration curve and receiver operating characteristic (ROC) analysis were also performed. RESULTS: 296 PI-RADS 5 lesions in 294 patients were randomly divided into the training and validation cohort (208 : 88). 132 and 56 lesions were confirmed to be clinically significant prostate cancer in the training and validation cohort respectively. The diagnostic nomogram was developed based on prostate specific antigen density, the maximum diameter of lesion, zonality of lesion, apparent diffusion coefficient minimum value and apparent diffusion coefficient minimum value ratio. The C-index of the model was 0.821 in the training cohort and 0.871 in the validation cohort. The calibration curve showed good agreement between the estimation and observation in the two cohorts. When the optimal cutoff values of ROC were 0.288 in the validation cohort, the sensitivity, specificity, PPV, and NPV were 90.6%, 67.9%, 61.7%, and 92.7% in the validation cohort, potentially avoiding 9.7% unnecessary prostate biopsies. CONCLUSIONS: We developed and validated a diagnostic nomogram by including 5 factors. False positive PI-RADS 5 lesions could be distinguished from clinically significant ones, thus avoiding unnecessary prostate biopsy.

Primary mucinous adenocarcinoma of the urethra: A contemporary clinicopathologic analysis of 17 patients.

Mucinous adenocarcinoma of the urethra is rare. Here we performed a contemporary clinicopathologic analysis of this entity in both male and female patients. All cases with secondary tumors involving the urethra were excluded. Clinicopathologic parameters and follow up was obtained. Seventeen patients were included in the study, 9/17 (53 %) male and 8/17 (47 %) female. The mean patient age was 68 years (range: 53-88 years). The majority (11/17, 65 %) of patients were African American, with an even greater incidence (7/8, 87 %) in female patients. In male patients, prostatic urethra was the most common part of the urethra (6/9, 67 %) where the tumor arose from. Immunohistochemical stains were performed in 11/17 (65 %) tumors and were positive for CK20 (11/11, 100 %), CDX2 (11/12, 92 %), CK7 (8/9, 88 %), GATA3 (3/8, 37 %) and negative for NKX3.1, PSA, p63, PAX8, and Beta-Catenin. In resection specimens, tumors were categorized as pT2 (3/11, 27 %), pT3 (1/11, 9 %), and pT4 (7/11, 64 %). Lymph node status was categorized as pN0 (6/9, 67 %), pN1 (1/9, 11 %), and pN2 (2/9, 22 %). Available follow up data showed 7/13 (54 %) patients developed recurrence after surgical resection and chemotherapy, of which 3/7 (43 %) died of widespread metastatic disease. It is critical for pathologists and urologic oncologists to be aware of this entity in both male and female patients in view of potential diagnostic pitfalls, prognosis, and therapeutic implications.

Untargeted metabolomics reveals that declined PE and PC in obesity may be associated with prostate hyperplasia.

BACKGROUND: Recent studies have shown that obesity may contribute to the pathogenesis of benign prostatic hyperplasia (BPH). However, the mechanism of this pathogenesis is not fully understood. METHODS: A prospective case-control study was conducted with 30 obese and 30 nonobese patients with BPH. Prostate tissues were collected and analyzed using ultra performance liquid chromatography ion mobility coupled with quadrupole time-of-flight mass spectrometry (UPLC-IMS-Q-TOF). RESULTS: A total of 17 differential metabolites (3 upregulated and 14 downregulated) were identified between the obese and nonobese patients with BPH. Topological pathway analysis indicated that glycerophospholipid (GP) metabolism was the most important metabolic pathway involved in BPH pathogenesis. Seven metabolites were enriched in the GP metabolic pathway. lysoPC (P16:0/0:0), PE (20:0/20:0), PE (24:1(15Z)/18:0), PC (24:1(15Z)/14:0), PC (15:0/24:0), PE (24:0/18:0), and PC (16:0/18:3(9Z,12Z,15Z)) were all significantly downregulated in the obesity group, and the area under the curve (AUC) of LysoPC (P-16:0/0/0:0) was 0.9922. The inclusion of the seven differential metabolites in a joint prediction model had an AUC of 0.9956. Thus, both LysoPC (P-16:0/0/0:0) alone and the joint prediction model demonstrated good predictive ability for obesity-induced BPH mechanisms. CONCLUSIONS: In conclusion, obese patients with BPH had a unique metabolic profile, and alterations in PE and PC in these patients be associated with the development and progression of BPH.

