Biomarker vs MRI-Enhanced Strategies for Prostate Cancer Screening: The STHLM3-MRI Randomized Clinical Trial.

Importance: Prostate cancer guidelines often recommend obtaining magnetic resonance imaging (MRI) before a biopsy, yet MRI access is limited. To date, no randomized clinical trial has compared the use of novel biomarkers for risk estimation vs MRI-based diagnostic approaches for prostate cancer screening. Objective: To evaluate biomarker-based risk estimation (Stockholm3 risk scores or prostate-specific antigen [PSA] levels) with systematic biopsies vs an MRI-enhanced strategy (PSA levels and MRI with systematic and targeted biopsy) for the detection of clinically significant prostate cancer in a screening setting. Design, Setting, and Participants: This open-label randomized clinical trial conducted in Stockholm, Sweden, between April 4, 2018, and December 10, 2020, recruited men aged 50 to 74 years with no history of prostate cancer. Participants underwent blood sampling for PSA and Stockholm3 tests to estimate their risk of clinically significant prostate cancer (Gleason score ≥3 + 4). After the blood tests were performed, participants were randomly assigned in a 2:3 ratio to receive a Stockholm3 test with systematic biopsy (biomarker group) or a PSA test followed by MRI with systematic and targeted biopsy (MRI-enhanced group). Data were analyzed from September 1 to November 5, 2023. Interventions: In the biomarker group, men with a Stockholm3 risk score of 0.15 or higher underwent systematic biopsies. In the MRI-enhanced group, men with a PSA level of 3 ng/mL or higher had an MRI and those with a Prostate Imaging-Reporting and Data System (PI-RADS) score of 3 or higher (range: 1-5, with higher scores indicating a higher likelihood of clinically significant prostate cancer) underwent targeted and systematic biopsies. Main Outcomes and Measures: Primary outcome was detection of clinically significant prostate cancer (Gleason score ≥3 + 4). Secondary outcomes included detection of clinically insignificant cancer (Gleason score ≤6) and the number of biopsy procedures performed. Results: Of 12 743 male participants (median [IQR] age, 61 [55-67] years), 5134 were assigned to the biomarker group and 7609 to the MRI-enhanced group. In the biomarker group, 8.0% of men (413) had Stockholm3 risk scores of 0.15 or higher and were referred for systematic biopsies. In the MRI-enhanced group, 12.2% of men (929) had a PSA level of 3 ng/mL or higher and were referred for MRI with biopsies if they had a PI-RADS score of 3 or higher. Detection rates of clinically significant prostate cancer were comparable between the 2 groups: 2.3% in the biomarker group and 2.5% in the MRI-enhanced group (relative proportion, 0.92; 95% CI, 0.73-1.15). More biopsies were performed in the biomarker group than in the MRI-enhanced group (326 of 5134 [6.3%] vs 338 of 7609 [4.4%]; relative proportion, 1.43 [95% CI, 1.23-1.66]), and more indolent prostate cancers were detected (61 [1.2%] vs 41 [0.5%]; relative proportion, 2.21 [95% CI, 1.49-3.27]). Conclusions and Relevance: Findings of this randomized clinical trial indicate that combining a Stockholm3 test with systematic biopsies is comparable with MRI-based screening with PSA levels and systematic and targeted biopsies for detection of clinically significant prostate cancer, but this approach resulted in more biopsies as well as detection of a greater number of indolent cancers. In regions where access to MRI is lacking, the Stockholm3 test can aid in selecting patients for systematic prostate biopsy. Trial Registration: ClinicalTrials.gov Identifier: NCT03377881.

Biparametric Quantitative MRI for Prostate Cancer Detection.

