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Background: α1-Adrenergic receptor antagonists are commonly used to treat benign prostatic hyperplasia. Preclinical studies suggest that they induce cell death and inhibit tumor growth. This study evaluated the risk of prostate cancer death in men using α1-adrenergic receptor antagonists., Methods: A population-based cohort study in Stockholm, Sweden (January 1, 2007, to December 31, 2019) included 451 779 men with a prostate-specific antigen test result. Study entry was 1 year after the first prostate-specific antigen test. Men were considered exposed at their second filled prescription. The primary outcome was prostate cancer mortality. Secondary outcomes were all-cause mortality and prostate cancer incidence. Cox proportional hazards regression models were used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for all outcomes. Inverse-probability weighting with marginal structural models accounted for time-dependent confounders., Results: Of 351 297 men in the final cohort, 39 856 (11.3%) were exposed to α1-adrenergic receptor antagonists. Median (interquartile range) follow-up for prostate cancer mortality was 8.9 (5.1-10.9) years; median (interquartile range) exposure time to α1-adrenergic receptor antagonists was 4.4 (2.0-7.6) years. There was no evidence of an association between α1-adrenergic receptor antagonist use and prostate cancer mortality, all-cause mortality, or high-grade prostate cancer. α1-Adrenergic receptor antagonist use was associated with an increased risk of prostate cancer (HR = 1.11, 95% CI = 1.06 to 1.17) and low-grade prostate cancer (HR = 1.22, 95% CI = 1.11 to 1.33). Men whose prostate cancer was treated with α1-adrenergic receptor antagonists underwent more frequent prostate-specific antigen testing., Conclusions: Our findings show no significant association between α1-adrenergic receptor adrenoceptor antagonist exposure and prostate cancer mortality or high-grade prostate cancer. Although the preclinical evidence indicates a potential chemopreventive effect, this study's findings do not support it., (© The Author(s) 2024. Published by Oxford University Press.)

Introduction: After radical cystectomy physical activity is important to reduce risk of complications, but patients with urinary bladder cancer have difficulties in achieving general recommendations on physical activity and exercise. The aim of this randomised controlled trial was therefore to evaluate the effects of a physical exercise programme in primary care, following discharge from hospital after robot-assisted radical cystectomy for urinary bladder cancer., Materials and Methods: Patients with urinary bladder cancer scheduled for robot-assisted radical cystectomy at Karolinska University Hospital, Sweden between September 2019 and October 2022 were invited to join the study. At discharge, they were randomised to intervention or active control group. The intervention group was planned to start exercise with physiotherapist in primary care during the third week; the programme included aerobic and strengthening exercises, twice a week for 12 weeks, and daily walks. The control group received unsupervised home-based exercise with daily walks and a sit-to-stand exercise. Assessments were conducted before surgery, at discharge and after four months regarding the primary outcome physical function (Six-minute walk test), and secondary outcomes physical activity, pain, health-related quality of life, fatigue, and psychological wellbeing., Results: Ninety patients were included, mean (sd) age 71.5 (8.5) years. An intention-to-treat analysis showed no intervention effect on the primary outcome physical function, or on pain or psychological wellbeing, but effect on physical activity with a difference from discharge to four months with a median (IQR) of 4790 (3000) and 2670 (4340) daily steps in the intervention and control group, respectively (p = 0.046), and for fatigue, and health-related quality of life, in favour of the intervention group., Conclusion: Both the intervention and control groups improved physical function, but the patients who exercised in primary care experienced additional positive effects on physical activity, fatigue, and health-related quality of life. Hence, exercise in primary care after discharge from hospital could be a promising method after radical cystectomy for urinary bladder cancer., Trial Registration: The study was registered in Clinical Trials with registration number NCT03998579, 20,190,607., (© 2024. The Author(s).)

