Mitofusin-2 Down-Regulation Predicts Progression of Non-Muscle Invasive Bladder Cancer

Identification of markers predicting disease outcome is a major clinical issue for non-muscle invasive bladder cancer (NMIBC). The present study aimed to determine the role of the mitochondrial proteins Mitofusin-2 (Mfn2) and caseinolytic protease P (ClpP) in predicting the outcome of NMIBC. The study population consisted of patients scheduled for transurethral resection of bladder tumor upon the clinical diagnosis of bladder cancer (BC). Samples of the main bladder tumor and healthy-looking bladder wall from patients classified as NMIBC were tested for Mfn2 and ClpP. The expression levels of these proteins were correlated to disease recurrence, progression. Mfn2 and ClpP expression levels were significantly higher in lesional than in non-lesional tissue. Low-risk NMIBC had significantly higher Mfn2 expression levels and significantly lower ClpP expression levels than high-risk NMIBC; there were no differences in non-lesional levels of the two proteins. Lesional Mfn2 expression levels were significantly lower in patients who progressed whereas ClpP levels had no impact on any survival outcome. Multivariable analysis adjusting for the EORTC scores showed that Mfn2 downregulation was significantly associated with disease progression. In conclusion, Mfn2 and ClpP proteins were found to be overexpressed in BC as compared to non-lesional bladder tissue and Mfn2 expression predicted disease progression

Biochemical Recurrence and Risk of Mortality Following Radiotherapy or Radical Prostatectomy

Importance: Stratifying patients with biochemical recurrence (BCR) after primary treatment for prostate cancer based on the risk of prostate cancer-specific mortality (PCSM) is essential for determining the need for further testing and treatments. Objective: To evaluate the association of BCR after radical prostatectomy or radiotherapy and its current risk stratification with PCSM. Design, Setting, and Participants: This population-based cohort study included a total of 16 311 male patients with 10 364 (64%) undergoing radical prostatectomy and 5947 (36%) undergoing radiotherapy with curative intent (cT1-3, cM0) and PSA follow-up in Stockholm, Sweden, between 2003 and 2019. Follow-up for all patients was until death, emigration, or end of the study (ie, December 31, 2018). Data were analyzed between September 2022 and March 2023. Main Outcomes and Measures: Primary outcomes of the study were the cumulative incidence of BCR and PCSM. Patients with BCR were stratified in low- and high-risk according to European Association of Urology (EAU) criteria. Exposures: Radical prostatectomy or radiotherapy. Results: A total of 16 311 patients were included. Median (IQR) age was 64 (59-68) years in the radical prostatectomy cohort (10 364 patients) and 69 (64-73) years in the radiotherapy cohort (5947 patients). Median (IQR) follow-up for survivors was 88 (55-138) months and 89 (53-134) months, respectively. Following radical prostatectomy, the 15-year cumulative incidences of BCR were 16% (95% CI, 15%-18%) for the 4024 patients in the low D'Amico risk group, 30% (95% CI, 27%-32%) for the 5239 patients in the intermediate D'Amico risk group, and 46% (95% CI, 42%-51%) for 1101 patients in the high D'Amico risk group. Following radiotherapy, the 15-year cumulative incidences of BCR were 18% (95% CI, 15%-21%) for the 1230 patients in the low-risk group, 24% (95% CI, 21%-26%) for the 2355 patients in the intermediate-risk group, and 36% (95% CI, 33%-39%) for the 2362 patients in the high-risk group. The 10-year cumulative incidences of PCSM after radical prostatectomy were 4% (95% CI, 2%-6%) for the 1101 patients who developed low-risk EAU-BCR and 9% (95% CI, 5%-13%) for 649 patients who developed high-risk EAU-BCR. After radiotherapy, the 10-year PCSM cumulative incidences were 24% (95% CI, 19%-29%) for the 591 patients in the low-risk EAU-BCR category and 46% (95% CI, 40%-51%) for the 600 patients in the high-risk EAU-BCR category. Conclusions and Relevance: These findings suggest the validity of EAU-BCR stratification system. However, while the risk of dying from prostate cancer in low-risk EAU-BCR after radical prostatectomy was very low, patients who developed low-risk EAU-BCR after radiotherapy had a nonnegligible risk of prostate cancer mortality. Improving risk stratification of patients with BCR is pivotal to guide salvage treatment decisions, reduce overtreatment, and limit the number of staging tests in the event of PSA elevations after primary treatment.</p

Radiomics in prostate cancer: an up-to-date review

: Prostate cancer (PCa) is the most common worldwide diagnosed malignancy in male population. The diagnosis, the identification of aggressive disease, and the post-treatment follow-up needs a more comprehensive and holistic approach. Radiomics is the extraction and interpretation of images phenotypes in a quantitative manner. Radiomics may give an advantage through advancements in imaging modalities and through the potential power of artificial intelligence techniques by translating those features into clinical outcome prediction. This article gives an overview on the current evidence of methodology and reviews the available literature on radiomics in PCa patients, highlighting its potential for personalized treatment and future applications

Artificial intelligence and radiomics in evaluation of kidney lesions: a comprehensive literature review