OBJECTIVES: This study sought to prospectively investigate a novel quantitative biparametric prostate magnetic resonance imaging (MRI) protocol to detect prostate cancer (PCa) in biopsy-naïve men. Secondarily, this study reports the accuracy of fractional order calculus (FROC) diffusion and quantitative T2 compared with the Prostate Imaging Reporting & Data System (PI-RADS). METHODS: This prospective pilot study (NCT04175730) enrolled 50 prostate biopsy-naïve men who met eligibility criteria. All men received 3T MRI with T2 and diffusion-weighted imaging (DWI) (b-values: 50-4,000 s/mm2). Men with PI-RADS lesions ≥3 underwent targeted and systematic prostate biopsy, omitting systematic biopsy cores in peripheral zone lesions. DWI series images were fit to signal decay to calculate ADC (mm2/s) and the FROC model for coefficient DF (mm2/s). The primary end point was detection of Gleason grade group ≥2 (GG≥2) PCa. Receiver operating characteristic regression and area under the curve (AUC) were reported. RESULTS: Forty-eight men underwent MRI and biopsy. Mean age was 61.5 years (56-68), 29% were White, 52% were African American, mean PSA was 6.0 ng/mL (4.9-8.0), and mean PSA density was 0.14 ng/mL2. In total, 61 PI-RADS ≥3 lesions were targeted for biopsy. GG≥2 PC was found in 7% (1/14) of PI-RADS 3 lesions, 28% (10/36) of PI-RADS 4 lesions, and 36% (4/11) of PI-RADS 5 lesions. The AUC for detection of GG≥2 PC was 0.63 (0.5-0.76) for PI-RADS, 0.82 (0.68-0.96) for ADC, and 0.87 (0.77-0.97) for the FROC model. CONCLUSION: This small prospective pilot study demonstrates the feasibility of a novel quantitative biparametic MRI protocol to detect prostate cancer in biopsy-naïve men.

Perioperative outcomes in male patients undergoing cystectomy, radical colorectal procedure or total pelvic exenteration.

Background: Total pelvic exenteration (TPE) in men is a surgical procedure to treat genitourinary and colorectal malignancies. Despite improvement in multimodal strategies and technology, mortality is still high and literature is limited about perioperative outcomes comparison to other radical procedures. Methods: We analyzed National Surgical Quality Improvement Program (NSQIP) baseline database of all male patients undergoing cystectomy, low anterior resection/abdominoperineal resection (LAR/APR) or TPE from January 1, 2005 to December 31, 2016. Postoperative complications within 30 days after surgery were measured including: Wound infection, septic complications, deep vein thrombosis, cardiovascular events, and return to the operating room or mortality, etc. Differences between groups were analyzed using analysis of variance (ANOVA) tests. Results: A total of 7,375 patients underwent radical cystectomy, 49,762 underwent LAR/APR and 792 underwent TPE. Cystectomy patients were on average older compared to TPE or LAR/APR patients (P<0.001). In univariable and multivariable analysis, patients undergoing TPE had greater infectious and septic complications compared to cystectomy (odds ratio =1.09; 95% confidence interval (CI): 1.06-1.12) and LAR/APR (odds ratio =1.08; 95% CI: 1.05-1.11). Moreover, TPE had a slightly higher mortality within the 30-day postoperatively than those who underwent LAR/APR (odds ratio =1.01; 95% CI: 1.00-1.02) and cystectomy (odds ratio =1.01; 95% CI: 1.00-1.01). Conclusions: Men undergoing TPE had greater rates of infections and postoperative complications compared to those undergoing radical cystectomy and LAR/APR. From a clinical standpoint, TPE has high morbidity that could provide opportunity for quality improvement projects with the goal of mitigating high complication rates.

Human reaching control in dynamic environments.

Closed-loop models of movement control have attracted growing interest in how the nervous system transforms sensory information into motor commands, and several brain structures have been identified as neural substrates for these computational operations. Recently, several studies have focused on how these models need to be updated when environmental parameters change. Current evidence suggests that when the task changes, rapid control updates enable flexible modifications of current actions and online decisions. At the same time, when movement dynamics change, humans use different strategies based on a combination of adaptation and modulation of controller sensitivity to exogenous perturbations (robust control). This review proposes a unified framework to capture these results based on online estimation of model parameters with dynamic updates in control. The reviewed studies also identify the time scales of associated behavioral mechanisms to guide future research on the neural basis of movement control.

External Validation of the Rotterdam Prostate Cancer Risk Calculator and Comparison with Stockholm3 for Prostate Cancer Diagnosis in a Swedish Population-based Screening Cohort.

