Prognostic Value of P63 Expression in Muscle-Invasive Bladder Cancer and Association with Molecular Subtypes-Preliminary Report.

There is an ongoing need for biomarkers that could reliably predict the outcome of BC and that could guide the management of this disease. In this setting, we aimed to explore the prognostic value of the transcription factor P63 in patients with muscle-invasive bladder cancer (MIBC) having undergone radical cystectomy. The correlation between P63 expression and clinicopathological features (tumor stage, nodes involvement, patterns of muscularis propria invasion, papillary architecture, anaplasia, concomitant carcinoma in situ, lymphovascular invasion, perineural invasion, necrosis) and molecular subtyping (basal and luminal type tumors) was tested in 65 radical cystectomy specimens and matched with cancer-specific survival (CSS) and overall survival (OS). P63-negative tumors displayed significantly higher rates of pattern 2 of muscularis propria invasion (50% vs. 14%, p = 0.002) and variant histology (45% vs. 19%, p = 0.022) compared to P63-positive ones. According to the combined expression of CK5/6 and CK20 (Algorithm #1), P63-positive and P63-negative tumors were mostly basal-like and double-negative, respectively (p = 0.004). Using Algorithm #2, based on the combined expression of CK5/6 and GATA3, the vast majority of tumors were luminal overall and in each group (p = 0.003). There was no significant difference in CSS and OS between P63-positive and P63-negative tumors, but the former featured a trend towards longer OS. Though associated with pathological features harboring negative prognostic potential, P63 status as such failed to predict CSS and OS. That said, it may contribute to better molecular subtyping of MIBC.

Techniques for Penile Augmentation Surgery: A Systematic Review of Surgical Outcomes, Complications, and Quality of Life.

The increase in practices related to enhancing penile size can be attributed to the belief that an improved genital appearance contributes to a man's virility, coupled with an altered self-perception of his body. It is crucial to tailor interventions to meet the genuine needs of patients by thoroughly assessing their history, psychological state, and potential surgical benefits, all while considering the associated risks of complications. This systematic review aims to summarize the available evidence on outcomes, complications, and quality of life after penile augmentation surgery, examining both minimally invasive and more radical techniques. A search of the PubMed and Scopus databases, focusing on English-language papers published in the last 15 years, was performed in December 2023. Papers discussing surgery in animal models and case reports were excluded from the present study unless further evaluated in a follow-up case series. The primary outcomes were changes in penile dimensions, specifically in terms of length and girth, as well as the incidence of surgical complications and the impact on quality of life. A total of 1670 articles were retrieved from the search and 46 were included for analysis. Procedures for penile length perceived enhancements include lipoplasty, skin reconstruction plasty, V-Y and Z plasty, flap reconstruction, scrotoplasty, ventral phalloplasty, and suspensory ligament release; techniques for increasing corporal penile length include penile disassembly, total phalloplasty, and sliding elongation. Finally, penile girth enhancement may be performed using soft tissue fillers, grafting procedures, biodegradable scaffolds, and Penuma®. In conclusion, while penile augmentation surgeries offer potential solutions for individuals concerned about genital size, the risks and complexities need to be accounted for.

Unilateral Pelvic Lymph Node Dissection in Prostate Cancer Patients Diagnosed in the Era of Magnetic Resonance Imaging-targeted Biopsy: A Study That Challenges the Dogma.

PURPOSE: Bilateral extended pelvic lymph node dissection at the time of radical prostatectomy is the current standard of care if pelvic lymph node dissection is indicated; often, however, pelvic lymph node dissection is performed in pN0 disease. With the more accurate staging achieved with magnetic resonance imaging-targeted biopsies for prostate cancer diagnosis, the indication for bilateral extended pelvic lymph node dissection may be revised. We aimed to assess the feasibility of unilateral extended pelvic lymph node dissection in the era of modern prostate cancer imaging. MATERIALS AND METHODS: We analyzed a multi-institutional data set of men with cN0 disease diagnosed by magnetic resonance imaging-targeted biopsy who underwent prostatectomy and bilateral extended pelvic lymph node dissection. The outcome of the study was lymph node invasion contralateral to the prostatic lobe with worse disease features, ie, dominant lobe. Logistic regression to predict lymph node invasion contralateral to the dominant lobe was generated and internally validated. RESULTS: Overall, data from 2,253 patients were considered. Lymph node invasion was documented in 302 (13%) patients; 83 (4%) patients had lymph node invasion contralateral to the dominant prostatic lobe. A model including prostate-specific antigen, maximum diameter of the index lesion, seminal vesicle invasion on magnetic resonance imaging, International Society of Urological Pathology grade in the nondominant side, and percentage of positive cores in the nondominant side achieved an area under the curve of 84% after internal validation. With a cutoff of contralateral lymph node invasion of 1%, 602 (27%) contralateral pelvic lymph node dissections would be omitted with only 1 (1.2%) lymph node invasion missed. CONCLUSIONS: Pelvic lymph node dissection could be omitted contralateral to the prostate lobe with worse disease features in selected patients. We propose a model that can help avoid contralateral pelvic lymph node dissection in almost one-third of cases.

