Hyaluronidase for Dermal Filler Complications: Review of Applications and Dosage Recommendations.

BACKGROUND: Hyaluronidase (Hyal) can reverse complications of hyaluronic acid (HA) fillers, which has contributed substantially to the popularity of such procedures. Still, there are differing opinions regarding Hyal treatment, including dosage recommendations in filler complication management. OBJECTIVE: We aimed to address unanswered questions regarding Hyal treatment for HA filler complications, including timing and dosage, skin pretesting, properties of various Hyals and interactions with HA gels, and pitfalls of the treatment. METHODS: PubMed and Google Scholar databases were searched from inception for articles on Hyal therapy for filler complications. Articles were evaluated regarding their contribution to the field. The extensive literature review includes international leaders' suggestions and expert panels' recommendations. RESULTS: There are limited controlled data but increasing clinical experience with Hyal treatment. The currently used Hyals provide good results and have an acceptable safety profile. Nonemergent complications such as the Tyndall effect, noninflamed nodules, and allergic or hypersensitivity reactions should be treated with low or moderate Hyal doses. Hyal should be considered with prior or simultaneous oral antibiotic treatment in managing inflammatory nodules. Hyal may be tried for granulomas that have not responded to intralesional steroids. Emergent complications such as vascular occlusion and blindness require immediate, high-dose Hyal treatment. Regarding blindness, the injection technique, retrobulbar versus supraorbital, remains controversial. Ultrasound guidance can increase the efficacy of the above interventions. CONCLUSIONS: Hyal is essential in aesthetic practice because it can safely treat most HA filler complications. Immediate Hyal treatment is required for emergent complications. Aesthetic practitioners should be versed in using Hyal and effective dosage protocols.

What are the Most Important Objectives of Patients Undergoing Radical Prostatectomy? A Narrative Review.

Purpose: This study aimed to evaluate what objectives are most important to men undergoing radical prostatectomy to allow treating physicians to personalize perioperative counselling and improve patient quality of life outcomes. Materials and Methods: A predefined search protocol of the Medline and Embase databases was performed from database inception to May 2023. The search was limited to English language and full text. All articles with a specific consideration of patient objectives, preferences or reasons for decision to undergo radical prostatectomy were included for review. Results: Ten articles out of 375 screened met inclusion criteria for review. All 10 articles utilized a qualitative design and originated across 5 countries across the developed world. A common theme of men placing importance on having their tumor physically removed was found. Methodologies allowing free response beyond predefined categories identified a breadth of considerations including personal circumstance, personal belief and current function in the decision-making process. An investigation on radical prostatectomy performed robotically found some men placed preference on the quicker treatment time with surgery compared to radiation therapy, reflective of shorter recovery times with the robotic approach. Conclusion: Variability in results across studies highlights the heterogeneity in patient preferences. Directed investigation of patient objectives with an open-ended questioning approach would personalize the perioperative experience and may improve patient satisfaction and quality of life outcomes.

A Chance Finding of High Grade Prostate Cancer in a 35-Year-Old Male - A Case Report and Outcomes of Robotic Radical Prostatectomy in Young Men with Prostate Cancer.

Background: Prostate cancer is often considered a disease of older men and this indeed fits with its peak incidence between 65-79 years of age. Reports of prostate cancer in men younger than 40 years of age and the outcomes of this age group following treatment are few in the literature. Here, we present the case of an unusual diagnosis of high grade prostate cancer in a very young man and outline early outcomes following treatment with robotic-assisted radical prostatectomy. Case Presentation: A 35-year-old male, intermittently taking finasteride for hair loss, was found to have an elevated prostate-specific antigen (PSA) of 12.5ng/mL leading to an incidental diagnosis of high grade prostate cancer. Targeted trans-perineal prostate biopsy found Gleason 4+5=9 acinar adenocarcinoma, without cribriform architecture but with features suspicious for extracapsular extension. Robotic radical prostatectomy with bilateral pelvic lymph node dissection was performed and found Gleason 4+5=9 adenocarcinoma with focal cribriform architecture, extra prostatic extension and clear margins, stage pT3a N0 M0. PSA was undetectable at 12 months, continence was immediate, and the patient reported strong erections soon after surgery. Family history of prostate cancer and genetic testing were both negative. Conclusion: This case highlights that not all clinically significant cancers will be identified by following PSA screening guidelines starting at 50 years of age (or 40 years of age for men with a family history of prostate cancer). While high grade prostate cancer in a man less than 40 years of age is uncommon, the literature suggests the incidence is increasing. Our case alongside series in the literature indicate that these men have better functional outcomes and equal oncological outcomes with early surgical intervention for localized disease when compared to the older population.

