The Mount Sinai Prebiopsy Risk Calculator for Predicting any Prostate Cancer and Clinically Significant Prostate Cancer: Development of a Risk Predictive Tool and Validation with Advanced Neural Networking, Prostate Magnetic Resonance Imaging Outcome Database, and European Randomized Study of Screening for Prostate Cancer Risk Calculator

Background: The European Association of Urology guidelines recommend the use of imaging, biomarkers, and risk calculators in men at risk of prostate cancer. Risk predictive calculators that combine multiparametric magnetic resonance imaging with prebiopsy variables aid as an individualized decision-making tool for patients at risk of prostate cancer, and advanced neural networking increases reliability of these tools.Objective: To develop a comprehensive risk predictive online web-based tool using magnetic resonance imaging (MRI) and clinical data, to predict the risk of any prostate cancer (PCa) and clinically significant PCa (csPCa) applicable to biopsy-naive men, men with a prior negative biopsy, men with prior positive low-grade cancer, and men with negative MRI.Design, setting, and participants: Institutional review board-approved prospective data of 1902 men undergoing biopsy from October 2013 to September 2021 at Mount Sinai were collected.Outcome measurements and statistical analysis: Univariable and multivariable analyses were used to evaluate clinical variables such as age, race, digital rectal examination, family history, prostate-specific antigen (PSA), biopsy status, Prostate Imaging Reporting and Data System score, and prostate volume, which emerged as predictors for any PCa and csPCa. Binary logistic regression was performed to study the probability. Validation was performed with advanced neural networking (ANN), multi-institutional European cohort (Prostate MRI Outcome Database [PROMOD]), and European Randomized Study of Screening for Prostate Cancer Risk Calculator (ERSPC RC) 3/4.Results and limitations: Overall, 2363 biopsies had complete clinical information, with 57.98% any cancer and 31.40% csPCa. The prediction model was significantly associated with both any PCa and csPCa having an area under the curve (AUC) of 81.9% including clinical data. The AUC for external validation was calculated in PROMOD, ERSPC RC, and ANN for any PCa (0.82 vs 0.70 vs 0.90) and csPCa (0.82 vs 0.78 vs 0.92), respectively. This study is limited by its retrospective design and over-estimation of csPCa in the PROMOD cohort.Conclusions: The Mount Sinai Prebiopsy Risk Calculator combines PSA, imaging and clinical data to predict the risk of any PCa and csPCa for all patient settings. With accurate validation results in a large European cohort, ERSPC RC, and ANN, it exhibits its efficiency and applicability in a more generalized population. This calculator is available online in the form of a free web-based tool that can aid clinicians in better patients counseling and treatment decision-making.Patient summary: We developed the Mount Sinai Prebiopsy Risk Calculator (MSP-RC) to assess the likelihood of any prostate cancer and clinically significant disease based on a combination of clinical and imaging characteristics. MSP-RC is applicable to all patient settings and accessible online. Crown Copyright (C) 2022 Published by Elsevier B.V. on behalf of European Association of Urology.</p

External evaluation of a novel prostate cancer risk calculator (ProstateCheck) based on data of the Swiss arm of the ERSPC

PURPOSE: To externally validate a novel prostate cancer (PCa) risk-calculator (RC), based on data of the Swiss arm of the European Randomize Study of Screening for Prostate Cancer (ERSPC), and to assess whether the RC (ProstateCheck) is superior to the PCPT RC and SWOP RC in an independent Swiss cohort. MATERIALS AND METHODS: Data of all men who underwent prostate biopsy in an academic tertiary care center between 2004 and 2012 were retrospectively analyzed. The probability of having any PCa or high-grade PCa (Gleason score ≥7) upon prostate biopsy was calculated using the ProstateCheck-RC. The RC's performance was assessed using calibration and discrimination and additionally compared with the PCPT- and SWOP-RC by decision curve analyses. RESULTS: Of 1615 men, 401 (25%) were diagnosed with any PCa and 196 (12%) with high-grade PCa. Our analyses of the ProstateCheck-RC revealed good calibration in the low risk range (0 to 0.4) and moderate overestimation in the higher risk range (0.4 to 1) for any and high-grade PCa. The AUC for the discrimination of any PCa and high-grade PCa was 0.69 and 0.72, respectively, which was slightly but significantly higher compared to the PCPT-RC (0.66 and 0.69, respectively) and SWOP-RC (0.64 and 0.70, respectively). Decision analysis taking into account the harms of transrectal ultrasound measurements of prostate volume, found little benefit for ProstateCheck-RC, with inferior properties to the PCPT- and SWOP-RC. CONCLUSION: Our independent external evaluation revealed moderate performance of the ProstateCheck-RC. Its clinical benefit is limited and inferior to the PCPT- and SWOP-RC

