| 1. |
- Godtman, Rebecka Arnsrud, 1981, et al.
(författare)
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Development and validation of a prediction model for identifying men with intermediate- or high-risk prostate cancer for whom bone imaging is unnecessary: a nation-wide population-based study
- 2019
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 53:6, s. 378-384
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To develop and validate a nomogram that identifies men for whom bone scan is unnecessary. Material and methods: The study datasets were derived from the National Prostate Cancer Register (NPCR) of Sweden. All men in the NPCR <= 80 years of age who were diagnosed with intermediate- or high-risk prostate cancer and who had pretreatment bone imaging (Tc-99m MDP scintigraphy, plain x-ray, computed tomography, magnetic resonance imaging, and/or positron emission tomography fused with computed tomography) were included. Men diagnosed from 2015-2016 formed a development dataset and men diagnosed in 2017 formed a validation dataset. Outcome was metastasis on bone imaging as registered in NPCR. Multivariable logistic regression was used to develop a nomogram. Results: In the development dataset 482/5084 men (10%) had bone metastasis, the corresponding percentage in the validation dataset was 282/2554 (11%). Gleason grade group, clinical T stage, and prostate-specific antigen were included in the final model. Discrimination and calibration were satisfactory in both the development (AUC 0.80, 95% CI 0.78-0.82) and validation dataset (AUC 0.80, 95% CI, 0.77-0.82). Compared with using the EAU guidelines' recommendation for selecting men for imaging, using the nomogram with a cut-off at 4% chance of bone metastasis, would have avoided imaging in 519/2068 men (25%) and miss bone metastasis in 10/519 (2%) men in the validation dataset. Conclusion: By use of our nomogram, bone scans of men with prostate cancer can be avoided in a large proportion of men.
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| 2. |
- Alterbeck, Max, et al.
(författare)
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Designing and Implementing a Population-based Organised Prostate Cancer Testing Programme.
- 2022
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Ingår i: European urology focus. - : Elsevier BV. - 2405-4569. ; 8:6, s. 1568-1574
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Tidskriftsartikel (refereegranskat)abstract
- European guidelines recommend that well-informed men at elevated risk of having prostate cancer (PCa) should be offered prostate-specific antigen (PSA) testing with risk-stratified follow-up. The Swedish National Board of Health and Welfare recommends against screening for PCa but supports regional implementation of organised prostate cancer testing (OPT).To report the process for designing and implementing OPT programmes.Population-based OPT programmes in two Swedish regions, designed to include men aged between 50 and 74 yr, launched in September 2020 for 50-yr-old men.The number of men invited, the participation rate, and the numbers of magnetic resonance imaging (MRI) scans, urological visits, and biopsies from September 2020 to June 2021 were recorded.Two Swedish regions co-designed an OPT programme with a risk-stratified diagnostic algorithm based on prostate-specific antigen (PSA), PSA density, MRI findings, and age. An automated administrative system was developed on a nationwide web-based platform. Invitation letters and test results are automatically generated and sent out by post. Men with PSA ≥3ng/ml, a suspicious MRI lesion, and/or PSA density ≥0.15ng/ml/cm3 are referred for a prostate biopsy. Test results are registered for quality control and research. By June 2021, a total of 16515 men were invited, of whom 6309 (38%) participated; 147 had an MRI scan and 39 underwent prostate biopsy. The OPT framework, algorithm, and diagnostic pathways have been working well.We designed and implemented a framework for OPT with a high grade of automation. The framework and organisational experiences may be of value for others who plan a programme for early detection of PCa.We describe the implementation of an organised testing programme for early detection of prostate cancer in two Swedish regions. This model is the first of its kind and may serve as a template for similar programmes.
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| 3. |
- Axén, Elin, et al.
(författare)
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Biochemical recurrence after radical prostatectomy - a large, comprehensive, population-based study with long follow-up
- 2022
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 56:4, s. 287-292
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Tidskriftsartikel (refereegranskat)abstract
- Objective We evaluated long-term risk for biochemical recurrence and subsequent prognosis in a population-based cohort. Material and Methods We used register-based data to evaluate 6 675 consecutive patients having radical prostatectomy in Vastra Gotaland county in Sweden during 1995-2014. Patients were followed until death or end of study, 31 December 2014. Data were collected from registers on national, regional and local level and linked by means of the Swedish personal identity number. Biochemical recurrence was defined as PSA >= 0.2 ng/ml; failure as hormonal treatment, metastasis or prostate cancer death. Survival analysis was used to estimate time to biochemical recurrence and time to failure after biochemical recurrence for patients with 0 - 2 years, 2-5 years, 5-10 years and >10 years interval to biochemical recurrence, respectively. Results A total of 1214 men had biochemical recurrence during follow-up. Biochemical recurrence-free survival was 83% (95% confidence interval [CI] 82-84%), 75% (95% CI 74-77%) and 69% (95% CI 67-71%) at 5, 10 and 15 years, respectively. Cumulative incidence of failure for all patients 15 years after biochemical recurrence was 50% (95% CI 43-55%) in competing risk analysis .The risk of failure after biochemical recurrence was highest among patients having biochemical recurrence within 2 years from surgery. Incomplete data on PSA-history is a limitation. Conclusions The risk for biochemical recurrence persists 15 years after surgery. Follow-up should continue as long as treatment would be considered in case of recurrent disease.
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| 4. |
- Axén, Elin, et al.
(författare)
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Degree of Preservation of Neurovascular Bundles in Radical Prostatectomy and Recurrence of Prostate Cancer
- 2021
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Ingår i: European Urology Open Science. - : Elsevier BV. - 2666-1691 .- 2666-1683. ; 30, s. 25-33
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Tidskriftsartikel (refereegranskat)abstract
- Background: Reports on possible benefits for continence with nerve-sparing (NS) radical prostatectomy have expanded the indications beyond preservation of erectile function. It is unclear whether NS surgery affects oncological outcomes. Objective: To determine whether the degree of NS during radical prostatectomy influences oncological outcomes. Design, setting, and participants: Of 4003 patients enrolled in a prospective, controlled trial comparing open and robotic radical prostatectomy during 2008–2011, we evaluated 2401 patients who received robotic radical prostatectomy at seven Swedish centres. Patients were followed for 8 yr. Outcome measurements and statistical analysis: Data for recurrence and positive surgical margin status were assessed using validated patient questionnaires, patient interviews, and clinical record forms before and at 3, 12, and 24 mo and 6 and 8 yr after surgery. Cox and logistic regressions were used to model the effect on recurrence and positive surgical margins (PSM), respectively. Results and limitations: A total of 481 men had PSM and 467 experienced recurrence during follow-up. Median follow-up for men without recurrence was 6.6 yr. There were no statistically significant differences in recurrence rate between degrees of NS. The PSM rate was significantly higher with a higher degree of NS: interfascial NS, odds ratio (OR) 2.32 (95% confidence interval [CI] 1.69–3.16); intrafascial NS, OR 3.23 (95% CI 2.17–4.80). Recurrence rates were higher for patients with pT2 disease and PSM (hazard ratio [HR] 3.32, 95% CI 2.43–4.53) than for patients with pT3 disease without PSM (HR 2.08, 95% CI 1.66–2.62). The lack of central review of pathological specimens is a limitation. Conclusions: A higher degree of NS significantly increased the risk of PSM but did not significantly increase the risk of cancer recurrence. Combined with the known functional benefits of NS surgery, these results underscore the need to identify an individualised balance. Patient summary: In this report we looked at the effect of a nerve-sparing approach during removal of the prostate on cancer outcomes for patients having robot-assisted surgery at seven Swedish hospitals. We found that a high degree of nerve-sparing increased the rate of cancer positivity at the margins of surgical specimens and that positive surgical margins increased the risk of recurrence of prostate cancer. © 2021 The Authors
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| 5. |
- Bratt, Ola, 1963, et al.