Cross-cultural perspectives on patient expectations in cosmetic dermatology: A comparative analysis across countries and ethnicities.

Patient expectations in cosmetic dermatology exhibit significant variations across countries, cultures, and ethnicities, thereby reflecting individual desires, concerns, and goals. While some individuals seek aesthetic enhancements, others prioritize addressing specific skin conditions within the context of beauty norms in their respective countries. The provision of personalized and culturally sensitive care plays a crucial role in meeting these diverse expectations. Skin characteristics and concerns differ among ethnicities, influencing treatment preferences. For instance, individuals with darker skin tones may prioritize the treatment of pigmentation disorders, whereas those with lighter skin tones may focus on achieving a fair complexion. Furthermore, differences in facial anatomy among various ethnicities necessitate tailored treatment approaches. This commentary aims to contribute to the effective understanding and management of patient expectations, ultimately leading to satisfactory outcomes. Additional research and regional studies are required to further deepen our understanding of patient expectations in cosmetic dermatology and enable the delivery of improved and culturally appropriate care on a global scale.

Impact of Preoperative Mental Health on Surgical Outcomes Following Robotic-assisted Radical Prostatectomy.

OBJECTIVES: To explore the association between preoperative mental health status and surgical outcomes following robotic-assisted radical prostatectomy (RARP). METHODS: This cohort study included consecutive patients undergoing RARP surgery for prostate cancer between October 2016 and May 2022 at a major public hospital in Sydney, Australia. The primary outcome was preoperative self-reported mental health status measured using the mental component score from the Short Form 36 survey. Other variables included patients' characteristics, surgical outcomes, postoperative quality of life, pain and decision regret. Data were analysed using linear regression analysis. RESULTS: A total of 266 men underwent RARP during the studied period. Of these, 242 patients (91%) completed the preoperative survey and were analyzed. Poorer preoperative mental health had significant univariate associations with younger age (P = .025), reduced access to economic resources (P = .043), diagnosis of a mental illness (P = .033), poorer mental health at 6 weeks and 6 months postoperatively (both P <.001), greater pain (P = .001), and higher decision regret (P = .001) 6 weeks following surgery. In the multivariate analysis, poorer preoperative mental health status was associated with younger age (P = .028) and poorer mental health at 6 weeks (P <.001) and 6 months (P = .025) postoperatively. CONCLUSION: For patients undergoing RARP, poor preoperative mental health status was associated with younger age and poorer postoperative mental health. Future studies should investigate if targeted preoperative psychological interventions would improve postoperative mental health outcomes, specifically in younger men undergoing RARP.

Decipher Score predicts prostate specific antigen persistence after prostatectomy.

BACKGROUND: The aim of this study was to evaluate genomic risk of patients with persistent prostate specific antigen (PSA) using mRNA expression analysis and a validated prognostic genomic-risk classifier. METHODS: Monocentric retrospective study including all patients who underwent radical prostatectomy (RP) by one surgeon and Decipher Test from October 2013 to December 2018. PSA persistent population was defined as all patients with two consecutive PSA>0.1 ng/mL at follow-up after the surgery. Neurovascular Structure-adjacent Frozen-section Examination (NeuroSAFE) was performed intraoperatively for research of positive surgical margins. Multivariate analysis was performed for persistent PSA (pPSA) predictors. A specific localized, organ-confined, and negative margins sub-population with PSA persistence was compared to a similar sub-population without PSA persistence for genomic differential expression analyses. RESULTS: A total of 564 patients were included and 61 of them had pPSA. Preoperative PSA was higher in the PSA persistent group (11.6 [6.4, 21.2] vs. 6.2 [4.7, 9.2] P=0.00010), as well as PSA density (PSAd) (0.3 [0.2, 0.5] vs. 0.2 [0.1, 0.3] P=0.0001). Postoperative characteristics, Gleason Score, and positive surgical margins were significantly higher in the PSA persistent population. 31 patients had pPSA in our specific subpopulation and were compared to 217 patients with no pPSA. On multivariate analysis, only Decipher Score (OR=5.64 [1.28; 24.89], P=0.022) and preoperative PSA (OR=1.06, [1.02; 1.09], P=0.001) were significant predictors for PSA persistence. We found two genes to be significantly upregulated with a 2.5-fold change in our specific subpopulation (SERPINB11 and PDE11A). CONCLUSIONS: We found unique genomic features of patients with pPSA, whilst confirming previous clinical findings that this condition behaves to a worse prognosis. Given this high genomic risk, further imaging studies should be performed to select patients for early treatment intensification.

