| 1. |
- Gatto, Francesco, 1987, et al.
(författare)
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Urinary Free Glycosaminoglycans Identify Adults at High Risk of Developing Early-stage High-grade Bladder Cancer
- 2024
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Ingår i: European Urology Open Science. - 2666-1683 .- 2666-1691. ; 68, s. 40-47
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Tidskriftsartikel (refereegranskat)abstract
- Background and objective: Screening for bladder cancer (BCa) could reduce mortality via early detection of early-stage high-grade (Ta/T1 N0 M0 grade 2–3) disease. Noninvasive biomarkers could aid in screening, but current markers lack the specificity required. The urinary free glycosaminoglycan profile (GAGome) is a promising biomarker for early detection of BCa metabolism. Methods: In a prospective case-control development study, we included patients with BCa or no evidence of disease (NED) and measured the urinary GAGome. We then developed a score to predict the probability of BCa using GAGome features that correlated with BCa versus NED according to Bayesian regression. Next, in a retrospective, population-based, case-control study, we included adults from the Lifelines Cohort Study who were presumed healthy at baseline. All cases with BCa confirmed in the cancer registry by the 2-yr or 6-yr study visit were matched to randomly selected control subjects. We developed a reference logistic regression model using age and sex to predict BCa at 7 yr after baseline. We then added the GAGome score to the model and assessed model improvement using the likelihood ratio test. We dichotomized outputs for the reference model and saturated model (reference + GAGome score) into high-risk versus low-risk categories using a 99% specificity cutoff and estimated the sensitivity for association with BCa at 7 yr. Key findings and limitations: We prospectively included 51 individuals with BCa and 38 with NED and observed alterations in three GAGome features compatible with BCa. We developed a score that discriminated BCa with an area under the receiver operating characteristic curve of 0.77 (95% confidence interval [CI] 0.67–0.87). We retrospectively selected a cohort of 1088 presumed healthy adults (median age 48 yr, 56% females), of whom 48 had developed BCa by 7 yr after baseline (median time to diagnosis 1.4 yr). The GAGome score was an independent predictor of BCa at 7 yr when added to the reference model (p < 0.001). The sensitivity for BCa at 7 yr for high-risk subjects was 31% (95% CI 20–43%) using the saturated model and 17% (95% CI 4.7–29%) using the reference model at 99% specificity (95% CI 98–99%). Conclusions and clinical implications: The urinary free GAGome is specifically altered in BCa and can be used for noninvasive identification of adults at high risk of developing BCa, independent of age and sex. This information could be useful for the design of risk-stratified targeted screening programs for BCa. Patient summary: We tested whether measurement of a class of sugars called glycosaminoglycans (GAGs) in urine could be used for early detection of bladder cancer. Our results show that GAG levels in urine can distinguish people at high risk of developing bladder cancer within 7 years, even if they are healthy at the time of the urine sampling.
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| 2. |
- Rajwa, Pawel, et al.
(författare)
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Research protocol for an observational health data analysis on the adverse events of systemic treatment in patients with metastatic hormone-sensitive prostate cancer : big data analytics using the PIONEER platform
- 2024
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Ingår i: European Urology Open Science. - : Elsevier. - 2666-1691 .- 2666-1683. ; 63, s. 81-88
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Tidskriftsartikel (refereegranskat)abstract
- Combination therapies in metastatic hormone-sensitive prostate cancer (mHSPC), which include the addition of an androgen receptor signaling inhibitor and/or docetaxel to androgen deprivation therapy, have been a game changer in the management of this disease stage. However, these therapies come with their fair share of toxicities and side effects. The goal of this observational study is to report drug-related adverse events (AEs), which are correlated with systemic combination therapies for mHSPC. Determining the optimal treatment option requires large cohorts to estimate the tolerability and AEs of these combination therapies in “real-life” patients with mHSPC, as provided in this study. We use a network of databases that includes population-based registries, electronic health records, and insurance claims, containing the overall target population and subgroups of patients defined by unique certain characteristics, demographics, and comorbidities, to compute the incidence of common AEs associated with systemic therapies in the setting of mHSPC. These data sources are standardised using the Observational Medical Outcomes Partnership Common Data Model. We perform the descriptive statistics as well as calculate the AE incidence rate separately for each treatment group, stratified by age groups and index year. The time until the first event is estimated using the Kaplan-Meier method within each age group. In the case of episodic events, the anticipated mean cumulative counts of events are calculated. Our study will allow clinicians to tailor optimal therapies for mHSPC patients, and they will serve as a basis for comparative method studies.
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| 3. |
- Thor, Anna, et al.