(författare)
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Population-based Organised Prostate Cancer Testing: Results from the First Invitation of 50-year-old Men
- 2024
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Ingår i: European Urology. - 0302-2838 .- 1873-7560. ; 85:3, s. 207-214
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Tidskriftsartikel (refereegranskat)abstract
- Background: The European Union recently recommended evaluation of the feasibility of organised prostate cancer screening. In Sweden, regional population-based organised prostate cancer testing (OPT) programmes were introduced in 2020. Objective: To describe initial participation rates and diagnostic outcomes. Design, setting, and participants: The three most populated Swedish regions invited all men aged 50 yr to OPT by a letter in 2020–2022. Men with prostate-specific antigen (PSA) ≥3 ng/ml were referred for prostate magnetic resonance imaging (MRI). PSA assays differed across regions. Men with Prostate Imaging Reporting and Data System (PI-RADS) 1–3 and PSA density ≥0.15 ng/ml/cm3 or PI-RADS 4–5 were referred for a biopsy. Data were obtained from the Swedish Register for Organised Prostate Cancer Testing. Outcome measurements and statistical analysis: Overall and regional participation rates, PSA distributions, PI-RADS score distributions, cancer detection, and treatment were evaluated. Results and limitations: A total of 23 855 (35%) of 68 060 invited men participated; 696 (2.9%) had PSA ≥3 ng/ml, and of them, 306 (44%) had a biopsy indication and 221 (32%) had a biopsy. On biopsy, 93 (42%) had Gleason grade group ≥2 (0.39% of PSA-tested men) and 44 (20%) Gleason grade group 1 cancer. Most men with cancer had treatment with curative intent (70%) or were under active surveillance (28%). Across regions, proportions of men with PSA ≥3 ng/ml ranged from 2.3% to 4.0%, and those with PI-RADS score 4–5 ranged from 12% to 21%. A limitation is that results are applicable only to first testing of men in their early 50s. Conclusions: The OPT programmes are feasible with good compliance to the diagnostic pathway. The use of MRI and PSA density avoided a biopsy for over half of the men with PSA ≥3 ng/ml. Inter-regional differences in diagnostic outcomes show a need for standardisation of the diagnostic pathway's components. Patient summary: We report the diagnostic outcomes of inviting 68 000 50-yr-old men to organised prostate cancer testing.
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| 6. |
- Bratt, Ola, 1963, et al.
(författare)
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Screening for prostate cancer: evidence, ongoing trials, policies and knowledge gaps
- 2023
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Ingår i: BMJ Oncology. ; 2:1, s. 1-9
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Forskningsöversikt (refereegranskat)abstract
- Long-term screening with serum prostate-specific antigen (PSA) and systematic prostate biopsies can reduce prostate cancer mortality but leads to unacceptable overdiagnosis. Over the past decade, diagnostic methods have improved and the indolent nature of low-grade prostate cancer has been established. These advances now enable more selective detection of potentially lethal prostate cancer. This non-systematic review summarises relevant diagnostic advances, previous and ongoing screening trials, healthcare policies and important remaining knowledge gaps. Evidence synthesis and conclusions: The strong association between low serum PSA values and minimal long-term risk of prostate cancer death allows for adjusting screening intervals. Use of risk calculators, biomarkers and MRI to select men with a raised PSA value for biopsy and lesion-targeting rather than systematic prostate biopsies reduce the detection of low-grade cancer and thereby overdiagnosis. These improvements recently led the European Union to recommend its member states to evaluate the feasibility and effectiveness of organised screening programmes for prostate cancer. Nonetheless, important knowledge gaps remain such as the performance of modern diagnostic methods in long-term screening programmes and their impact on mortality. The knowledge gaps are currently being addressed in three large randomised screening trials. Population-based pilot programmes will contribute critical practical experience.
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| 7. |
- Carlsson, Sigrid, 1982, et al.
(författare)
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Young Age on Starting Prostate-specific Antigen Testing Is Associated with a Greater Reduction in Prostate Cancer Mortality: 24-Year Follow-up of the Goteborg Randomized Population-based Prostate Cancer Screening Trial
- 2023
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838. ; 83:2, s. 103-109
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Tidskriftsartikel (refereegranskat)abstract
- Background: The risk of death from prostate cancer (PC) depends on age, but the age at which to start prostate-specific antigen (PSA) screening remains uncertain. Objective: To study the relationship between risk reduction for PC mortality and age at first PSA screening. Design, setting, and participants: The randomized Goteborg-1 trial invited men for bien-nial PSA screening between the ages of 50 and 70 yr (screening, n = 10 000) or no invi-tation but exposure to opportunistic PSA testing (control, n = 10 000). Intervention: Regular versus opportunistic PSA screening or no PSA. Outcome measurements and statistical analysis: We modeled the nonlinear association between starting age and the absolute risk reduction in PC mortality in three settings: (1) intention-to-screen (randomized arms); (2) historical control (screening group and 1990-1994 registry data); and (3) attendees only (screening attendees and matched controls). We tested whether the effect of screening on PC mortality depends on the age at starting screening by comparing survival models with and without an interaction between trial arm and age (intention-to-screen and attendees only). Results and limitations: Younger age on starting PSA testing was associated with a greater reduction in PC mortality. Starting screening at age 55 yr approximately halved the risk of PC death compared to first PSA at age 60 yr. The test of association between starting age and the effect of screening on PC mortality was slightly greater than the con-ventional level of statistical significance (p = 0.052) for the entire cohort, and statistically significant among attendees (p = 0.002). This study is limited by the low number of disease-specific deaths for men starting screening before age 55 yr and the difficulty in discriminating between the effect of starting age and screening duration. Conclusions: Given that prior screening trials included men aged up to 70 yr on starting screening, our results suggest that the effect size reported in prior trials underestimates that of currently recommended programs starting at age 50-55 yr. Patient summary: In this study from the Goteborg-1 trial, we looked at the effect of prostate-specific antigen (PSA) screening in reducing men's risk of dying from prostate cancer given the age at which they begin testing. Starting at a younger age reduced the risk of prostate cancer death by a greater amount. We recommend that PSA screen-ing should start no later than at age 55 yr. (c) 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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| 8. |
- Cazzaniga, Walter, et al.
(författare)
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Population-based, nationwide registration of prostatectomies in Sweden
- 2019
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Ingår i: Journal of Surgical Oncology. - : Wiley. - 0022-4790 .- 1096-9098. ; 120:4, s. 803-812
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Radical prostatectomy (RP) is a common surgical procedure with a risk of postoperative erectile dysfunction and urinary incontinence. There is a need for data on RP as a basis for quality assurance and benchmarking. Methods In 2015, prostatectomies in Sweden (PiS) form was implemented in the National Prostate Cancer Register (NPCR) of Sweden with data on pre-, peri- and post-operative variables. Results Out of all radical prostatectomies performed in 2016 in Sweden, 3096/3881 (80%) were registered in PiS. A total of 2605 (84%) were robot-assisted radical prostatectomy (RARP) and 491 (16%) were RRP (retropubic radical prostatectomy). RARP was performed by 91 surgeons of whom 47% operated more than 25 RP/year; and RRP was performed by 69 surgeons of whom 10% performed more than 25 RP/year. RARP had a longer operative time (median operating time: RARP 155 minutes [IQR 124-190]; RRP 129 minutes [IQR 105-171]; P < .001) but was associated with smaller bleeding (median intraoperative blood loss: RARP 100 mL [IQR 50-200], RRP 700 mL [IQR 500-1100]; P < .001). Conclusions We report on a nationwide, population-based register with transparent reporting of data on the performance of radical prostatectomy. These data are needed as a basis for quality assurance with comparisons of results from individual surgeons and hospitals.
