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INTRODUCTION: To investigate whether initial tumor burden at biopsy could predict adverse features after radical prostatectomy (RP) in International Society of Urological Pathology (ISUP) 1 prostate cancer (PCa) patients. METHODS: This retrospective study was conducted in six referral centers. The cohort included patients with ISUP 1 PCa at systematic and MRI-targeted biopsy. We defined a high tumor burden at biopsy if ≥ 20% of cores were positive. The endpoint of the study was adverse features at RP, defined as ≥ pT3a stage and/or N1 and/or ISUP ≥ 3. Sensitivity analyses were performed to assess associations between different thresholds on biopsy (percentage of positive cores [PPC] ≥ 25%, ≥ 33%, ≥ 50%, bilateral positivity and positive cores > 3) and adverse features. As the number of targeted biopsies sampled may influence the number of positive cores, we used a virtual biopsy model in which all targeted biopsy results were interpreted as a single targeted biopsy. RESULTS: A total of 312 contemporary patients were included. At final pathology, 99 patients (32%) had adverse features. In multivariate logistic regression analysis, there was no statistical association between PPC > 20% and adverse features (OR = 1.22; 95%CI:0.69-2.22, p = 0.5). In sensitivity analysis, tumor burden at biopsy was not associated with the risk of adverse features, regardless of the definition used (all p > 0.05). When we considered a unique virtual targeted biopsy, tumor burden remained not associated with adverse features (all p > 0.05). CONCLUSIONS: ISUP 1 PCa tumor burden at biopsy did not predict adverse features in this study, suggesting that it should not be used alone as an exclusion criterion when assessing eligibility for active surveillance.

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Histotripsy is a noninvasive focused ultrasound therapy that mechanically fractionates tissue to create well-defined lesions. In a previous clinical pilot trial to treat benign prostatic hyperplasia (BPH), histotripsy did not result in consistent objective improvements in symptoms, potentially because of the fibrotic and mechanically tough nature of this tissue. In this study, we aimed to identify the dosage required to homogenize BPH tissue by different histotripsy modalities, including boiling histotripsy (BH) and cavitation histotripsy (CH). A method for histotripsy lesion quantification via entropy (HLQE) analysis was developed and utilized to quantify lesion area of the respective treatments. These data were correlated to changes in mechanical stiffness measured by ultrasound shear-wave elastography before and after treatment with each parameter set and dose. Time points corresponding to histologically observed complete lesions were qualitatively evaluated and quantitatively measured. For the BH treatment, complete lesions occurred with > = 30 s treatment time, with a corresponding maximum reduction in stiffness of -90.9 ± 7.2(s.d.)%. High pulse repetition frequency (PRF) CH achieved a similar reduction to that of BH at 288 s (-91.6 ± 6.0(s.d.)%), and low-PRF CH achieved a (-82.1 ± 5.1(s.d.)%) reduction in stiffness at dose > = 144 s. Receiver operating characteristic curve analysis showed that a > ~ 75% reduction in stiffness positively correlated with complete lesions observed histologically, and can provide an alternative metric to track treatment progression.

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Prostate cancer (PCa) is the most common cancer diagnosed in men worldwide and was the second leading cause of cancer-related deaths in US males in 2022. Prostate cancer also represents the second highest cancer mortality disparity between non-Hispanic blacks and whites. However, there is a relatively small number of prostate normal and cancer cell lines compared to other cancers. To identify the molecular basis of PCa progression, it is important to have prostate epithelial cell (PrEC) lines as karyotypically normal as possible. Our lab recently developed a novel methodology for the rapid and efficient immortalization of normal human PrEC that combines simultaneous CRISPR-directed inactivation of CDKN2A exon 2 (which directs expression of p16INK4A and p14ARF) and ectopic expression of an hTERT transgene. To optimize this methodology to generate immortalized lines with minimal genetic alterations, we sought to target exon 1α of the CDKN2A locus so that p16INK4A expression is ablated while the exons encoding p14ARF remains unaltered. Here we describe the establishment of two cell lines: one with the above-mentioned p16INK4A only loss, and a second line targeting both products in the CDKN2A locus. We characterize the potential lineage origin of these new cell lines along with our previously obtained clones, revealing distinct gene expression signatures. Based on the analyses of protein markers and RNA expression signatures, these cell lines are most closely related to a subpopulation of basal prostatic cells. Given the simplicity of this one-step methodology and the fact that it uses only the minimal genetic alterations necessary for immortalization, it should also be suitable for the establishment of cell lines from primary prostate tumor samples, an urgent need given the limited number of available prostate cancer cell lines.