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

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

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

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

Matrix effects on hydrogen bonding and proton transfer in fluoropyridine - HCl complexes.

We report an extensive computational and spectroscopic study of several fluoropyridine-HCl complexes, and the parent, pyridine-HCl system. Matrix-IR spectra for pentafluoropyridine-HCl, 2,6-difluororpyridine-HCl, and 3,5-difluororpyridine-HCl in solid neon exhibit shifts for the H-Cl stretching band that parallel the effects of fluorination on hydrogen-bond strength. Analogous spectral shifts observed across various host environments (solid neon, argon, and nitrogen) for pentafluoropyridine-HCl and 2,6-difluororpyridine-HCl convey a systematically varying degree of matrix stabilization on the hydrogen bonds in these complexes. An extended quantum-chemical study of pyridine-HCl and eight fluorinated analogs, including 2-, 3-, and 4-fluoropyridine-HCl, 2,6- and 3,5-difluororpyridine-HCl, 2,4,6- and 3,4,5-trifluropyridine-HCl, as well as pentafluoropyridine-HCl, was also performed. Equilibrium structures and binding energies for the gas-phase complexes illustrate two clear trends in how fluorine substitution affects hydrogen bond strength; increasing fluorination weakens these interactions, yet substitution at the 2- and 6-positions has the most pronounced effect. Bonding analyses for a select subset of these systems reveal shifts in electron density that accompany hydrogen bonding, and most notably, the values of the electron density at the N-H bond critical points among the stronger systems in this subset significantly exceed those typical for moderately strong hydrogen-bonds. We also explored the effects of dielectric media on the structural and bonding properties of these systems. For pyridine-HCl, 3-fluoropyridine-HCl, and 3,5-difluororpyridine-HCl, a transition to proton transfer-type structures is observed at ε-values of 1.2, 1.5, and 2.0, respectively. This is signaled by key structural changes, as well as an increase in the negative charge on the chorine, and dramatic shifts in topological properties of the H-Cl and N-H bonds. In the case of pentafluoropyridine-HCl, and 2,6-difluororpyridine-HCl, we do not predict proton transfer in dielectric media up to ε = 20.0. However, there are clear indications that the media enhance hydrogen-bond strength, and moreover, these observations are completely consistent with the experimental IR spectra.

Is night-time surgical procedure for renal graft at higher risk than during the day? A single center study cohort of 179 patients.

INTRODUCTION: Various surgical centers tend to postpone a kidney transplantation (KT) to the following morning than to operate at night-time. The objective of our study was to assess whether there was any difference between daytime and night-time renal transplantation in our institution. METHOD: This study is a retrospective monocentric study including all the KTs that were performed between 2012 and 2013 by transplant expert surgeons in our institution. Clavien-Dindo (CD) complications were classified according to 7 variables going from 1 to 5. Time before postgraft diuresis and delayed graft function (DGF) were also analyzed. Two groups of patients were formed according to threshold value of incision time (6.30 p.m.). Data comparison were performed using the Kruskal-Wallis nonparametric test. RESULTS: A total of 179 patients were included. Median follow-up was 24 months. Cold ischemia time was longer in the night-time transplantation (1082 vs. 807 min, p < .001), but rewarming time was shorter (47.24 vs. 52.15 min, p = .628). No statistically significant differences were observed between the two groups using the Kruskal-Wallis method for CD complications (Qobs: 0.076; p = .735). CD complications proportion was similar, with a majority of grade II complications (72.7% daytime group vs. 75.4% night-time group (p = .735). DGF (19 patients for daytime group vs. 13 patients for night-time group, p = .359) and time before postgraft diuresis (4.65 days daytime group vs. 5.27 days night-time group, p = .422) were similar between both groups. Multivariate analysis did not show significant predictors of CD complications Grade 3 and more. CONCLUSION: Night-time renal transplantation did not induce more postoperative CD complications than diurnal procedures in our cohort, challenging the false preconceptions that allow surgical teams to delay this surgery.