BACKGROUND: The Rotterdam Prostate Cancer Risk Calculator (RPCRC) and Stockholm3 can be used to aid urologists in their decision to refer men to magnetic resonance imaging (MRI) or biopsy for early detection of prostate cancer. OBJECTIVE: To assess the external validity of the RPCRC and compare it with using PSA and Stockholm3 to detect clinically significant prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: Using data from the prospective, population-based, randomised STHLM3-MRI screening trial, we included participants with prostate-specific antigen (PSA) ≥3 ng/ml or Stockholm3 risk threshold ≥11% in the standard group who underwent systematic prostate biopsies. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Probabilities for clinically significant prostate cancer (csPC, International Society of Urological Pathology grade ≥2) were calculated for each participant using the RPCRC and Stockholm3 with and without prostate volume. Performance of the risk calculators was assessed by discrimination, calibration, and clinical benefits. RESULTS AND LIMITATIONS: In total, 666 men with a median age of 67 yr (interquartile range [IQR]: 61-71) and PSA of 3.4 ng/ml (2.5-5.0) were included, of whom 154 (23%) had csPC. Risk distribution of the RPCRC was narrow: median risks of 2% (IQR 1-4%) compared with 14% (IQR: 9.5-23%) for Stockholm3. Using RPCRC's recommended risk threshold of ≥4% for finding csPC, 54% of all csPC cases would be detected versus 94% using Stockholm3 with a threshold of ≥11%. Calibration of Stockholm3 was adequate while RPCRC underestimated the risk of csPC. The Stockholm3 test showed positive net benefits at clinically relevant thresholds, while the RPCRC showed negative net benefits. Compared with PSA, the RPCRC was associated with lower detection of csPC (84 vs 103; 0.82 [0.71-0.93]), while Stockholm3 was associated with higher detection of csPC (143 vs 103; 1.40 [1.23-1.57]). The main limitation was that Stockholm3 was evaluated in a similar population to where it was developed. CONCLUSIONS: The performance of the RPCRC in a Swedish population-based cohort is suboptimal with a considerable underestimation of prostate cancer risk, while the Stockholm3 test showed superior performance and a positive clinical benefit. PATIENT SUMMARY: The use of the Rotterdam Prostate Cancer Risk Calculator available online to predict the risk of prostate cancer in a Swedish cohort was found to be clinically harmful as it underpredicted the risk of clinically significant prostate cancer, while the Stockholm3 test performed well showing clinical benefits.

Cardiovascular, bone, and metabolic health in men with castrate-resistant prostate cancer treated with androgen deprivation: a matched cohort study.

BACKGROUND: Descriptive data on late effects associated with castrate-resistant prostate cancer (CRPC) are sparse. We aimed to define the timing and incidence of cardiovascular disease (CVD), fractures, and diabetes in a patient population with CRPC. METHODS: In the population-based STHLM0 cohort 1464 men with CRPC were identified and matched with three men free from prostate cancer (PC) in the Stockholm region of Sweden. Kaplan-Meier estimates of net survival were used to describe time to CVD, fracture, and diabetes. Cox regression was used to compare incidence rates (IRRs) for the respective late effects. Cumulative incidence analyses of late effects in the presence of the competing risk of death were performed to estimate absolute risks. RESULTS: The Kaplan Meier estimates demonstrated a higher net probability for CVD, fracture, and diabetes among men diagnosed with CRPC compared to the matched comparators. The IRRs were 1.94 (95% CI: 1.79-2.12) for CVD, 2.08 (95% CI: 1.70-2.53) for fracture, and 2.00 (95% CI: 1.31-3.05) for diabetes, respectively, comparing men diagnosed with CRPC to men free from PC. The cumulative incidence of CVD at 12 months of follow-up was higher in men diagnosed with CRPC compared to healthy controls regardless of age with a difference in cumulative incidence being 0.20 for men aged <65 and 0.11 for men aged >84. CONCLUSIONS: In this cohort, the incidence of CVD was significantly higher among men with CRPC compared to healthy controls. Despite having this end-stage disease this finding proves that clinicians must recognize this late effect in men diagnosed with CRPC to improve preventive actions. These men did not have a higher absolute risk of fractures and diabetes after accounting for deaths due to any cause compared to healthy controls.

Progression on active surveillance for prostate cancer in Black men: a systematic review and meta-analysis.

BACKGROUND: Several studies evaluated prostate cancer (PCa) outcomes in Black men on active surveillance (AS); most studies contained few Black men and results were conflicting. We performed a systematic review and meta-analyze of race and outcomes on AS. METHODS: A systematic search was performed for articles of men with Grade Group 1 or 2 (GG1 or GG2) PCa on AS. All studies required race-specific comparative progression data. Progression to treatment, PSA, or biopsy progression were considered and relative risk (RR) estimates of Black men progressing were extracted and pooled using random-effects models. Differences by study-level characteristics were evaluated using subgroup and a cumulative meta-analysis by time. RESULTS: In total, 12 studies were included (3137 Black and 12,206 non-Black men); eight prospective (27%, n = 4210) and four retrospectives (73%, n = 11,133) cohorts. The overall RR of progression for Black men was 1.62 (95%CI, 1.21-2.17), I2 = 64% (95% CI, 32-80%), (χ2 = 30.23; P = 0.001; τ2 = 0.16). Black men with GG1 PCa alone had a higher pooled progression: RR = 1.81 (95% CI, 1.23-2.68). Including only studies with clinical progression (excluding progression to treatment), potentiated results: RR = 1.82 (95%CI, 1.27-2.60). However, a cumulative meta-analysis demonstrated decreasing pooled effect over time, with contemporary studies after 2019 showing a tempered effect (RR: 1.29, 95% CI: 1.20-1.39). CONCLUSIONS: Many studies attribute racial disparity in PCa to delayed presentation of disease, however, AS is unique since all AS eligible men have a low grade and stage PCa. Our findings suggest Black men may have an increased risk of progression during AS, but the association is not so strong that Black men should be discouraged from undergoing AS. Indeed, contemporary evidence suggests stricter inclusion, better confirmatory testing or better access to care may temper these findings. Importantly, these results utilize self-reported race, a social construct that has many limitations.