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BACKGROUND: Understanding the lineage differentiation of human prostate not only is crucial for basic research on human developmental biology but also significantly contributes to the management of prostate-related disorders. Current knowledge mainly relies on studies on rodent models, lacking human-derived alternatives despite clinical samples may provide a snapshot at certain stage. Human embryonic stem cells can generate all the embryonic lineages including the prostate, and indeed a few studies demonstrate such possibility based on co-culture or co-transplantation with urogenital mesenchyme into mouse renal capsule. METHODS: To establish a stepwise protocol to obtain prostatic organoids in vitro from human embryonic stem cells, we apply chemicals and growth factors by mimicking the regulation network of transcription factors and signal transduction pathways, and construct cell lines carrying an inducible NKX3-1 expressing cassette, together with three-dimensional culture system. Unpaired t test was applied for statistical analyses. RESULTS: We first successfully generate the definitive endoderm, hindgut, and urogenital sinus cells. The embryonic stem cell-derived urogenital sinus cells express prostatic key transcription factors AR and FOXA1, but fail to express NKX3-1. Therefore, we construct NKX3-1-inducible cell line by homologous recombination, which is eventually able to yield AR, FOXA1, and NKX3-1 triple-positive urogenital prostatic lineage cells through stepwise differentiation. Finally, combined with 3D culture we successfully derive prostate-like organoids with certain structures and prostatic cell populations. CONCLUSIONS: This study reveals the crucial role of NKX3-1 in prostatic differentiation and offers the inducible NKX3-1 cell line, as well as provides a stepwise differentiation protocol to generate human prostate-like organoids, which should facilitate the studies on prostate development and disease pathogenesis.

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Importance: Planning complex operations such as robotic-assisted laparoscopic radical prostatectomy (RALP) requires surgeons to review 2-dimensional magnetic resonance imaging (MRI) scans to understand 3-dimensional (3D) patient anatomy. Three-dimensional digital models for planning RALP may allow better understanding of patient anatomy and may lead to better patient outcomes, although data are currently limited. Objective: To determine surgical outcomes after RALP when surgeons reviewed 3D digital models during operative planning. Design, Setting, and Participants: This study was a planned secondary analysis of a multicenter, single-blind, randomized clinical trial conducted at 6 large teaching hospitals in the US. The study was conducted between January 1, 2019, and December 31, 2022, and included patients undergoing RALP. Patients were assessed and recruited at the time of surgical consultation. Final data analysis was conducted between August and December 2023. Intervention: Patients were randomized to either a control group undergoing usual preoperative planning with prostate biopsy results and multiparametric MRI only or to an intervention group in which imaging and biopsy results were supplemented with a 3D digital model. This model was viewed on the surgeon's mobile phone in 3D format and picture-in-picture on the robotic console screen. Main Outcomes and Measures: The primary outcome measure for the overall study was oncologic outcomes after RALP, measured as prostate-specific antigen (PSA) detectability. Secondary outcomes were sexual function and urinary function, measured with Sexual Health Inventory for Men (SHIM) scores and rates of urinary incontinence, respectively, as well as use of salvage or adjuvant radiation therapy (RT) or androgen deprivation therapy (ADT). Trifecta outcomes were defined as undetectable PSA without RT or ADT, SHIM score categorically the same or greater than preoperatively, and complete continence. Univariate analysis was performed to compare outcomes between groups. Results: This trial included 92 patients undergoing RALP (51 in the control group and 41 in the intervention group). Their mean (SD) age was 62 (7.4) years; 10 patients (10.9%) were Black and 67 (72.8%) were White. At 18 months postsurgery, the intervention group had lower rates of biochemical recurrence (PSA level >0.1 ng/mL, 0 vs 7 [17.9%]; absolute difference, 17.9% [95% CI, 1.8% to 31.8%]; P = .01) and were significantly less likely to undergo adjuvant or salvage RT (1 [3.1%] vs 12 [31.6%]; absolute difference, 28.5% [95% CI, 10.1% to 46.7%]; P = .002) compared with the control group. Sexual function at 18 months postsurgery was significantly better in the intervention group (mean [SD] SHIM score, 16.8 [8.7] vs 9.8 [7.7]; absolute difference, 7.0 [95% CI, 2.6 to 11.4]; P = .002) and urinary function was unchanged (total continence, 22 [78.6%] vs 29 [80.6%]; absolute difference, 2.0% [95% CI, -17.9% to 21.9%]; P = .84) compared with the control group. Trifecta outcomes were achieved for 12 (48.0%) patients in the intervention group and 3 patients (10.0%) in the control group (absolute difference, 38.0% [95% CI, 14.4% to 61.6%]; P = .002). Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, patients whose surgical planning of RALP involved 3D digital models had better oncologic and functional outcomes. Further work should assess the effect of 3D models in a broader set of patients, physicians, and hospital settings. Trial Registration: ClinicalTrials.gov Identifier: NCT03943368.