When to order genomic tests: development and external validation of a model to predict high-risk prostate cancer at the genotypic level.

PURPOSE: The aim of this study was to develop a model to predict high-genomic-risk prostate cancer (PCa) according to Decipher score, a validated 22 gene prognostic panel. By doing so, one might select the individuals who are likely to benefit from genomic testing and improve pre-op counseling about the need for adjuvant treatments. METHODS: We retrospectively reviewed IRB-approved databases at two institutions. All patients had preoperative magnetic resonance imaging (MRI) and Decipher prostate radical prostatectomy (RP), a validated 22 gene prognostic panel. We used binary logistic regression to estimate high-risk Decipher (Decipher score > 0.60) probability on RP specimen. Area under the curve (AUC) and calibration were used to assess the accuracy of the model in the development and validation cohort. Decision curve analysis (DCA) was performed to assess the clinical benefit of the model. RESULTS: The development and validation cohort included 622 and 185 patients with 283 (35%) and 80 (43%) of those with high-risk Decipher. The multivariable model included PSA density, biopsy Gleason Grade Group, percentage of positive cores and MRI extracapsular extension. AUC was 0.73 after leave-one-out cross-validation. DCA showed a clinical benefit in a range of probabilities between 15 and 60%. In the external validation cohort, AUC was 0.70 and calibration showed that the model underestimates the actual probability of the outcome. CONCLUSIONS: The proposed model to predict high-risk Decipher score at RP is helpful to improve risk stratification of patients with PCa and to assess the need for additional testing and treatments.

HER2 Expression in Bladder Cancer: A Focused View on Its Diagnostic, Prognostic, and Predictive Role.

Bladder cancer (BC) is a heterogeneous disease from a molecular, morphological, and clinical standpoint. HER2 is a known oncogene involved in bladder carcinogenesis. Assessing HER2 overexpression as a result of its molecular changes in a routine pathology practice using immunohistochemistry might be a useful adjunct in several scenarios, namely (1) to correctly identify flat urothelial lesions and inverted urothelial lesions in the diagnostic setting; (2) to provide prognostic hints in both non-muscle invasive (NMI) and muscle invasive (MI) tumors, thus supplementing risk stratification tools, especially when evaluating higher-risk tumors such as those with variant morphology; (3) to improve antibody panels as a surrogate marker of BC molecular subtyping. Furthermore, the potential of HER2 as a therapeutic target has been only partly explored so far, in light of the ongoing development of novel target therapies.

Clinicopathological Features and Survival Analysis in Molecular Subtypes of Muscle-Invasive Bladder Cancer.

Molecular subtyping of bladder cancer (BC) aims to capture the biological heterogeneity of this complex disease in order to provide better patient risk stratification. Immunohistochemical (IHC) markers are regarded as promising surrogates to classify BCs into luminal and basal subtypes in routine practice. We investigated the correlation between the molecular subclassification, assessed through IHC, and the conventional prognostic variables of a cohort of 93 muscle-invasive BCs (MIBCs), with a focus on the pattern of muscularis propria (MP) invasion, and evaluated their association with outcome. Basal, luminal, double-positive (DP), and double-negative (DN) phenotypes were identified according to the coordinate expression of 1 basal (CK5/6) and 2 luminal (CK20, GATA3) markers, and accounted for 33.3%, 32.3%, 3.2%, and 31.2% (Scheme #1) and 9.7%, 60.2%, 26.9%, and 3.2% (Scheme #2). There was a significant association between the pattern of MP invasion and the molecular subtypes according to Scheme #2, in that all 8 basal and DN cases, as well as 83% of DP cases, had a non-infiltrative invasion pattern. No consistent differences were observed in terms of OS and CSS between the molecular subtypes obtained through surrogate IHC markers. In keeping with previous studies, we report the correlation between the identification of BC subtypes and the presence of morphological prognostic factors, supporting the need for a comprehensive pathological evaluation, including clinicopathological and molecular parameters, in order to improve the diagnosis and management of MIBC.