Multiphoton Microscopy for Identifying Collagen Signatures Associated with Biochemical Recurrence in Prostate Cancer Patients.

Prostate cancer is a heterogeneous disease that remains dormant for long periods or acts aggressively with poor clinical outcomes. Identifying aggressive prostate tumor behavior using current glandular-focused histopathological criteria is challenging. Recent evidence has implicated the stroma in modulating prostate tumor behavior and in predicting post-surgical outcomes. However, the emergence of stromal signatures has been limited, due in part to the lack of adoption of imaging modalities for stromal-specific profiling. Herein, label-free multiphoton microscopy (MPM), with its ability to image tissue with stromal-specific contrast, is used to identify prostate stromal features associated with aggressive tumor behavior and clinical outcome. MPM was performed on unstained prostatectomy specimens from 59 patients and on biopsy specimens from 17 patients with known post-surgery recurrence status. MPM-identified collagen content, organization, and morphological tumor signatures were extracted for each patient and screened for association with recurrent disease. Compared to tumors from patients whose disease did not recur, tumors from patients with recurrent disease exhibited higher MPM-identified collagen amount and collagen fiber intensity signal and width. Our study shows an association between MPM-identified stromal collagen features of prostate tumors and post-surgical disease recurrence, suggesting their potential for prostate cancer risk assessment.

Using biomarkers in patients with positive multiparametric magnetic resonance imaging: 4Kscore predicts the presence of cancer outside the index lesion.

OBJECTIVES: To evaluate if the blood biomarker, 4Kscore, in addition to multiparametric magnetic resonance imaging information could identify patients who would benefit from undergoing only a targeted biopsy. METHODS: We retrospectively analyzed a population of 256 men with positive multiparametric magnetic resonance imaging who underwent standard + targeted biopsy at Mount Sinai Hospital, New York, NY, USA. 4Kscore (OPKO Health, Miami, FL, USA) was sampled from all patients before biopsy. Uni- and multivariable binary logistic regression analyses were carried out to predict clinically significant prostate cancer, defined as International Society of Urological Pathology grade group ≥2, in standard biopsy cores. The model with the best area under the curve was selected and internal validation was carried out using the leave-one-out cross-validation. RESULTS: The developed model showed an area under the curve of 0.86. Carrying out only targeted biopsy in patients with a model-derived probability <12.5% resulted in 39.5% (n = 101) fewer standard biopsies and a 33.9% (n = 20) reduction of detecting grade group 1 disease, while missing grade group ≥2 in 5.2% (n = 4) using standard biopsy only and 1.1% (n = 1) using standard biopsy + targeted biopsy. CONCLUSIONS: 4Kscore in combination with multiparametric magnetic resonance imaging can help to reduce unnecessary standard biopsy and decrease detection of clinically insignificant prostate cancer.

Hood Technique for Robotic Radical Prostatectomy-Preserving Periurethral Anatomical Structures in the Space of Retzius and Sparing the Pouch of Douglas, Enabling Early Return of Continence Without Compromising Surgical Margin Rates.

BACKGROUND: A common side effect following radical prostatectomy is urinary incontinence. Here, we describe a novel surgical technique to reduce postoperative urinary incontinence and facilitate early return of continence. OBJECTIVE: To describe the novel "hood technique" for robotic-assisted radical prostatectomy (RARP). DESIGN, SETTING, AND PARTICIPANTS: This is an institutional review board-approved prospective study of 300 patients (median age 64 yr) with localized prostate cancer treated with the RARP hood technique at a major urban hospital between April 2018 and March 2019. The exclusion criteria were as follows: patients with anterior tumor location based on biopsy or multiparametric magnetic resonance imaging. All but one patient participated in follow-up over 12 mo after the procedure. SURGICAL PROCEDURE: The RARP "hood technique" was performed to preserve the detrusor apron, puboprostatic ligament complex, arcus tendineus, endopelvic fascia, and pouch of Douglas. MEASUREMENTS: Clinical data collected included pre- and intraoperative variables, and postoperative functional and oncological outcomes and complications. Descriptive statistical analysis was performed. RESULTS AND LIMITATIONS: Continence rates at 1, 2, 4, 6 12, 24, and 48 wk after catheter removal were 21%, 36%, 83%, 88%, 91%, 94%, and 95%, respectively. Positive surgical margin rate was 6%. Thirty patients (9.7%) experienced complications after RARP: 17 (5.7%), 11 (3.6%), and one (0.4%) had Clavien-Dindo grade I, II, and III complications, respectively. This study was conducted within a single health system and may not be generalizable. The study lacked randomization and a comparative arm. CONCLUSIONS: Results indicate that the hood technique spares musculofascial structures anterior to the urethral sphincter complex with early return of continence after surgery, without compromising positive surgical margin rates. Exclusion of anterior tumor location contributed to a reduction in positive surgical margins. PATIENT SUMMARY: By better preservation of anatomical structures around the urethra, we were able to achieve early return of urinary continence without a negative impact on complications and cancer outcomes.