Importance: There is evidence that 5α-reductase inhibitors (5-ARIs), a standard treatment of benign prostate hyperplasia, are associated with a decrease in the incidence of prostate cancer (PCa). However, studies to date have had conflicting results regarding the association with prostate cancer mortality (PCM)., Objective: To evaluate the association of treatment with 5-ARIs with PCM in men without a prior diagnosis of PCa., Design, Setting, and Participants: This population-based cohort study was conducted in Stockholm, Sweden, between January 1, 2007, and December 31, 2018, and included 429 977 men with a prostate-specific antigen (PSA) test within the study period. Study entry was set to 1 year after the first PSA test. Data were analyzed from September 2021 to December 2021., Exposures: After their initial PSA test, men with 2 or more newly dispensed prescriptions of 5-ARI, finasteride, or dutasteride were considered 5-ARI users (n = 26 190)., Main Outcomes and Measures: Primary outcome was PCM. Cox proportional hazards regression models were used to calculate multivariable-adjusted hazard ratios (HRs) and 95% CIs for all-cause mortality and PCM., Results: The study cohort included 349 152 men. The median (IQR) age for those with 2 or more filled prescriptions of 5-ARI was 66 (61-73) years and 57 (50-64) years for those without. The median follow-up time was 8.2 (IQR, 4.9-10) years with 2 257 619 person-years for the unexposed group and 124 008 person-years for the exposed group. The median exposure to treatment with 5-ARI was 4.5 (IQR, 2.1-7.4) years. During follow-up, 35 767 men (8.3%) died, with 852 deaths associated with PCa. The adjusted multivariable survival analysis showed a lower risk of PCM in the 5-ARI group with longer exposure times (0.1-2.0 years: adjusted HR, 0.89; 95% CI, 0.64-1.25; >8 years: adjusted HR, 0.44; 95% CI, 0.27-0.74). No statistically significant differences were seen in all-cause mortality between the exposed and unexposed group. Men treated with 5-ARIs underwent more PSA tests and biopsies per year than the unexposed group (median of 0.63 vs 0.33 and 0.22 vs 0.12, respectively)., Conclusions and Relevance: The results of this cohort study suggest that there was no association between treatment with 5-ARI and increased PCM in a large population-based cohort of men without a previous PCa diagnosis. Additionally, a time-dependent association was seen with decreased risk of PCM with longer 5-ARI treatment. Further research is needed to determine whether the differences are because of intrinsic drug effects or PCa testing differences.

Repurposing of existing drugs and vaccines for diseases that they were not originally intended for is a promising research field. Recently there has been evidence that oral cholera vaccine might be used in the treatment of inflammatory disease and some common cancers. Specifically, Ji et al showed that the administration of cholera vaccine after a prostate cancer diagnosis reduced prostate cancer specific mortality rates by almost 50%. In a cohort of men from Stockholm, Sweden, with more detailed cancer data and a higher coverage of exposure to vaccine, we replicated these findings using a marginal structural Cox model. We showed that administration of cholera vaccine after prostate cancer diagnosis is associated with a significant reduction in mortality (HR 0.46, 95% CI 0.31-0.69, p-value 0.0001) even after adjusting for all known confounders. However, the same effect (or even stronger) could be seen for several other traveling vaccines and malaria prophylaxis. Therefore, we conclude that this effect is most likely due to a healthy traveler bias and is an example of residual confounding., Competing Interests: Declaration of Competing Interest Janet Hoogstraate reports a relationship with Valneva Sweden AB that includes: employment. Adrian Spillmann reports a relationship with Valneva Austria GmbH that includes: employment. Klaus Schwamborn reports a relationship with Valneva SE that includes: employment., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Screening for prostate cancer using prostate-specific antigen (PSA) reduces prostate cancer mortality but can lead to adverse outcomes. We aimed to compare a traditional screening approach with a diagnostic strategy of blood-based risk prediction combined with MRI-targeted biopsies., Methods: We did a prospective, population-based, randomised, open-label, non-inferiority trial (STHLM3-MRI) in Stockholm county, Sweden. Men aged 50-74 years were randomly selected by Statistics Sweden and invited by mail to participate in screening; those with an elevated risk of prostate cancer, defined as either a PSA of 3 ng/mL or higher or a Stockholm3 score of 0·11 or higher were eligible for randomisation. Men with a previous prostate cancer diagnosis, who had undergone a prostate biopsy within 60 days before the invitation to participate, with a contraindication for MRI, or with severe illness were excluded. Eligible participants were randomly assigned (2:3) using computer-generated blocks of five, stratified by clinically significant prostate cancer risk, to receive either systematic prostate biopsies (standard group) or biparametric MRI followed by MRI-targeted and systematic biopsy in MRI-positive participants (experimental group). The primary outcome was the detection of clinically significant prostate cancer at prostate biopsy, defined as a Gleason score of 3 + 4 or higher. We used a margin of 0·78 to assess non-inferiority for the primary outcome. Key secondary outcome measures included the proportion of men with clinically insignificant prostate cancer (defined as a Gleason score of 3 + 3), and the number of any prostate MRI and biopsy procedures done. We did two comparisons: Stockholm3 (using scores of 0·11 and 0·15 as cutoffs) versus PSA