Purpose
To evaluate clinical variables, including magnetic resonance imaging (MRI) predictive of adverse pathology (AP) at radical prostatectomy (RP) in men initially enrolled in active surveillance ...(AS).
Methods
A population-based cohort study of men diagnosed with low-risk prostate cancer (PCa), in Stockholm County, Sweden, during 2008–2017 enrolled in AS their intended primary treatment followed by RP. AP was defined as ISUP grade group ≥ 3 and/or pT-stage ≥ T3. Association between clinical variables at diagnosis and time to AP was evaluated using Cox regression and multivariate logistic regression to evaluate the association between AP and clinical variables at last biopsy before RP.
Results
In a cohort of 6021 patients with low-risk PCa, 3116 were selected for AS and 216 underwent RP. Follow-up was 10 years, with a median time on AS of 23 months. 37.7% of patients had AP at RP. Clinical T-stage Hazard ratio (HR): 1.81, 95% confidence interval (CI) 1.04–3.18 and PSA (HR: 1.31, 95% CI 1.17–1.46) at diagnosis and age Odds Ratio (OR): 1.09, 95% CI 1.02–1.18), PSA (OR: 1.22, 95% CI 1.07–1.41), and PI-RADS (OR 1.66, 95% CI 1.11–2.55) at last re-biopsy were significantly associated with AP.
Conclusion
PI-RADS score is significantly associated with AP at RP and support current guidelines recommending MRI before enrollment in AS. Furthermore, age, cT-stage, and PSA are significantly associated with AP.
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•Method developed for categorizing the cost-effectiveness of district heating.•Biomass and natural gas district heating effectively mitigate GHG emissions.•District heating is ...competitive with other energy-saving building strategies.•Performance of natural gas is highest due to efficiency in electricity generation.
Biomass resources could be used in the Northeastern U.S. in centralized district heating networks supplied by combined heat and power (CHP) plants to reduce consumption of petroleum resources (fuel oil), generate renewable electricity, and cost-effectively reduce greenhouse gas (GHG) emissions when supplying buildings with space and water heating. Alternatively, the CHP plants could be powered by natural gas, which would reduce GHG emissions relative to conventional, individual heating solutions owing to the improved efficiency of cogeneration. To assess the potential for investment in these technologies, hourly heat load demand in residential and commercial buildings in all New England and New York state towns (populations > 5000) was estimated and used to optimize the energy efficiency of district heating networks using MODEST software. All of the 116 studied locations without access to natural gas distribution infrastructure showed negative carbon abatement costs, the majority between −$250 and −$38 per Mg CO2 equivalents (eq.), when biomass-fed district heating was implemented due to significantly reduced operational costs and life cycle GHG emissions. Similarly, almost all (465 out of 467) locations connected to the natural gas grid were found to have negative GHG abatement costs, ranging from −$4500 to −$400 per Mg CO2 eq., demonstrating strong economic feasibility for district heating. Natural has an economic advantage over biomass in district heating due to its combined cycle CHP plants being able to generate more electricity per heat unit compared to biomass CHP plants and its lower O&M costs. District heating in all locations could abate 2.6 billion Mg of CO2 eq. at an economic surplus over 30 ears of continuous operation. Using a framework that integrated spatial tools, optimization, LCA, and cost evaluation, this study uniquely identified promising locations in the U.S. where district heating could be both environmentally and economically beneficial. This framework can be applied to other global regions that have significant space heating needs, for CHP implementation, and as a tool for identifying alternative building energy investments, such as improved insulation or individual space heating solutions, which in some cases could yield higher GHG reductions per dollar.
Bladder cancer (BC) is a heterogeneous disease with highly variable clinical and pathological features, and resulting in different outcomes. Such heterogeneity ensues from distinct pathogenetic ...mechanisms and may consistently affect treatment responses in single patients. Thus, over the last few years, several groups have developed molecular classification schemes for BC, mainly based on their mRNA expression profiles. A “consensus” classification has recently been proposed to combine the published systems, agreeing on a six-cluster scheme with distinct prognostic and predictive features. In order to implement molecular subtyping as a risk-stratification tool in routine practice, immunohistochemistry (IHC) has been explored as a readily accessible, relatively inexpensive, standardized surrogate method, achieving promising results in different clinical settings. The first part of this review deals with the steps resulting in the development of a molecular subtyping of BC, its prognostic and predictive implications, and the main features of immunohistochemical markers used as surrogates to stratify BC into pre-defined molecular clusters.
Abstract 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.
Following several attempts to achieve a molecular stratification of bladder cancer (BC) over the last decade, a “consensus” classification has been recently developed to provide a common base for the ...molecular classification of bladder cancer (BC), encompassing a six-cluster scheme with distinct prognostic and predictive characteristics. In order to implement molecular subtyping (MS) as a risk stratification tool in routine practice, immunohistochemistry (IHC) has been explored as a readily accessible, relatively inexpensive, standardized surrogate method, achieving promising results in different clinical settings. The second part of this review deals with the pathological and clinical features of the molecular clusters, both in conventional and divergent urothelial carcinoma, with a focus on the role of IHC-based subtyping.