Exosomes as A Next-Generation Diagnostic and Therapeutic Tool in Prostate Cancer

Extracellular vesicles (EVs) have brought great momentum to the non-invasive liquid biopsy procedure for the detection, characterization, and monitoring of cancer. Despite the common use of PSA (prostate-specific antigen) as a biomarker for prostate cancer, there is an unmet need for a more specific diagnostic tool to detect tumor progression and recurrence. Exosomes, which are EVs that are released from all cells, play a large role in physiology and pathology, including cancer. They are involved in intercellular communication, immune function, and they are present in every bodily fluid studied—making them an excellent window into how cells are operating. With liquid biopsy, EVs can be isolated and analyzed, enabling an insight into a potential therapeutic value, serving as a vehicle for drugs or nucleic acids that have anti-neoplastic effects. The current application of advanced technology also points to higher-sensitivity detection methods that are minimally invasive. In this review, we discuss the current understanding of the significance of exosomes in prostate cancer and the potential diagnostic value of these EVs in disease progression

A Decision Aide for the Risk Stratification of GU Cancer Patients at Risk of SARS-CoV-2 Infection, COVID-19 Related Hospitalization, Intubation, and Mortality

Treatment decisions for both early and advanced genitourinary (GU) malignancies take into account the risk of dying from the malignancy as well as the risk of death due to other causes such as other co-morbidities. COVID-19 is a new additional and immediate risk to a patient&rsquo;s morbidity and mortality and there is a need for an accurate assessment as to the potential impact on of this syndrome on GU cancer patients. The aim of this work was to develop a risk tool to identify GU cancer patients at risk of diagnosis, hospitalization, intubation, and mortality from COVID-19. A retrospective case showed a series of GU cancer patients screened for COVID-19 across the Mount Sinai Health System (MSHS). Four hundred eighty-four had a GU malignancy and 149 tested positive for SARS-CoV-2. Demographic and clinical variables of &gt;38,000 patients were available in the institutional database and were utilized to develop decision aides to predict a positive SARS-CoV-2 test, as well as COVID-19-related hospitalization, intubation, and death. A risk tool was developed using a combination of machine learning methods and utilized BMI, temperature, heart rate, respiratory rate, blood pressure, and oxygen saturation. The risk tool for predicting a diagnosis of SARS-CoV-2 had an AUC of 0.83, predicting hospitalization for management of COVID-19 had an AUC of 0.95, predicting patients requiring intubation had an AUC of 0.97, and for predicting COVID-19-related death, the risk tool had an AUC of 0.79. The models had an acceptable calibration and provided a superior net benefit over other common strategies across the entire range of threshold probabilities

Social Determinants Contribute to Disparities in Test Positivity, Morbidity and Mortality: Data from a Multi-Ethnic Cohort of 1094 GU Cancer Patients Undergoing Assessment for COVID-19