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| 9. |
- Delbro, Dick, 1950-, et al.
(författare)
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The extracellular matrix-degrading protein ADAMTS5 is expressed in the nuclei of urothelial cells in healthy rats
- 2018
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 52:2, s. 139-142
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to investigate whether protein expression of the extracellular matrix-degrading protease ADAMTS5 can be demonstrated in the urinary bladder of healthy rats, and, if so, to determine the localization of this enzyme. Materials and methods: The experiments were conducted with eight inbred male Sprague-Dawley rats. Immunohistochemistry was used to investigate the expression of ADAMTS5 in the urinary bladder. Negative controls were established by either excluding the primary antibody or applying the antibody after it had been preabsorbed with its immunogenic peptide. Confocal microscopy was used to visualize the distribution of ADAMTS5 in the urinary bladder tissue. Results: Immunoreactivity for ADAMTS5 was demonstrated in the urothelium and in the detrusor. This expression was localized not only in the cytoplasm, but also in the nuclei. Confocal microscopy corroborated these findings. Conclusion: Expression of ADAMTS5 was demonstrated in the cytoplasm as well as in the nuclei of the urothelium and detrusor cells, suggesting that it may play a role at the transcriptional level.
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| 10. |
- Frånlund, Maria, et al.
(författare)
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Prostate cancer risk assessment in men with an initial P.S.A. below 3 ng/mL : results from the Göteborg randomized population-based prostate cancer screening trial
- 2018
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 52:4, s. 256-262
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Objective: To evaluate the long-term outcome of men with an initial prostate-specific antigen (PSA) level below 3 ng/mL and whether the free-to-total (F/T PSA) ratio is a useful prognostic marker in this range. Materials and methods: This study is based on 5,174 men aged 50–66 years, who in 1995–1996 participated in the first round of the Göteborg randomized screening trial (initial T-PSA level <3 ng/mL). These men were subsequently invited biennially for PSA and F/T PSA screening until they reached the upper age limit (on average 69 years). Biopsy was recommended if PSA ≥ 3 ng/mL. Results: After a median follow-up of 18.9 years, 754 men (14.6%) were diagnosed with prostate cancer (PC). The overall cumulative PC incidence was 17.2%. It increased from 7.9% among men with T-PSA of ≤0.99 ng/mL to 26.0% in men with T-PSA levels of 1–1.99 ng/mL and 40.3% in men between 2–2.99 ng/mL (p < 0.001). The initial PSA was also related to the incidence of Gleason ≥7 PC (3.7% vs 9.7% vs 10.9%) and PC death (0.3% vs 1.1% vs 1.5%). Adding F/T PSA did not improve PC prediction in terms of Harrell concordance index (base model 0.76 vs 0.76) nor improvement of the likelihood of the model (p = 0.371). Conclusions: Some men with initial PSA < 3 ng/mL will be diagnosed too late, despite participating in an organized screening program, indicating that prompt diagnosis is justified in these men. PC incidence and risk of PC death was associated with PSA., but F/T PSA had no predictive value.
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| 11. |
- Frånlund, Maria, et al.
(författare)
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Results from 22 years of Followup in the Göteborg Randomized Population-Based Prostate Cancer Screening Trial
- 2022
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Ingår i: Journal of Urology. - 0022-5347 .- 1527-3792. ; 208:2, s. 292-300
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Tidskriftsartikel (refereegranskat)abstract
- Purpose:Our goal was to analyze results from 22 years of followup in the Göteborg randomized prostate cancer (PC) screening trial.Materials and Methods:In December 1994, 20,000 men born 1930-1944 were randomly extracted from the Swedish population register and were randomized (1:1) into either a screening group (SG) or to a control group (CG). Men in the SG were repeatedly invited for biennial prostate specific antigen testing up to an average age of 69 years. Main endpoints were PC incidence and mortality (intention-to-screen principle).Results:After 22 years, 1,528 men in the SG and 1,124 men in the CG had been diagnosed with PC. In total, 112 PC deaths occurred in the SG and 158 in the CG. Compared with the CG, the SG showed a PC incidence rate ratio (RR) of 1.42 (95% CI, 1.31-1.53) and a PC mortality RR of 0.71 (95% CI, 0.55-0.91). The 22-year cumulative PC mortality rate was 1.55% (95% CI, 1.29-1.86) in the SG and 2.13% (95% CI, 1.83-2.49) in the CG. Correction for nonattendance (Cuzick method) yielded a RR of PC mortality of 0.59 (95% CI, 0.43-0.80). Number needed to invite and number needed to diagnose was estimated to 221 and 9, respectively. PC death risk was increased in the following groups: nontesting men, men entering the program after age 60 and men with >10 years of followup after screening termination.Conclusions:Prostate specific antigen-based screening substantially decreases PC mortality. However, not attending, starting after age 60 and stopping at age 70 seem to be major pitfalls regarding PC death risk.
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| 12. |
- Godtman, Rebecka Arnsrud, 1981, et al.
(författare)
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Association of surgeon and hospital volume with short-term outcomes after robot-assisted radical prostatectomy: Nationwide, population-based study
- 2021
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 16:6
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Tidskriftsartikel (refereegranskat)abstract
- Background and objective Few studies have investigated the association between surgical volume and outcome of robot-assisted radical prostatectomy (RARP) in an unselected cohort. We sought to investigate the association between surgical volume with peri-operative and short-term outcomes in a nation-wide, population-based study group. Methods 9,810 RARP's registered in the National Prostate Cancer Register of Sweden (2015-2018) were included. Associations between outcome and volume were analyzed with multivariable logistic regression including age, PSA-density, number of positive biopsy cores, cT stage, Gleason score, and extent of lymph node dissection. Results Surgeons and hospitals in the highest volume group compared to lowest group had shorter operative time; surgeon (OR 9.20, 95% CI 7.11-11.91), hospital (OR 2.16, 95% CI 1.53-3.06), less blood loss; surgeon (OR 2.58. 95% CI 2.07-3.21) hospital (no difference), more often nerve sparing intention; surgeon (OR 2.89, 95% CI 2.34-3.57), hospital (OR 2.02, 95% CI 1.66-2.44), negative margins; surgeon (OR 1.90, 95% CI 1.54-2.35), hospital (OR 1.28, 95% CI 1.07-1.53). There was wide range in outcome between hospitals and surgeons with similar volume that remained after adjustment. Conclusions High surgeon and hospital volume were associated with better outcomes. The range in outcome was wide in all volume groups, which indicates that factors besides volume are of importance. Registration of surgical performance is essential for quality control and improvement.
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| 13. |
- Godtman, Rebecka Arnsrud, 1981, et al.
(författare)
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Constitutive expression of inducible nitric oxide synthase in healthy rat urothelium?
