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BACKGROUND: High rates of overdiagnosis are a critical barrier to organized prostate cancer screening. Magnetic resonance imaging (MRI) with targeted biopsy has shown the potential to address this challenge, but the implications of its use in the context of organized prostate cancer screening are unknown. METHODS: We conducted a population-based noninferiority trial of prostate cancer screening in which men 50 to 74 years of age from the general population were invited by mail to participate; participants with prostate-specific antigen (PSA) levels of 3 ng per milliliter or higher were randomly assigned, in a 2:3 ratio, to undergo a standard biopsy (standard biopsy group) or to undergo MRI, with targeted and standard biopsy if the MRI results suggested prostate cancer (experimental biopsy group). The primary outcome was the proportion of men in the intention-to-treat population in whom clinically significant cancer (Gleason score ≥7) was diagnosed. A key secondary outcome was the detection of clinically insignificant cancers (Gleason score 6). RESULTS: Of 12,750 men enrolled, 1532 had PSA levels of 3 ng per milliliter or higher and were randomly assigned to undergo biopsy: 603 were assigned to the standard biopsy group and 929 to the experimental biopsy group. In the intention-to-treat analysis, clinically significant cancer was diagnosed in 192 men (21%) in the experimental biopsy group, as compared with 106 men (18%) in the standard biopsy group (difference, 3 percentage points; 95% confidence interval [CI], -1 to 7; P<0.001 for noninferiority). The percentage of clinically insignificant cancers was lower in the experimental biopsy group than in the standard biopsy group (4% [41 participants] vs. 12% [73 participants]; difference, -8 percentage points; 95% CI, -11 to -5). CONCLUSIONS: MRI with targeted and standard biopsy in men with MRI results suggestive of prostate cancer was noninferior to standard biopsy for detecting clinically significant prostate cancer in a population-based screening-by-invitation trial and resulted in less detection of clinically insignificant cancer. (Funded by the Swedish Research Council and others; STHLM3-MRI ClinicalTrials.gov number, NCT03377881.).
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Biópsia/métodos , Imageamento por Ressonância Magnética , Próstata/patologia , Neoplasias da Próstata/patologia , Idoso , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Próstata/diagnóstico por imagem , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico por imagemRESUMO
BACKGROUND: Risk assessment for ischemic stroke (IS) and myocardial infarction (MI) is done routinely before surgery, but the increase in risks associated with surgery is not known. The aim of this study is to assess the risk of arterial ischemic events during the first year after oncological surgery. METHODS: We used Swedish healthcare databases to identify 443,300 patients who underwent cancer surgery between 1987 and 2016 and 4,127,761 matched comparison subjects. We estimated odds ratios (ORs) for myocardial infarction and ischemic stroke during the hospitalization with logistic regression and calculated 1-year cumulative incidences and hazard ratios (HRs) with 95% confidence intervals (CIs) for the outcomes after discharge. RESULTS: The cumulative incidences of myocardial infarction and ischemic stroke during the first postoperative year were 1.33% and 1.25%, respectively. In the comparison cohort, the corresponding 1-year cumulative incidences were 1.04% and 1.00%. During the hospitalization, the OR for myocardial infarction was 8.81 (95% CI 8.24-9.42) and the OR for ischemic stroke was 6.71 (95% CI 6.22-7.23). After discharge, the average HR during follow-up for 365 days was 0.90 (95% CI 0.87-0.93) for myocardial infarction and 1.02 (95% CI 0.99-1.05) for ischemic stroke. CONCLUSIONS: We found an overall increased risk of IS and MI during the first year after cancer surgery that was attributable to events occurring during the hospitalization period. After discharge from the hospital, the overall risk of myocardial infarction was lower among the cancer surgery patients than among matched comparison subjects.
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Isquemia Encefálica , AVC Isquêmico , Infarto do Miocárdio , Neoplasias , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/epidemiologia , Isquemia Encefálica/epidemiologia , AVC Isquêmico/complicações , Fatores de Risco , Infarto do Miocárdio/complicações , Infarto do Miocárdio/epidemiologia , Isquemia/complicações , Neoplasias/complicaçõesRESUMO
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.