Does race impact functional outcomes in patients undergoing robotic partial nephrectomy?

BACKGROUND: The role of race on functional outcomes after robotic partial nephrectomy (RPN) is still a matter of debate. We aimed to evaluate the clinical and pathologic characteristics of African American (AA) and Caucasian patients who underwent RPN and analyzed the association between race and functional outcomes. METHODS: Data was obtained from a multi-institutional database of patients who underwent RPN in 6 institutions in the USA. We identified 999 patients with complete clinical data. Sixty-three patients (6.3%) were AA, and each patient was matched (1:3) to Caucasian patients by age at surgery, gender, Charlson Comorbidity Index (CCI) and renal score. Bivariate and multivariate logistic regression analyses were used to evaluate predictors of acute kidney injury (AKI). Kaplan-Meier method and multivariable semiparametric Cox regression analyses were performed to assess prevalence and predictors of significant eGFR reduction during follow-up. RESULTS: Overall, 252 patients were included. AA were more likely to have hypertension (58.7% vs. 35.4%, P=0.001), even after 1:3 match. Overall 42 patients (16.7%) developed AKI after surgery and 35 patients (13.9%) developed significant eGFR reduction between 3 and 15 months after RAPN. On multivariate analysis, AA race did not emerge as a significant factor for predicting AKI (OR 1.10, P=0.8). On Cox multivariable analysis, only AKI was found to be associated with significant eGFR reduction between 3 and 15 months after RAPN (HR 2.49, P=0.019). CONCLUSIONS: Although African American patients were more likely to have hypertension, renal function outcomes of robotic partial nephrectomies were not significantly different when stratified by race. However, future studies with larger cohorts are necessary to validate these findings.

Neoadjuvant versus adjuvant chemotherapy for upper tract urothelial carcinoma.

BACKGROUND: Presently, no level I evidence is available to support the use of neoadjuvant chemotherapy (N)(AC) in patients diagnosed with high-grade upper tract urothelial carcinoma (UTUC). We aimed to compare outcomes of patients treated with radical nephroureterectomy (RNU) who received NAC vs. those who received AC. METHODS: The National Cancer Database was queried for UTUC patients with cT2-4N0M0 disease treated with RNU and NAC or AC. The role of NAC or AC on overall survival (OS) was evaluated by means of a multivariable Cox regression. Time to death was evaluated from diagnosis. RESULTS: Overall, 936 patients were identified, 128 (14%) received NAC whereas 808 (86%) received AC. No difference was observed between NAC vs. AC in terms of OS (P = 0.9). When sub-stratifying patients who received NAC in responders (cT>pT, given pN0; n = 46 [36%]) vs. nonresponders (n = 82 [64%]), we found that, relatively to AC, the subgroup of patients who did not respond to NAC had higher risk of dying from any cause (hazard ratio [HR]: 1.41; 95% confidence interval [CI]: 1.03,1.91; P = 0.03), whereas the sub-group who responded to NAC had better OS (HR: 0.45; 95% CI: 0.24,0.85; P = 0.01). The 5-year OS rates for responders to NAC vs. nonresponders vs. AC were: 71% vs. 26% vs. 43%, respectively. A landmark analysis fitted at 6 months after diagnosis, including 903 patients (NAC: 126 vs. AC: 777) confirmed our findings. CONCLUSION: while we found no difference in outcomes between NAC vs. AC in high-grade UTUC, we found a hypothesis-generating association between survival and response to NAC. Further studies aimed at identifying potential responders to NAC are warranted.

Bioptic intraprostatic chronic inflammation predicts adverse pathology at radical prostatectomy in patients with low-grade prostate cancer.