Detecting androgen receptor (AR), AR variant 7 (AR-V7), prostate-specific membrane antigen (PSMA), and prostate-specific antigen (PSA) gene expression in CTCs and plasma exosome-derived cfRNA in patients with metastatic castration-resistant prostate cancer (mCRPC) by integrating the VTX-1 CTC isolation system with the QIAGEN AdnaTest.

BACKGROUND: Therapies for metastatic castration-resistant prostate cancer (mCRPC) include targeting the androgen receptor (AR) with androgen receptor inhibitors (ARIs) and prostate-specific membrane antigen (PSMA). Having the ability to detect AR, AR splice variant 7 (AR-V7), or PSMA in circulating tumor cells (CTCs) or circulating exosomal cell-free RNA (cfRNA) could be helpful to guide selection of the appropriate therapy for each individual patient. The Vortex Biosciences VTX-1 system is a label-free CTC isolation system that enables the detection of the expression of multiple genes in both CTCs and exosomal cfRNA from the same blood sample in patients with mCRPC. Detection of both AR-V7 and PSMA gene expression in both CTCs and cfRNA simultaneously has not yet been reported. METHODS: To characterize the combined VTX-1-AdnaDetect workflow, 22Rv1 cancer cells were spiked into blood from healthy donors and processed with the VTX-1 to mimic patient samples and assess performances (capture efficiency, purity, AR and AR-V7 expression). Then, we collected 19 blood samples from 16 patients with mCRPC and therapeutic resistance to androgen receptor inhibitors (ARIs). Plasma was separated and the plasma-depleted blood was processed further with the VTX-1 to collect CTCs. Both plasma exosomal cfRNA and CTCs were subsequently analyzed for AR, AR-V7, PSMA, and prostate-specific antigen (PSA) mRNA expression using the AdnaTest ProstateCancerPanel AR-V7 assay. RESULTS: AR-V7 expression could be detected in 22Rv1 cells spiked into blood from healthy volunteers as well as in CTCs and plasma-derived exosomal cfRNA from patients with mCRPC by processing blood with the VTX-1 CTC isolation system followed by the AdnaTest ProstateCancerPanel AR-V7 assay. 94.7% of patient blood samples (18/19) had detectable AR expression in either CTCs or exosomal cfRNA (16 in CTCs, 12 in cfRNA). 15.8% of the 19 patient blood samples (3/19) were found to have AR-V7-positive (AR-V7+) CTCs, one of which was also AR-V7+ in the exosomal cfRNA analysis. 42.1% of patient blood samples (8/19) were found to be PSMA positive (PSMA+): 26.3% (5/19) were PSMA+ in the CTC analysis and 31.6% (6/19) were PSMA+ in the exosomal cfRNA analysis. Of those 8 PSMA+ samples, 2 had detectable PSMA only in CTCs, and 3 had detectable PSMA only in exosomal cfRNA. CONCLUSION: VTX-1 enables isolation of CTCs and plasma exosomes from a single blood draw and can be used for detecting AR-V7 and PSMA mRNA in both CTCs and cfRNA in patients with mCRPC and resistance to ARIs. This technology facilitates combining RNA measurements in CTCs and exosomal cfRNA for future studies to develop potentially clinically relevant cancer biomarker detection in blood.

Dishevelled Segment Polarity Protein 3 (DVL3) Induced by Bacterial LPS Promotes the Proliferation and Migration of Prostate Cancer Cells through the TLR4 Pathway.

BACKGROUND: Chronic inflammation is associated with various malignant tumors. Bacterial lipopolysaccharides (LPSs) play a significant part in the event and development of prostate cancer. Dishevelled segment polarity protein 3 (DVL3) is a shared component of the Wnt/ß-catenin and Notch signaling pathways, which are involved in tumor progression, chemoresistance, and maintenance of stem cell-like properties. According to reports, prostatic cancer cell invasion and proliferation are mediated by toll-like receptor 4 (TLR4). However, the role and regulation of DVL3 in prostate cancer and its relationship with TLR4 remain unclear. METHODS: Survival curves were plotted to evaluate the relationship between DVL3 expression and prognosis in patients with prostate cancer. DVL3 was silenced in PC3 and DU145 cells using small interfering RNAs (siRNAs). Subsequently, cell counting kit-8 (CCK-8) assay, colony formation assay, transwell migration assay, and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) were performed to investigate the role of DVL3 in cell proliferation and migration in vitro. The protein markers of potential pathways were analyzed via western blotting. RESULTS: DVL3 expression was linked to prognosis in patients with prostate cancer; In particular, patients with high DVL3 expression had a poor prognosis. LPS stimulation increased (p < 0.01) the expression of DVL3 in PC3 cells. DVL3 regulated tumor cell proliferation and migration by mediating the increase (p < 0.01) in TLR4 expression. Knockout of TLR4 validated that TLR4 played a crucial role in LPS-induced DVL3 expression. Silencing of DVL3 decreased (p < 0.01) the LPS-induced proliferation and migration of PC3 cells. CONCLUSIONS: Bacterial LPS-induced DVL3 promoted the multiplication and migration of prostate cancer cells through the TLR4 pathway. This study offers a valuable reference for the development and clinical application of targeted drugs for prostate cancer.