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Cistectomia , Terapia por Exercício , Atenção Primária à Saúde , Qualidade de Vida , Procedimentos Cirúrgicos Robóticos , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/reabilitação , Cistectomia/métodos , Cistectomia/reabilitação , Cistectomia/efeitos adversos , Feminino , Masculino , Idoso , Terapia por Exercício/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Pessoa de Meia-Idade , Suécia , Exercício Físico , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the cause-specific mortality in the postoperative period after radical prostatectomy (RP) for prostate cancer (PCa). METHODS: In the National Prostate Cancer Register of Sweden (NPCR), we identified all men who died within 90 days after RP performed 1998-2018 and we assessed cause of death in a chart review. We compared the adjudications of death from our medical record review with those in in the Swedish Cause of Death Registry (CDR). RESULTS: Out of 44 635, 58 (0.13%) men who had undergone RP from 1998 through 2018 died within 90 days after RP. Per medical record review the most common causes of death were cardiac disease (30%) and venous thromboembolic events (VTE; 21%). No men died of metastatic PCa as was first indicated in the CDR. After robot-assisted RP (RARP) or open retropubic RP (RRP), the postoperative mortality was 0.09% (19/21 520) and 0.19% (37/19 635), respectively. The effect off modality was confounded mainly by year of surgery, age at surgery, Charlson Comorbidity Index score and the concomitant pelvic lymph node dissection. CONCLUSION: The validated absolute 90-day mortality after RP was 1.3/1000 during the 21-year study period. Cardiovascular diseases were the most common causes of death after RP. Our validation of the CDR refuted the occurrence of postoperative deaths from metastatic PCa. There were differences in rates and type of mortality between RRP and RARP, but the RARP cohort was more recent than the RRP cohort, which likely explain the differences.
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Prostatectomia , Neoplasias da Próstata , Causas de Morte , Estudos de Coortes , Humanos , Excisão de Linfonodo , Masculino , Neoplasias da Próstata/patologia , Resultado do TratamentoRESUMO
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.
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Doenças Cardiovasculares , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Antagonistas de Androgênios/efeitos adversos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/epidemiologia , Estudos de Coortes , Androgênios , Progressão da Doença , Doenças Cardiovasculares/epidemiologiaRESUMO
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.
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Detecção Precoce de Câncer/métodos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Idoso , Biomarcadores Tumorais/sangue , Humanos , Biópsia Guiada por Imagem , Análise de Intenção de Tratamento , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Prospectivos , Próstata/diagnóstico por imagem , Próstata/patologia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Curva ROC , Distribuição Aleatória , Medição de Risco , Suécia/epidemiologiaRESUMO
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.
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Cistectomia/reabilitação , Terapia por Exercício/métodos , Complicações Pós-Operatórias/epidemiologia , Procedimentos Cirúrgicos Robóticos/reabilitação , Neoplasias da Bexiga Urinária/cirurgia , Adolescente , Adulto , Idoso , Criança , Cistectomia/efeitos adversos , Cistectomia/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Readmissão do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Suécia , Resultado do Tratamento , Bexiga Urinária/patologia , Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/complicações , Adulto JovemRESUMO
BACKGROUND: Patient-related factors such as concern about cancer are believed to influence both men's decisions to undergo prostate specific antigen (PSA) testing and to have definitive treatment if diagnosed with low risk prostate cancer (PCa). The potential link between screening frequency and choice of active surveillance (AS) for low risk disease has not been studied previously. Our aim was to investigate whether there is any association between PCa screening frequency or previous negative prostate biopsy and uptake of AS among men with low risk PCa. METHODS: This register-based study included all men ≤75 years from Stockholm who were diagnosed with low risk PCa from 2008 to 2014 (n = 4336). Pre-diagnostic PSA testing and biopsy histories were obtained from the Stockholm PSA and Biopsy Register, a population-based register for the Stockholm country. The association between previous screening/biopsy history and AS uptake (based on primary treatment recorded in the National Prostate Cancer Register) was examined using multivariable logistic regression. RESULTS: Forty seven percent of men with low risk PCa underwent AS. Uptake was associated with older age, very low risk disease, more recent diagnosis and absence of family history. None of the screening/biopsy measures (testing frequency, mean interval, PSA velocity, highest pre-diagnostic PSA or prior negative biopsy) were associated with uptake of AS among men with low risk PCa. Generalisability to settings with different policies and practices may be limited. CONCLUSION: We found no evidence that screening frequency and negative biopsy influence uptake of AS among Swedish men with low risk PCa. Further research is required to determine factors that still present barriers for men taking up AS.