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PURPOSE: To investigate the early implementation of combined systematic and targeted (cBx) primary biopsy in prostate cancer diagnosis and define the concordance in Gleason grading (GG) of different biopsy techniques with radical prostatectomy (RP) pathology. METHODS: This population-based analysis includes data on all men in Denmark who underwent primary cBx or standalone systematic (sBx) prostate biopsy between 2012 and 2016. Biopsy results were compared to RP pathology if performed within a year. Concordance measurement was estimated using Cohen's Kappa, and the cumulative incidence of cancer-specific death was estimated at 6 years with the Aalen-Johansen estimator. RESULTS: Concordance between biopsy and RP pathology was 0.53 (95CI: 0.43-0.63), 0.38 (95CI: 0.29-0.48), and 0.16 (95CI: 0.11-0.21) for cBx, targeted biopsy (tBx), and sBx, respectively. For standalone sBx and RP, concordance was 0.29 (95CI: 0.27-0.32). Interrelated GG concordance between tBx and sBx was 0.67 (95CI: 0.62-0.71) in cBx. The proportion of correctly assessed GG based on RP pathology was 54% in both cBx and standalone sBx. Incidence of prostate cancer-specific death was 0% regardless of biopsy technique in GG 1, and 22% (95CI: 11-32), 30% (95CI: 15-44), and 19% (95CI: 7.0-30) in GG 5 for cBx, tBx, or sBx, respectively. CONCLUSION: Overall, the cBx strategy demonstrates higher concordance to RP pathology than the standalone sBx. However, cBx exhibits more overgrading of the GG of RP pathology compared to sBx. Ultimately, the classic grading system does not take change in the diagnostic pathway into account, and grading should be altered accordingly to ensure appropriate treatment.

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BACKGROUND: Prostate tuberculosis (TB) is a rare and often underdiagnosed condition due to its nonspecific symptoms and imaging features, which can mimic malignancies on 18F-fluorodeoxyglucose positron emission tomography (PET) scans. This resemblance poses a challenge in differentiating TB from prostate cancer, especially in patients with preexisting tumors such as diffuse large B-cell lymphoma. The purpose of this study is to highlight the importance of considering TB in the differential diagnosis of patients with atypical imaging findings, even in the presence of known malignancies. CASE: We present a case of a 60-year-old man with diffuse large B-cell lymphoma who was initially misdiagnosed with a prostate tumor based on 18F-fluorodeoxyglucose PET/computed tomography scans. The subsequent ultrasound-guided prostate biopsy confirmed the presence of prostate TB, not malignancy. CONCLUSIONS: This case report underscores the critical role of considering TB as a potential diagnosis in patients with hematological tumors and atypical imaging results. It serves as a reminder for clinicians to exercise caution when interpreting PET/computed tomography scans and to incorporate TB into their differential diagnoses, thereby avoiding misdiagnosis and inappropriate treatment.

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Chronic inflammation is a recognized risk factor for various cancers, including prostate cancer (PCa). We aim to explore the potential protective effects of aged black garlic extract (ABGE) against inflammation-induced prostate damage and its impact on prostate cancer cell lines. We used an ex vivo model of inflammation induced by Escherichia coli lipopolysaccharide (LPS) on C57BL/6 male mouse prostate specimens to investigate the anti-inflammatory properties of ABGE. The gene expression levels of pro-inflammatory biomarkers (COX-2, NF-κB, and TNF-α, IL-6) were measured. Additionally, we evaluated ABGE's therapeutic effects on the prostate cancer cell lines through in vitro functional assays, including colony formation, tumorsphere formation, migration assays, and phosphorylation arrays to assess the signaling pathways (MAPK, AKT, JAK/STAT, and TGF-ß). ABGE demonstrated significant anti-inflammatory and antioxidant effects in preclinical models, partly attributed to its polyphenolic content, notably catechin and gallic acid. In the ex vivo model, ABGE reduced the gene expression levels of COX-2, NF-κB, TNF-α, and IL-6. The in vitro studies showed that ABGE inhibited cell proliferation, colony and tumorsphere formation, and cell migration in the prostate cancer cells, suggesting its potential as a therapeutic agent. ABGE exhibits promising anti-inflammatory and anti-cancer properties, supporting further investigation into ABGE as a potential agent for managing inflammation and prostate cancer.