: Radiomics and artificial intelligence (AI) may increase the differentiation of benign from malignant kidney lesions, differentiation of angiomyolipoma (AML) from renal cell carcinoma (RCC), differentiation of oncocytoma from RCC, differentiation of different subtypes of RCC, to predict Fuhrman grade, to predict gene mutation through molecular biomarkers and to predict treatment response in metastatic RCC undergoing immunotherapy. Neural networks analyze imaging data. Statistical, geometrical, textural features derived are giving quantitative data of contour, internal heterogeneity and gray zone features of lesions. A comprehensive literature review was performed, until July 2022. Studies investigating the diagnostic value of radiomics in differentiation of renal lesions, grade prediction, gene alterations, molecular biomarkers and ongoing clinical trials have been analyzed. The application of AI and radiomics could lead to improved sensitivity, specificity, accuracy in detecting and differentiating between renal lesions. Standardization of scanner protocols will improve preoperative differentiation between benign, low-risk cancers and clinically significant renal cancers and holds the premises to enhance the diagnostic ability of imaging tools to characterize renal lesions

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

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

Prospective Validation of Pentraxin-3 as a Novel Serum Biomarker to Predict the Risk of Prostate Cancer in Patients Scheduled for Prostate Biopsy

Purpose: To test and internally validate serum Pentraxin-3 (PTX3) levels as a potential PCa biomarker to predict prostate biopsy (PBx) results. Materials and Methods: Serum PSA and serum PTX3 were prospectively assessed in patients scheduled for PBx at our Institution due to increased serum PSA levels or abnormal digital rectal examination. Uni- and multivariable logistic regression analysis, area under the receiver operating characteristic curve (AUC), and decision curve analysis (DCA), were used to test the accuracy of serum PTX3 in predicting anyPCa and clinically significant PCa (csPCa) defined as Gleason Grade (GG) ≥ 2. Results: Among the 455 eligible patients, PCa was detected in 49% and csPCa in 25%. During univariate analysis, PTX3 outperformed other variables in predicting both anyPCa and csPCa. The addition of PTX3 to multivariable models based on standard clinical variables, significantly increased each model’s predictive accuracy for anyPCa (AUC from 0.73 to 0.82; p &lt; 0.001) and csPCa (AUC from 0.79 to 0.83; p &lt; 0.001). At DCA, PTX3, and PTX3, density showed higher net benefit than PSA and PSA density and increased the net benefit of multivariable models in deciding when to perform PBx. Conclusions: Serum PTX3 levels might be of clinical utility in predicting prostate biopsy results. Should our findings be confirmed, this novel reflex test could be used to reduce the number and burden of unnecessary prostate biopsies

The impact the COVID-19 pandemic on urology literature: a bibliometric analysis

Introduction: The COVID-19 pandemic has caused wide-reaching change to many aspects of life on a worldwide scale. The impact of these changes on peer-reviewed research journals, including those dedicated to urology, is still unknown. Material and methods: The Web of Science database was queried to retrieve all COVID-19 urological articles written in English language and published between January 1st, 2020 and December 10th, 2021. Only original and review articles were considered. A bibliometric analysis of the total number of papers, citations, institutions and publishing journals was performed. Non-COVID-19 publications were also retrieved to compare the duration of publication stages. Results: A total of 428 COVID-19 articles and 14,874 non-COVID-19 articles were collected. Significant differences in the duration of all the publication stages were found between COVID-19 and non-COVID-19 articles (all p <0.001). The most productive countries were the USA (100 articles), Italy (59 articles) and the United Kingdom (55 articles). The published literature has focused on four topics: COVID-19 genitourinary manifestations, management of urological diseases during the pandemic, repercussions on quality of life and impact on healthcare providers. Conclusions: A significant reduction in peer review time for COVID-19 articles might raise concerns regarding the quality of peer review itself. USA, Italy and UK published the highest number of COVID-19 related articles. Restrictive measures taken by governments to reduce the spread of infection had a strong impact on mental stress and anxiety of patients and healthcare professionals. A coerced deferral of diagnosis and treatment of emergencies and uro-oncological cases represented the most challenging task from a clinical standpoint

Oncological outcomes of whole-gland cryoablation in patients with prostate cancer and high risk of lymph node invasion

Purpose: Prostate cryoablation has been proposed as an alternative to radical prostatectomy for men with localized prostate cancer (PCa); however, it is limited by the lack of data regarding oncological outcomes and the impossibility of performing a lymph node dissection. The aim of this study was to assess if whole-gland cryoablation is oncologically safe, especially for patients in whom pelvic lymph node dissection would be necessary. Materials and Methods: After institutional review board approval, we identified 102 patients who underwent whole-gland prostate cryoablation between 2013 and April 2019. Lymph node invasion (LNI) probability was computed using Briganti nomogram, and a 5% cutoff probability was used to stratify the population in two groups. Biochemical recurrence after procedure was assessed using Phoenix criteria. Multiparametric magnetic resonance imaging, (CT), and bone scan or choline positron-emission tomography/CT were performed for the detection of distant metastases. Results: Seventeen (17%) patients were treated for a low-risk PCa, 48 (47%) patients were at intermediate-risk PCa, and 37 (36%) patients were at high-risk PCa. Patients with a probability of LNI &gt; 5% (n = 46) exhibited higher prostate-specific antigen (PSA), PSA density, ISUP Grade Group, CT stage, and european association of urology (EAU) risk. Recurrence-free survival rates at 3 years' follow-up were 93%, 82%, and 72%, respectively for low-, intermediate-, and high-risk patients. At a median follow-up of 37 months (17-62), additional treatment and metastasis-free survival were 84% and 97%, respectively. No differences in oncological outcomes were found in patients with a probability of LNI above and below 5%. Conclusions: Prostate whole-gland cryoablation can be considered a safe procedure with acceptable outcomes in low- and intermediate-risk patients. A high preoperative risk of nodal involvement could not be considered an exclusion criterion to perform cryoablation. Further studies are required