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Detecção Precoce de Câncer/estatística & dados numéricos , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Conduta Expectante/estatística & dados numéricos , Idoso , Biópsia , Estudos de Coortes , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/patologia , Medição de RiscoRESUMO
This corrects the article DOI: 10.1038/bjc.2017.231.
RESUMO
Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain â¼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same region.
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Mapeamento Cromossômico/métodos , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/genética , População Branca/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Desequilíbrio de Ligação , MasculinoRESUMO
BACKGROUND: Evidence on height and prostate cancer risk is mixed, however, recent studies with large data sets support a possible role for its association with the risk of aggressive prostate cancer. METHODS: We analysed data from the PRACTICAL consortium consisting of 6207 prostate cancer cases and 6016 controls and a subset of high grade cases (2480 cases). We explored height, polymorphisms in genes related to growth processes as main effects and their possible interactions. RESULTS: The results suggest that height is associated with high-grade prostate cancer risk. Men with height >180 cm are at a 22% increased risk as compared to men with height <173 cm (OR 1.22, 95% CI 1.01-1.48). Genetic variants in the growth pathway gene showed an association with prostate cancer risk. The aggregate scores of the selected variants identified a significantly increased risk of overall prostate cancer and high-grade prostate cancer by 13% and 15%, respectively, in the highest score group as compared to lowest score group. CONCLUSIONS: There was no evidence of gene-environment interaction between height and the selected candidate SNPs.Our findings suggest a role of height in high-grade prostate cancer. The effect of genetic variants in the genes related to growth is seen in all cases and high-grade prostate cancer. There is no interaction between these two exposures.
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Estatura/genética , Neoplasias da Próstata/genética , Idoso , Estudos de Casos e Controles , Interação Gene-Ambiente , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/patologia , Medição de RiscoRESUMO
The HOXB13 gene has been implicated in prostate cancer (PrCa) susceptibility. We performed a high resolution fine-mapping analysis to comprehensively evaluate the association between common genetic variation across the HOXB genetic locus at 17q21 and PrCa risk. This involved genotyping 700 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of 3195 SNPs in 20,440 PrCa cases and 21,469 controls in The PRACTICAL consortium. We identified a cluster of highly correlated common variants situated within or closely upstream of HOXB13 that were significantly associated with PrCa risk, described by rs117576373 (OR 1.30, Pâ=â2.62×10(-14)). Additional genotyping, conditional regression and haplotype analyses indicated that the newly identified common variants tag a rare, partially correlated coding variant in the HOXB13 gene (G84E, rs138213197), which has been identified recently as a moderate penetrance PrCa susceptibility allele. The potential for GWAS associations detected through common SNPs to be driven by rare causal variants with higher relative risks has long been proposed; however, to our knowledge this is the first experimental evidence for this phenomenon of synthetic association contributing to cancer susceptibility.
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Predisposição Genética para Doença , Variação Genética , Proteínas de Homeodomínio/genética , Neoplasias da Próstata/genética , Alelos , Cromossomos Humanos Par 17/genética , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/patologia , Fatores de RiscoRESUMO
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).