- 2021
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 55:6, s. 493-497
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Tidskriftsartikel (refereegranskat)abstract
- Background Contrasting findings have been reported regarding a possible constitutive expression of inducible nitric oxide synthase (iNOS) in a normal mammalian bladder. The current study was designed to further investigate such putative iNOS expression. Materials and methods The experiments were conducted with paraffin-embedded archival material from the urinary bladder of 6 normal, male Sprague-Dawley rats. In addition, two normal female mice (C57BL/6) were sacrificed and the urinary bladders were harvested. The occurrence of iNOS mRNA was examined by the RNAScope in situ hybridization method. Protein expression of iNOS and 3-nitrotyrosine (the latter used as an indicator of oxidative stress) was investigated by immunohistochemistry. Results No expression of iNOS mRNA was observed in the bladder tissue. iNOS protein and 3-nitrotyrosine were strongly expressed in the urothelium. iNOS was also expressed perinuclearly in the detrusor. Conclusions Although the RNAScope methodology could not demonstrate mRNA for iNOS in the normal urinary bladder, the results by immunohistochemistry strongly suggest the occurrence of iNOS in particular, in the urothelium. Positive reactivity for 3-nitrotyrosine may indicate ongoing oxidative stress of the urothelium. The finding of perinuclear iNOS immunoreactivity could suggest an intracrine signaling function by iNOS to the nucleus.
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| 14. |
- Godtman, Rebecka Arnsrud, 1981, et al.
(författare)
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High accuracy of Swedish death certificates in men participating in screening for prostate cancer: A comparative study of official death certificates with a cause of death committee using a standardized algorithm.
- 2011
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Ingår i: Scandinavian journal of urology and nephrology. - : Informa UK Limited. - 1651-2065 .- 0036-5599.
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Objective. Recently, the first mortality data from the Göteborg Randomized Population-based Prostate Cancer Screening Trial showed a 44% reduction in prostate cancer (PC)-specific mortality as a result of screening with prostate-specific antigen (PSA). As death of PC is the main endpoint, an accurate determination of the cause of death (COD) is crucial. The aim of this study was therefore to investigate the accuracy of death certificates of men in the Göteborg Randomized Population-based Prostate Cancer Screening Trial. Material and methods. Men with a PC diagnosis and who died within the study period (1995-2008) were included. Relevant medical information, including death certificate, was collected. An independent COD committee reviewed the material following a flowchart to classify the COD. The committee's decision was compared with the COD on the death certificate. Results. Of the 285 men included in the study, 278 men were eligible for a comparative analysis. The committee and the death certificates agreed on PC as the underlying COD in 116 men and causes other than PC in 151. There were 11 discordant cases, for an overall agreement of 96%. Men with PC in the screening group had, compared with the control group, a significantly lower PC-specific mortality but did not differ in non-PC-specific mortality. Conclusion. This study concludes that Swedish death certificates are of high accuracy and can be used for endpoint evaluation in screening studies for PC.
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| 15. |
- Godtman, Rebecka Arnsrud, 1981, et al.
(författare)
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Intervention-related Deaths in the European Randomized Study of Screening for Prostate Cancer
- 2021
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Ingår i: European Urology Open Science. - : Elsevier BV. - 2666-1691 .- 2666-1683. ; 34, s. 27-32
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Tidskriftsartikel (refereegranskat)abstract
- Background: Identification of intervention-related deaths is important for an accurate assessment of the ratio of benefit to harm in screening trials. Objective: To investigate intervention-related deaths by study arm in the European Randomized Study of Prostate Cancer Screening (ERSPC). Design, setting, and participants: ERSPC is a multicenter trial initiated in the 1990s to investigate whether screening on the basis of prostate-specific antigen (PSA) can decrease prostate cancer mortality. The present study included men in the core age group (55-69 yr: screening group n = 112 553, control group n = 128 681) with 16-yr follow-up. Outcome measurements and statistical analysis: Causes of death among men with prostate cancer in ERSPC were predominantly evaluated by independent national committees via review of medical records according to a predefined algorithm. Intervention-related deaths were defined as deaths caused by complications during the screening procedure, treatment, or follow-up. Descriptive statistics were used for the results. Results and limitations: In total, 34 deaths were determined to be intervention-related, of which 21 were in the screening arm and 13 in the control arm. The overall risk of intervention-related death was 1.41 (95% confidence interval 0.99-1.99) per 10 000 randomized men for both arms combined and varied among centers from 0 to 7.0 per 10 000 randomized men. A limitation of this study is that differences in procedures among centers decreased the comparability of the results. Conclusions: Intervention-related deaths were rare in ERSPC. Monitoring of intervention-related deaths in screening trials is important for assessment of harms. Patient summary: We investigated deaths due to screening or treatment to assess harm in a trial of prostate cancer screening. Few such deaths were identified. (c) 2021 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-NC-ND license (http://creative- commons.org/licenses/by-nc-nd/4.0/).
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| 16. |
- Godtman, Rebecka Arnsrud, 1981, et al.
(författare)
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Long-Term Outcomes after Deferred Radical Prostatectomy in Men Initially Treated with Active Surveillance
- 2018
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Ingår i: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5347 .- 1527-3792. ; 200:4, s. 779-785
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: We sought to determine long-term outcomes after deferred radical prostatectomy. Materials and Methods: The study population consisted of all 132 men with screening detected prostate cancer who underwent deferred radical prostatectomy from January 1, 1995 to December 31, 2014 after active surveillance in the Goteborg Randomized, Population-based Prostate Cancer Screening Trial. The last date of followup was May 15, 2017. Followup during active surveillance was performed with prostate specific antigen tests every 3 to 6 months and repeat biopsies every 2 to 4 years. Triggers for radical prostatectomy were disease progression based on prostate specific antigen, grade and/or stage, or patient request. Outcomes included adverse pathology findings at radical prostatectomy, defined as Gleason score greater than 3 thorn 4, extraprostatic extension, positive margins, seminal vesicle invasion and/or Nthorn, whether the index tumor at radical prostatectomy was identified at biopsy and prostate specific antigen relapse-free survival. Kaplan-Meier analysis was performed. Results: Median time from diagnosis to surgery was 1.9 years (IQR 1.2-4.2) and median postoperative followup was 10.9 years (IQR 7.5-14.5). A total of 52 men (39%) experienced at least 1 unfavorable pathology feature at radical prostatectomy. The 10-year prostate specific antigen relapse-free survival was 79.5%. The index tumor was not identified in the diagnostic biopsy in 38 of the 132 men (29%) or at the last repeat biopsy that preceded radical prostatectomy 22 of 105 (21%). Conclusions: A large proportion of men had unfavorable pathology findings at deferred radical prostatectomy and the index tumor was frequently not identified. There is a clear need for better risk classification and protocols to determine disease progression during active surveillance.
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| 17. |
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| 18. |
- Godtman, Rebecka Arnsrud, 1981, et al.