Radical prostatectomy technique in the robotic evolution: from da Vinci standard to single port-a single surgeon pathway.

To describe perioperative outcomes following robot-assisted prostatectomy performed by a single surgeon during transitions between da Vinci standard/Si/Xi and the single port. Perioperative data were retrospectively evaluated of the first 40 consecutive robot-assisted radical prostatectomies performed by a single surgeon using the da Vinci standard, Si, Xi and single port. A total of 160 patients were included. We matched standard vs Si (Match 1), Si vs Xi (Match 2) and Xi vs single port (Match 3) cohort. Mann-Whitney and Fisher's tests were used to test the difference among the groups. Univariate and multivariate logistic regression analyses were adopted to evaluate the predictors of overall and major complications. Single-port procedures in Match 3 showed significant shorter median operative time than Xi. Both Si and single-port groups showed significantly less median blood loss, a shorter median length of stay, respectively, than standard group in Match 1 and than Xi group in Match 3. 1 standard group patient required conversion to open surgery for an unsolvable conflict of the robotic arms. No other intraoperative complications were noted. On univariate and multivariate analyses, the da Vinci platform model was not a predicting factor of major complications (Clavien-Dindo ≥ 3). We described how technological progress impacted peri and postoperative outcomes during transitions between robotic surgical platforms for radical prostatectomy. In particular, the technological improvements associated to the increased surgeon's expertise made the transition to the single port safe and effective when compared with previous platforms.

Single-Port robot assisted partial nephrectomy: initial experience and technique with the da Vinci Single-Port platform (IDEAL Phase 1).

BACKGROUND: The aim of this paper was to evaluate the safety and feasibility of robotic-assisted laparoscopic partial nephrectomy (RAPN) performed using the da Vinci Single-Port (SP) platform. METHODS: A retrospective review was conducted from December 2018 to December 2019 of 14 consecutive patients with localized renal cancer who underwent SP robot-assisted partial nephrectomy at a single institution. The procedures were performed by 2 experienced robotic surgeons, reproducing the steps of the standard multiport robotic approach to partial nephrectomy. A transperitoneal approach was utilized with a 2.5 cm para-rectus incision with one assistant 12 mm laparoscopic port. RESULTS: No conversions to open or laparoscopic surgery occurred and no additional laparoscopic assistant ports were required. The median total operative time was 202 (162-231) minutes and the median total room time was 258 (215-295) minutes. The warm ischemia time averaged 20±8 minutes. 2 patients required angioembolization due to postoperative acute bleeding (Clavien-Dindo Grade 3a complication). Trifecta outcome (<25 min warm ischemia, no perioperative complications and negative margins) was achieved in 79% of patients. In one case, a positive margin was present. The median length of stay was of 1 day (Interquartile Range 1-2) with a median pain score on post-operative day 1 of 3.5 (Interquartile Range 2.4-5); 1/14 (7%) patient needed narcotic use at one week from discharge. At a median follow up of 5.0 (4.0-8.0) months, no patients have had evidence of disease recurrence. CONCLUSIONS: In this initial cohort, considering the introduction of a new technology, we observed satisfactory outcomes for several key perioperative variables including operative time, warm ischemia time, surgical margins, hospital stay, pain requirements in patients undergoing RAPN with the SP platform. For experienced robotic surgeons, RAPN with the SP platform is a safe and feasible approach for single site partial nephrectomy.

A study of risk factors and complications in elderly hypertensive subjects.