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Modern research has shown that Cucurbitacin B (Cu B) possesses various biological activities such as liver protection, anti-inflammatory, and anti-tumor effects. However, the majority of research has primarily concentrated on its hepatoprotective effects, with limited attention devoted to exploring its potential impact on the prostate. Our research indicates that Cu B effectively inhibits the proliferation of human prostate stromal cells (WPMY-1) and fibroblasts (HPRF), while triggering apoptosis in prostate cells. When treated with 100 nM Cu B, the apoptosis rates of WPMY-1 and HPRF cells reached 51.73 ± 5.38% and 26.83 ± 0.40%, respectively. In addition, the cell cycle assay showed that Cu B had a G2/M phase cycle arrest effect on WPMY-1 cells. Based on RNA-sequencing analysis, Cu B might inhibit prostate cell proliferation via the p53 signaling pathway. Subsequently, the related gene and protein expression levels were measured using quantitative real-time PCR (RT-qPCR), immunocytochemistry (ICC), and enzyme-linked immunosorbent assays (ELISA). Our results mirrored the regulation of tumor protein p53 (TP53), mouse double minute-2 (MDM2), cyclin D1 (CCND1), and thrombospondin 1 (THBS1) in Cu B-induced prostate cell apoptosis. Altogether, Cu B may inhibit prostate cell proliferation and correlate to the modulation of the p53/MDM2 signaling cascade.

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AIMS: Obesity is a global public health issue, and some studies have linked it to an increased risk of prostatic diseases. This study aimed to evaluate the effects of a high-fat diet on metabolic parameters and prostate morphology in wild-type (WT) and adiponectin knockout (KO) mice. MAIN METHODS: Male WT and KO mice were fed a control diet (CD) or high-fat diet (HFD) for 6 months. Serum metabolic parameters, inflammatory cytokines in epididymal fat tissue, dorsal prostatic lobe morphometry and histopathology were analyzed. KEY FINDINGS: CD WT and CD KO mice did not exhibit altered metabolic or prostatic parameters. However, HFD WT mice showed altered glucose and insulin tolerance even without excessive weight gain. On the other hand, HFD KO mice developed obesity, with an increase in low-density lipoprotein (11.8 ± 5.1 vs. 31.4 ± 3.6 mg/dL), high-density lipoprotein (73.4 ± 7.4 vs. 103.4 ± 2.5 mg/dL), and total cholesterol levels (126.2 ± 16.1 vs. 294.6 ± 23.2 mg/dL), a decrease in insulin levels (28.7 ± 12.2 vs. 4.6 ± 2.3 µIU/mL), and glucose and insulin resistance. We also observed that HFD KO animals display an increase in inflammatory cytokines, such as IL6, IL1ß, and IL1RA. The dorsal prostate from HFD KO animals also presented significant increases in the mast cells (1.9 ± 0,7 vs. 5,3 ± 1.5 cells/field) and Ki67 index (2.91 ± 0.6 vs. 4.7 ± 0.4 %). SIGNIFICANCE: The above findings highlight the complex interactions between adiponectin, metabolism, malnutrition, and prostate health. Metabolic deregulation combined with adipose inflammation potentially induces a proliferative and inflammatory microenvironment in the prostate gland under conditions of low adiponectin production, potentially impairing prostate morphophysiology in the context of obesity and aging.