(författare)
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Men's Acceptance of Screening for Prostate Cancer with Prostate-specific Antigen, Magnetic Resonance Imaging, and Prostate Biopsy
- 2024
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Ingår i: EUROPEAN UROLOGY ONCOLOGY. - 2588-9311. ; 7:3, s. 553-562
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Tidskriftsartikel (refereegranskat)abstract
- Background: A prerequisite before introducing a screening program is that the screening examinations are acceptable to participants. Objective: To evaluate the acceptance and bother of prostate cancer screening examinations. Design, setting, and participants: The randomized population -based G & Ouml;TEBORG-2 prostate cancer screening trial invited >37 000 men for prostate -specific antigen (PSA) testing followed by magnetic resonance imaging (MRI) in case of elevated PSA and prostate biopsy (targeted and/or systematic) if indicated. Outcome measurements and statistical analysis: Participants were asked to fill out a questionnaire and rate the level of bother associated with each examination (PSA, MRI, and prostate biopsy) on a categorical scale ranging from 1 to 5 (1 = "not at all bothersome" and 5 = "very bothersome"), and to rate their willingness to repeat the examinations, by marking an X on a continuous scale ranging from 0 to 10 (0 = "yes, without any hesitation" and 10 = "no, absolutely not''). Wilcoxon signed rank test was used. Results and limitations: Compliance with MRI was 96% (1790/1872), compliance with biopsy was 89% (810/907), and the response rate to the questionnaire was 75% (608/810). Men who underwent all examinations ( n = 577) responded that biopsy was more bothersome than PSA test ( p < 0.001) and MRI ( p < 0.001). High levels of bother (>= 4 out of 5) were reported by 2% (12/577) for PSA test, 8% (46/577) for MRI, and 43% (247/577) for biopsy. Men were more willing to repeat MRI than biopsy ( p < 0.001), but the difference was small (median 0.2 [interquartile range 0.1-0.6] vs 0.5 [0.1-2.0]). Conclusions: Biopsies are more bothersome than MRI, but a large majority of men accept to repeat both examinations if necessary. Omitting biopsy for MRI-negative men and shifting to targeted biopsies only will reduce bother for men participating in prostate cancer screening. Patient summary: We asked men how bothersome they found the prostate -specific antigen (PSA) test, magnetic resonance imaging (MRI), and prostate biopsies. Biopsies were more bothersome than PSA and MRI, but most men were willing to repeat all procedures if necessary. (c) 2023 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 -NC -ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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| 19. |
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| 20. |
- Godtman, Rebecka Arnsrud, 1981, et al.
(författare)
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Outcome Following Active Surveillance of Men with Screen-detected Prostate Cancer. Results from the Göteborg Randomised Population-based Prostate Cancer Screening Trial.
- 2013
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Ingår i: European urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 63:1, s. 101-107
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Active surveillance (AS) has emerged as a treatment strategy for reducing overtreatment of screen-detected, low-risk prostate cancer (PCa). OBJECTIVE: To assess outcomes following AS of men with screen-detected PCa. DESIGN, SETTING, AND PARTICIPANTS: Of the 968 men who were diagnosed with screen-detected PCa between 1995 and 2010 in the Göteborg randomised, population-based PCa screening trial, 439 were managed with AS and were included in this study. Median age at diagnosis was 65.4 yr of age, and median follow-up was 6.0 yr from diagnosis. INTERVENTION: The study participants were followed at intervals of 3-12 mo and were recommended to switch to deferred active treatment in case of a progression in prostate-specific antigen, grade, or stage. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The end points-overall survival (OS), treatment-free survival, failure-free (no relapse after radical treatment) survival, and cancer-specific survival-were calculated for various risk groups (very low, low, intermediate, and high) with Kaplan-Meier estimates. A Cox proportional hazards model as well as a competing risk analysis were used to assess whether risk group or age at diagnosis was associated with failure after AS. RESULTS AND LIMITATIONS: Forty-five per cent of all screen-detected PCa were managed with AS, and very low-risk and low-risk PCa constituted 60% of all screen-detected PCa. Thirty-seven per cent (162 of 439) switched from surveillance to deferred active treatment, and 39 men failed AS. The 10-yr OS, treatment-free survival, and failure-free survival were 81.1%, 45.4%, and 86.4%, respectively (Kaplan-Meier estimates). Men with low-, intermediate-, and high-risk tumours had a hazard ratio for failure of 2.1 (p=0.09), 3.6 (p=0.002), and 4.6 (p=0.15), respectively, compared to very low-risk tumours (Cox regression). Only one PCa death occurred, and one patient developed metastasis (both in the intermediate-risk group). The main limitation of this study is the relatively short follow-up. CONCLUSIONS: A large proportion of men with screen-detected PCa can be managed with AS. AS appears safe for men with low-risk PCa.
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| 21. |
- Godtman, Rebecka Arnsrud, 1981, et al.
(författare)
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[Prostate cancer - diagnostics and screening]. : Prostatacancer – utredning, klinisk diagnostik och screening.
- 2024
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Ingår i: Lakartidningen. - 1652-7518. ; 121
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Tidskriftsartikel (refereegranskat)abstract
- Prostate-specific antigen (PSA) based screening is controversial, even though randomised trials show that screening can reduce prostate cancer mortality. The main reason is that screening leads to overdiagnosis of indolent cancers that would never have surfaced clinically in the absence of screening. Recently, several large studies have shown that magnetic resonance imaging (MRI) improves prostate cancer diagnostics. With MRI, up to half of all men with elevated PSA values can be spared a biopsy. When a biopsy is needed, the needles can be directed towards the suspicious area in the prostate, which increases the detection of clinically significant tumors. In Sweden, regional programmes with organised prostate cancer testing were introduced in 2020. These programmes aim to make prostate cancer testing more standardized, efficient, and equitable. In the future, biomarkers and AI-based systems will likely be important to further improve prostate cancer diagnostics.
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| 22. |
- Godtman, Rebecka Arnsrud, 1981
(författare)
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Prostate Cancer Screening - Aspects of Overdiagnosis
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall aim of this thesis is to explore aspects of overdiagnosis, i.e. the diagnosis of a tumor that in the absence of screening would never have been diagnosed, in prostate cancer (PC) screening. The four papers in this thesis all emerge from the Göteborg randomized population-based PC screening trial, in which 10,000 men were invited to biennial prostate-specific antigen (PSA)-screening between 1995 and 2014 and 10,000 non-invited constituted a control group. In paper I, the accuracy of cause of death (COD) certificates, for men with PC, is evaluated by comparison with the COD as assigned by an independent committee after blinded review of medical records. Paper II assesses outcomes for men with screen-detected PC managed with, so called “active surveillance”. In paper III, organized screening is compared with opportunistic screening with respect to effectiveness in reducing PC mortality, measured as the number needed to invite (NNI) to screening and overdiagnosis, measured as number needed to diagnose (NND) to prevent one man from dying from PC. Paper IV investigates the risk of being diagnosed with PC depending on age at screening and the number of screens. The overall agreement between COD certificates and the committee was 96%. A large proportion of men screen-detected PC has low-risk PC (60%) and could safely be managed with active surveillance, at least with intermediate follow-up. Organized screening was more effective in reducing PC mortality and was associated with less overdiagnosis than opportunistic screening (NNI 139, NND 13 versus NNI 493, NNI 23). The risk of being diagnosed with PC increased dramatically with age but there was no apparent relation to the number of screens. From this thesis it can be concluded that Swedish COD certificates have a high accuracy and can be used for COD determination for men with PC, at least in the age-range studied (50-64 years old at the start of screening). Active surveillance appears safe for men with low-risk PC and should be used as a treatment strategy in order to reduce overtreatment. In order to reduce overdiagnosis and improve the benefit harm ratio of PC screening, screening should be conducted within the frameworks of an organized program where “younger” men could be screened relatively intense but where “older” men are screened more selectively.
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| 23. |
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| 24. |
- Godtman, Rebecka Arnsrud, 1981, et al.
(författare)
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Surgeon volume and patient-reported urinary incontinence after radical prostatectomy. Population-based register study in Sweden
- 2022
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813.