PURPOSE: To determine the potential role of bioptic inflammation (Irani score) in predicting adverse pathology (AP) at radical prostatectomy (RP) in patients with low-grade (ISUP Gleason Group [ISUP GG] 1 and 2) prostate cancer (CaP). METHODS: After institutional review board-approval, we identified patients who underwent prostate biopsy, had bioptic Irani score assessment, were diagnosed with low-grade CaP (ISUP GG 1-2, prostate-specific antigen [PSA] <20 ng/ml), and underwent RP. The impact of standard clinicopathological variables and bioptic Irani Score (G = grade and A = aggressiveness) on AP at RP, defined as stage ≥T3 and/or ISUP GG ≥3, was assessed by univariate and multivariate logistic regression analysis. RESULTS: A total of 282 patients were eligible for this study. AP at RP occurred in 37 of 214 (17.3%) patients with ISUP GG 1, and 26 of 68 (38.2%) with ISUP GG 2. At univariate analysis, serum PSA, PSA density, bioptic ISUP GG, number of positive cores, total percentage of core involvement and Irani G score emerged as significant risk factors of AP. At multivariate analysis, however, only PSA density, bioptic ISUP GG, total percentage of core, and Irani G score kept statistical significance. The area under the curve for the resulting model was 0.75. CONCLUSIONS: This is the first study demonstrating that low-grade inflammation is associated with a significantly increased risk of AP at RP. These findings would support the concept of prostatic inflammation being inversely correlated with presence and aggressiveness of CaP. Further studies are needed to externally validate the role of this readily available parameter in the decision-making process of patients with low-grade CaP.

Performance of prostate multiparametric MRI for prediction of prostate cancer extra-prostatic extension according to NCCN risk categories: implication for surgical planning.

BACKGROUND: Prediction of extra-prostatic extension (EPE) in men undergoing radical prostatectomy (RP) is of utmost importance. Great variability in the performance of multiparametric magnetic resonance imaging (mpMRI) has been reported for prediction of EPE. The present study aimed to determine the diagnostic performance of mpMRI for predicting EPE in different National Comprehensive Cancer Network (NCCN) risk categories. METHODS: Overall 664 patients who underwent radical prostatectomy with a staging mpMRI were enrolled in this single-center, retrospective study. Patients with mpMRI report non-compliant with PI-RADSv2.0, were excluded. Patients were stratified according to NCCN criteria: very low/low (VLR-LR) to High Risk (HR) in order to assess final pathology EPE rates (focal and established). Sensitivity, specificity, positive and negative predictive values of staging mpMRI were computed in each group. Univariable and multivariable analysis were used to evaluate predictors of positive surgical margins. RESULTS: Pathological evaluation demonstrated established and focal EPE in 60 (9%) and 106 (16%) patients, respectively, while mpMRI suspicion for EPE was present in 180 (27%) patients. Age, preoperative PSA, PSA density, number of positive cores, NCCN groups, prostate volume, mpMRI suspicion for EPE, PIRADSv2.0 and lesion size differed significantly between the patients with any EPE and without EPE (all P≤0.05). The sensitivity of mpMRI in detecting any EPE varied from 12% (95% CI: 0.6-53%) in VLR-LR to 83% (66-93%) in HR while the corresponding values for the specificity were 92% (85-96%) and 63% (45-78%), respectively. Patients with false-negative mpMRI EPE prediction were more likely to have positive surgical margins in univariable (OR: 2.14; CI: 1.18, 3.87) as well as multivariable analysis adjusting for NCCN risk categories (OR: 1.97; CI: 1.08, 3.60). CONCLUSIONS: The performance of mpMRI for prediction of EPE varies greatly between different NCCN risk categories with a low positive predicting value in patients at low to favorable intermediate risk and a low negative predictive value in patients at Unfavorable intermediate to high risk PCa. Given that mpMRI EPE misdiagnosis could have a negative impact on oncological and functional outcomes, NCCN risk categories should be considered when interpreting mpMRI findings in PCa patients.

Staging Accuracy of Multiparametric Magnetic Resonance Imaging in Caucasian and African American Men Undergoing Radical Prostatectomy.