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Biomarcadores Tumorais , Detecção Precoce de Câncer/métodos , Neoplasias da Próstata/diagnóstico , Idoso , Área Sob a Curva , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Biópsia , Técnicas de Apoio para a Decisão , Seguimentos , Fator 15 de Diferenciação de Crescimento/sangue , Humanos , Calicreínas/sangue , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Polimorfismo de Nucleotídeo Único , Valor Preditivo dos Testes , Estudos Prospectivos , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/genética , Proteínas Secretadas pela Próstata/sangue , Curva ROC , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Suécia , Calicreínas Teciduais/sangueRESUMO
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.
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Bacteriemia/epidemiologia , Biópsia/estatística & dados numéricos , Próstata/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/etiologia , Biópsia/efeitos adversos , Estudos de Coortes , Farmacorresistência Bacteriana Múltipla , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/microbiologia , Estudos Retrospectivos , Suécia/epidemiologiaRESUMO
BACKGROUND: Polygenic risk scores comprising established susceptibility variants have shown to be informative classifiers for several complex diseases including prostate cancer. For prostate cancer it is unknown if inclusion of genetic markers that have so far not been associated with prostate cancer risk at a genome-wide significant level will improve disease prediction. METHODS: We built polygenic risk scores in a large training set comprising over 25,000 individuals. Initially 65 established prostate cancer susceptibility variants were selected. After LD pruning additional variants were prioritized based on their association with prostate cancer. Six-fold cross validation was performed to assess genetic risk scores and optimize the number of additional variants to be included. The final model was evaluated in an independent study population including 1,370 cases and 1,239 controls. RESULTS: The polygenic risk score with 65 established susceptibility variants provided an area under the curve (AUC) of 0.67. Adding an additional 68 novel variants significantly increased the AUC to 0.68 (P = 0.0012) and the net reclassification index with 0.21 (P = 8.5E-08). All novel variants were located in genomic regions established as associated with prostate cancer risk. CONCLUSIONS: Inclusion of additional genetic variants from established prostate cancer susceptibility regions improves disease prediction.
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Marcadores Genéticos , Predisposição Genética para Doença , Neoplasias da Próstata/genética , Variação Genética , Humanos , Desequilíbrio de Ligação , Masculino , Fatores de RiscoRESUMO
BACKGROUND: Complications after radical cystectomy for urinary bladder cancer are common. Physical activity after surgery is thought to reduce complications. However, patients with urinary bladder cancer have low levels of physical activity, and interventions supporting physical exercise are needed. This study aimed to evaluate the feasibility of a physical exercise intervention in primary health care. One of the aims of the larger clinical trial will be to reduce complications. METHODS: Patients with urinary bladder cancer and who were scheduled for a robotic-assisted radical cystectomy were recruited from Karolinska University Hospital, between February and May 2019. The patients had to be mobile, understand Swedish, and live in Stockholm. The exercise programme was conducted at one primary health care setting over 12 weeks. The exercise programme included supervised aerobic and strengthening exercises, which were performed twice a week, as well as daily walks. Feasibility was measured with process feasibility, including eligibility criteria, adherence, and acceptability, and scientific feasibility, including the ability of outcomes to indicate change, safety, and progression in the exercise programme. RESULTS: Ten patients with a median age of 70 years (min 53-max 86) were included. Adherence to all parts of the intervention was not feasible because of patients' postoperative complications, resulting in dropouts. For the patients who took part in the exercise programme, adherence and acceptability for the exercise period were feasible, but the 6-min walk test was not feasible at discharge from the hospital. Physiotherapists in the primary health care setting perceived the process as feasible. Moreover, the ability of outcomes to indicate change and progression in the exercise programme was feasible, meanwhile no adverse events were registered. CONCLUSIONS: The exercise intervention was feasible for the patients that took part in the exercise programme, with respect to safety and progression through the exercise programme. Furthermore, this study suggests that some improvements needed to be implemented in the process, prior to the upcoming randomised controlled trial.