BACKGROUND: Hypertension among the elderly is a major, highly prevalent yet treatable cardiovascular disease. AIMS & OBJECTIVES: Study aims to highlight the risk factors for hypertension in the elderly in an urban setup for the benefit of improving quality of life and also reduce the incidence of the cardiovascular related complications. METHODOLOGY: This is a Cross-sectional observational study. Included 125 study subjects based on selection criteria. The selected patients were subjected to a preformed and pretested schedule of questions pertaining to the risk factors. RESULTS: Among the known hypertensive patients above 60 years of age, 125 subjects were included in the study. Smoking (62%), alcohol consumption (21%), family history of hypertension (26%), family history of diabetes (70%) were statistically significant risk factors observed for the development of hypertension. CONCLUSION: Sedentary lifestyle (physically less active) and anthropometric measures like overweight and obesity, abnormal waist circumference, and abnormal waist hip ratio were all identified as remarkable risk for hypertension. Myocardial infarction (20%), stroke (14%), and heart failure (12%) were the chart buster complications of hypertension in the vulnerable geriatric population.

Real world treatment utilization patterns in patients with castration-resistant prostate cancer.

BACKGROUND: Studies describing treatment utilization for castration-resistant prostate cancer (CRPC) are limited. We aimed to describe the treatment utilization of a contemporary population-based CRPC cohort between 2006 and 2016. METHODS: We identified 1699 men with a PC diagnosis between 2005 and 2015, who developed CRPC between 2006 and 2015 in the Stockholm region of Sweden. Demographic information, stage and grade at PC diagnosis, stage at CRPC, prostate-specific antigen (PSA) nadir, PSA doubling time, treatment utilization rate within 1 year of CRPC diagnosis, reason for stopping therapy, treatment sequence trajectory, overall and PC specific survival was described. RESULTS: Treatment for men with de novo metastatic disease (n = 463) was 32%, treatment for men with progressive metastatic disease after PC diagnosis (n = 66) was 44%, treatment for men with nonmetastatic CRPC (n = 113) was 34% and treatment for those with an unknown stage at time of CRPC diagnosis (n = 857) was 12%. Docetaxel was used in 39%, abiraterone acetate plus prednisone in 15%, enzalutamide in 13%, cabazitaxel in 11% and radium-223 in 5% of treatments. Treatment increased from 22% in 2006-2009 for metastatic cancer to 50% in 2013-2015 (p < .001). Factors associated with treatment were an unknown stage at diagnosis (OR: 0.3, 95% CI: 0.2-0.4), age ≥75 years (OR: 0.2, 95% CI: 0.1 - 0.3), PSA doubling time >3 months (OR: 0.4, 95% CI: 0.3 - 0.6) and a diagnosis between 2013 and 2015 (OR: 3.4, 95% CI: 2.0 - 5.8). CONCLUSIONS: Despite treatment availability, in this large real-world cohort we found treatment utilization to remain low.

Association between environmental quality and prostate cancer stage at diagnosis.

BACKGROUND: Prostate cancer (PC) etiology is up to 57% heritable, with the remainder attributed to environmental exposures. There are limited studies regarding national level environmental exposures and PC aggressiveness, which was the focus of this study METHODS: SEER was queried to identify PC cases between 2010 and 2014. The environmental quality index (EQI) is a county-level metric for 2000-2005 combining data from 18 sources and reports an overall ambient environmental quality index, as well as 5 environmental quality sub-domains (air, water, land, built, and sociodemographic) with higher values representing lower environmental quality. PC stage at diagnosis was determined and, multivariable logistic regression models which adjusted for age at diagnosis (years) and self-reported race (White, Black, Other, Unknown) were used to test associations between quintiles of EQI scores and advanced PC stage at diagnosis. RESULTS: The study cohort included 252,164 PC cases, of which 92% were localized and 8% metastatic at diagnosis. In the adjusted regression models, overall environmental quality EQI (OR 1.20, CI 1.15-1.26), water EQI (OR: 1.34, CI: 1.27-1.40), land EQI (OR: 1.35, CI: 1.29-1.42) and sociodemographic EQI (OR: 1.29, CI: 1.23-1.35) were associated with metastatic PC at diagnosis. For these domains there was a dose response increase in the OR from the lowest to the highest quintiles of EQI. Black race was found to be an independent predictor of metastatic PC at diagnosis (OR: 1.36, CI: 1.30-1.42) and in stratified analysis by race; overall EQI was more strongly associated with metastatic PC in Black men (OR: 1.53, CI: 1.35-1.72) compared to White men (OR: 1.18, CI: 1.12-1.24). CONCLUSION(S): Lower environmental quality was associated with advanced stage PC at diagnosis. The water, land and sociodemographic domains showed the strongest associations. More work should be done to elucidate specific modifiable environmental factors associated with aggressive PC.

Erythroderma (exfoliative dermatitis). Part 2: energy homeostasis and dietetic management strategies.