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the association between surgeon volume and urinary incontinence after radical prostatectomy. Methods: A total of 8326 men in The National Prostate Cancer Register of Sweden (NPCR) underwent robot-assisted radical prostatectomy (RARP) between 2017 and 2019 of whom 56% (4668/8 326) had responded to a questionnaire one year after RARP. The questionnaire included the question: ‘How much urine leakage do you experience?’ with the response alternatives ‘Not at all’, ‘A little’, defined as continence and ‘Moderately’, ‘Much/Very much’ as incontinence. Association between incontinence and mean number of RARPs/year/surgeon was analysed with multivariable logistic regression including age, Charlson Comorbidity Index (CCI), PSA, prostate volume, number of biopsy cores with cancer, cT stage, Gleason score, lymph node dissection, nerve sparing intent and response rate to the questionnaire. Results: 14% (659/4 668) of the men were incontinent one year after RARP. There was no statistically significant association between surgeon volume and incontinence. Older age (>75 years vs. < 65 years, OR 2.29 [95% CI 1.48–3.53]), higher CCI (CCI 2+ vs. CCI 0, OR 1.37 [95% CI 1.04–1.80]) and no nerve sparing intent (no vs. yes OR 1.53 [95% CI 1.26–1.85]) increased risk of incontinence. There were large differences in the proportion of incontinent men between surgeons with similar annual volumes, which remained after adjustment. Conclusions: The lack of association between surgeon volume and incontinence and the wide range in outcome between surgeons with similar volumes underline the importance of individual feedback to surgeons on functional results. © 2022 The Author(s). Published by Informa UK Limited trading as Taylor & Francis Group.
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| 25. |
- Godtman, Rebecka Arnsrud, 1981, et al.
(författare)
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The Association Between Age, Prostate Cancer Risk, and Higher Gleason Score in a Long-term Screening Program: Results from the Göteborg-1 Prostate Cancer Screening Trial
- 2022
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838. ; 82:3, s. 311-317
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies have suggested associations between greater age, increased risk of prostate cancer (PC), and higher Gleason score. Objective: The present study aimed at investigating these associations within the Göteborg-1 randomized, population-based PC screening trial. Design, setting, and participants: The screening arm of the Göteborg-1 screening trial comprises 10 000 randomly selected men (aged 50–64 yr at randomization) from the Göteborg region of Sweden. Between 1995 and 2014, they were biennially invited to prostate-specific antigen (PSA) testing to an upper age limit of 70 yr (range 67–71 yr). PSA ≥3 ng/ml triggered a prostate biopsy (sextant biopsy 1995–2009, thereafter a ten-core biopsy). Outcome measurements and statistical analysis: The impact of age on Gleason score, given a screen-detected PC, was investigated with multinomial logistic regression analyses adjusted for year of testing and screening round. Results and limitations: Overall, 7625 men had at least one PSA test and 1022 men were diagnosed with PC. For men with screen-detected PC, age was associated with the risk of clinically significant PC above and beyond screening round and year of testing (p < 0.001). For each 1-yr increase in age, the risk of being diagnosed with a Gleason score ≥3 + 4 cancer (vs <7) increased by 11% (95% confidence interval [CI] 4.7–17), whereas the risk of being diagnosed with a Gleason score ≥4 + 3 cancer (vs <7) increased by 8.5% (95% CI –1.6 to 20). Conclusions: The increased risk of a higher Gleason score in older men should be considered when counseling men regarding early diagnosis and treatment for PC. Patient summary: We found that older age increased both the risk of prostate cancer and the risk of more aggressive prostate cancer. © 2022 The Authors
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| 26. |
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| 27. |
- Godtman, Rebecka Arnsrud, 1981, et al.
(författare)
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The extracellular matrix proteoglycan versican is strongly expressed in the urothelium of healthy rats
- 2019
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 53:6, s. 431-434
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We have previously demonstrated protein expression of the extracellular matrix degrading protein ADAMTS5 in the nuclei of urothelial cells in healthy rats. The proteoglycan versican constitutes one of the main substrates for this protease. In this follow up study we investigated a potential co-localization of versican and ADAMTS5 in the urinary bladder wall. Material and Methods: The study was conducted with archive material (paraffin embedded bladder tissue from our previous study, i.e., 8 male Sprague-Dawley rats). Protein expression of versican was investigated by immunohistochemistry. Furthermore, the occurrence of versican mRNA was examined by in-situ hybridization. Results: Positive immunoreactivity for versican was evident in the urothelium but also, weakly, in the detrusor. This expression was localized only in the cytoplasm, leaving the nuclei devoid of reactivity. Interestingly, versican mRNA was only sparsely observed in the urothelial cells. Conclusions: We found by immunohistochemistry that the substrate for ADAMTS5, versican, was localized in the cytosol of urothelial cells. This demonstrates a difference regarding the expression of ADAMTS5, which was emphasized in the nuclei. This could imply an additional, non-enzymatic, function of ADAMTS5 in the urothelium.
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| 28. |
- Hugosson, Jonas, 1955, et al.
(författare)
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A 16-yr Follow-up of the European Randomized study of Screening for Prostate Cancer
- 2019
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838. ; 76:1, s. 43-51
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Tidskriftsartikel (refereegranskat)abstract
- Background: The European Randomized study of Screening for Prostate Cancer (ERSPC) has previously demonstrated that prostate-specific antigen (PSA) screening decreases prostate cancer (PCa) mortality. Objective: To determine whether PSA screening decreases PCa mortality for up to 16 yr and to assess results following adjustment for nonparticipation and the number of screening rounds attended. Design, setting, and participants: This multicentre population-based randomised screening trial was conducted in eight European countries. Report includes 182 160 men, followed up until 2014 (maximum of 16 yr), with a predefined core age group of 162 389 men (55-69 yr), selected from population registry. Outcome measurements and statistical analysis: The outcome was PCa mortality, also assessed with adjustment for nonparticipation and the number of screening rounds attended. Results and limitations: The rate ratio of PCa mortality was 0.80 (95% confidence interval [CI] 0.72-0.89, p < 0.001) at 16 yr. The difference in absolute PCa mortality increased from 0.14% at 13 yr to 0.18% at 16 yr. The number of men needed to be invited for screening to prevent one PCa death was 570 at 16 yr compared with 742 at 13 yr. The number needed to diagnose was reduced to 18 from 26 at 13 yr. Men with PCa detected during the first round had a higher prevalence of PSA >20 ng/ml (9.9% compared with 4.1% in the second round, p < 0.001) and higher PCa mortality (hazard ratio = 1.86, p < 0.001) than those detected subsequently. Conclusions: Findings corroborate earlier results that PSA screening significantly reduces PCa mortality, showing larger absolute benefit with longer follow-up and a reduction in excess incidence. Repeated screening may be important to reduce PCa mortality on a population level. Patient summary: In this report, we looked at the outcomes from prostate cancer in a large European population. We found that repeated screening reduces the risk of dying from prostate cancer. (C) 2019 Published by Elsevier B.V. on behalf of European Association of Urology.
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| 29. |
- Hugosson, Jonas, 1955, et al.