in the experimental group (paired analyses) and PSA plus standard biopsy versus Stockholm3 plus MRI-targeted and systematic biopsy (unpaired, randomised analyses). All analyses were intention to treat. This study is registered with ClinicalTrials.gov, NCT03377881., Findings: Between Feb 5, 2018, and March 4, 2020, 49 118 men were invited to participate, of whom 12 750 were enrolled and provided blood specimens, and 2293 with elevated risk were randomly assigned to the experimental group (n=1372) or the standard group (n=921). The area under the receiver-operating characteristic curve for detection of clinically significant prostate cancer was 0·76 (95% CI 0·72-0·80) for Stockholm3 and 0·60 (0·54-0·65) for PSA. In the experimental group, a Stockholm3 of 0·11 or higher was non-inferior to a PSA of 3 ng/mL or higher for detection of clinically significant prostate cancer (227 vs 192; relative proportion [RP] 1·18 [95% CI 1·09-1·28], p<0·0001 for non-inferiority), and also detected a similar number of low-grade prostate cancers (50 vs 41; 1·22 [0·96-1·55], p=0·053 for superiority) and was associated with more MRIs and biopsies. Compared with PSA of 3 ng/mL or higher, a Stockholm3 of 0·15 or higher provided identical sensitivity to detect clinically significant cancer, and led to fewer MRI procedures (545 vs 846; 0·64 [0·55-0·82]) and fewer biopsy procedures (311 vs 338; 0·92 (0·86-1·03). Compared with screening using PSA and systematic biopsies, a Stockholm3 of 0·11 or higher combined with MRI-targeted and systematic biopsies was associated with higher detection of clinically significant cancers (227 [3·0%] men tested vs 106 [2·1%] men tested; RP 1·44 [95% CI 1·15-1·81]), lower detection of low-grade cancers (50 [0·7%] vs 73 [1·4%]; 0·46 [0·32-0·66]), and led to fewer biopsy procedures. Patients randomly assigned to the experimental group had a lower incidence of prescription of antibiotics for infection (25 [1·8%] of 1372 vs 41 [4·4%] of 921; p=0·0002) and a lower incidence of admission to hospital (16 [1·2%] vs 31 [3·4%]; p=0·0003) than those in the standard group., Interpretation: The Stockholm3 test can inform risk stratification before MRI and targeted biopsies in prostate cancer screening. Combining the Stockholm3 test with an MRI-targeted biopsy approach for prostate cancer screening decreases overdetection while maintaining the ability to detect clinically significant cancer., Funding: The Swedish Cancer Society, the Swedish Research Council, and Stockholm City Council., Competing Interests: Declaration of interests HG and ME report four pending prostate cancer diagnostic-related patents: method for indicating a presence or non-presence of aggressive prostate cancer (WO2013EP7425920131120); prognostic method for individuals with prostate cancer (WO2013EP7427020131120); method for indicating a presence of prostate cancer in individuals with particular characteritics (WO2018EP5247320180201); and method for indicating the presence or non-presence of prostate cancer (WO2013SE5055420130516).HG reports one additional pending prostate cancer diagnostic-related patent: method for detecting solid tumour cancer (WO2015SE5027220150311). The Karolinska Institutet collaborates with A3P Biomedical in developing the technology for the Stockholm3 test. HG, ME, and TN report owning shares in A3P Biomedical. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Patients who have undergone radical cystectomy for urinary bladder cancer are not sufficiently physically active and therefore may suffer complications leading to readmissions. A physical rehabilitation programme early postoperatively might prevent or at least alleviate these potential complications and improve physical function. The main aim of the CanMoRe trial is to evaluate the impact of a standardised and individually adapted exercise intervention in primary health care to improve physical function (primary outcome) and habitual physical activity, health-related quality of life, fatigue, psychological wellbeing and readmissions due to complications in patients undergoing robotic-assisted radical cystectomy for urinary bladder cancer., Methods: In total, 120 patients will be included and assigned to either intervention or control arm of the study. All patients will receive preoperative information on the importance of early mobilisation and during the hospital stay they will follow a standard protocol for enhanced mobilisation. The intervention group will be given a referral to a physiotherapist in primary health care close to their home. Within the third week after discharge, the intervention group will begin 12 weeks of biweekly exercise. The exercise programme includes aerobic and strengthening exercises. The control group will receive oral and written information about a home-based exercise programme. Physical function will serve as the primary outcome and will be measured using the Six-minute walk test. Secondary outcomes are gait speed, handgrip strength, leg strength, habitual physical activity, health-related quality of life, fatigue, psychological wellbeing and readmissions due to complications. The measurements will be conducted at discharge (i.e. baseline), post-intervention and 1 year after surgery. To evaluate the effects of the intervention mixed or linear regression models according to the intention to treat procedure will be used., Discussion: This proposed randomised controlled trial has the potential to provide new knowledge within rehabilitation after radical cystectomy for urinary bladder cancer. The programme should be easy to apply to other patient groups undergoing abdominal surgery for cancer and has the potential to change the health care chain for these patients., Trial Registration: ClinicalTrials.gov. Clinical trial registration number NCT03998579 . First posted June 26, 2019.