Assessment of the accuracy of biparametric MRI/TRUS fusion-guided biopsy for index tumor evaluation using postoperative pathology specimens.

BACKGROUND: Multiparametric MRI (mpMRI) is widely used for the diagnosis, surveillance, and staging of prostate cancer. However, it has several limitations, including higher costs, longer examination times, and the use of gadolinium-based contrast agents. This study aimed to investigate the accuracy of preoperatively assessed index tumors (ITs) using biparametric MRI (bpMRI)/transrectal ultrasound (TRUS) fusion biopsy compared with radical prostatectomy (RP) specimens. METHODS: We included 113 patients diagnosed with prostate cancer through bpMRI/TRUS fusion-guided biopsies of lesions with a Prostate Imaging Reporting and Data System (PI-RADS) category ≥ 3. These patients underwent robot-assisted laparoscopic radical prostatectomy (RARP) at our institution between July 2017 and March 2023. We examined the localization of preoperative and postoperative ITs, the highest Gleason score (GS), and tumor diameter in these patients. RESULTS: The preoperative cT stage matched the postoperative pT stage in 53 cases (47%), while 31 cases (27%) were upstaged, and 29 cases (26%) were downstaged (Weighted Kappa = 0.21). The preoperative and postoperative IT localizations were consistent in 97 cases (86%). The concordance rate between Gleason groups in targeted biopsies and RP specimens was 51%, with an upgrade in 25 cases (23%) and a downgrade in 27 cases (25%) (Weighted Kappa = 0.42). The maximum diameter of the IT and the maximum cancer core length on biopsy were correlated with the RP tumor's maximum diameter (p < 0.001 for both). CONCLUSION: The diagnostic accuracy of bpMRI/TRUS fusion biopsy is comparable to mpMRI, suggesting that it can be a cost-effective and time-saving alternative.

Exploring the relation of active surveillance schedules and prostate cancer mortality.

BACKGROUND: Active surveillance (AS), where treatment is deferred until cancer progression is detected by a biopsy, is acknowledged as a way to reduce overtreatment in prostate cancer. However, a consensus on the frequency of taking biopsies while in AS is lacking. In former studies to optimize biopsy schedules, the delay in progression detection was taken as an evaluation indicator and believed to be associated with the long-term outcome, prostate cancer mortality. Nevertheless, this relation was never investigated in empirical data. Here, we use simulated data from a microsimulation model to fill this knowledge gap. METHODS: In this study, the established MIcrosimulation SCreening Analysis model was extended with functionality to simulate the AS procedures. The biopsy sensitivity in the model was calibrated on the Canary Prostate Cancer Active Surveillance Study (PASS) data, and four (tri-yearly, bi-yearly, PASS, and yearly) AS programs were simulated. The relation between detection delay and prostate cancer mortality was investigated by Cox models. RESULTS: The biopsy sensitivity of progression detection was found to be 50%. The Cox models show a positive relation between a longer detection delay and a higher risk of prostate cancer death. A 2-year delay resulted in a prostate cancer death risk of 2.46%-2.69% 5 years after progression detection and a 10-year risk of 5.75%-5.91%. A 4-year delay led to an approximately 8% greater 5-year risk and an approximately 25% greater 10-year risk. CONCLUSION: The detection delay is confirmed as a surrogate for prostate cancer mortality. A cut-off for a "safe" detection delay could not be identified.

NKX3.1 Expression in Non-Prostatic Tumors and Characterizing its Expression in Esophageal/Gastroesophageal Adenocarcinoma.