Erythroderma (exfoliative dermatitis) is associated with important metabolic changes that include an enhancement in energy expenditure. The key components to total energy expenditure (TEE) include basal metabolic rate (~68% of TEE), physical activity (~22% of TEE) and thermic effect of food (~10% of TEE). In the erythrodermic state, there are likely multiple contributors to the increase in basal metabolic rate, such as 'caloric drain' resulting from increased evaporation of water from enhanced transepidermal water loss, increased activity of the cardiovascular system (including high-output cardiac failure), increased nonshivering thermogenesis and hormonal changes such as hypercortisolaemia. A change in the patient's level of physical activity and appetite as a result of ill health status may further impact on their TEE and energy consumption. In Part 2 of this two-part concise review, we explore the key constituents of energy homeostasis and the potential mechanisms influencing energy homeostasis in erythroderma, and suggest much-needed dietetic management strategies for this important condition.

Erythroderma (exfoliative dermatitis). Part 1: underlying causes, clinical presentation and pathogenesis.

Erythroderma (exfoliative dermatitis), first described by Von Hebra in 1868, manifests as a cutaneous inflammatory state, with associated skin barrier and metabolic dysfunctions. The annual incidence of erythroderma is estimated to be 1-2 per 100 000 population in Europe with a male preponderance. Erythroderma may present at birth, or may develop acutely or insidiously (due to progression of an underlying primary pathology, including malignancy). Although there is a broad range of diseases that associate with erythroderma, the vast majority of cases result from pre-existing and chronic dermatoses. In the first part of this two-part concise review, we explore the underlying causes, clinical presentation, pathogenesis and investigation of erythroderma, and suggest potential treatment targets for erythroderma with unknown causes.

Incorporating Magnetic Resonance Imaging and Biomarkers in Active Surveillance Protocols - Results From the Prospective Stockholm3 Active Surveillance Trial (STHLM3AS).

BACKGROUND: Active surveillance (AS) for men with low-risk prostate cancer (PC) can lead to patient morbidity and healthcare overutilization. The aim of this study was to evaluate an AS protocol using the Stockholm3 test and magnetic resonance imaging (MRI) to reduce biopsy intensity. METHODS: We conducted a prospective multicenter study of 280 invited men from a contemporary screening study (STHLM3), with Gleason Score (GS) 3 + 3 PC on a current AS protocol. Patients underwent prostate-MRI and blood sampling for analysis of the Stockholm3 test including protein biomarkers, genetic variants, and clinical variables to predict risk of GS ≥3 + 4 PC followed by systematic biopsies and targeted biopsies (for Prostate Imaging Reporting and Data System version 2 ≥3 lesions) in all men. Primary outcomes were reclassification to GS ≥3 + 4 PC and clinically significant PC (csPCa), including unfavorable intermediate risk PC or higher based on National Comprehensive Cancer Network guidelines. RESULTS: Adding MRI-targeted biopsies to systematic biopsies increased sensitivity of GS ≥3 + 4 PC compared with systematic biopsies alone (relative sensitivity [RS] = 1.52, 95% confidence interval [CI] = 1.28 to 1.85). Performing biopsies in only MRI positive increased sensitivity of GS ≥3 + 4 PC (RS = 1.30, 95% CI = 1.04 to 1.67) and reduced number of biopsy procedures by 49.3% while missing 7.2% GS ≥3 + 4 PC and 1.4% csPCa. Excluding men with negative Stockholm3 test reduced the number of MRI investigations at follow-up by 22.5% and biopsies by 56.8% while missing 6.9% GS ≥3 + 4 PC and 1.3% csPCa. CONCLUSION: Including MRI and targeted/systematic biopsies in the follow-up for men on AS increased sensitivity of PC reclassification. Incorporation of risk prediction models including biomarkers may reduce the need for MRI use in men with low-risk PC.

Biomarker discrimination and calibration with MRI-targeted biopsies: an analysis with the Stockholm3 test.