Background: This study investigated prostate cancer (PC)-specific survival and overall survival (OS) in a population-based castration-resistant PC (CRPC) cohort. Methods: Data from Stockholm Prostate-Specific Antigen (PSA) and Biopsy Register patients with increasing PSA despite gonadotropin-releasing hormone treatment or surgical castration ( n  = 1,712) included PSA values and biopsies from 2003 to 2015 and were linked to the National Prostate Cancer Register and Prescribed Drug Register. Kaplan-Meier method estimated PC-specific survival and OS, stratified by metastasis at PC diagnosis, and Cox regression estimated hazard ratios (HRs) for Gleason score and T-stage at PC diagnosis and for age and calendar period at CRPC onset by metastasis status at diagnosis. Results: Median OS after CRPC onset was 23.2 months (95% CI = 21.0-25.9) among patients without metastases (M0) at primary diagnosis, and 13.2 months (11.3-14.5) among patients with metastases (M1). Median PC-specific survival from CRPC onset was 30.3 (27.5-34.1) months and 13.3 (12.1-15.8) months for M0 and M1 patients, respectively. Biopsy Gleason score ≥ 8 was associated with higher all-cause mortality than ≤6 (HR = 2.07 [95% CI = 1.43-3.01]) and PC-specific mortality (2.07 [1.27-3.40]) after CRPC among patients with M0 disease. Patients developing CRPC from 2012 onward had lower all-cause mortality (HR = 0.71 [95% CI = 0.60-0.85] [M0]; 0.60 [0.47-0.77] [M1]) and PC-specific mortality (0.73 [0.57-0.94] [M0]; 0.62 [0.46-0.84] [M1]) compared with those prior to 2012. Conclusions: M1 disease at PC diagnosis was associated with worse survival after CRPC onset versus M0. Higher Gleason score at diagnosis was associated with higher mortality after CRPC onset in M0 patients at diagnosis.

Background: There is conflicting evidence about the association between prostate cancer and Lower Urinary Tract Symptoms (LUTS). We aimed to describe the prevalence of LUTS and its association with prostate cancer risk. Methods: We studied the association between International Prostate Symptom Score (IPSS) and prostate cancer in a population-based sample of men ( n  = 45,595) aged 50-69 years from the Stockholm3 study. Men with PSA ≥3 ng/ml ( n  = 4579) underwent systematic prostate biopsies. We used the International Society of Urological Pathology Gleason Grading (ISUP grade) and performed regression analysis for risk of any cancer ( n  = 1797), ISUP grade ≥2 ( n  = 840) and advanced cancer, defined as ISUP grade ≥3 or cT ≥3 ( n  = 353). Results: 74.6% of all men had no or mild LUTS (IPSS ≤7) and 3.2% had severe LUTS (IPSS >19). Men with any, ISUP grade ≥2 or advanced cancer had lower median IPSS compared to men with benign biopsy (any cancer: 4 (IQR 2-9); ISUP grade ≥2: 4 (2-8); advanced cancer: 4 (2-8); benign biopsy: 6 (3-11); p  < 0.05). IPSS was not associated with increased risk of cancer in multivariate analyses (OR (any cancer) 0.97; 95% CI 0.96-0.98; OR (ISUP grade ≥2) 0.97; 95% CI 0.96-0.99; OR (advanced cancer) 0.99; 95% CI 0.99-1.01). Conclusions: Three-quarters of men aged 50-69 years report no or mild LUTS. Our data do not support any clinically meaningful association between LUTS and prostate cancer. Specifically, men with advanced prostate cancer did not exhibit more urinary symptoms than men without cancer.

Importance: Diabetic men appear to have a lower risk of prostate cancer. Whether antidiabetic medications are protective or potentially mask prostate cancer by lowering prostate-specific antigen (PSA) levels is unclear., Objective: To examine the associations of antidiabetic medication use with (1) PSA levels, (2) frequency of PSA testing, (3) receipt of biopsy following elevated PSA results, and (4) prostate cancer detection at biopsy., Design, Setting, and Participants: Population-based cohort study using data from the Stockholm PSA and Biopsy Register. Participants were all prostate cancer-free men aged 40 to 79 years residing in Stockholm County, Sweden, between January 1, 2006, and December 31, 2015. Data were analyzed from November 2018 to March 2019., Exposures: One or more prescription for metformin, sulfonylurea, or insulin, as recorded in Sweden's National Prescribed Drug Register., Main Outcomes and Measures: Levels of PSA following first exposure to antidiabetic medications were assessed using multivariable linear regression. Frequency of PSA testing was assessed via multivariable Poisson regression. Biopsy following elevated PSA (≥3.0 ng/mL) and prostate cancer detection at biopsy were assessed via multivariable logistic regression., Results: The cohort of 564 666 men (median [range] age, 65 [40-79] years) consisted of 4583 men initially exposed to metformin, 1104 exposed to sulfonylurea, and 978 exposed to insulin who were age matched with unexposed men (1:5). Exposed men had lower median (interquartile range) PSA levels before starting antidiabetic medications compared with unexposed men (1.2 [0.7-2.5] vs 1.6 [0.8-3.2] ng/mL). After accounting for baseline differences, PSA levels did not vary from those of unexposed men following exposure to antidiabetic medications. Frequency of PSA testing was higher for those receiving metformin (rate ratio, 1.07; 95% CI, 1.06-1.09) and sulfonylurea (rate ratio, 1.06; 95% CI, 1.03-1.08) but was lower for those receiving insulin (rate ratio, 0.79; 95% CI, 0.77- 0.81). Likelihood of biopsy after elevated PSA was lower among men receiving metformin (odds ratio, 0.87; 95% CI, 0.80-0.96) and insulin (odds ratio, 0.83; 95% CI, 0.74-0.93). There were no differences in prostate cancer detection at biopsy, regardless of PSA levels that triggered the biopsy., Conclusions and Relevance: This study's findings do not support the hypothesis that the inverse association between diabetes and prostate cancer is mediated through antidiabetic medications lowering PSA levels to mask prostate cancer. They do suggest potential detection bias due to fewer biopsies among men receiving antidiabetic medications, which may explain the lower prostate cancer risk in men with diabetes.