The NKX3.1 immunohistochemical stain is widely recognized as a highly sensitive and specific marker for prostate adenocarcinoma. Nevertheless, its expression has been documented in various nonprostatic tissues and malignancies. This review aims to provide an overview of NKX3.1 expression in diverse tumor types, with a specific focus on its aberrant expression in esophageal/gastroesophageal adenocarcinoma (E/GE-ADC). In our investigation, we explored the expression of NKX3.1 in a series of E/GE-ADC to shed light on its prevalence in this tumor category. A total of 50 samples, comprising primary and metastatic E/GE-ADC specimens from 34 patients, were subjected to immunohistochemical analysis. Stained sections were scored based on the intensity and distribution-categorized as negative, weak, moderate, or strong in either a focal or diffuse pattern. Strong staining corresponds to the intensity observed in normal prostate controls, while focal and diffuse staining denote <50% and ≥50% of tumor nuclei staining positive, respectively. Our semiquantitative scoring revealed that 6 (12%) of the primary and metastatic E/GE-ADC specimens exhibited variable positivity for NKX3.1. This finding suggests that E/GE-ADC can sporadically stain positive for NKX3.1, introducing potential challenges in definitively determining the primary site of origin in certain clinical scenarios. Along with a literature review of NKX3.1 expression in other tumor types, our study provides additional important information about the extent to which this immunostain can be seen in E/GE-ADCs, which, to our knowledge, has not been reported.

Defining the challenges and opportunities for using patient-derived models in prostate cancer research.

BACKGROUND: There are relatively few widely used models of prostate cancer compared to other common malignancies. This impedes translational prostate cancer research because the range of models does not reflect the diversity of disease seen in clinical practice. In response to this challenge, research laboratories around the world have been developing new patient-derived models of prostate cancer, including xenografts, organoids, and tumor explants. METHODS: In May 2023, we held a workshop at the Monash University Prato Campus for researchers with expertise in establishing and using a variety of patient-derived models of prostate cancer. This review summarizes our collective ideas on how patient-derived models are currently being used, the common challenges, and future opportunities for maximizing their usefulness in prostate cancer research. RESULTS: An increasing number of patient-derived models for prostate cancer are being developed. Despite their individual limitations and varying success rates, these models are valuable resources for exploring new concepts in prostate cancer biology and for preclinical testing of potential treatments. Here we focus on the need for larger collections of models that represent the changing treatment landscape of prostate cancer, robust readouts for preclinical testing, improved in vitro culture conditions, and integration of the tumor microenvironment. Additional priorities include ensuring model reproducibility, standardization, and replication, and streamlining the exchange of models and data sets among research groups. CONCLUSIONS: There are several opportunities to maximize the impact of patient-derived models on prostate cancer research. We must develop large, diverse and accessible cohorts of models and more sophisticated methods for emulating the intricacy of patient tumors. In this way, we can use the samples that are generously donated by patients to advance the outcomes of patients in the future.

The Transatlantic Recommendations for Prostate Gland Evaluation with Magnetic Resonance Imaging After Focal Therapy (TARGET): A Systematic Review and International Consensus Recommendations.

BACKGROUND AND OBJECTIVE: Magnetic resonance imaging (MRI) can detect recurrences after focal therapy for prostate cancer but there is no robust guidance regarding its use. Our objective was to produce consensus recommendations on MRI acquisition, interpretation, and reporting after focal therapy. METHODS: A systematic review was performed in July 2022 to develop consensus statements. A two-round consensus exercise was then performed, with a consensus meeting in January 2023, during which 329 statements were scored by 23 panellists from Europe and North America spanning urology, radiology, and pathology with experience across eight focal therapy modalities. Using RAND Corporation/University of California-Los Angeles methodology, the Transatlantic Recommendations for Prostate Gland Evaluation with MRI after Focal Therapy (TARGET) were based on consensus for statements scored with agreement or disagreement. KEY FINDINGS AND LIMITATIONS: In total, 73 studies were included in the review. All 20 studies (100%) reporting suspicious imaging features cited focal contrast enhancement as suspicious for cancer recurrence. Of 31 studies reporting MRI assessment criteria, the Prostate Imaging-Reporting and Data System (PI-RADS) score was the scheme used most often (20 studies; 65%), followed by a 5-point Likert score (six studies; 19%). For the consensus exercise, consensus for statements scored with agreement or disagreement increased from 227 of 295 statements (76.9%) in round one to 270 of 329 statements (82.1%) in round two. Key recommendations include performing routine MRI at 12 mo using a multiparametric protocol compliant with PI-RADS version 2.1 standards. PI-RADS category scores for assessing recurrence within the ablation zone should be avoided. An alternative 5-point scoring system is presented that includes a major dynamic contrast enhancement (DCE) sequence and joint minor diffusion-weighted imaging and T2-weighted sequences. For the DCE sequence, focal nodular strong early enhancement was the most suspicious imaging finding. A structured minimum reporting data set and minimum reporting standards for studies detailing MRI data after focal therapy are presented. CONCLUSIONS AND CLINICAL IMPLICATIONS: The TARGET consensus recommendations may improve MRI acquisition, interpretation, and reporting after focal therapy for prostate cancer and provide minimum standards for study reporting. PATIENT SUMMARY: Magnetic resonance imaging (MRI) scans can detect recurrent of prostate cancer after focal treatments, but there is a lack of guidance on MRI use for this purpose. We report new expert recommendations that may improve practice.