Background: The COVID-19 pandemic exploits existing inequalities in the social determinants of health (SDOH) that influence disease burden and access to healthcare. The role of health behaviours and socioeconomic status in genitourinary (GU) malignancy has also been highlighted. Our aim was to evaluate predictors of patient-level and neighbourhood-level factors contributing to disparities in COVID-19 outcomes in GU cancer patients. Methods: Demographic information and co-morbidities for patients screened for COVID-19 across the Mount Sinai Health System (MSHS) up to 10 June 2020 were included. Descriptive analyses and ensemble feature selection were performed to describe the relationships between these predictors and the outcomes of positive SARS-CoV-2 RT-PCR test, COVID-19-related hospitalisation, intubation and death. Results: Out of 47,379 tested individuals, 1094 had a history of GU cancer diagnosis; of these, 192 tested positive for SARS-CoV-2. Ensemble feature selection identified social determinants including zip code, race/ethnicity, age, smoking status and English as the preferred first language&mdash;being the majority of significant predictors for each of this study&rsquo;s four COVID-19-related outcomes: a positive test, hospitalisation, intubation and death. Patient and neighbourhood level SDOH including zip code/ NYC borough, age, race/ethnicity, smoking status, and English as preferred language are amongst the most significant predictors of these clinically relevant outcomes for COVID-19 patients. Conclusion: Our results highlight the importance of these SDOH and the need to integrate SDOH in patient electronic medical records (EMR) with the goal to identify at-risk groups. This study&rsquo;s results have implications for COVID-19 research priorities, public health goals, and policy implementations

A risk calculator to inform the need for a prostate biopsy: a rapid access clinic cohort

Background: Prostate cancer (PCa) represents a significant healthcare problem. The critical clinical question is the need for a biopsy. Accurate risk stratification of patients before a biopsy can allow for individualised risk stratification thus improving clinical decision making. This study aims to build a risk calculator to inform the need for a prostate biopsy. Methods: Using the clinical information of 4801 patients an Irish Prostate Cancer Risk Calculator (IPRC) for diagnosis of PCa and high grade (Gleason ≥7) was created using a binary regression model including age, digital rectal examination, family history of PCa, negative prior biopsy and Prostate-specific antigen (PSA) level as risk factors. The discrimination ability of the risk calculator is internally validated using cross validation to reduce overfitting, and its performance compared with PSA and the American risk calculator (PCPT), Prostate Biopsy Collaborative Group (PBCG) and European risk calculator (ERSPC) using various performance outcome summaries. In a subgroup of 2970 patients, prostate volume was included. Separate risk calculators including the prostate volume (IPRCv) for the diagnosis of PCa (and high-grade PCa) was created. Results: IPRC area under the curve (AUC) for the prediction of PCa and high-grade PCa was 0.6741 (95% CI, 0.6591 to 0.6890) and 0.7214 (95% CI, 0.7018 to 0.7409) respectively. This significantly outperforms the predictive ability of cancer detection for PSA (0.5948), PCPT (0.6304), PBCG (0.6528) and ERSPC (0.6502) risk calculators; and also, for detecting high-grade cancer for PSA (0.6623) and PCPT (0.6804) but there was no significant improvement for PBCG (0.7185) and ERSPC (0.7140). The inclusion of prostate volume into the risk calculator significantly improved the AUC for cancer detection (AUC = 0.7298; 95% CI, 0.7119 to 0.7478), but not for high-grade cancer (AUC = 0.7256; 95% CI, 0.7017 to 0.7495). The risk calculator also demonstrated an increased net benefit on decision curve analysis. Conclusion: The risk calculator developed has advantages over prior risk stratification of prostate cancer patients before the biopsy. It will reduce the number of men requiring a biopsy and their exposure to its side effects. The interactive tools developed are beneficial to translate the risk calculator into practice and allows for clarity in the clinical recommendations

Social Determinants Contribute to Disparities in Test Positivity, Morbidity and Mortality: Data from a Multi-Ethnic Cohort of 1094 GU Cancer Patients Undergoing Assessment for COVID-19