Background: Although prostate-specific antigen (PSA) testing is common, little is known about the pattern of retesting by either PSA values or subsequent prostate biopsies. Poor follow-up of high PSA values may lead to delayed diagnosis., Objective: To estimate the probabilities of follow-up (including retesting, prostate biopsies, diagnosis, and cause-specific death) for men undergoing prostate cancer testing at a population level., Design, Setting, and Participants: Cohort study design for men living in Stockholm with no previous diagnosis of prostate cancer between 2003 and 2015. Men were linked to the national health and population registries in Sweden. We report follow-up for men aged 50-79 yr at 2003 or at their index PSA test., Outcome Measurements and Statistical Analysis: State probabilities with 95% confidence intervals (CIs) were calculated using multistate Markov models., Results and Limitations: Among men not previously diagnosed with prostate cancer with an initial PSA value of ≥10ng/ml, the proportions at 1 yr with no subsequent testing or only elevated PSA test values >3ng/ml were 21.7% (95% CI: 19.5, 23.9), 25.2% (95% CI: 23.9, 26.6), and 47.7% (95% CI: 46.2, 49.1) for those aged 50-59, 60-69, and 70-79 yr, respectively. No significant changes were noticed when stratifying by comorbidities. Limitations include the lack of detail from patient medical charts. This detail would have allowed for more accurate assessment of appropriate clinical follow-up., Conclusions: Regardless of medical history, a large proportion of men with PSA≥10ng/ml were not followed appropriately at 1 yr after the index PSA test. This may partially explain why opportunistic testing is not as effective as screening within trials to reduce prostate cancer mortality., Patient Summary: For men aged 50-69 yr, who undertake a prostate-specific antigen (PSA) test, a PSA level of >10ng/ml should prompt further investigation. However, we found that one out of 10 of these men did not receive repeat testing within 1 yr of the initial test. This may partially explain why opportunistic prostate cancer testing is less effective than screening trials., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Several blood-based tests have been suggested to improve prostate cancer testing. The Stockholm3 test has been shown to reduce the number of prostate biopsies, to decrease detection of low-grade cancer and to maintain the detection rate of ISUP Gleason Group (GG) ≥ 2 cancer in a screening-by-invitation setting. We aimed to validate the performance of the Stockholm3 test in an independent, clinical practice cohort., Methods: The study-population consisted of 533 men in ages 45-75 without previous diagnosis of prostate cancer scheduled for prostate biopsy at any of three centers in Norway and Sweden. Blood samples for Stockholm3 analysis were drawn prior to systematic prostate biopsies. Clinically significant prostate cancer was defined as any finding of ISUP Grade Group (GG) 2 or higher. We calculated area under the curve (AUC) for predicting prostate cancer at biopsy and calculated. Models including PSA and PSA-density (PSA/prostate volume) were compared to a model including also clinical information, protein levels and single nucleotide polymorphisms (SNP)., Results: 263 of 533 (49%) participants were diagnosed with prostate cancer. 162 men had prostate cancer with GG ≥ 2. The Stockholm3 test discriminated better for GG ≥ 2 prostate cancer than PSA in combination with PSA-density AUC 8.9 (95% CI 82.7-89.2) and AUC 74.8 (95% CI 70.3-79.3). Using a Stockholm3 cut-off of 10% risk of GG ≥ 2 cancer, 38% of the biopsy procedures were saved, however delaying diagnosis for 6% (n = 10) of men with GG ≥ 2 cancer. Using PSA-density 0.1 as cut-off for biopsy saved 35% of biopsies, delaying diagnosis for 16% (n = 26) of men with GG ≥ 2 cancer., Conclusion: A prediction model including clinical information, protein levels and SNPs was independently validated in a clinical practice cohort and reduces the number of un-necessary biopsies while delaying diagnosis for a limited number of men.