Revisiting the issue of "beach balls" in holmium laser enucleation of prostate: clinical and histological characterization.

PURPOSE: To clinically and histologically characterize prostatic nodules resistant to morcellation ("beach balls," BBs). PATIENTS AND METHODS: We reviewed a consecutive cohort of 559 holmium laser enucleation of the prostate (HoLEP) procedures performed between January 2020 and November 2023. The BBs group comprised 55 men (10%) and the control group comprised 504 men (90%). The clinical, intraoperative, outcome, and histologic data were statistically processed for the prediction of the presence of BBs and their influence on the perioperative course and outcome. RESULTS: The BBs group in comparison to the controls was older (75 vs 73 years, respectively, p = 0.009) and had higher rates of chronic retention (51 vs 29%, p = 0.001), larger prostates on preoperative abdominal ultrasound (AUS) (140 vs 80 cc, p = 0.006E-16), longer operating time (120 vs 80 min, p = 0.001), higher weights of removed tissue (101 vs 60 gr, p = 0.008E-10), higher complication rates (5 vs 1%, p = 0.03), and longer hospitalization (p = 0.014). A multivariate analysis revealed that larger prostates on preoperative AUS and older age independently predicted the presence of BBs which would prolong operating time. ROC analyses revealed that a threshold of 103 cc on AUS predicted BBs with 94% sensitivity and 84% specificity. BBs were mostly characterized histologically by stromal component (p = 0.005). CONCLUSIONS: BBs are expected in older patients and cases of chronic retention. Prostatic volume is the most reliable predictor of their presence. They contribute to prolonged operating time and increased risk of complications. The predominantly stromal composition of the BBs apparently confers their resistance to morcellation.

Magnetic Resonance Imaging, Clinical, and Biopsy Findings in Suspected Prostate Cancer: A Systematic Review and Meta-Analysis.

Importance: Multiple strategies integrating magnetic resonance imaging (MRI) and clinical data have been proposed to determine the need for a prostate biopsy in men with suspected clinically significant prostate cancer (csPCa) (Gleason score ≥3 + 4). However, inconsistencies across different strategies create challenges for drawing a definitive conclusion. Objective: To determine the optimal prostate biopsy decision-making strategy for avoiding unnecessary biopsies and minimizing the risk of missing csPCa by combining MRI Prostate Imaging Reporting & Data System (PI-RADS) and clinical data. Data Sources: PubMed, Ovid MEDLINE, Embase, Web of Science, and Cochrane Library from inception to July 1, 2022. Study Selection: English-language studies that evaluated men with suspected but not confirmed csPCa who underwent MRI PI-RADS followed by prostate biopsy were included. Each study had proposed a biopsy plan by combining PI-RADS and clinical data. Data Extraction and Synthesis: Studies were independently assessed for eligibility for inclusion. Quality of studies was appraised using the Quality Assessment of Diagnostic Accuracy Studies 2 tool and the Newcastle-Ottawa Scale. Mixed-effects meta-analyses and meta-regression models with multimodel inference were performed. Reporting of this study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Main Outcomes and Measures: Independent risk factors of csPCa were determined by performing meta-regression between the rate of csPCa and PI-RADS and clinical parameters. Yields of different biopsy strategies were assessed by performing diagnostic meta-analysis. Results: The analyses included 72 studies comprising 36 366 patients. Univariable meta-regression showed that PI-RADS 4 (ß-coefficient [SE], 7.82 [3.85]; P = .045) and PI-RADS 5 (ß-coefficient [SE], 23.18 [4.46]; P < .001) lesions, but not PI-RADS 3 lesions (ß-coefficient [SE], -4.08 [3.06]; P = .19), were significantly associated with a higher risk of csPCa. When considered jointly in a multivariable model, prostate-specific antigen density (PSAD) was the only clinical variable significantly associated with csPCa (ß-coefficient [SE], 15.50 [5.14]; P < .001) besides PI-RADS 5 (ß-coefficient [SE], 9.19 [3.33]; P < .001). Avoiding biopsy in patients with lesions with PI-RADS category of 3 or less and PSAD less than 0.10 (vs <0.15) ng/mL2 resulted in reducing 30% (vs 48%) of unnecessary biopsies (compared with performing biopsy in all suspected patients), with an estimated sensitivity of 97% (vs 95%) and number needed to harm of 17 (vs 15). Conclusions and Relevance: These findings suggest that in patients with suspected csPCa, patient-tailored prostate biopsy decisions based on PI-RADS and PSAD could prevent unnecessary procedures while maintaining high sensitivity.