District heating (DH) systems can improve energy efficiency, reduce greenhouse gas (GHG) emissions, and be a cost‐effective residential space heating alternative over conventional decentralized ...heating. This study uses radiative forcing (RF), a time‐sensitive life cycle assessment metric, to evaluate space heating alternatives. We compare forest residue and willow biomass resources and natural gas as fuel sources against decentralized heating using heating oil. The comparison is performed for selected locations in the Northeastern United States over a 30‐year production timeline and 100 observation years. The natural gas and willow scenarios are compared with scenarios where available forest residue is unused and adds a penalty of GHG emissions due to microbial decay. When forest residues are available, their use is recommended before considering willow production. Investment in bioenergy‐based DH with carbon capture and storage and natural‐gas‐based DH with carbon capture and storage (CCS) technology is considered to assess their influence on RF. Its implementation further improves the net carbon mitigation potential of DH despite the carbon and energy cost of CCS infrastructure. Soil carbon sequestration from willow production reduces RF overall, specifically when grown on land converted from cropland to pasture, hay, and grassland. The study places initial GHG emissions spikes from infrastructure and land‐use change into a temporal framework and shows a payback within the first 5 years of operation for DH with forest residues and willow.
Replacing conventional heating oil‐based decentralized residential heating with natural gas, forest residue, or willow feedstocks, and centralized‐district heating (DH) infrastructure significantly improves environmental performance. The study implements a temporal analysis using radiative forcing for 30 production years and 100 observation years, identifying the inflection points of greenhouse gas (GHG) emissions for the various residential heating feedstocks. Consideration of carbon capture and storage (CCS) and bioenergy CCS for natural gas and biomass‐based DH respectively shows significant atmospheric carbon capture. Such carbon capture technology supplements soil carbon sequestration‐based environmental GHG sequestration, for willow when grown on pasture, hay, and grasslands.
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).
To evaluate the association of treatment with 5-ARIs with PCM in men without a prior diagnosis of PCa.
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.
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).
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.
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).
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.
Many men with lethal prostate cancer did not undergo prostate-specific antigen (PSA) testing before diagnosis, or if they did, were not subsequently followed up. This could implicate deficiencies in ...current opportunistic PSA testing strategies.
Prostate cancer (PC) is the fifth leading cause of cancer-related mortality in men worldwide. Opportunistic testing with prostate-specific antigen (PSA) has limited impact on PC mortality. Our objective was to assess prediagnostic PSA testing patterns and clinical characteristics at diagnosis in men with lethal PC.
We conducted a population-based observational study of all men dying from PC in Stockholm County, Sweden, from 2015 to 2019. Data were retrieved from the National Prostate Cancer Register and the Stockholm PSA and Biopsy Register. If the first PSA was registered within 1 yr before diagnosis, men were categorised as PSA naïve. If an elevated PSA level was registered >1 yr before diagnosis without leading to prostate biopsy or repeating PSA within 1 yr, men were categorised as having delayed diagnosis. If a normal PSA level was registered within 5 yr before diagnosis, followed by an elevated PSA level that resulted in PC diagnosis within 1 yr, men were categorised as PSA tested. Clinical characteristics at diagnosis were stratified with D’Amico risk group classification.
Among 1473 men dying from PC, PSA test history was available for 995. Of these men, 60% (n = 592) were PSA naïve, 25% (n = 250) received delayed diagnosis, and 15% (n = 153) were PSA tested. After examining all 1473 men, 25% (n = 350) were diagnosed with low- or intermediate-risk cancer, 48% (n = 687) with high-risk cancer, and 27% (n = 385) with metastatic disease. Limitations include the retrospective design.
Many men with lethal PC lacked PSA testing before diagnosis or had been tested without subsequent follow-up. Nearly half of the study population was diagnosed with high-risk cancer and almost one-third with metastatic disease. These findings suggest further evaluation of the current opportunistic PSA testing approach.
Data from a population-based observational study of men dying from prostate cancer showed that many of them did not undergo either prostate-specific antigen (PSA) testing before diagnosis or subsequent follow-up if tested. These findings implicate deficiencies in the current opportunistic PSA testing approach.
Prostate cancer guidelines often recommend obtaining magnetic resonance imaging (MRI) before a biopsy, yet MRI access is limited. To date, no randomized clinical trial has compared the use of novel ...biomarkers for risk estimation vs MRI-based diagnostic approaches for prostate cancer screening.
To evaluate biomarker-based risk estimation (Stockholm3 risk scores or prostate-specific antigen PSA levels) with systematic biopsies vs an MRI-enhanced strategy (PSA levels and MRI with systematic and targeted biopsy) for the detection of clinically significant prostate cancer in a screening setting.
