| 1. |
- Bergengren, Oskar, et al.
(author)
-
Variation in Prostate-Specific Antigen Testing Rates and Prostate Cancer Treatments and Outcomes in a National 20-Year Cohort
- 2021
-
In: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 4:5
-
Journal article (peer-reviewed)abstract
- IMPORTANCE: The diagnostic activity for prostate cancer has increased during the past decades. However, the benefit and harm of the increased diagnostic activity have not been quantified in detail for a country or a large region.OBJECTIVE: The aim of this study was to evaluate and quantify the association between increases in diagnostic activity driven by prostate-specific antigen testing and incidence of prostate cancer diagnosis, treatment, and mortality.DESIGN, SETTING, AND PARTICIPANTS: This cohort study used the Proxy-Based Risk-Stratified Incidence Simulation Model-Prostate Cancer to examine observed data on all Swedish men with prevalent prostate cancer and compare them with a corresponding, hypothetical, simulated scenario with more restrictive diagnostic activity. All men aged 40 to 100 years living in Sweden during the time period 1996 to 2016 with incident and prevalent prostate cancer were included. The second scenario is the corresponding, hypothetical, simulated scenario where diagnostic activity remained constant as of 1996 (the beginning of the prostate-specific antigen testing era) throughout the study period.EXPOSURES: High or low diagnostic activity for prostate cancer.MAIN OUTCOMES AND MEASURES: Incidence of prostate cancer diagnosis, treatment (deferred treatment, curative treatment, and hormonal treatment), and prostate cancer mortality.RESULTS: During the study period from 1996 to 2016, 188 884 men were diagnosed with prostate cancer at a median (interquartile range) age of 71 (64-77) years. Compared with the low-diagnostic activity scenario, in the high-diagnostic activity scenario, the number of men diagnosed with prostate cancer was 48% higher (423 vs 286 [95% CI, 271-302] per 100 000 men per year), 148% more men were diagnosed with low- or intermediate-risk cancer (221 vs 89 [95% CI, 73-105] per 100 000 men per year), and 108% more men received curative treatment (152 vs 73 [95% CI: 66-85] per 100 000 men per year). There were up to 15% fewer prostate cancer deaths in the scenario with high-diagnostic activity (incidence rate ratio, 0.85; 95% CI, 0.82-0.88).CONCLUSIONS AND RELEVANCE: This studys results suggest that increased prostate-specific antigen testing and diagnostic activity are associated with a larger number of men being diagnosed with prostate cancer, predominately with low- and intermediate-risk disease. The increased diagnostic activity was associated with a 2-fold increase in curative treatment and a modest decrease in mortality.
|
|
| 2. |
|
|
| 3. |
- Bonander, Carl, et al.
(author)
-
Colorectal cancer screening with fecal immunochemical testing or primary colonoscopy : inequities in diagnostic yield
- 2024
-
In: JNCI Cancer Spectrum. - : Oxford University Press. - 2515-5091. ; 8:3
-
Journal article (peer-reviewed)abstract
- BackgroundSocioeconomic inequalities in the uptake of colorectal cancer screening are well documented, but the implications on inequities in health gain remain unclear.MethodsSixty-year-olds were randomly recruited from the Swedish population between March 2014 and March 2020 and invited to undergo either 2 rounds of fecal immunochemical testing (FIT) 2 years apart (n = 60 137) or primary colonoscopy just once (n = 30 400). By linkage to Statistics Sweden’s registries, we obtained socioeconomic data. In each defined socioeconomic group, we estimated the cumulative yield of advanced neoplasia in each screening arm (intention-to-screen analysis). In the biennial FIT arm, we predicted the probability of exceeding the yield in the primary colonoscopy arm by linear extrapolation of the cumulative yield to (hypothetical) additional rounds of FIT.ResultsIn the lowest income group, the yield of advanced neoplasia was 1.63% (95% confidence interval [CI] = 1.35% to 1.93%) after 2 rounds of FIT vs 1.93% (95% CI = 1.49% to 2.40%) in the primary colonoscopy arm. Extrapolation to a third round of FIT implied a 86% probability of exceeding the yield in the primary colonoscopy arm. In the highest income group, we found a more pronounced yield gap between the 2 screening strategies—2.32% (95% CI = 2.15% to 2.49%) vs 3.71% (95% CI = 3.41% to 4.02%)— implying a low (2%) predicted probability of exceeding yield after a third round of FIT.ConclusionsYield of advanced neoplasia from 2 rounds of FIT 2 years apart was poorer as compared with primary colonoscopy, but the difference was less in lower socioeconomic groups.