The effectiveness of mapping-targeted biopsies on the index lesion in transperineal prostate biopsies.

PURPOSE: To evaluate the effectiveness of mapping-targeted biopsies (MTB) on the index lesion for the detection of clinically significant prostate cancer (csPCa) in transperineal fusion-image prostate biopsies. MATERIALS AND METHODS: A retrospective analysis was conducted on 309 men with suspected PCa who underwent prostate biopsies at the Creu Blanca reference center in Barcelona, Spain. The Prostate Imaging-Reporting and Data System (PI-RADS v.2.1) of the magnetic resonance images (MRI) were reclassified by an expert radiologist reading of pre-biopsy biparametric MRI used for segmentation of suspected lesions. Transperineal MTB of suspicious lesions and 12-core systematic biopsies were performed using the Artemis™ platform. CsPCa was defined as International Society of Urological Pathology grade group ≥ 2. RESULTS: CsPCa was detected in 192 men (62.1%), with detection rates of 6.3% for PI-RADS 2, 26.8% for PI-RADS 3, 87.3% for PI-RADS 4, and 93.1% for PI-RADS 5. MTB of the index lesion identified 185 csPCa (96.3%). CsPCa was detected solely in systematic biopsies in three cases (1.6%), while an additional four cases (2.1%) were identified only in the second suspected lesion. A predictive model for csPCa detection in MTB of the index lesion was developed, with an AUC of 0.918 (95% CI 0.887-0.950). CONCLUSIONS: This model had the potential to avoid 23.3% of prostate biopsies without missing additional csPCa cases. MTB of the index lesion was highly effective for identifying csPCa in fusion transperineal prostate biopsies. A developed predictive model successfully reduced the need for almost one quarter of biopsies without missing csPCa cases.

Is the learning curve of the urology resident for conventional radical prostatectomy similar to that of staff initiating robot-assisted radical prostatectomy?

INTRODUCTION: The superiority of the functional results of robot-assisted radical prostatectomyis still controversial. Despite this, it is known that minimally invasive surgery obtains better results when analyzing blood loss, blood transfusion and length of stay, for example. Several studies have analyzed the impact of the resident physician's involvement on the results of urological surgeries. The simple learning curve for robot-assisted radical prostate surgery is estimated to be around 10 to 12 cases. Learning curve data for robotic surgeons is heterogeneous, making it difficult to analyze. Rare studies compare the results of a radical prostatectomy of an inexperienced surgeon starting his training in open surgery, with the results of the same surgeon, a few years later, starting training in robotic surgery. OBJECTIVE: to analyze the results of open radical prostatectomy surgeries (ORP) performed by urology residents, comparing them to the results of robot-assisted radical prostatectomy (RARP), performed by these same surgeons, after completing their training in urology. MATERIALS AND METHODS: a retrospective analysis of the cases of only 3 surgeons was performed. 50 patients underwent ORP (group A). The surgeons who operated on the ORP patients were in the 3rd and final year of the urology residency program and beginners in ORP surgery, but with at least 4 years of experience in open surgery. The same surgeons, already trained urologists, began their training in robotic surgery and performed 56 RARP surgeries (group B). For the comparative analysis, data were collected on age, number of lymph nodes removed, surgery time, hospitalization time, drain volume, drain permanence time, indwelling bladdercateter (IBC) permanence time, positive surgical margin, biochemical recurrence, risk classification (ISUP), intra and postoperative complications, urinary incontinence (UI) and erectile dysfunction (ED). The console used was the Da Vinci Si, from Intuitive®. For statistical analysis, the Shapiro-Wilk test verified that the data did not follow normality, the Levene test guaranteed homogeneity, and the Mann-Whitney test performed the comparative analysis of the quantitative data. For the analysis of qualitative data, the Chi-square test was used for nominal variables and the Mann-Whitney U test for ordinal variables. Additionally, the Friedman test analyzed whether there was an improvement in the perception of UI or ED over the months, for each group individually (without comparing them), and the post-hoc Durbin-Conover test, for the results with statistically significant difference. We used a p-value < 0.05, and the Jamovi® program (Version 2.0). RESULTS: there was no statistically significant difference between the groups for age, number of lymph nodes removed, positive surgical margin, biochemical recurrence, risk classification and urinary incontinence. Additionally, we observed that the surgical time was longer in group B. On the other hand, the length of stay, drain volume, drain time, IBC time, complication rate and levels of erectile dysfunction in the third and sixth months were higher in group A, when compared to group B. We also observed that there was no evolutionary improvement in ED over the months in both groups, and that there was a perception of improvement in UI from the 1st to the 3rd month in group A, and from the 1st to the 6th month, and from the 3rd to the 12th month, in group B. CONCLUSION: the learning curve of RARP is equivalent to the curve of ORP. In general, the results for the robotic group were better, however, the functional results were similar between the groups, with a slight tendency of advantage for the robotic arm.