This open-label randomized clinical trial conducted in Stockholm, Sweden, between April 4, 2018, and December 10, 2020, recruited men aged 50 to 74 years with no history of prostate cancer. Participants underwent blood sampling for PSA and Stockholm3 tests to estimate their risk of clinically significant prostate cancer (Gleason score ≥3 + 4). After the blood tests were performed, participants were randomly assigned in a 2:3 ratio to receive a Stockholm3 test with systematic biopsy (biomarker group) or a PSA test followed by MRI with systematic and targeted biopsy (MRI-enhanced group). Data were analyzed from September 1 to November 5, 2023.
In the biomarker group, men with a Stockholm3 risk score of 0.15 or higher underwent systematic biopsies. In the MRI-enhanced group, men with a PSA level of 3 ng/mL or higher had an MRI and those with a Prostate Imaging-Reporting and Data System (PI-RADS) score of 3 or higher (range: 1-5, with higher scores indicating a higher likelihood of clinically significant prostate cancer) underwent targeted and systematic biopsies.
Primary outcome was detection of clinically significant prostate cancer (Gleason score ≥3 + 4). Secondary outcomes included detection of clinically insignificant cancer (Gleason score ≤6) and the number of biopsy procedures performed.
Of 12 743 male participants (median IQR age, 61 55-67 years), 5134 were assigned to the biomarker group and 7609 to the MRI-enhanced group. In the biomarker group, 8.0% of men (413) had Stockholm3 risk scores of 0.15 or higher and were referred for systematic biopsies. In the MRI-enhanced group, 12.2% of men (929) had a PSA level of 3 ng/mL or higher and were referred for MRI with biopsies if they had a PI-RADS score of 3 or higher. Detection rates of clinically significant prostate cancer were comparable between the 2 groups: 2.3% in the biomarker group and 2.5% in the MRI-enhanced group (relative proportion, 0.92; 95% CI, 0.73-1.15). More biopsies were performed in the biomarker group than in the MRI-enhanced group (326 of 5134 6.3% vs 338 of 7609 4.4%; relative proportion, 1.43 95% CI, 1.23-1.66), and more indolent prostate cancers were detected (61 1.2% vs 41 0.5%; relative proportion, 2.21 95% CI, 1.49-3.27).
Findings of this randomized clinical trial indicate that combining a Stockholm3 test with systematic biopsies is comparable with MRI-based screening with PSA levels and systematic and targeted biopsies for detection of clinically significant prostate cancer, but this approach resulted in more biopsies as well as detection of a greater number of indolent cancers. In regions where access to MRI is lacking, the Stockholm3 test can aid in selecting patients for systematic prostate biopsy.
ClinicalTrials.gov Identifier: NCT03377881.
Purpose
The primary aim of this study was to evaluate if exposure to 5-alpha-reductase inhibitors (5-ARIs) modifies the effect of MRI for the diagnosis of clinically significant Prostate Cancer ...(csPCa) (ISUP Gleason grade ≥ 2).
Methods
This study is a multicenter cohort study including patients undergoing prostate biopsy and MRI at 24 institutions between 2013 and 2022. Multivariable analysis predicting csPCa with an interaction term between 5-ARIs and PIRADS score was performed. Sensitivity, specificity, and negative (NPV) and positive (PPV) predictive values of MRI were compared in treated and untreated patients.
Results
705 patients (9%) were treated with 5-ARIs median age 69 years, Interquartile range (IQR): 65, 73; median PSA 6.3 ng/ml, IQR 4.0, 9.0; median prostate volume 53 ml, IQR 40, 72 and 6913 were 5-ARIs naïve (age 66 years, IQR 60, 71; PSA 6.5 ng/ml, IQR 4.8, 9.0; prostate volume 50 ml, IQR 37, 65). MRI showed PIRADS 1–2, 3, 4, and 5 lesions in 141 (20%), 158 (22%), 258 (37%), and 148 (21%) patients treated with 5-ARIs, and 878 (13%), 1764 (25%), 2948 (43%), and 1323 (19%) of untreated patients (
p
< 0.0001). No difference was found in csPCa detection rates, but diagnosis of high-grade PCa (ISUP GG ≥ 3) was higher in treated patients (23% vs 19%,
p
= 0.013). We did not find any evidence of interaction between PIRADS score and 5-ARIs exposure in predicting csPCa. Sensitivity, specificity, PPV, and NPV of PIRADS ≥ 3 were 94%, 29%, 46%, and 88% in treated patients and 96%, 18%, 43%, and 88% in untreated patients, respectively.
Conclusions
Exposure to 5-ARIs does not affect the association of PIRADS score with csPCa. Higher rates of high-grade PCa were detected in treated patients, but most were clearly visible on MRI as PIRADS 4 and 5 lesions.
Trial registration
The present study was registered at ClinicalTrials.gov number: NCT05078359.
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