BACKGROUND: The validated Stockholm3 test is used to improve PC detection. Stockholm3, however, was developed using systematic biopsies. We aimed to assess Stockholm3 operating performance when using MRI-targeted biopsies for PC detection. METHODS: A prospective cohort of 532 men was considered for prostate biopsy during 2016-2017. All men underwent Stockholm3 testing and MRI before biopsy. All PIRADs ≥3 lesion underwent targeted biopsy; all men underwent systematic biopsy. The primary outcome was ISUP Grade Group ≥2 (GG ≥ 2) PC. Detection strategies included: (1) systematic biopsies alone, (2) targeted biopsies alone, (3) targeted with associated systematic biopsies for MRI+, and (4) all biopsies in all men. For each strategy, the Stockholm3 operating characteristics were assessed with discrimination, calibration, and decision curve analysis (DCA). RESULTS: Median age was 65 years, median PSA was 6.2 ng/mL, median Stockholm3 score was 16.5%, and overall detection of GG ≥ 2 PC was 36% (193/532). Stockholm3 showed accurate discrimination for separating GG ≥ 2 cancer from benign and GG1, with an area under the curve of 0.84-0.86 depending on the biopsy strategy. Calibration analysis showed that Stockholm3 underestimated risks for GG ≥ 2 PC risk using MRI-targeted biopsies: there was a net benefit over biopsies in all men for Stockholm3 at risk thresholds varying from >3% in systematic biopsies to >15% in targeted with systematic biopsies in MRI+ men. When using a Stockholm3 score of >10% cutoff, a range of 32-38% of biopsies could be avoided while missing 5-11% of GG ≥ 2 PC and 0-3% of GG ≥ 3 PC. CONCLUSIONS: Stockholm3 shows high discriminatory performance in an MRI-targeted biopsy setting, however risks are underpredicted due to MRI-targeted biopsies being more sensitive than the systematic biopsies for which Stockholm3 was developed. Stockholm3, along with any risk prediction model developed for systematic prostate biopsy decisions, will need recalibration for optimal use in an MRI-driven biopsy setting.

Ethnic variation in prostate cancer detection: a feasibility study for use of the Stockholm3 test in a multiethnic U.S. cohort.

BACKGROUND: The Stockholm3 test improves Gleason Grade Group ≥2 (GG ≥ 2) prostate cancer (PC) detection, however it has not been evaluated in an American cohort where clinical practice patterns and ethnicity differ. We aimed to identify subgroups within a Stockholm population with PC risk profiles matching American ethnicity-specific subgroups and compare the detection of PC and describe Stockholm3 performance within these subgroups. METHODS: All men age 49-70 years presenting for prostate biopsies were evaluated at UIC from 2016 to 2019, as well as men in Stockholm from 2012 to 2014 in the STHLM3 study. Propensity scores (PS) were estimated for each person using logistic regression for age, PSA, prostate volume, family history of PC, 5-alpha reductase inhibitor use, and prior biopsy. 3:1 PS matching was performed for Stockholm to Chicago ethnicity-specific cohorts and odds ratios (OR) were computed to compare detection of GG ≥ 2 PC between groups. RESULTS: 504 Chicago men and 6980 Stockholm men were included. In African American (AA) men, 51% had GG ≥ 2 PC detected, while in risk-matched Stockholm men, 34% had GG ≥ 2 PC detected (OR: 2.1, p < 0.001). There was no statistical difference in GG ≥ 2 PC detected when matching Stockholm men to non-Hispanic Caucasian men (31% vs. 24%, OR: 0.7, p = 0.30) or Hispanic Caucasian men (31% vs. 27%, OR: 1.2, p = 0.42). The AUC for the Stockholm3 test of the matched Stockholm cohorts for AA, non-Hispanic Caucasian, and Hispanic Caucasian men was 0.85, 0.89, and 0.90, respectively. CONCLUSIONS: Using statistical techniques to simulate a multi-ethnic Chicago cohort within the STHLM3 population, we found an excess risk of GG ≥ 2 PC among AA men. Our hypothesis that the Stockholm3 may have good predictive value in a multiethnic cohort is strengthened, and that recalibration to at least AA men seems likely to be needed to obtain well-calibrated predictions.

Morbidity and Mortality of Total Pelvic Exenteration for Malignancy in the US.

BACKGROUND: Total pelvic exenterations (TPEs) for malignancies are complex operations often performed by multidisciplinary teams. The differences among primary cancer for TPE and multicentered results are not well described. We aimed to describe TPE outcomes for different malignant origins in a national multicentered sample. METHODS: Patients from the National Surgical Quality Improvement Program (NSQIP) database who underwent TPE between 2005 and 2016 for all malignant indications (colorectal, gynecologic, urologic, or other) were included. Chi square and Kruskal-Wallis tests were used to compare patient characteristics by primary malignancy. Multivariate logistic and linear regression models were used to determine factors associated with any 30-day Clavien-Dindo grade 3 or higher complication, length of hospital stay (LOS; days), 30-day wound infection, and 30-day mortality. RESULTS: Overall, 2305 patients underwent TPE. Indications for surgery included 33% (749) colorectal, 15% (335) gynecologic, 9% (196) other, and 45% (1025) urologic malignancies. Median LOS decreased from 10 to 8 days during the study period (p < 0.001), 36% were males, and 50% required blood transfusion. High-grade complications occurred in 15% of patients and were associated with bowel diversion [odds ratio (OR) 1.6, 95% confidence interval (CI) 1.1-2.4], disseminated cancer (OR 1.8, 95% CI 1.4-2.3), and gynecologic cancers (OR 2.9, 95% CI 1.8-4.7). Mortality was 2% and was associated with disseminated cancer (OR 2.2, 95% CI 1.1-4.3) and male sex (OR 2.4, 95% CI 1.3-4.4). CONCLUSIONS: TPE is associated with high rates of complications, however mortality rates remain low. Preoperative and perioperative outcomes differ depending on the origin of the primary malignancy.