Performance of standard systematic biopsy versus MRI/TRUS fusion biopsy using the Navigo® system in contemporary cohort.

INTRODUCTION: The introduction of multi parameter magnetic resonance imaging (mpMRI) of the prostate in combination with MRI/TRUS fusion and systematic biopsy resulted in improved detection of prostate cancer. The aim of the current study was to document the performance of MRI/TRUS fusion biopsy of the prostate using the Navigo™ software in a contemporary cohort of patients from nonreferral centers. MATERIAL AND METHODS: We performed a two centers prospective data collection (2014-2020) for men with clinically suspected Pca and patients on active surveillance for low-risk Pca that were referred for TRUS biopsy after performing mpMRI of the prostate with a visible lesion. The primary outcome was detection of clinically significant cancer (csPca) defined as ISUP grade group ≥2. Patients were stratified according to biopsy technique and PI-RADS category. RESULTS: The study group included 236 patients of whom 129 (54.9%) were diagnosed with Pca and 82 (34.7%) with csPca (GG ≥ 2) on combined biopsy. The overall detection of csPca was 31% for targeted vs. 25.4% for systematic biopsy with an absolute difference of 5.6% in favor of the fusion technique. No significant difference between the two techniques was observed for detection of benign prostate or GG1 disease. The improved performance of the targeted approach was noted only in patients with PI-RADS 4 and 5 lesions. Of the patients with csPca 10 (12%) were diagnosed only by the systematic biopsy while 20 (24%) were detected only in the fusion biopsy. Systematic biopsy of prostate lobe without MRI lesion detected only 2 cases (∼1%) with high grade disease. CONCLUSIONS: Detection of csPca by mpMRI/TRUS fusion biopsy using the 3D Navigo™ system is feasible. The targeted approach outperforms the systematic one, however the later technique also detects high risk disease and should be included in the biopsy procedure. The overall detection rate (34.9%) of clinically significant prostate cancer by both targeted and systematic sampling is relatively low.

Comparative analysis of prognosis and gene expression in prostate cancer patients with site-specific visceral metastases.

INTRODUCTION: Prostate cancer patients with visceral metastases often exhibited poor prognoses. Few researches had compared the prognostic impact and gene expression profiles among distinct visceral metastatic sites. Therefore, we conducted a comprehensive study utilizing data from the Surveillance, Epidemiology, and End Results (SEER) database and the Gene Expression Omnibus database. PATIENTS AND METHODS: We analyzed the prostate cancer-specific mortality (PCSM) risk for 8,170 patients diagnosed with metastatic prostate cancer (mPCa) between 2000 and 2019, utilizing data from the SEER 17 registry database. Patients with metastatic disease in nonregional lymph nodes, bones, brains, livers, and lungs were identified. Competing risks regression was employed to evaluate the effect of visceral metastatic disease sites on PCSM. Differentially expressed genes (DEGs) between visceral metastases were assessed using data from the GSE6752 dataset. A relative protein-protein interaction (PPI) network was constructed based on STRING analysis. Furthermore, we explored the distribution of DEGs in various normal tissues and tumor tissues using the Human Protein Atlas and GEPIA. RESULTS: Competing risks regression analysis revealed that liver and lung metastases had a substantial impact on PCSM (hazard ratio 2.24, 95% confidence interval 1.70-2.95, P < 0.001; hazard ratio 1.30, 95% confidence interval 1.06-1.59, P = 0.012, respectively). Seven significant DEGs were identified from samples of liver and lung metastases (HERV-FRD, NUDT12, FAM63A, SCGB3A1, CEACAM6, LOC440416, SFTPB) and were associated with respiratory gaseous exchange, pulmonary surfactant metabolism, and fibronectin matrix formation in PPI network analysis. Notably, the expression levels of the three DEGs significantly upregulated in lung metastases were also found to be higher in normal lung tissues compared to normal liver tissues. CONCLUSION: Patients diagnosed with mPCa and presenting with liver and/or lung metastases exhibit poorer prognoses. SCGB3A1, identified as a tumor suppressor gene, may contribute to the better survival prognosis observed in patients with prostate cancer lung metastases compared to those with liver metastases. The gene expression profiles in these two specific metastatic sites reveal a combination of both heterogeneity and homogeneity.