Background: The COVID-19 pandemic exploits existing inequalities in the social determinants of health (SDOH) that influence disease burden and access to healthcare. The role of health behaviours and socioeconomic status in genitourinary (GU) malignancy has also been highlighted. Our aim was to evaluate predictors of patient-level and neighbourhood-level factors contributing to disparities in COVID-19 outcomes in GU cancer patients. Methods: Demographic information and co-morbidities for patients screened for COVID-19 across the Mount Sinai Health System (MSHS) up to 10 June 2020 were included. Descriptive analyses and ensemble feature selection were performed to describe the relationships between these predictors and the outcomes of positive SARS-CoV-2 RT-PCR test, COVID-19-related hospitalisation, intubation and death. Results: Out of 47,379 tested individuals, 1094 had a history of GU cancer diagnosis; of these, 192 tested positive for SARS-CoV-2. Ensemble feature selection identified social determinants including zip code, race/ethnicity, age, smoking status and English as the preferred first language—being the majority of significant predictors for each of this study’s four COVID-19-related outcomes: a positive test, hospitalisation, intubation and death. Patient and neighbourhood level SDOH including zip code/ NYC borough, age, race/ethnicity, smoking status, and English as preferred language are amongst the most significant predictors of these clinically relevant outcomes for COVID-19 patients. Conclusion: Our results highlight the importance of these SDOH and the need to integrate SDOH in patient electronic medical records (EMR) with the goal to identify at-risk groups. This study’s results have implications for COVID-19 research priorities, public health goals, and policy implementations

Small Molecule, Multimodal, [F-18]-PET and Fluorescence Imaging Agent Targeting Prostate-Specific Membrane Antigen: First-in-Human Study

A number of radioactive tracers are currently being actively examined to image prostate-specific membrane antigen positive (PSMA+) tumors, especially in primary and recurrent prostate cancer. We report a first-in-human study of [18F]-BF3-Cy3-ACUPA by determining its safety, biodistribution, radiation dosimetry, and feasibility of tumor detection by preoperative positron emission tomography, as well as intraoperative fluorescence imaging, in patients with PSMA+ tumors

A Novel Risk Calculator Incorporating Clinical Parameters, Multiparametric Magnetic Resonance Imaging, and Prostate-Specific Membrane Antigen Positron Emission Tomography for Prostate Cancer Risk Stratification Before Transperineal Prostate Biopsy

Background: Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) can detect multiparametric magnetic resonance imaging (mpMRI)-invisible prostate tumours and improve the sensitivity of detection of prostate cancer (PCa) in comparison to mpMRI alone. Numerous risk calculators have been validated as tools for stratification of men at risk of being diagnosed with clinically significant (cs)PCa. Objective: To develop a novel risk calculator using clinical parameters and imaging parameters from mpMRI and PSMA PET/CT in a cohort of patients undergoing mpMRI and PSMA PET/CT before biopsy. Design, setting, and participants: A total of 291 men from the PRIMARY prospective trial underwent mpMRI and PSMA PET/CT before transperineal prostate biopsy with sampling of systematic and targeted cores. Outcome measurements and statistical analysis: Novel risk calculators were developed using multivariable logistic regression analysis to predict detection of overall PCa (International Society of Urological Pathology grade group [GG] ≥1) and csPCa (GG ≥2). The risk calculators were then compared with the European Randomised Study of Screening for Prostate Cancer risk calculator incorporating mpMRI (ERSPC-MRI). Resampling methods were used to evaluate the discrimination and calibration of the risk calculators and to perform decision curve analysis. Results and limitations: Age, prostate-specific antigen, prostate volume, and mpMRI Prostate Imaging-Reporting and Data System scores were included in the MRI risk calculator, resulting in area under the receiver operating characteristic curve (AUC) values of 0.791 for overall PCa (GG ≥1) and 0.812 for csPCa (GG ≥2). Addition of the maximum standardised uptake value (SUVmax) on PSMA PET/CT for the prostate lesion, and of SUVmax for the mpMRI lesions for the MRI-PSMA risk calculator resulted in AUCs of 0.831 for overall PCa and 0.876 for csPCa (≥ISUP2).The ERSPC-MRI risk calculator had AUCs of 0.758 (p = 0.02) for overall PCa and 0.805 (p = 0.001) for csPCa. Both the MRI and MRI-PSMA risk calculators were superior to the ERSPC-MRI for both overall PCa and csPCa. Conclusions: These novel risk calculators incorporate clinical and radiological parameters for stratification of men at risk of csPCa. The risk calculator including PSMA PET/CT data is superior to a calculator incorporating mpMRI data alone. Patient summary: We evaluated a new risk calculator that uses clinical information and results from two types of scan to predict the risk of clinically significant prostate cancer on prostate biopsy. This risk model can guide patients and clinicians in shared decision-making and may help in avoiding unnecessary prostate biopsies