PURPOSE: We compared the performance of multiparametric magnetic resonance imaging for the prediction of extraprostatic extension in African American and Caucasian American men and evaluated racial disparities in pathological outcomes after radical prostatectomy. MATERIALS AND METHODS: We identified 975 patients who underwent radical prostatectomy with preoperative multiparametric magnetic resonance imaging between January 2013 and April 2019 at our institution. Multivariable logistic regression analysis was performed predicting pathological extraprostatic extension, high grade prostate cancer (final pathology GGG [Gleason Grade Group] 3 or greater) in the overall population and pathological upgrading (final pathology GGG 3 or greater) in patients with a diagnosis of GGG 1-2 prostate cancer. Adverse pathology was defined as pT3 and/or GGG 3 or greater. RESULTS: A total of 221 (23%) patients were African American. Preoperatively 594 (60.9%) were GGG 1-2 (low risk group) and 381 (39.1%) GGG 3 or greater (high risk group). In the low risk group rates of pathological extraprostatic extension (18% vs 12.8%, p=0.14), adverse pathology (18% vs 13.4%, p=0.2) or upgrading (9.4% vs 12.1%, p=0.4) were similar between races. Similarly, in the high risk group there was no difference in rates of pathological extraprostatic extension. On multivariable analysis multiparametric magnetic resonance imaging predicted the presence of extraprostatic extension (OR 1.80, 95% CI 1.29-2.50) and high grade prostate cancer (OR 1.82, 95% CI 1.25-2.67) on final pathology. Conversely, race did not predict the outcomes of interest (all values p >0.05). Multiparametric magnetic resonance imaging showed comparable sensitivity (22.22% vs 27.84%), specificity (89.2% vs 79.2%), positive predictive value (89.2% vs 83.4%) and negative predictive value (89.2% vs 83.4%) between African American and Caucasian America men, respectively. CONCLUSIONS: The accuracy of multiparametric magnetic resonance imaging in staging prostate cancer was similar in African American and Caucasian American patients and no difference was found between races in pathological outcomes after radical prostatectomy. These findings suggest that access to and use of advanced diagnostic tests may help mitigate prostate cancer racial disparities.

Avoiding Unnecessary Magnetic Resonance Imaging (MRI) and Biopsies: Negative and Positive Predictive Value of MRI According to Prostate-specific Antigen Density, 4Kscore and Risk Calculators.

The 2019 European Association of Urology guidelines recommend multiparametric magnetic resonance imaging (mpMRI) for biopsy-naïve patients with clinical suspicion of prostate cancer (PC) and avoiding biopsy in patients with negative mpMRI and low clinical suspicion. However, consensus on the optimal definition of low clinical suspicion is lacking. We evaluated 266 biopsy-naïve patients who underwent mpMRI, the 4Kscore test, and prostate biopsy to define the best strategy to avoid unnecessary testing and biopsies. The European Randomized Study of Screening for Prostate Cancer risk calculator (ERSPC-RC) and prostate-specific antigen density (PSAd) were also considered. For men with Prostate Imaging-Reporting and Data System v2.0 (PI-RADS) 1â¿¿2 lesions, the highest negative predictive value was observed for those with low or intermediate 4Kscore risk (96.9% and 97.1%), PSAd <0.10ng/ml/cm3 (98.7%), and ERSPC-RC <2% (98.7%). For men with PI-RADS 3â¿¿5 lesions the lowest positive predictive value was observed for those with low 4Kscore risk (0%), PSAd <0.10ng/ml/cm3 (13.2%), and ERSPC-RC <2% (12.3%). The best biopsy strategy was an initial 4Kscore followed by mpMRI if the 4Kscore was>7.5% and a subsequent biopsy if the mpMRI was positive (PI-RADS 3â¿¿5) or the 4Kscore was â¿¥18%. This would result in missing 2.7% (2/74) of clinically significant PCs (csPCs) and avoiding 34.2% of biopsies. Initial mpMRI followed by biopsy for negative mpMRI (PI-RADS 1â¿¿2) if the 4Kscore was â¿¥18% or PSAd was â¿¥0.10ng/ml/cm3 resulted in a similar percentage of csPC missed (2.7% [2/74] and 1.3% [1/74]) but slightly fewer biopsies avoided (25.2% and 28.1%). Physicians should consider clinical risk screening tools when ordering and interpreting mpMRI results to avoid unnecessary testing and diagnostic errors. PATIENT SUMMARY: Performing the 4Kscore test in conjunction with multiparametric magnetic resonance imaging for men with a clinical suspicion of prostate cancer may help to reduce unnecessary biopsies.