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PURPOSE: To investigate the relationship between prostatic urethral angle (PUA) and the development of surgical capsule calculi (SCC) within the prostate, and to examine the presence and impact of intravesical prostatic protrusion (IPP). MATERIALS AND METHODS: A retrospective analysis was conducted on 90 patients who underwent radical prostatectomy, with preoperative assessments using both transrectal ultrasound of the prostate (TRUS) and magnetic resonance imaging. Patients were divided into groups with and without SCC and further categorized into type 1 and type 2 stones based on the location and severity of the calculi. Statistical analysis included chi-square and independent sample t-tests, with p<0.05 considered significant. RESULTS: Of the patients, 82.2% were diagnosed with SCC. No significant difference in PUA was found between patients with and without SCC. However, a notable disparity in IPP presence was observed, suggesting an inverse correlation with SCC development. Additionally, no significant differences were identified when comparing the two types of SCC based on PUA and IPP measurements. CONCLUSIONS: The presence of IPP exhibited an inverse relationship with SCC, suggesting diminished urine flow pressure over the prostatic urethra may reduce the likelihood of SCC formation. However, no direct association between PUA and the presence or severity of SCC was identified. These findings highlight the complexity of factors contributing to prostatic calculi development and the potential role of IPP in this context.

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Benign prostatic hyperplasia (BPH) is a prevalent age-related condition often characterized by debilitating urinary symptoms. Its etiology is believed to stem from hormonal imbalance, particularly an elevated estradiol-to-testosterone ratio and chronic inflammation. Our previous studies using a mouse steroid hormone imbalance model identified a specific increase in macrophages that migrated and accumulated in the prostate lumen where they differentiated into lipid-laden foam cells in mice implanted with testosterone and estradiol pellets, but not in sham animals. The current study focused on further characterizing the cellular heterogeneity of the prostate in this model as well as identifying the specific transcriptomic signature of the recruited foam cells. Moreover, we aimed to identify epithelia-derived signals that drive macrophage infiltration and luminal translocation. Male C57BL/6J mice were implanted with slow-release testosterone and estradiol pellets (T + E2) or sham surgery was performed and the ventral prostates were harvested two weeks later for scRNA-seq analysis. We identified Ear2 + and Cd72 + macrophages that were elevated in response to steroid hormone imbalance, whereas a Mrc1 + resident macrophage population did not change. In addition, an Spp1 + foam cell cluster was almost exclusively found in T + E2 mice. Further markers of foam cells were also identified, including Gpnmb and Trem2, and GPNMB was confirmed as a novel histological marker with immunohistochemistry. Foam cells were also shown to express known pathological factors Vegf, Tgfb1, Ccl6, Cxcl16 and Mmp12. Intriguingly, a screen for chemokines identified the upregulation of epithelia-derived Cxcl17, a known monocyte attractant, in T + E2 prostates suggesting that it might be responsible for the elevated macrophage number as well as their translocation to the lumen. Our study identified macrophage subsets that responded to steroid hormone imbalance as well as further confirmed a potential pathological role of luminal foam cells in the prostate. These results underscore a potential pathological role of the identified prostate foam cells and suggests CXCL17-mediated macrophage migration as a critical initiating event.

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The purpose of this study is to evaluate whether the periprostatic adipose tissue thickness (PPATT) is an independent prognostic factor for prostate cancer patients after laparoscopic radical prostatectomy (LRP). This retrospective cohort study included consecutive prostate cancer patients who underwent LRP treatment at Wuhan Union Hospital from June 2, 2016, to September 7, 2023. PPATT was defined as the thickness of periprostatic fat and was obtained by measuring the shortest vertical distance from the pubic symphysis to the prostate on the midsagittal T2-weighted MR images. Subcutaneous adipose tissue thickness (SATT) was obtained by measuring the shortest vertical distance from the pubic symphysis to the skin at the same slice with PPATT. The primary outcome of the study was biochemical recurrence (BCR), and the secondary outcome was overall survival (OS). Multivariable Cox regression analysis was used to identify independent prognostic factors for prostate cancer survival and prognosis. Based on the optimal cutoff value, 162 patients were divided into a low PPATT/SATT group (n = 82) and a high PPATT/SATT group (n = 80). During the entire follow-up period (median 23.5 months), 26 patients in the high PPATT/SATT group experienced BCR (32.5%), compared to 18 in the low PPATT/SATT group (22.0%). Kaplan-Meier curve analysis indicated that the interval to BCR was significantly shorter in the high PPATT/SATT group (P = 0.037). Multivariable Cox regression analysis revealed that an increase in the PPATT/SATT ratio was associated with BCR (hazard ratio: 1.90, 95% CI, 1.03-3.51; P = 0.040). The PPATT/SATT ratio is a significant independent risk factor for BCR after LRP for prostate cancer patients.