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Importance: The risks and benefits of thromboprophylaxis therapy after cancer surgery are debated. Studies that determine thrombosis risk after cancer surgery with high accuracy are needed. Objectives: To evaluate 1-year risk of venous thromboembolic events after major cancer surgery and how these events vary over time. Design, Setting, and Participants: This register-based retrospective observational matched cohort study included data on the full population of Sweden between 1998 and 2016. All patients who underwent major surgery for cancer of the bladder, breast, colon or rectum, gynecologic organs, kidney and upper urothelial tract, lung, prostate, or gastroesophageal tract were matched in a 1:10 ratio with cancer-free members of the general population on year of birth, sex, and county of residence. Data were analyzed from February 13 to December 5, 2023. Exposure: Major surgery for cancer. Main Outcomes and Measures: The main outcome was incidence of venous thromboembolic events within 1 year after the surgery. Crude absolute risks and risk differences of events within 1 year and adjusted time-dependent cause-specific hazard ratios (HRs) of postdischarge events were calculated. Results: A total of 432â¯218 patients with cancer (median age, 67 years [IQR, 58-75 years]; 68.7% women) and 4â¯009â¯343 cancer-free comparators (median age, 66 years [IQR, 57-74 years]; 69.3% women) were included in the study. The crude 1-year cumulative risk of pulmonary embolism was higher among the cancer surgery population for all cancers, with the following absolute risk differences: for bladder cancer, 2.69 percentage points (95% CI, 2.33-3.05 percentage points); for breast cancer, 0.59 percentage points (95% CI 0.55-0.63 percentage points); for colorectal cancer, 1.57 percentage points (95% CI, 1.50-1.65 percentage points); for gynecologic organ cancer, 1.32 percentage points (95% CI, 1.22-1.41 percentage points); for kidney and upper urinary tract cancer, 1.38 percentage points (95% CI, 1.21-1.55 percentage points); for lung cancer, 2.61 percentage points (95% CI, 2.34-2.89 percentage points); for gastroesophageal cancer, 2.13 percentage points (95% CI, 1.89-2.38 percentage points); and for prostate cancer, 0.57 percentage points (95% CI, 0.49-0.66 percentage points). The cause-specific HR of pulmonary embolism comparing patients who underwent cancer surgery with matched comparators peaked just after discharge and generally plateaued 60 to 90 days later. At 30 days after surgery, the HR was 10 to 30 times higher than in the comparison cohort for all cancers except breast cancer (colorectal cancer: HR, 9.18 [95% CI, 8.03-10.50]; lung cancer: HR, 25.66 [95% CI, 17.41-37.84]; breast cancer: HR, 5.18 [95% CI, 4.45-6.05]). The hazards subsided but never reached the level of the comparison cohort except for prostate cancer. Similar results were observed for deep vein thrombosis. Conclusions and Relevance: This cohort study found an increased rate of venous thromboembolism associated with cancer surgery. The risk persisted for about 2 to 4 months postoperatively but varied between cancer types. The increased rate is likely explained by the underlying cancer disease and adjuvant treatments. The results highlight the need for individualized venous thromboembolism risk evaluation and prophylaxis regimens for patients undergoing different surgery for different cancers.