(författare)
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Eighteen-year follow-up of the Göteborg Randomized Population-based Prostate Cancer Screening Trial : effect of sociodemographic variables on participation, prostate cancer incidence and mortality
- 2018
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 52:1, s. 27-37
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study examined whether previously reported results, indicating that prostate-specific antigen (PSA) screening can reduce prostate cancer (PC) mortality regardless of sociodemographic inequality, could be corroborated in an 18 year follow-up. Materials and methods: In 1994, 20,000 men aged 50–64 years were randomized from the Göteborg population register to PSA screening or control (1:1) (study ID: ISRCTN54449243). Men in the screening group (n = 9950) were invited for biennial PSA testing up to the median age of 69 years. Prostate biopsy was recommended for men with PSA ≥2.5 ng/ml. Last follow-up was on 31 December 2012. Results: In the screening group, 77% (7647/9950) attended at least once. After 18 years, 1396 men in the screening group and 962 controls had been diagnosed with PC [hazard ratio 1.51, 95% confidence interval (CI) 1.39–1.64]. Cumulative PC mortality was 0.98% (95% CI 0.78–1.22%) in the screening group versus 1.50% (95% CI 1.26–1.79%) in controls, an absolute reduction of 0.52% (95% CI 0.17–0.87%). The rate ratio (RR) for PC death was 0.65 (95% CI 0.49–0.87). To prevent one death from PC, the number needed to invite was 231 and the number needed to diagnose was 10. Systematic PSA screening demonstrated greater benefit in PC mortality for men who started screening at age 55–59 years (RR 0.47, 95% CI 0.29–0.78) and men with low education (RR 0.49, 95% CI 0.31–0.78). Conclusions: These data corroborate previous findings that systematic PSA screening reduces PC mortality and suggest that systematic screening may reduce sociodemographic inequality in PC mortality.
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| 30. |
- Hugosson, Jonas, 1955, et al.
(författare)
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Prostate Cancer Screening with PSA and MRI Followed by Targeted Biopsy Only.
- 2022
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Ingår i: The New England journal of medicine. - 1533-4406. ; 387:23, s. 2126-2137
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Tidskriftsartikel (refereegranskat)abstract
- Screening for prostate cancer is burdened by a high rate of overdiagnosis. The most appropriate algorithm for population-based screening is unknown.We invited 37,887 men who were 50 to 60 years of age to undergo regular prostate-specific antigen (PSA) screening. Participants with a PSA level of 3 ng per milliliter or higher underwent magnetic resonance imaging (MRI) of the prostate; one third of the participants were randomly assigned to a reference group that underwent systematic biopsy as well as targeted biopsy of suspicious lesions shown on MRI. The remaining participants were assigned to the experimental group and underwent MRI-targeted biopsy only. The primary outcome was clinically insignificant prostate cancer, defined as a Gleason score of 3+3. The secondary outcome was clinically significant prostate cancer, defined as a Gleason score of at least 3+4. Safety was also assessed.Of the men who were invited to undergo screening, 17,980 (47%) participated in the trial. A total of 66 of the 11,986 participants in the experimental group (0.6%) received a diagnosis of clinically insignificant prostate cancer, as compared with 72 of 5994 participants (1.2%) in the reference group, a difference of -0.7 percentage points (95% confidence interval [CI], -1.0 to -0.4; relative risk, 0.46; 95% CI, 0.33 to 0.64; P<0.001). The relative risk of clinically significant prostate cancer in the experimental group as compared with the reference group was 0.81 (95% CI, 0.60 to 1.1). Clinically significant cancer that was detected only by systematic biopsy was diagnosed in 10 participants in the reference group; all cases were of intermediate risk and involved mainly low-volume disease that was managed with active surveillance. Serious adverse events were rare (<0.1%) in the two groups.The avoidance of systematic biopsy in favor of MRI-directed targeted biopsy for screening and early detection in persons with elevated PSA levels reduced the risk of overdiagnosis by half at the cost of delaying detection of intermediate-risk tumors in a small proportion of patients. (Funded by Karin and Christer Johansson's Foundation and others; GÖTEBORG-2 ISRCTN Registry number, ISRCTN94604465.).
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| 31. |
- Kohestani, Kimia, et al.
(författare)
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The Göteborg prostate cancer screening 2 trial: a prospective, randomised, population-based prostate cancer screening trial with prostate-specific antigen testing followed by magnetic resonance imaging of the prostate
- 2021
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 55:2, s. 116-124
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Tidskriftsartikel (refereegranskat)abstract
- Objective To describe the study design of the GoTEBORG prostate cancer screening (PC) 2 (Goteborg-2), a prospective, randomised, population-based trial of PC screening. This trial evaluates whether prostate-specific antigen (PSA) testing followed by 3 Tesla prostate magnetic resonance imaging (MRI) and targeted biopsy can reduce overdiagnosis, while maintaining the detection of clinically significant cancer, compared to PSA-screening and systematic biopsy. Materials and methods A random sample of men 50-60 years in the Goteborg area, Sweden, identified from the Total Population Register, were randomised to either a screening or control group (CG). Participants in the screening group (SG) were further randomised into one of three arms: (1) PSA-test; if PSA >= 3 ng/mL, then MRI and systematic biopsy, plus targeted biopsy to suspicious lesions as per Prostate Imaging - Reporting and Data System, version 2 (PI-RADSv2) 3-5; (2) PSA-test; if PSA >= 3 ng/mL, then MRI, and targeted biopsy only if PI-RADSv2 3-5; (3) identical to Arm 2, except lower PSA-cut-off >= 1.8 ng/mL. The primary outcome is the detection rate of clinically insignificant PC (defined as Gleason Score 3 + 3 [Grade Group 1]) comparing all men with PSA >= 3 ng/mL in Arm 1 vs. Arm 2 + 3. Results Randomisation and enrolment started in September 2015. Accrual has hitherto resulted in 38,770 men randomised to the SG. The participation rate is 50%. Invitation to the first screening round was completed in June 2020. Conclusions The Goteborg-2 trial will provide new knowledge about the performance of prostate MRI in a screening setting.
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| 32. |
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| 33. |
- Möller, Fredrik, 1990, et al.
(författare)
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Prostate Cancers in the Prostate-specific Antigen Interval of 1.8-3 ng/ml: Results from the Göteborg-2 Prostate Cancer Screening Trial.
- 2024
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Ingår i: European Urology. - 0302-2838. ; 86:2, s. 95-100
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Tidskriftsartikel (refereegranskat)abstract
- Magnetic resonance imaging (MRI) and targeted biopsies reduce overdiagnosis of prostate cancer (PC). It is uncertain how this strategy performs for low prostate-specific antigen (PSA) levels.To investigate the Prostate Imaging Reporting and Data System (PI-RADS) distribution, frequency, and characteristics of screen-detected PC with PSA of 1.8-<3 ng/ml and 3-<10 ng/ml.In the population-based Göteborg-2 screening study, 17974 men choose to participate by having a PSA test (2015-2020). One-third of the participants (n=6006) were randomized to arm 3, men with a PSA value of ≥1.8 ng/ml were recommended for MRI. Men with positive MRI (PI-RADS 3-5) had four targeted biopsies from each MRI-visible lesion.Clinically significant PC was defined as Gleason score ≥3+4.A total of 6006 men were included. The median age was 55.9 yr (interquartile range [IQR] 52.6-59.6). Of them, 4929 (82%) had PSA of <1.8 ng/ml, 670 (11%) had PSA of 1.8-<3 ng/ml (low-PSA group, median PSA 2.1 ng/ml [IQR 1.9-2.5]), and 377 (6.3%) had PSA of 3-<10 ng/ml (high-PSA group, median PSA 3.9 ng/ml [IQR 3.3-5.0]). PI-RADS scores of 3, 4, and 5 were observed in 7.8%, 15%, and 1.0% of men in the low-PSA group, and in 6.9%, 17%, and 5.3% of men in the high-PSA group, respectively. PC was found in 64 men (41%, 95% confidence interval [CI] 0.33-0.49) with positive MRI findings in the low-PSA group, of whom 33 (21%) had Gleason 6 (insignificant PC) and 31 (20%) had Gleason ≥7 (significant PC). In the high-PSA group, PC was detected in 61 men (56%, 95% CI 0.46-0.66), of whom 26 (24%) had Gleason 6 (insignificant PC) and 35 (32%) had Gleason ≥7 (significant PC). Limitations include results from only a single screening round.A non-negligible number of men with PSA 1.8-3 ng/ml have clinically significant PC. Whether a delay in the diagnosis of these tumors until they reached PSA ≥3 ng/ml would impair their chance of cure remains to be evaluated.We studied screening using prostate-specific antigen (PSA) and magnetic resonance imaging in men with PSA 1.8-3 ng/ml. We found a non-negligible number of potentially harmful prostate cancers in these men.