Background: More specific diagnostic for prostate cancer is needed to decrease overdetection and number of diagnostic procedures., Objective: To assess the performance of combining a blood-based biomarker panel and magnetic resonance imaging (MRI)-targeted biopsies for prostate cancer detection., Design, Setting, and Participants: We used a prospective, multicenter, paired diagnostic study design. A total of 532 men aged 45-74 yr referred for prostate cancer workup were included during 2016-2017., Intervention: Participants underwent blood sampling for analysis of the Stockholm3 test including protein biomarkers, genetic polymorphisms, and clinical variables; 1.5 T MRI; systematic prostate biopsies; and MRI-targeted biopsies to lesions with Prostate Imaging Reporting and Data System version 2 ≥3., Outcome Measurements and Statistical Analysis: The main outcome was numbers of detected prostate cancer characterized by grade group (GG) and the number of performed biopsies using relative sensitivity (RS)., Results and Limitations: Median prostate-specific antigen was 6.3 ng/ml, and mean age was 63.9 yr. Targeted and systematic biopsies detected 170 and 162 GG ≥2 tumors, respectively (RS 1.05; 95% confidence interval [CI] 0.96-1.14). Compared with performing systematic biopsies on all men, performing targeted and systematic biopsies only on men with >10% risk of GG ≥2 cancer, as predicted by the Stockholm3 test, required 62% (95% CI 58-66) of the biopsy procedures and detected 58% (95% CI 48-70) of GG 1 disease, with increased sensitivity for GG ≥2 detection (RS 1.10; 95% CI 1.02-1.17). Performing only targeted biopsies in men with elevated Stockholm3 test altered these results only slightly. Compared with performing systematic and targeted biopsies on all men, performing this only for men with an elevated Stockholm3 test decreased detection of GG ≥2 cancer slightly (RS 0.92; 95% CI 0.88-0.95). Limitations include lacking knowledge of true disease prevalence., Conclusions: These findings provide evidence that strategies combining the blood-based Stockholm3 test and MRI-targeted biopsies can be used to inform biopsy decision making., Patient Summary: In this study, 532 men coming for prostate cancer workup underwent blood sampling, and both traditional and magnetic resonance imaging/fusion-guided prostate biopsies. We report that performing targeted biopsies only in men with an elevated risk as assessed by the Stockholm3 test saved biopsies, decreased overdetection, and maintained the number of detected high-grade cancers., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: It has been shown that the Stockholm-3 model (S3M) outperforms prostate-specific antigen (PSA) as a screening tool for prostate cancer., Objective: To update the S3M, to give a detailed account of the value of each predictor in the S3M, and to evaluate the S3M as a reflex test for men with PSA ≥3ng/ml., Design, Setting, and Participants: During 2012-2015, the Stockholm-3 study evaluated the S3M relative to PSA as tests for Gleason score ≥7 prostate cancers among men aged 50-69 yr. The participants (n=59 159) underwent both tests, and biopsy was recommended if at least one was positive. A total of 5073 men had a biopsy because of elevated PSA (≥3ng/ml)., Outcome Measurements and Statistical Analysis: Logistic regression was used to update the S3M: intact PSA was removed, HOXB13 was included, and the model was fitted to data from the Stockholm-3 training and validation cohorts. To compare S3M with PSA, we fixed the sensitivity for detection of high-grade cancer and evaluated the performance as the number of biopsies needed to achieve that sensitivity for each test., Results and Limitations: The updated S3M slightly improved the area under the receiver operating characteristic curve compared to previously published results (0.75 vs 0.74). When used as a reflex test for men with PSA ≥3ng/ml, S3M reduced the number of biopsies needed by 34% compared to the use of PSA alone, with equal sensitivity. A limitation is the ethnically homogeneous population., Conclusions: A major problem with PSA screening-too many unnecessary biopsies-can be mitigated if S3M is used as a reflex test., Patient Summary: To find aggressive prostate cancer with the minimum number of negative biopsies and detection of clinically insignificant cancers, we evaluated the use of a personalized diagnostic prediction model as a second test for men with a positive prostate-specific antigen (PSA) test. We found that this two-step approach could reduce prostate biopsies by a third compared to using PSA alone., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: The prostate-specific antigen (PSA) test is used to screen for prostate cancer but has a high false-positive rate that translates into unnecessary prostate biopsies and overdiagnosis of low-risk prostate cancers. We aimed to develop and validate a model to identify high-risk prostate cancer (with a Gleason score of at least 7) with better test characteristics than that provided by PSA screening alone., Methods: The Stockholm 3 (STHLM3) study is a prospective, population-based, paired, screen-positive, diagnostic study of men without prostate cancer aged 50 to 69 years randomly invited by date of birth from the Swedish Population Register kept by the Swedish Tax Agency. Men with prostate cancer at enrolment were excluded from the study. The predefined STHLM3 model (a combination of plasma protein biomarkers [PSA, free PSA, intact PSA, hK2, MSMB, MIC1], genetic polymorphisms [232 SNPs], and clinical variables [age, family, history, previous prostate biopsy, prostate exam]), and PSA concentration were both tested in all participants enrolled. The primary aim was to increase the specificity compared with PSA without decreasing the sensitivity to diagnose high-risk prostate cancer. The primary outcomes were number of detected high-risk cancers (sensitivity) and the number of performed prostate biopsies (specificity). The STHLM3 training cohort was used to train the STHLM3 model, which was prospectively tested in the STHLM3 validation cohort. Logistic regression was used to test for associations between biomarkers and clinical variables and prostate cancer with a Gleason score of at least 7. This study is registered with ISCRTN.com, number ISRCTN84445406., Findings: The STHLM3 model performed significantly better than PSA alone for detection of cancers with a Gleason score of at least 7 (P<0.0001), the area under the curve was 0·56 (95% CI: 0·55-0·60) with PSA alone and 0·74 (95% CI: 0·72-0·75) with the STHLM3 model. All variables used in the STHLM3 model were significantly associated with prostate cancers with a Gleason score of at least 7 (P<0·05) in a multiple logistic regression model. At the same level of sensitivity as the PSA test using a cutoff of≥3ng/ml to diagnose high-risk prostate cancer, use of the STHLM3 model could reduce the number of biopsies by 32% (95% CI: 24-39) and could avoid 44% (35-54) of benign biopsies., Interpretation: The STHLM3 model could reduce unnecessary biopsies without compromising the ability to diagnose prostate cancer with a Gleason score of at least 7, and could be a step towards personalised risk-based prostate cancer diagnostic programmes., Funding: Stockholm County Council (Stockholms Läns Landsting)., (Copyright © 2017. Published by Elsevier Inc.)