Assuntos
Neoplasias da Mama , Neoplasias Colorretais , Neoplasias dos Genitais Femininos , Neoplasias Pulmonares , Neoplasias da Próstata , Embolia Pulmonar , Tromboembolia Venosa , Trombose Venosa , Idoso , Feminino , Humanos , Masculino , Assistência ao Convalescente , Anticoagulantes , Neoplasias da Mama/complicações , Estudos de Coortes , Neoplasias Colorretais/complicações , Neoplasias dos Genitais Femininos/cirurgia , Neoplasias Pulmonares/complicações , Alta do Paciente , Neoplasias da Próstata/complicações , Embolia Pulmonar/epidemiologia , Embolia Pulmonar/etiologia , Estudos Retrospectivos , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/complicações , Trombose Venosa/etiologia , Pessoa de Meia-IdadeRESUMO
BACKGROUND: α1-antagonists are commonly used to treat benign prostatic hyperplasia. Preclinical studies suggest they induce cell death and inhibit tumor growth. This study evaluates the risk of prostate cancer death in men using α1-antagonists. METHODS: A population-based cohort study in Stockholm, Sweden (January 1, 2007 to December 31, 2019) including 451,779 men with a prostate-specific antigen (PSA) test. Study entry was one year after the first PSA test. Men were considered exposed at their second filled prescription. Primary outcome: prostate cancer mortality. Secondary outcomes: all-cause mortality and prostate cancer incidence. Cox proportional hazard regression models were used to calculate adjusted hazard ratios (HRs) and 95% CIs for all outcomes. Inverse probability weighting with marginal structural models accounted for time-dependent confounders. RESULTS: Of 351,297 men in the cohort, 39,856 (11.3%) were exposed to α1-antagonists. Median follow-up for prostate cancer mortality was 8.9 years and median exposure time to α1-antagonists was 4.4 years. There was no evidence of an association between α1-antagonist use and prostate cancer mortality, all-cause mortality, or high-grade prostate cancer. α1-antagonist-use was associated with an increased risk of prostate cancer (HR: 1.11, 95% CI: 1.06-1.17) and low-grade prostate cancer (HR: 1.22, 95% CI: 1.11-1.33). Men treated with α1-antagonists had more frequent PSA testing. CONCLUSIONS: Our findings show no significant association between α1-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.
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BACKGROUND: Positive surgical margins (PSMs) are frequent in patients undergoing radical prostatectomy (RP). The impact of PSMs on cancer-specific (CSM) and overall (OM) mortality has not yet been proved definitively. OBJECTIVE: To evaluate whether the presence and the features of PSMs were associated with CSM and OM in patients who underwent robotic-assisted RP. DESIGN, SETTING, AND PARTICIPANTS: A cohort of 8141 patients underwent robotic-assisted RP with >10 yr of follow-up. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cox multivariable analyses assessed the impact of margin status (positive vs negative) and PSM features (negative vs <3 mm vs >3 mm vs multifocal) on the risk of CSM, OM, and biochemical recurrence (BCR) after adjusting for potential confounders. We repeated our analyses after stratifying patients according to clinical (Cancer of the Prostate Risk Assessment [CAPRA] categories) and pathological characteristics (adverse: pT 3-4 and/or grade group [GG] 4-5 and/or pN1 and/or prostate-specific antigen [PSA] persistence). RESULTS AND LIMITATIONS: PSMs were found in 1348 patients (16%). Among these, 48 (3.6%) patients had multifocal PSMs. Overall, 1550 men experienced BCR and 898 men died, including 130 for prostate cancer. At Cox multivariable analyses, PSMs were associated with CSM in patients with adverse clinical (Intermediate risk: hazard ratio [HR]: 1.71, p = 0.048; high risk: HR: 2.20, p = 0.009) and pathological (HR: 1.79, p = 0.005) characteristics. Only multifocal PSMs were associated with CSM and OM in the whole population (HR for CSM: 4.68, p < 0.001; HR for OM: 1.82, p = 0.037) and in patients with adverse clinical (intermediate risk: HR for CSM: 7.26, p = 0.006; high risk: HR for CSM: 9.26, p < 0.001; HR for OM: 2.97, p = 0.006) and pathological (HR for CSM: 9.50, p < 0.001; HR for OM: 2.59, p = 0.001) characteristics. Potential limitations include a selection bias and a lack of information on the Gleason score at PSM location. CONCLUSIONS: We did not find an association between unifocal PSMs and mortality. Conversely, our results underscore the importance of avoiding multifocal PSMs in patients with adverse clinical (intermediate- and high-risk CAPRA score) and pathological (GG ≥4, pT ≥3, pN1, or PSA persistence) characteristics, to enhance overall survival and reduce CSM. PATIENT SUMMARY: In this study, we evaluated whether the presence and the characteristics of positive surgical margins were associated with mortality in patients who underwent robotic-assisted radical prostatectomy. We found that the presence of positive surgical margins, particularly multifocal margins, was associated with mortality only in patients with adverse clinical and pathological characteristics.