Morphologic features of prostate cancer-encased native vessels: An image analysis study.

BACKGROUND: Vasculature plays a crucial role in the progression of prostate cancer (PC). Changes to the prostatic native vessels have not been studied since 2000 when Garcia et al. demonstrated marked media hypercellularity and increased artery thickness in prostatic native arteries within PC. We aim to further evaluate and characterize prostatic native vessels with a more accurate method with the use of virtual slides and digital analysis. DESIGN: Pathologist-annotated whole-mount digital slides from 96 entirely submitted prostatectomies were annotated for PC (color-coded by Gleason) using Omero platform. A subset of 44 cases met criteria for further analysis of media thickness, cellularity, and wall thickness to lumen ratio. Cases were included based on containing ≥5 native arteries (≥100 µm diameter) encased on at least 3 sides by PC, with vessels (≥100 µm diameter) designated as controls if they were ≥ 1000 µm away from PC. Annotated vessels were segmented and processed using Matlab 2023b. Mean media thickness (corrected for oblique sections), media: lumen ratio (based on numbers of pixels), and media cellularity (nuclei count) were studied by analysis with SPSS by linear mixed model with nested random effects for subject and slide to account for repeated measures. RESULTS: Vessels encased by PC showed greater media thickness (p=0.02), cellularity (p=0.02) and wall thickness/lumen ratio (p= <0.001) compared to vessels away from PC. These values showed an increasing trend according to stage in cellularity (p=0.14), media thickness (p=0.12) and wall thickness/ lumen ratio (p= 0.33) with higher stage (pT3). A Gleason group comparison showed a borderline-significant gradewise trend when analyzing wall thickness/lumen ratio (p=0.06). Grade 5 emerged as significantly different (p=0.02) from grades 3 or 4 non-cribriform. CONCLUSIONS: Similar to the 2000 study, increased media thickness and hypercellularity of vessels encased by PC were evident compared to controls. Borderline grade-dependent increased vessel cellularity changes were seen, suggesting a possible role in PC progression; the predictive value of these changes for outcome is uncertain. Whether the etiology of changes reflects locally increased intravascular pressure of vessels within tumor should be investigated.

Different diagnostic strategies combining prostate health index and magnetic resonance imaging for predicting prostate cancer: A multicentre study.

OBJECTIVE: To explore how prostate health index (PHI) and multiparametric magnetic resonance imaging (mpMRI) should be used in concert to improve diagnostic capacity for clinically significant prostate cancers (CsCaP) in patients with prostate-specific antigen (PSA) between 4 and 20 ng/ml. METHODS: About 426 patients fulfilling the inclusion criteria were included in this study. Univariable and multivariable logistic analyses were performed to analyze the association between the clinical indicators and CaP/CsCaP. We used the Delong test to compare the differences in the area under the curve (AUC) values of four models for CaP and CsCaP. Decision curve analysis (DCA) and calibration plots were used to assess predictive performance. We compared clinical outcomes of different diagnostic strategies constructed using different combinations of the models by the chi-square test and the McNemar test. RESULTS: The AUC of PHI-MRI (a risk prediction model based on PHI and mpMRI) was 0.859, which was significantly higher than those of PHI (AUC = 0.792, P < 0.001) and mpMRI (AUC = 0.797, P < 0.001). PHI-MRI had a higher net benefit on DCA for predicting CaP and CsCaP in comparison to PHI and mpMRI. Adding the PHI-MRI in diagnostic strategies for CsCaP, such as use PHI-MRI alone or sequential use of PHI followed by PHI-MRI, could reduce the number of biopsies by approximately 20% compared to use PHI followed by mpMRI (256 vs 316, 257 vs 316, respectively). CONCLUSIONS: The PHI-MRI model was superior to PHI and MRI alone. It may reduce the number of biopsies and ensure the detection rate of CsCaP under an appropriate sensitivity at the cost of an increased number of MRI scans.