Foggia Prostate Cancer Risk Calculator 2.0: A Novel Risk Calculator including MRI and Bladder Outlet Obstruction Parameters to Reduce Unnecessary Biopsies.

Risk calculator (RC) combining PSA with other clinical information can help to better select patients at risk of prostate cancer (PCa) for prostate biopsy. The present study aimed to develop a new Pca RC, including MRI and bladder outlet obstruction parameters (BOOP). The ability of these parameters in predicting PCa and clinically significant PCa (csPCa: ISUP GG ≥ 2) was assessed by binary logistic regression. A total of 728 patients were included from two institutions. Of these, 395 (54.3%) had negative biopsies and 161 (22.11%) and 172 (23.6%) had a diagnosis of ISUP GG1 PCa and csPCa. The two RC ultimately included age, PSA, DRE, prostate volume (pVol), post-voided residual urinary volume (PVR), and PIRADS score. Regarding BOOP, higher prostate volumes (csPCa: OR 0.98, CI 0.97,0.99) and PVR ≥ 50 mL (csPCa: OR 0.27, CI 0.15, 0.47) were protective factors for the diagnosis of any PCa and csPCa. AUCs after internal validation were 0.78 (0.75, 0.82) and 0.82 (0.79, 0.86), respectively. Finally, decision curves analysis demonstrated higher benefit compared to the first-generation calculator and MRI alone. These novel RC based on MRI and BOOP may help to better select patient for prostate biopsy after prostate MRI.

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.

The Role of miRNA in Testicular Cancer: Current Insights and Future Perspectives.

Background and Objectives: Despite advancements in the diagnosis and treatment of testicular germ cell tumours (TGTCs), challenges persist in identifying reliable biomarkers for early detection and precise disease management. This narrative review addresses the role of microRNAs (miRNAs) as potential diagnostic tools and therapeutic targets in the treatment of TGCTs. Materials and Methods: Three databases (PubMed®, Web of Science™, and Scopus®) were queried for studies investigating the utility of miRNA as diagnostic tools, assessing their prognostic significance, and evaluating their potential to guide TGCT treatment. Different combinations of the following keywords were used, according to a free-text protocol: "miRNA", "non-coding RNA", "small RNA", "Testicular Cancer", "seminomatous testicular germ cell", "non-seminomatous testicular germ cell". Results: The potential of miRNAs as possible biomarkers for a non-invasive diagnosis of TGCT is appealing. Their integration into the diagnostic pathway for TGCT patients holds the potential to enhance the discriminative power of conventional serum tumour markers (STMs) and could expedite early diagnosis, given that miRNA overexpression was observed in 50% of GCNIS cases. Among miRNAs, miR-371a-3p stands out with the most promising evidence, suggesting its relevance in the primary diagnosis of TGCT, particularly when conventional STMs offer limited value. Indeed, it demonstrated high specificity (90-99%) and sensitivity (84-89%), with good positive predictive value (97.2%) and negative predictive value (82.7%). Furthermore, a direct relationship between miRNA concentration, disease burden, and treatment response exists, regardless of disease stages. The initial evidence of miRNA decrease in response to surgical treatment and systemic chemotherapy has been further supported by more recent results suggesting the potential utility of this tool not only in evaluating treatment response but also in monitoring residual disease and predicting disease relapse. Conclusions: MiRNAs could represent a reliable tool for accurate diagnosis and disease monitoring in the treatment of TGCT, providing more precise tools for early detection and treatment stratification. Nevertheless, well-designed clinical trials and comprehensive long-term data are needed to ensure their translation into effective clinical tools.

Prostate cancer biomarkers: a practical review based on different clinical scenarios.