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Prostate cancer (PC) is an age-related disease and represents, after lung cancer, the second cause of cancer death in males worldwide. Mortality is due to the metastatic disease, which mainly involves the bones, lungs, and liver. In the last 20 years, the incidence of metastatic PC has increased in Western Countries, and a further increase is expected in the near future, due to the population ageing. Current treatment options, including state of the art cancer immunotherapy, need to be more effective to achieve long-term disease control. The most significant anatomical barrier to overcome to improve the effectiveness of current and newly designed drug strategies consists of the prostatic stroma, in particular the fibroblasts and the extracellular matrix, which are the most abundant components of both the normal and tumor prostatic microenvironment. By weaving a complex communication network with the glandular epithelium, the immune cells, the microbiota, the endothelium, and the nerves, in the healthy prostatic microenvironment, the fibroblasts and the extracellular matrix support organ development and homeostasis. However, during inflammation, ageing and prostate tumorigenesis, they undergo dramatic phenotypic and genotypic changes, which impact on tumor growth and progression and on the development of therapy resistance. Here, we focus on the characteristics and functions of the prostate associated fibroblasts and of the extracellular matrix in health and cancer. We emphasize their roles in shaping tumor behavior and the feasibility of manipulating and/or targeting these stromal components to overcome the limitations of current treatments and to improve precision medicine's chances of success.

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BACKGROUND: One-fourth of men older than 70 years have lower urinary tract symptoms (LUTS) that impair their quality of life. Transurethral resection of the prostate (TURP) is considered the gold standard for surgical treatment of LUTS caused by benign prostatic hyperplasia (BPH) that cannot be managed conservatively or pharmacologically. However, TURP is only an option for patients fit for surgery and can result in complications. Transurethral microwave thermotherapy (TUMT) and prostatic artery embolisation (PAE) are alternative minimally invasive surgical therapies (MISTs) performed in an outpatient setting. Both treatments have shown to reduce LUTS with a similar post-procedure outcome in mean International Prostate Symptom Score (IPSS). It is however still unknown if TUMT and PAE perform equally well as they have never been directly compared in a randomised clinical trial. The objective of this clinical trial is to assess if PAE is non-inferior to TUMT in reducing LUTS secondary to BPH. METHODS: This study is designed as a multicentre, non-inferiority, open-label randomised clinical trial. Patients will be randomised with a 1:1 allocation ratio between treatments. The primary outcome is the IPSS of the two arms after 6 months. The primary outcome will be evaluated using a 95% confidence interval against the predefined non-inferiority margin of + 3 points in IPSS. Secondary objectives include the comparison of patient-reported and functional outcomes at short- and long-term follow-up. We will follow the patients for 5 years to track long-term effect. Assuming a difference in mean IPSS after treatment of 1 point with an SD of 5 and a non-inferiority margin set at the threshold for a clinically non-meaningful difference of + 3 points, the calculated sample size was 100 patients per arm. To compensate for 10% dropout, the study will include 223 patients. DISCUSSION: In this first randomised clinical trial to compare two MISTs, we expect non-inferiority of PAE to TUMT. The most prominent problems with MIST BPH treatments are the unknown long-term effect and the lack of proper selection of candidates for a specific procedure. With analysis of the secondary outcomes, we aspire to contribute to a better understanding of durability and provide knowledge to guide treatment decisions. TRIAL REGISTRATION: ClinicalTrials.gov NCT05686525. Registered on January 17, 2023, https://clinicaltrials.gov/study/NCT05686525 .

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INTRODUCTION: Most men diagnosed with very-low and low-risk prostate cancer are candidates for active surveillance; however, there is still a misclassification risk. We examined whether PI-RADS category 4 or 5 combined with ISUP 1 on prostate biopsy predicts upgrading and/or adverse pathology at radical prostatectomy. MATERIALS AND METHODS: A total of 127 patients had ISUP 1 cancer on biopsy after multiparametric MRI (mpMRI) and then underwent radical prostatectomy. We then evaluated them for ISUP upgrading and/or adverse pathology on radical prostatectomy. RESULTS: Eight-nine patients (70%) were diagnosed with PI-RADS 4 or 5 lesions. ISUP upgrading was significantly higher among patients with PI-RADS 4-5 lesions (84%) compared to patients with equivocal or non-suspicious mpMRI findings (26%, p < 0.001). Both PI-RADS 4-5 lesions (OR 24.3, 95% CI 7.3, 80.5, p < 0.001) and stage T2 on DRE (OR 5.9, 95% CI 1.2, 29.4, p = 0.03) were independent predictors of upgrading on multivariate logistic regression analysis. Men with PI-RADS 4-5 lesions also had significantly more extra-prostatic extension (51% vs. 3%, p < 0.001) and positive surgical margins (16% vs. 3%. p = 0.03). The only independent predictor of adverse pathology was PI-RADS 4-5 (OR 21.7, 95% CI 4.8, 99, p < 0.001). CONCLUSION: PI-RADS 4 or 5 lesions on mpMRI were strong independent predictors of upgrading and adverse pathology. Incorporating mpMRI findings when selecting patients for active surveillance must be further evaluated in future studies.