|
|
| 4. |
- Bonde, Tiago M., et al.
(author)
-
Time to castration-resistant prostate cancer and prostate cancer death according to PSA response in men with non-metastatic prostate cancer treated with gonadotropin releasing hormone agonists
- 2022
-
In: Scandinavian journal of urology. - : Taylor & Francis Group. - 2168-1805 .- 2168-1813. ; 56:3, s. 169-175
-
Journal article (peer-reviewed)abstract
- Objectives: To predict castration-resistant prostate cancer (CRPC) and prostate cancer (Pca) death by use of clinical variables at Pca diagnosis and PSA levels after start of gonadotropin-releasing hormone agonists (GnRH) in men with non-metastatic castration sensitive prostate cancer (nmCSPC).Materials and Methods: PSA values for 1603 men with nmCSPC in the National Prostate Cancer Register of Sweden who received GnRH as primary treatment were retrieved from Uppsala-Örebro PSA Cohort and Stockholm PSA and Biopsy Register. All men had measured PSA before (pre-GnRH PSA) and 3–6 months after (post-GnRH PSA) date of start of GnRH. Unadjusted and adjusted Cox models were used to predict CRPC by PSA levels. PSA levels and ISUP grade were used to construct a risk score to stratify men by tertiles according to risk of CRPC and Pca death.Results: 788 (49%) men reached CRPC and 456 (28%) died of Pca during follow-up. Post-GnRH PSA predicted CRPC regardless of pre-GnRH PSA. CRPC risk increased with higher post-GnRH PSA, HR 4.7 (95% CI: 3.4–6.7) for PSA > 16 ng/mL vs 0–0.25 ng/mL and with ISUP grade, HR 3.7 (95%: 2.5–5.4) for ISUP 5 vs ISUP 1. Risk of Pca death in men above top vs bellow bottom tertile of post-GnRH PSA and ISUP grade was HR 4.1 (95% CI: 3.0–5.5).Conclusion: A risk score based on post-GnRH PSA and ISUP grade could be used for early identification of a target group for future clinical trials on additional therapy to GnRH.
|
|
| 5. |
- Corsini, Christian, et al.