Traditionally, diagnosis and staging of prostate cancer (PCa) have been based on prostate-specific antigen (PSA) level, digital rectal examination (DRE), and transrectal ultrasound (TRUS) guided prostate biopsy. Biomarkers have been introduced into clinical practice to reduce the overdiagnosis and overtreatment of low-grade PCa and increase the success of personalized therapies for high-grade and high-stage PCa. The purpose of this review was to describe available PCa biomarkers and examine their use in clinical practice. A nonsystematic literature review was performed using PubMed and Scopus to retrieve papers related to PCa biomarkers. In addition, we manually searched websites of major urological associations for PCa guidelines to evaluate available evidence and recommendations on the role of biomarkers and their potential contribution to PCa decision-making. In addition to PSA and its derivates, thirteen blood, urine, and tissue biomarkers are mentioned in various PCa guidelines. Retrospective studies have shown their utility in three main clinical scenarios: (1) deciding whether to perform a biopsy, (2) distinguishing patients who require active treatment from those who can benefit from active surveillance, and (3) defining a subset of high-risk PCa patients who can benefit from additional therapies after RP. Several validated PCa biomarkers have become commercially available in recent years. Guidelines now recommend offering these tests in situations in which the assay result, when considered in combination with routine clinical factors, is likely to affect management. However, the lack of direct comparisons and the unproven benefits, in terms of long-term survival and cost-effectiveness, prevent these biomarkers from being integrated into routine clinical use.

Are We Ready to Implement Molecular Subtyping of Bladder Cancer in Clinical Practice? Part 1: General Issues and Marker Expression.

Bladder cancer (BC) is a heterogeneous disease with highly variable clinical and pathological features, and resulting in different outcomes. Such heterogeneity ensues from distinct pathogenetic mechanisms and may consistently affect treatment responses in single patients. Thus, over the last few years, several groups have developed molecular classification schemes for BC, mainly based on their mRNA expression profiles. A "consensus" classification has recently been proposed to combine the published systems, agreeing on a six-cluster scheme with distinct prognostic and predictive features. In order to implement molecular subtyping as a risk-stratification tool in routine practice, immunohistochemistry (IHC) has been explored as a readily accessible, relatively inexpensive, standardized surrogate method, achieving promising results in different clinical settings. The first part of this review deals with the steps resulting in the development of a molecular subtyping of BC, its prognostic and predictive implications, and the main features of immunohistochemical markers used as surrogates to stratify BC into pre-defined molecular clusters.

Are We Ready to Implement Molecular Subtyping of Bladder Cancer in Clinical Practice? Part 2: Subtypes and Divergent Differentiation.

Following several attempts to achieve a molecular stratification of bladder cancer (BC) over the last decade, a "consensus" classification has been recently developed to provide a common base for the molecular classification of bladder cancer (BC), encompassing a six-cluster scheme with distinct prognostic and predictive characteristics. In order to implement molecular subtyping (MS) as a risk stratification tool in routine practice, immunohistochemistry (IHC) has been explored as a readily accessible, relatively inexpensive, standardized surrogate method, achieving promising results in different clinical settings. The second part of this review deals with the pathological and clinical features of the molecular clusters, both in conventional and divergent urothelial carcinoma, with a focus on the role of IHC-based subtyping.

Advanced ureteroscopic techniques for the management of kidney stones.

PURPOSE OF REVIEW: Recent years witnessed significant changes in the endourological management of renal tones because of the development of new, more advanced instruments. Retrograde intrarenal surgery (RIRS) has gained particular advantage from such technological progress and now tends to be considered the gold standard treatment for uncomplicated less than 20 mm renal stones. Using a step-by-step approach, this review aims to highlight current achievements but also unsolved problems in RIRS. RECENT FINDINGS: Several technical details of RIRS, including preoperative stenting, use of ureteral access sheets, lithotripsy method, and renal drainage, remain open to discussion and linked to surgeon's preference. Moreover, there is a wide range of variation in efficacy and safety data, with major complications being episodic but often under-reported. SUMMARY: RIRS has gained increased popularity among the urological community. This is certainly because of the continuous technological advancements, which have continuously improved the RIRS performance but also to the perception of ease and safety of this procedure when compared with the other available treatment modalities, particularly percutaneous nephrolitotomy. Indeed, the reported advances in RIRS technique have significantly improved the outcomes of this procedure but care should be taken not to underestimate its potential challenges.

Nomogram predicting 30-day mortality after nephrectomy in the contemporary era: Results from the SEER database.