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Three-dimensional (3D) freehand ultrasound (US) is a widely used imaging modality that allows non-invasive imaging of medical anatomy without radiation exposure. Surface reconstruction of US volume is vital to acquire the accurate anatomical structures needed for modeling, registration, and visualization. However, traditional methods cannot produce a high-quality surface due to image noise. Despite improvements in smoothness, continuity, and resolution from deep learning approaches, research on surface reconstruction in freehand 3D US is still limited. This study introduces FUNSR, a self-supervised neural implicit surface reconstruction method to learn signed distance functions (SDFs) from US volumes. In particular, FUNSR iteratively learns the SDFs by moving the 3D queries sampled around volumetric point clouds to approximate the surface, guided by two novel geometric constraints: sign consistency constraint and on-surface constraint with adversarial learning. Our approach has been thoroughly evaluated across four datasets to demonstrate its adaptability to various anatomical structures, including a hip phantom dataset, two vascular datasets and one publicly available prostate dataset. We also show that smooth and continuous representations greatly enhance the visual appearance of US data. Furthermore, we highlight the potential of our method to improve segmentation performance, and its robustness to noise distribution and motion perturbation.

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MRI-guided targeted biopsy (MRGB) was recommended as part of biopsy paradigm of prostate cancers by current guidelines. This study aimed to analyze the diagnostic efficacy of MRGB and systemic biopsy (SB), and to compare diagnostic capabilities within subgroups of MRGB: MRI-cognitive biopsy (MRCB) and MRI-fusion biopsy (MRFB). We retrospectively enrolled patients who underwent MRGB for suspicious malignant lesion(s) identified on MRI in a single tertiary center, sample size was 74 patients. An mpMRI was performed prior to biopsy and reviewed by an experienced radiologist specialized in prostate cancer. Per-person results of MRGB and each concomitant SB were analyzed as independent biopsies for its positive biopsy rate and positive core percentage. Per-lesion results of MRFB and MRCB were compared for the detection rate. Variables of interest were analyzed with t-test, chi-squared test, and logistic regression analysis. Statistical analyses were performed with IBM Statistical Product and Service Solutions (SPSS), Version 23 (IBM, Armonk, New York). Total of 74 patients fulfilled the inclusion criteria and were enrolled. MRFB had higher PCa detection rate comparing to both MRCB and SB (56.1%, 30.3%, and 33.9% respectively, p value = 0.036); clinically significant prostate cancer (csPCa) detection rate was also significantly higher in MRFB group (43.9%, 24.2%, and 16.9% in each group respectively, p value = 0.011). In per-lesion analysis, MRCB and MRFB had no significant difference in PCa and csPCa detection rate (41.0% vs. 26.2% and 29.5% vs. 16.7% respectively, p value = 0.090 and 0.103). In the lesion ≦ 1.3 cm group, MRFB could achieve higher PCa detection rate, comparing to MRCB (36.4% vs. 14.3%, p value = 0.047); there were also higher positive rates for PCa and csPCa per biopsied cores (22.1% vs. 6.8% and 15.6% vs. 2.7%, p value = 0.029 and 0.028, respectively). Further logistic regression of multi-variate analysis in subgroup of lesion ≦ 1.3 cm revealed that PIRADS score and biopsy method were significant predictors of positive biopsy result for PCa (p value = 0.045 and 0.026, respectively) and for csPCa (p value = 0.043 and 0.025, respectively). In patients receiving trans-perineal prostate biopsy, MRFB had higher cancer detection rate than MRCB and SB. In per lesion comparison, MRFB and MRCB had similar diagnostic accuracy. However, in lesions with diameter less than 1.3 cm, MRFB can provided better diagnose value for PCa and csPCa than MRCB.

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