(author)
-
Patient-reported side effects 1 year after radical prostatectomy or radiotherapy for prostate cancer : a register-based nationwide study
- 2024
-
In: European Urology Oncology. - : Elsevier. - 2588-9311. ; 7:3, s. 605-613
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Data on functional and psychological side effects following curative treatment for prostate cancer are lacking from large, contemporary, unselected, population-based cohorts.OBJECTIVE: To assess urinary symptoms, bowel disturbances, erectile dysfunction (ED), and quality of life (QoL) 12 mo after robot-assisted radical prostatectomy (RARP) and radiotherapy (RT) using patient-reported outcome measures in the Swedish prostate cancer database.DESIGN, SETTING, AND PARTICIPANTS: This was a nationwide, population-based, cohort study in Sweden of men who underwent primary RARP or RT between January 1, 2018 and December 31, 2020.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Absolute proportions and odds ratios (ORs) were calculated using multivariable logistic regression, with adjustment for clinical characteristics.RESULTS AND LIMITATIONS: A total of 2557 men underwent RARP and 1741 received RT. Men who underwent RT were older (69 vs 65 yr) and had more comorbidities at baseline. After RARP, 13% of men experienced incontinence, compared to 6% after RT. The frequency of urinary bother was similar, at 18% after RARP and 18% after RT. Urgency to defecate was reported by 14% of men after RARP and 34% after RT. At 1 yr, 73% of men had ED after RARP, and 77% after RT. High QoL was reported by 85% of men after RARP and 78% of men after RT. On multivariable regression analysis, RT was associated with lower risks of urinary incontinence (OR 0.25, 95% confidence interval [CI] 0.19-0.33), urinary bother (OR 0.79, 95% CI 0.66-0.95), and ED (OR 0.54, 95% CI 0.46-0.65), but higher risk of bowel symptoms (OR 2.86, 95% CI 2.42-3.39). QoL was higher after RARP than after RT (OR 1.34, 95% CI 1.12-1.61).CONCLUSIONS: Short-term specific side effects after curative treatment for prostate cancer significantly differed between RARP and RT in this large and unselected cohort. Nevertheless, the risk of urinary bother was lower after RT, while higher QoL was common after RARP.PATIENT SUMMARY: In our study of patients treated for prostate cancer, urinary bother and overall quality of life are comparable at 1 year after surgical removal of the prostate in comparison to radiotherapy, despite substantial differences in other side effects.
|
|
| 6. |
- Corsini, Christian, et al.
(author)
-
Patient-reported Side Effects 1 Year After Radical Prostatectomy or Radiotherapy for Prostate Cancer : A Register-based Nationwide Study
- 2024
-
In: European Urology Oncology. - : Elsevier. - 2588-9311. ; 7:3, s. 605-613
-
Journal article (peer-reviewed)abstract
- Background: Data on functional and psychological side effects following curative treatment for prostate cancer are lacking from large, contemporary, unselected, populationbased cohorts. Objective: To assess urinary symptoms, bowel disturbances, erectile dysfunction (ED), and quality of life (QoL) 12 mo after robot -assisted radical prostatectomy (RARP) and radiotherapy (RT) using patient -reported outcome measures in the Swedish prostate cancer database. Design, setting, and participants: This was a nationwide, population -based, cohort study in Sweden of men who underwent primary RARP or RT between January 1, 2018 and December 31, 2020. Outcome measurements and statistical analysis: Absolute proportions and odds ratios (ORs) were calculated using multivariable logistic regression, with adjustment for clinical characteristics. Results and limitations: A total of 2557 men underwent RARP and 1741 received RT. Men who underwent RT were older (69 vs 65 yr) and had more comorbidities at baseline. After RARP, 13% of men experienced incontinence, compared to 6% after RT. The frequency of urinary bother was similar, at 18% after RARP and 18% after RT. Urgency to defecate was reported by 14% of men after RARP and 34% after RT. At 1 yr, 73% of men had ED after RARP, and 77% after RT. High QoL was reported by 85% of men after RARP and 78% of men after RT. On multivariable regression analysis, RT was associated with lower risks of urinary incontinence (OR 0.25, 95% confidence interval [CI] 0.19- 0.33), urinary bother (OR 0.79, 95% CI 0.66-0.95), and ED (OR 0.54, 95% CI 0.46-0.65), but higher risk of bowel symptoms (OR 2.86, 95% CI 2.42-3.39). QoL was higher after RARP than after RT (OR 1.34, 95% CI 1.12-1.61). Conclusions: Short-term specific side effects after curative treatment for prostate cancer significantly differed between RARP and RT in this large and unselected cohort. Nevertheless, the risk of urinary bother was lower after RT, while higher QoL was common after RARP. Patient summary: In our study of patients treated for prostate cancer, urinary bother and overall quality of life are comparable at 1 year after surgical removal of the prostate in comparison to radiotherapy, despite substantial differences in other side effects. (c) 2024 The Authors. Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY -NC -ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
|
|
| 7. |
- Corsini, Christian, et al.