OBJECTIVES: To assess contemporary 30-day mortality rates after partial and radical nephrectomy in USA, and to develop a predictive model of 30-day mortality. METHODS: We relied on the National Cancer Institute Surveillance, Epidemiology and End Results database. A multivariable logistic regression analysis was fitted to predict 30-day mortality. A nomogram was built based on the coefficients of the logit function. Internal validation was carried out using the leave-one-out cross-validation. Calibration was graphically investigated. RESULTS: A total of 102 146 patients who underwent partial nephrectomy (n = 36 425; 35.7%) or radical nephrectomy (n = 65 721; 64.3%) between 2005 and 2015 were included in the analysis. The median age at diagnosis was 62 years. A total of 11 921 (11.7%) patients were African American. The clinical stage was T1-T2 in 79 452 (77.8%), T3 in 16 141 (15.8%) and T4/T1-4-M1 in 6553 (6.4%) patients. Overall, 497 deaths occurred during the initial 30 days after nephrectomy (0.49% 30-day mortality rate). Stratified by type of surgery, the 30-day mortality rate was 0.16% for partial nephrectomy and 0.67% for radical nephrectomy. At univariate analyses, age, tumor size, stage and surgical procedure emerged as predictors of 30-day mortality (all P < 0.001). All of these covariates were included in the multivariable logistic regression model. The area under the curve after leave-one-out cross-validation was 0.808 (95% confidence interval 0.788-0.828), and the model showed good calibration in the range of predicted probability <10%. CONCLUSIONS: Contemporary rates of 30-day mortality in patients undergoing radical or partial nephrectomy are very low. Age and tumor stage are key determinants of 30-day mortality. We present a predictive model that provides individual probabilities of 30-day mortality after nephrectomy, and it can be used for patient counseling prior surgery.

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.

Mini and Standard Percutaneous Nephrolithotomy in Obese Patients. Results from a Single-surgeon Large Series.

Background and objective: Percutaneous nephrolithotomy (PCNL) is the recommended treatment for large or complex renal stones. This study aims to evaluate the outcomes of mini PCNL in obese and nonobese patients and to compare the outcomes of mini and standard PCNL in the obese population. Methods: We retrospectively reviewed our PCNL database to identify patients who had undergone mini (Amplatz sheath size 17.5Ch) or standard (Amplatz sheath size ≥26Ch) PCNL between 2005 and 2022. First, we compared the outcomes of the two procedures in the obese (body mass index [BMI] ≥30) and nonobese (BMI<30) patients. Second, we compared the outcomes of mini and standard PCNL in the obese population. A multivariable logistic regression analysis was performed to assess the variables associated with stone-free rate (SFR) and complications. Key findings and limitations: A total of 781 patients underwent mini PCNL; there was no difference between nonobese (578) and obese (133) patients in surgical time, number of tubeless procedures, postoperative stay, SFR, and overall complication rates. Similar outcomes were also seen in the 356 patients who had undergone standard PCNL, including 276 nonobese and 80 obese patients. The comparison of mini and standard PCNL in the obese population (213 patients) showed that mini PCNL provided significant benefits in surgical time (60 vs 94 min), SFR (85% vs 63.8%), and blood transfusion rate (2% vs 10%). The multivariable analysis confirmed that mini PCNL resulted in significantly higher odds of being stone free (odds ratio [OR] 1.79) and lower odds of having a blood transfusion (OR 0.28). Conclusions and clinical implications: Obese patients can safely undergo either mini or standard PCNL; in this series, mini performed better than standard PCNL in terms of SFR and blood transfusion rates. Patient summary: In this study, we compared the outcomes of mini and standard percutaneous nephrolithotomy (PCNL) in the obese population. We found that mini PCNL had lower surgical time and blood transfusion rate, and better stone-free rate than its standard counterpart in obese patients.

Integrating the PD-L1 Prognostic Biomarker in Non-Muscle Invasive Bladder Cancer in Clinical Practice-A Comprehensive Review on State-of-the-Art Advances and Critical Issues.

Bladder cancer (BC) is one of the most prevalent cancers worldwide. Non-muscle invasive bladder cancer (NMIBC), comprising the majority of initial BC presentations, requires accurate risk stratification for optimal management. This review explores the evolving role of programmed cell death ligand 1 (PD-L1) as a prognostic biomarker in NMIBC, with a particular focus on its implications in the context of Bacillus Calmette-Guérin (BCG) immunotherapy. The literature suggests a potential association between elevated PD-L1 status and adverse outcomes, resistance to BCG treatment, and disease progression. However, conflicting findings and methodological issues highlight the heterogeneity of PD-L1 assessment in NMIBC, probably due to the complex biological mechanisms that regulate the interaction between PD-L1 and the tumor microenvironment. The identification of PD-L1 as a prognostic biomarker provides ground for tailored therapeutic interventions, including immune checkpoint inhibitors (ICIs). Nevertheless, challenges such as intratumoral heterogeneity and technical issues underscore the need for standardized protocols and larger, homogeneous trials. This review contributes to the ongoing debate on the personalized management of NMIBC patients, focusing on the advances and perspectives of incorporating PD-L1 as a biomarker in this setting.