(författare)
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Primary retroperitoneal lymph node dissection as treatment for low-volume metastatic seminoma in a population-based cohort : the Swedish Norwegian testicular cancer group experience
- 2024
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Ingår i: European Urology Open Science. - : Elsevier. - 2666-1691 .- 2666-1683. ; 65, s. 13-19
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Tidskriftsartikel (refereegranskat)abstract
- Background and objective: There is an unmet need to avoid long-term morbidity associated with standard cytotoxic treatment for low-volume metastatic seminoma. Our aim was to assess the oncological efficacy and surgical safety of retroperitoneal lymph node dissection (RPLND) as treatment in a population-based cohort of metastatic seminoma patients with limited retroperitoneal lymphadenopathy.Methods: Sixty-two seminoma patients in Norway and Sweden were included in the cohort from 2019 to 2022. Patients with lymphadenopathy ≤3 cm, having primary clinical stage (CS) IIA/B or CS I with a relapse, were operated with uni- or bilateral template RPLND, open or robot assisted. The outcome measures included surgical complications as per Clavien-Dindo, and Kaplan-Meier survival estimates for 24-mo progression-free survival (PFS) and overall survival (OS).Key findings and limitations: In the cohort, 33 (53%) had CS I with a relapse during surveillance, six (10%) CS I with a relapse following adjuvant chemotherapy, and 23 (37%) initial CS IIA/B. Metastatic seminoma was verified in 58 patients (94%) with a median largest diameter of 18 mm (interquartile range [IQR] 13–24). Robot-assisted RPLND was performed in 40 patients (65%). Clavien-Dindo III complications were observed in three patients (5%); no grade ≥IV complications occurred. Eighteen patients (29%) received adjuvant chemotherapy after surgery. The median follow-up was 23 mo (IQR 16–30), and recurrence occurred in six patients (10%) after a median of 8 mo (IQR 4–14). PFS was 90% (95% confidence interval: 0.86–1) and OS was 100% at 24 mo.Conclusions and clinical implications: RPLND as primary treatment is an option for selected low-stage seminomas with a limited burden of disease, showing low complications and low relapse rates, with the potential to reduce long-term morbidity.Patient summary: In seminoma patients with limited metastatic spread, surgery is a treatment option offering an alternative to chemotherapy or radiation. This paper covers the first 62 patients operated in Norway and Sweden.
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| 4. |
- Örtegren, Joakim, et al.
(författare)
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Risk Factors for Infection After Transrectal Prostate Biopsy: A Population-based Register Study
- 2024
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Ingår i: EUROPEAN UROLOGY OPEN SCIENCE. - 2666-1691 .- 2666-1683. ; 67, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- Background and objective: Infection after transrectal prostate biopsy (TPBx) is a well-known risk. A comprehensive investigation of risk factors may identify measures for safe TPBx as an alternative to a change in biopsy route. The aim of this study was to identify risk factors for infection after TPBx. Methods: We included all outpatient TPBx cases in Region Kronoberg, Sweden, from January 2010 to December 2019. The primary outcome was post-TPBx infection, defined as prescription of antibiotics indicated for urinary tract infection (UTI) or inpatient care for infection within 30 d. We analysed the following factors in relation to post-TPBx infection: age, diabetes mellitus, prostate cancer diagnosed at index biopsy, previous prostate biopsy, two or more biopsies in the past 24 mo, a positive urine culture, two or more negative urine cultures (UCs) in the past 24 mo, antibiotic treatment grouped as four types, and medication for benign prostatic hyperplasia (BPH). Logistic regression was used to calculate odds ratios (ORs). Key findings and limitations: Of 5788 TPBx procedures in 4040 patients, 405 (7.0%) led to an infection and 170 (2.9%) to inpatient care for infection. Risk factors for post-TPBx infection (ORs 1.5-2.5) were diabetes mellitus, antibiotic treatment for a UTI, fluoroquinolone treatment, and a positive urine culture. Weaker risk factors (ORs 1.3-1.5) were non-UTI antibiotic treatment, BPH medication, and negative UCs before TPBx. Conclusions and clinical implications: Our results confirm that diabetes mellitus and previous UTI are risk factors for infection after TPBx. Lower urinary tract symptoms and treatment with any kind of antibiotic were associated with infection, which has not been previously reported. Patient summary: In a large population-based study from Sweden, we investigated which clinical factors increase the risk of an infection after transrectal prostate biopsy. Our results confirm that diabetes and a previous urinary tract infection are risk factors. We also found two new factors associated with the risk of infection after biopsy: lower urinary tract symptoms and any antibiotic treatment. (c) 2024 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/).
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| 7. |
- Kalinen, Sofia, et al.
(författare)
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Differences in Gut Microbiota Profiles and Microbiota Steroid Hormone Biosynthesis in Men with and Without Prostate Cancer.