(author)
-
Survival Trend in Individuals With De Novo Metastatic Prostate Cancer After the Introduction of Doublet Therapy
- 2023
-
In: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 6:10
-
Journal article (peer-reviewed)abstract
- IMPORTANCE: Recently, life-prolonging treatments for patients with advanced prostate cancer have been introduced in clinical practice.OBJECTIVE: To investigate if the introduction of doublet therapy is associated with changes in survival on a population-basis.DESIGN, SETTING, AND PARTICIPANTS: This nationwide population-based cohort study used data from the Prostate Cancer data Base Sweden from 2008 to 2020. Men registered with de novo metastatic castration-sensitive prostate cancer (mCSPC) were included.EXPOSURE: The proportion of men with mCSPC who received doublet therapy, ie, androgen deprivation therapy plus androgen receptor pathway inhibitor drugs or chemotherapy was assessed.MAIN OUTCOMES AND MEASURES: Standardized overall survival, taking age, comorbidity, and cancer characteristics into consideration, was estimated by use of a parametric survival model.RESULTS: A total of 11 382 men were included in this study (median [IQR] age, 74.0 [68-81] years). There was a shift toward less advanced prostate cancer during the study period with a decrease in median (IQR) prostate-specific antigen at diagnosis in men with mCSPC from 145 (39-571) ng/mL to 107 (27-426) ng/mL. Upfront treatment with doublet therapy in these men simultaneously increased from 1% (7 of 991) in 2016 to 44% (402 of 922) in 2020. The adjusted 5-year overall survival increased from 26% (95% CI, 25%-28%) from 2008 to 2012 to 35% (95% CI, 31%-40%) from 2017 to 2020. During the first 5 years after diagnosis, there was an increase in mean survival of 6 months, from 2.7 (95% CI, 2.6-2.8) years from 2008 to 2012 to 3.2 (95% CI, 3.1-3.1) years from 2017 to 2020.CONCLUSIONS AND RELEVANCE: In parallel with improvements in treatment of advanced prostate cancer, a clinically meaningful increase in mean survival was observed in men with de novo mCSPC in Sweden between 2008 and 2020 in this study.
|
|
| 8. |
- Degerman, Marcus, et al.
(author)
-
A Model-Based Approach to Determine the Design Space of Preparative Chromatography
- 2009
-
In: Chemical Engineering & Technology. - : Wiley. - 1521-4125 .- 0930-7516. ; 32:8, s. 1195-1202
-
Journal article (peer-reviewed)abstract
- A dream of many pharmaceutical companies is to be able to register a large design space with the regulatory agencies. The problem is that this will require both time and money, so an intelligent method of validating a design space is needed. The design space should only cover operating points at which the process runs optimally. This means that the process should be optimized for different process scenarios and objective functions and the found operating points should be registered as design space. This paper presents a method of determining a good design space by creating Pareto fronts for the ideal case and for various process disturbance scenarios. Optimal operating points are found for varying ratios between feed costs and operating costs, making it possible to make a quantitative choice of an operating point based on this ratio and a qualitative choice based on the whole front. The analysis will show how the chromatographic process can be made more robust when optimizing for higher yields, and how the effect of the critical process parameters can change. To be certain that a robust process is found and that it has a high performance, process disturbances must be taken into account when optimizing a process.
|
|
| 9. |
- Degerman, Marcus, et al.