Background: The prostate-specific antigen (PSA) test is used to screen for prostate cancer but has a high false-positive rate that translates into unnecessary prostate biopsies and overdiagnosis of low-risk prostate cancers. We aimed to develop and validate a model to identify high-risk prostate cancer (with a Gleason score of at least 7) with better test characteristics than that provided by PSA screening alone., Methods: The Stockholm 3 (STHLM3) study is a prospective, population-based, paired, screen-positive, diagnostic study of men without prostate cancer aged 50-69 years randomly invited by date of birth from the Swedish Population Register kept by the Swedish Tax Agency. Men with prostate cancer at enrolment were excluded from the study. The predefined STHLM3 model (a combination of plasma protein biomarkers [PSA, free PSA, intact PSA, hK2, MSMB, MIC1], genetic polymorphisms [232 SNPs], and clinical variables [age, family, history, previous prostate biopsy, prostate exam]), and PSA concentration were both tested in all participants enrolled. The primary aim was to increase the specificity compared with PSA without decreasing the sensitivity to diagnose high-risk prostate cancer. The primary outcomes were number of detected high-risk cancers (sensitivity) and the number of performed prostate biopsies (specificity). The STHLM3 training cohort was used to train the STHLM3 model, which was prospectively tested in the STHLM3 validation cohort. Logistic regression was used to test for associations between biomarkers and clinical variables and prostate cancer with a Gleason score of at least 7. This study is registered with ISCRTN.com, number ISRCTN84445406., Findings: The STHLM3 model performed significantly better than PSA alone for detection of cancers with a Gleason score of at least 7 (p<0·0001), the area under the curve was 0·56 (95% CI 0·55-0·60) with PSA alone and 0·74 (95% CI 0·72-0·75) with the STHLM3 model. All variables used in the STHLM3 model were significantly associated with prostate cancers with a Gleason score of at least 7 (p<0·05) in a multiple logistic regression model. At the same level of sensitivity as the PSA test using a cutoff of ≥3 ng/mL to diagnose high risk prostate cancer, use of the STHLM3 model could reduce the number of biopsies by 32% (95% CI 24-39) and could avoid 44% (35-54) of benign biopsies., Interpretation: The STHLM3 model could reduce unnecessary biopsies without compromising the ability to diagnose prostate cancer with a Gleason score of at least 7, and could be a step towards personalised risk-based prostate cancer diagnostic programmes., Funding: Stockholm County Council (Stockholms Läns Landsting)., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Bloodstream infection following a transrectal prostate biopsy is a well-known and feared complication. Previous studies have shown an increase in multi-resistant bacterial infections as a consequence of higher usage of antibiotics in investigated populations. Our aim was to analyze bacterial resistance patterns in positive blood cultures, after prostate biopsies in Stockholm, Sweden, where the use of antibiotics has been low and decreasing during the last 10 years., Methods: From the three pathology laboratories in Stockholm, reports of prostate examinations were retrieved (n = 56,076) from 2003 to 2012. By linking men to the National Patient Register all but prostate core biopsies were excluded (n = 12,024). Prostate biopsies in men younger than 30 years of age were excluded (n = 5) leaving 44,047 biopsies for analysis. From laboratory information systems data regarding blood cultures were retrieved. Proportions of blood cultures within 30 days by year were calculated. Crude and adjusted logistic regression models were used to estimate ORs., Results: In total, 44,047 prostate biopsies were performed in 32,916 men over 10 years. On 620 occasions a blood culture was drawn within 30 days of the biopsy; 266 of these were positive. The proportions with positive blood cultures in 2003 and 2012 were 0.38 and 1.14%, respectively. The proportion of multidrug-resistant bacteria increased significantly during the study. In the crude and the adjusted analysis, the year of biopsy and Charlson Comorbidity Index were associated with the risk of having a positive blood culture., Conclusion: Multidrug-resistant enteric bacilli are becoming a problem in Sweden, despite low antimicrobial use. Men need to be informed about the increasing risks of infectious complications of transrectal prostate biopsy. One out of 50 men undergoing a prostate biopsy will develop symptoms suggestive of a bloodstream infection after the biopsy and one in 100 men will have a positive blood culture., (© 2015 Wiley Periodicals, Inc.)