Factors contributing to healthcare professional burnout during the COVID-19 pandemic: A rapid turnaround global survey.

BACKGROUND: Healthcare professionals (HCPs) on the front lines against COVID-19 may face increased workload and stress. Understanding HCPs' risk for burnout is critical to supporting HCPs and maintaining the quality of healthcare during the pandemic. METHODS: To assess exposure, perceptions, workload, and possible burnout of HCPs during the COVID-19 pandemic we conducted a cross-sectional survey. The main outcomes and measures were HCPs' self-assessment of burnout, indicated by a single item measure of emotional exhaustion, and other experiences and attitudes associated with working during the COVID-19 pandemic. FINDINGS: A total of 2,707 HCPs from 60 countries participated in this study. Fifty-one percent of HCPs reported burnout. Burnout was associated with work impacting household activities (RR = 1·57, 95% CI = 1·39-1·78, P<0·001), feeling pushed beyond training (RR = 1·32, 95% CI = 1·20-1·47, P<0·001), exposure to COVID-19 patients (RR = 1·18, 95% CI = 1·05-1·32, P = 0·005), and making life prioritizing decisions (RR = 1·16, 95% CI = 1·02-1·31, P = 0·03). Adequate personal protective equipment (PPE) was protective against burnout (RR = 0·88, 95% CI = 0·79-0·97, P = 0·01). Burnout was higher in high-income countries (HICs) compared to low- and middle-income countries (LMICs) (RR = 1·18; 95% CI = 1·02-1·36, P = 0·018). INTERPRETATION: Burnout is present at higher than previously reported rates among HCPs working during the COVID-19 pandemic and is related to high workload, job stress, and time pressure, and limited organizational support. Current and future burnout among HCPs could be mitigated by actions from healthcare institutions and other governmental and non-governmental stakeholders aimed at potentially modifiable factors, including providing additional training, organizational support, and support for family, PPE, and mental health resources.

Factors Contributing to Healthcare Professional Burnout During the COVID-19 Pandemic: A Rapid Turnaround Global Survey.

BACKGROUND: Healthcare professionals (HCPs) on the front lines against COVID-19 may face increased workload, and stress. Understanding HCPs risk for burnout is critical to supporting HCPs and maintaining the quality of healthcare during the pandemic. METHODS: To assess exposure, perceptions, workload, and possible burnout of HCPs during the COVID-19 pandemic we conducted a cross-sectional survey. The main outcomes and measures were HCPs self-assessment of burnout and other experiences and attitudes associated with working during the COVID-19 pandemic. FINDINGS: A total of 2,707 HCPs from 60 countries participated in this study. Fifty-one percent of HCPs reported burnout. Burnout was associated with work impacting household activities (RR=1.57, 95% CI=1.39-1.78, P<0.001), feeling pushed beyond training (RR=1.32, 95% CI=1.20-1.47, P<0.001), exposure to COVID-19 patients (RR=1.18, 95% CI=1.05-1.32, P=0.005), making life prioritizing decisions (RR=1.16, 95% CI=1.02-1.31, P=0.03). Adequate personal protective equipment (PPE) was protective against burnout (RR=0.88, 95% CI=0.79-0.97, P=0.01). Burnout was higher in high-income countries (HICs) compared to low- and middle-income countries (LMICs) (RR=1.18; 95% CI=1.02-1.36, P=0.018). INTERPRETATION: Burnout is prevalent at higher than previously reported rates among HCPs working during the COVID-19 pandemic and is related to high workload, job stress, and time pressure, and limited organizational support. Current and future burnout among HCPs could be mitigated by actions from healthcare institutions and other governmental and non-governmental stakeholders aimed at potentially modifiable factors, including providing additional training, organizational support, support for family, PPE, and mental health resources. FUNDING: N/A.