(author)
-
Determining Critical Process Parameters and Process Robustness in Preparative Chromatography - A Model-Based Approach
- 2009
-
In: Chemical Engineering & Technology. - : Wiley. - 1521-4125 .- 0930-7516. ; 32:6, s. 903-911
-
Journal article (peer-reviewed)abstract
- This paper presents a model-based method to aid in the process validation for the purification of pharmaceutical drugs. The critical process parameters are identified by simulating process disturbances, and this information is then used to determine if the process control space is robust. Simulations are chosen to analyze the entire control space to also find nonlinearities and interaction effects between the process disturbances, which are used to determine where in the control space the critical quality attributes are the lowest, i.e., the worst case scenario. The real process conditions are estimated by running simulations according to plausible probability distributions using Latin hypercube sampling. The probability of batch failure can be estimated from this and it is shown that the worst case scenario is improbable for most cases. This information can help in planning validation experiments or determine which critical process parameters need a tighter control. Three case studies are used to illustrate the usefulness of the methods. It was found that the main critical process parameters in all three case Studies were variations in the modifier concentrations, for example, salt in ion-exchange chromatography and hydrophobic interaction chromatography, and the organic modifier in reversed-phase chromatography.
|
|
| 10. |
- Forsberg, Anna, et al.
(author)
-
Once-only colonoscopy or two rounds of faecal immunochemical testing 2 years apart for colorectal cancer screening (SCREESCO): preliminary report of a randomised controlled trial
- 2022
-
In: The Lancet Gastroenterology & Hepatology. - : ELSEVIER INC. - 2468-1253. ; 7:6, s. 513-521
-
Journal article (peer-reviewed)abstract
- Background Screening for colorectal cancer is done with lower gastrointestinal endoscopy or stool-based tests. There is little evidence from randomised trials to show primary colonoscopy reduces mortality in colorectal cancer We aimed to investigate the effect of screening with once-only colonoscopy or two rounds of faecal immunochemical test screening on colorectal cancer mortality and incidence. Methods We did a randomised controlled trial in Sweden (SCREESCO). Residents in 18 of 21 regions who were age 60 years in the year of randomisation were identified from a population register maintained by the Swedish Tax Agency. A statistician with no further involvement in the trial used a randomised block method to assign individuals to once-only colonoscopy, two rounds of faecal immunochemical testing (OC-Sensor; 2 years apart), or a control group (no intervention; standard diagnostic pathways), in a ratio of 1:6 for colonoscopy versus control and 1:2 for faecal immunochemical testing versus control. Masking was not possible due to the nature of the trial. The primary endpoints of the trial are colorectal cancer mortality and colorectal cancer incidence. Here, we report preliminary participation rates, baseline findings, and adverse events from March, 2014, to December, 2020, in the two intervention groups after completion of recruitment and screening, up to the completion of the second faecal immunochemical testing round. Analyses were done in the intention-to-screen population, defined as all individuals who were randomly assigned to the respective study group. This study is registered with Clinical Trials.gov, NCT02078804. Findings Between March 1, 2014, and Dec 31, 2020, 278 280 people were induded in the study; 31 140 were assigned to the colonoscopy group, 60 300 to the faecal immunochemical test group, and 186 840 to the control group. 10 679 (35.1%) of 30 400 people who received an invitation for colonoscopy participated. 33 383 (55.5%) of 60 137 people who received a postal faecal immunochemical test participated. In the intention-to-screen analysis, colorectal cancer was detected in 49 (0.16%) of 31140 people in the colonoscopy group versus 121 (0. 20%) of 60 300 in the faecal immunochemical test group (relative risk [RR] 0.78, 95% CI 0.56-1.09). Advanced adenomas were detected in 637 (2.05%) people in the colonoscopy group and 968 (1.61%) in the faecal immunochemical test group (RR 1.27, 95% CI 1.15-1.41). Colonoscopy detected more right-sided advanced adenomas than faecal immunochemical testing. There were two perforations and 15 major bleeds in 16 555 colonoscopies. No intervention-related deaths occurred. Interpretation The diagnostic yield and the low number of adverse events indicate that the design from this trial, both for once-only colonoscopy and faecal immunochemical test screening, could be transferred to a population-based screening service if a benefit in disease-specific mortality is subsequently shown. Copyright (C) 2022 Elsevier Ltd. All rights reserved.
|
|