Background: A rare but recurrent missense mutation (G84E, rs138213197) in the gene homeobox B13 (HOXB13) was recently reported to be associated with hereditary prostate cancer., Objective: To explore the prevalence and penetrance of HOXB13 G84E in a general population., Design, Setting, and Participants: G84E and 14 additional HOXB13 polymorphisms were genotyped in two population-based, Swedish, case-control samples (Cancer of the Prostate in Sweden [CAPS] and Stockholm-1) comprising 4693 controls and 5003 prostate cancer cases. CAPS collected data on patients and population controls nationally between 2001 and 2003. Stockholm-1 collected data on biopsy-positive patients and biopsy-negative controls in the Stockholm area between 2005 and 2007., Outcome Measurements and Statistical Analysis: The outcome was pathologically verified prostate cancer. Relative and absolute risks among HOXB13 G84E mutation carriers were explored, as was the combined impact on disease risk of G84E and a polygenic score based on 33 established, common, low-risk variants., Results and Limitations: HOXB13 G84E was observed in 1.3% of population controls and was strongly associated with prostate cancer risk (CAPS: odds ratio [OR]: 3.4; 95% confidence interval [CI], 2.2-5.4; Stockholm-1: OR: 3.5; 95% CI, 2.4-5.2). The strongest association was observed for young-onset (OR: 8.6; 95% CI, 5.1-14.0) and hereditary (OR: 6.6; 95% CI, 3.3-12.0) prostate cancer. Haplotype analyses supported that G84E is a founder mutation. G84E carriers have an estimated 33% (95% CI, 23-46) cumulative risk to age 80 yr of prostate cancer, compared to 12% (95% CI, 11-13) among noncarriers. For G84E carriers within the top quartile of a polygenic score of established susceptibility variants, the cumulative risk was estimated at 48% (95% CI, 36-64)., Conclusions: HOXB13 G84E is prevalent in >1% of the Swedish population and is associated with a 3.5-fold increased risk of prostate cancer. One-third of G84E carriers will be diagnosed with prostate cancer, which has implications for surveillance in mutation carriers., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: More than 1 million prostate biopsies are conducted yearly in the United States. The low specificity of prostate-specific antigen (PSA) results in diagnostic biopsies in men without prostate cancer (PCa). Additional information, such as genetic markers, could be used to avoid unnecessary biopsies., Objective: To determine whether single nucleotide polymorphisms (SNPs) associated with PCa can be used to determine whether biopsy of the prostate is necessary., Design, Settings, and Participants: The Stockholm-1 cohort (n = 5241) consisted of men who underwent a prostate biopsy during 2005 to 2007. PSA levels were retrieved from databases and family histories were obtained using a questionnaire. Thirty-five validated SNPs were analysed and converted into a genetic risk score that was implemented in a risk-prediction model., Results and Limitations: When comparing the nongenetic model (based on age, PSA, free-to-total PSA, and family history) with the genetic model and using a fixed number of detected PCa cases, it was found that the genetic model required significantly fewer biopsies than the nongenetic model, with 480 biopsies (22.7%) avoided, at a cost of missing a PCa diagnosis in 3% of patients characterised as having an aggressive disease. However, the overall genetic model does not discriminate between aggressive and nonaggressive cases., Conclusion: Although the genetic model reduced the number of biopsies more than the nongenetic model, the clinical significance of this finding requires further evaluation., (Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Aim: To study the leadership and management skills of first-line managers (FLMs) of elderly care and their work environment in Egypt and Sweden., Background: FLMs in Egypt and Sweden are directly responsible for staff and quality of care. However, FLMs in Sweden, in elderly care, have smaller units/organizations to manage than do their colleagues in Egypt. Furthermore, family care of the elderly has been the norm in Egypt, but in recent years institutional care has increased, whereas in Sweden, residential living homes have existed for a longer period., Methods: A convenience sample of FLMs, 49 from Egypt and 49 from Sweden, answered a questionnaire measuring leadership and management skills, structural and psychological empowerment, job satisfaction and psychosomatic health., Results: In both countries, FLMs' perceptions of their leadership and management skills and psychological empowerment were quite high, whereas scores for job satisfaction and psychosomatic health were lower. FLMs had higher values in several factors/study variables in Egypt compared with in Sweden., Conclusion and Implications: The work environment, both in Egypt and Sweden, needs to be improved to increase FLMs' job satisfaction and decrease stress. The cultural differences and levels of management have an effect on the differences between the two countries., (© 2010 The Authors. Journal compilation © 2010 Blackwell Publishing Ltd.)