- 2024
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Ingår i: European urology open science. - 2666-1683. ; 62, s. 140-150
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Tidskriftsartikel (refereegranskat)abstract
- Although prostate cancer (PCa) is the most common cancer in men in Western countries, there is significant variability in geographical incidence. This might result from genetic factors, discrepancies in screening policies, or differences in lifestyle. Gut microbiota has recently been associated with cancer progression, but its role in PCa is unclear.Characterization of the gut microbiota and its functions associated with PCa.In a prospective multicenter clinical trial (NCT02241122), the gut microbiota profiles of 181 men with a clinical suspicion of PCa were assessed utilizing 16S rRNA sequencing.Sequences were assigned to operational taxonomic units, differential abundance analysis, and α- and β-diversities, and predictive functional analyses were performed. Plasma steroid hormone levels corresponding to the predicted microbiota steroid hormone biosynthesis profiles were investigated.Of 364 patients, 181 were analyzed, 60% of whom were diagnosed with PCa. Microbiota composition and diversity were significantly different in PCa, partially affected by Prevotella 9, the most abundant genus of the cohort, and significantly higher in PCa patients. Predictive functional analyses revealed higher 5-α-reductase, copper absorption, and retinol metabolism in the PCa-associated microbiome. Plasma testosterone was associated negatively with the predicted microbial 5-α-reductase level.Gut microbiota of the PCa patients differed significantly compared with benign individuals. Microbial 5-α-reductase, copper absorption, and retinol metabolism are potential mechanisms of action. These findings support the observed association of lifestyle, geography, and PCa incidence.In this report, we found that several microbes and potential functions of the gut microbiota are altered in prostate cancer compared with benign cases. These findings suggest that gut microbiota could be the link between environmental factors and prostate cancer.
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| 8. |
- Lawlor, Ailbhe, et al.
(författare)
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Predictive Models for Assessing Patients’ Response to Treatment in Metastatic Prostate Cancer : A Systematic Review
- 2024
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Ingår i: European Urology Open Science. - 2666-1691. ; 63, s. 126-135
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Forskningsöversikt (refereegranskat)abstract
- Background and objective: The treatment landscape of metastatic prostate cancer (mPCa) has evolved significantly over the past two decades. Despite this, the optimal therapy for patients with mPCa has not been determined. This systematic review identifies available predictive models that assess mPCa patients’ response to treatment. Methods: We critically reviewed MEDLINE and CENTRAL in December 2022 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Only quantitative studies in English were included with no time restrictions. The quality of the included studies was assessed using the PROBAST tool. Data were extracted following the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews criteria. Key findings and limitations: The search identified 616 citations, of which 15 studies were included in our review. Nine of the included studies were validated internally or externally. Only one study had a low risk of bias and a low risk concerning applicability. Many studies failed to detail model performance adequately, resulting in a high risk of bias. Where reported, the models indicated good or excellent performance. Conclusions and clinical implications: Most of the identified predictive models require additional evaluation and validation in properly designed studies before these can be implemented in clinical practice to assist with treatment decision-making for men with mPCa. Patient summary: In this review, we evaluate studies that predict which treatments will work best for which metastatic prostate cancer patients. We found that existing studies need further improvement before these can be used by health care professionals.
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| 11. |
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| 12. |
- Örtegren, Joakim, et al.
(författare)
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Risk Factors for Infection After Transrectal Prostate Biopsy : A Population-based Register Study
- 2024
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Ingår i: European Urology Open Science. - 2666-1691. ; 67, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVE: Infection after transrectal prostate biopsy (TPBx) is a well-known risk. A comprehensive investigation of risk factors may identify measures for safe TPBx as an alternative to a change in biopsy route. The aim of this study was to identify risk factors for infection after TPBx.METHODS: We included all outpatient TPBx cases in Region Kronoberg, Sweden, from January 2010 to December 2019. The primary outcome was post-TPBx infection, defined as prescription of antibiotics indicated for urinary tract infection (UTI) or inpatient care for infection within 30 d. We analysed the following factors in relation to post-TPBx infection: age, diabetes mellitus, prostate cancer diagnosed at index biopsy, previous prostate biopsy, two or more biopsies in the past 24 mo, a positive urine culture, two or more negative urine cultures (UCs) in the past 24 mo, antibiotic treatment grouped as four types, and medication for benign prostatic hyperplasia (BPH). Logistic regression was used to calculate odds ratios (ORs).KEY FINDINGS AND LIMITATIONS: Of 5788 TPBx procedures in 4040 patients, 405 (7.0%) led to an infection and 170 (2.9%) to inpatient care for infection. Risk factors for post-TPBx infection (ORs 1.5-2.5) were diabetes mellitus, antibiotic treatment for a UTI, fluoroquinolone treatment, and a positive urine culture. Weaker risk factors (ORs 1.3-1.5) were non-UTI antibiotic treatment, BPH medication, and negative UCs before TPBx.CONCLUSIONS AND CLINICAL IMPLICATIONS: Our results confirm that diabetes mellitus and previous UTI are risk factors for infection after TPBx. Lower urinary tract symptoms and treatment with any kind of antibiotic were associated with infection, which has not been previously reported.PATIENT SUMMARY: In a large population-based study from Sweden, we investigated which clinical factors increase the risk of an infection after transrectal prostate biopsy. Our results confirm that diabetes and a previous urinary tract infection are risk factors. We also found two new factors associated with the risk of infection after biopsy: lower urinary tract symptoms and any antibiotic treatment.
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