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| 34. |
- Padhani, Anwar R., et al.
(författare)
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Key learning on the promise and limitations of MRI in prostate cancer screening
- 2024
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Ingår i: EUROPEAN RADIOLOGY. - 0938-7994 .- 1432-1084.
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Forskningsöversikt (refereegranskat)abstract
- MRI retains its ability to reduce the harm of prostate biopsies by decreasing biopsy rates and the detection of indolent cancers in population-based screening studies aiming to find clinically significant prostate cancers. Limitations of low positive predictive values and high reader variability in diagnostic performance require optimisations in patient selection, imaging protocols, interpretation standards, diagnostic thresholds, and biopsy methods. Improvements in diagnostic accuracy could come about through emerging technologies like risk calculators and polygenic risk scores to select men for MRI. Furthermore, artificial intelligence and workflow optimisations focused on streamlining the diagnostic pathway, quality control, and assurance measures will improve MRI variability. Clinical relevance statement MRI significantly reduces harm in prostate cancer screening, lowering unnecessary biopsies and minimizing the overdiagnosis of indolent cancers. MRI maintains the effective detection of high-grade cancers, thus improving the overall benefit-to-harm ratio in population-based screenings with or without using serum prostate-specific antigen (PSA) for patient selection. Key Points center dot The use of MRI enables the harm reduction benefits seen in individual early cancer detection to be extended to both risk-stratified and non-stratified prostate cancer screening populations. center dot MRI limitations include a low positive predictive value and imperfect reader variability, which require standardising interpretations, biopsy methods, and integration into a quality diagnostic pathway. center dot Current evidence is based on one-time point use of MRI in screening; MRI effectiveness in multiple rounds of screening is not well-documented.
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| 35. |
- Palmstedt, Emmeli, et al.
(författare)
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Long-term Outcomes for Men in a Prostate Screening Trial with an Initial Benign Prostate Biopsy: A Population-based Cohort
- 2019
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Ingår i: European Urology Oncology. - : Elsevier BV. - 2588-9311. ; 2:6, s. 716-722
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Tidskriftsartikel (refereegranskat)abstract
- Background: The optimal follow-up regimen for men after a benign prostate biopsy remains unknown. Objective: To investigate long-term outcomes for men after an initial benign prostate biopsy. Design, setting, and participants: All men with a benign biopsy in the first screening round of the Goteborg prostate cancer (PC) screening trial were included. The follow-up period was January 1, 1995-May 15, 2017. Intervention: Prostate-specific antigen (PSA) tests were performed every second year (upper median age limit 69 yr). Men with PSA >= 3 ng/ml underwent prostate biopsy (sextant biopsy up to 2009). Outcome measurement and statistical analysis: The 20-yr cumulative PC incidence and PC mortality were calculated using the 1 minus Kaplan-Meier method. Results and limitations: Of 452 men with a benign biopsy and followed for a median of 21.1 yr, 169 were diagnosed with PC and five died from PC. The 20-yr cumulative PC incidence and PC mortality were 40.0% and 1.4%, respectively. The corresponding figures were 38.8% and 0.6% for men with initial PSA <= 10 ng/ml, and 64.4% and 21.4% for PSA >10 ng/ml. The proportion of men untreated at final follow-up was similar in the two PSA groups (22% vs 23%). The use of sextant biopsy for many years of the trial is a limitation. Conclusions: Men with an initial benign prostate biopsy run a very low risk of dying from PC when participating in a screening program. However, if followed for a long period, many men will be diagnosed and treated for PC. Low-intensity follow-up, as in the Goteborg trial, appears sufficient for men with PSA <= 10 ng/ml after a benign biopsy. Patient summary: This study shows that men who participate in a prostate cancer screening trial have a low risk of dying from prostate cancer if the first biopsy does not show cancer. (C) 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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| 36. |
- Pasanen, Niko, et al.
(författare)
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Which men benefit from prostate cancer screening? Prostate cancer mortality by subgroup in the European Randomised Study of Screening for Prostate Cancer
- 2024
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Ingår i: BJU INTERNATIONAL. - 1464-4096 .- 1464-410X.
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo evaluate whether a subgroup of men can be identified that would benefit more from screening than others.Materials and MethodsThis retrospective cohort study was based on three European Randomised Study of Screening for Prostate Cancer (ERSPC) centres, Finland, the Netherlands and Sweden. We identified 126 827 men aged 55-69 years in the study who were followed for maximum of 16 years after randomisation. The primary outcome was prostate cancer (PCa) mortality. We analysed three age groups 55-59, 60-64 and 65-69 years and PCa cases within four European Association of Urology (EAU) risk groups: low, intermediate, high risk, and advanced disease.ResultsThe hazard ratio (HR) for PCa mortality in the screening arm relative to the control arm for men aged 55-59 years was 0.96 (95% confidence interval [CI] 0.75-1.24) in Finland, 0.70 (95% CI 0.44-1.12) in the Netherlands and 0.42 (95% CI 0.24-0.73) in Sweden. The HR for men aged 60-64 years was 1.03 (95% CI 0.77-1.37) in Finland, 0.76 (95% CI 0.50-1.16) in the Netherlands and 0.97 (95% CI 0.64-1.48) in Sweden. The HR for men aged 65-69 years was 0.80 (95% CI 0.62-1.03) in Finland and 0.57 (95% CI 0.38-0.83) in the Netherlands, and this age group was absent in Sweden. In the EAU risk group analysis, PCa mortality rates were materially lower for men with advanced disease at diagnosis in all three countries: 0.67 (95% CI 0.56-0.82) in Finland, 0.28 (95% CI 0.18-0.44) in the Netherlands, and 0.48 (95% CI 0.30-0.78) in Sweden.ConclusionWe were unable to unequivocally identify the optimal age group for screening, as mortality reduction differed among centres and age groups. Instead, the screening effect appears to depend on screening duration, and the number and frequency of screening rounds. PCa mortality reduction by screening is largely attributable to stage shift.
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| 37. |
- Remmers, S., et al.
(författare)
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Relationship Between Baseline Prostate-specific Antigen on Cancer Detection and Prostate Cancer Death: Long-term Follow-up from the European Randomized Study of Screening for Prostate Cancer
- 2023
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Ingår i: European Urology. - 0302-2838. ; 84:5, s. 503-509
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Tidskriftsartikel (refereegranskat)abstract
- Background: The European Association of Urology guidelines recommend a risk-based strategy for prostate cancer screening based on the first prostate-specific antigen (PSA) level and age.Objective: To analyze the impact of the first PSA level on prostate cancer (PCa) detection and PCa-specific mortality (PCSM) in a population-based screening trial (repeat screening every 2-4 yr). Design, setting, and participants: We evaluated 25 589 men aged 55-59 yr, 16 898 men aged 60-64 yr, and 12 936 men aged 65-69 yr who attended at least one screening visit in the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial (screening arm: repeat PSA testing every 2-4 yr and biopsy in cases with elevated PSA; control arm: no active screening offered) during 16-yr follow-up (FU).Outcome measurements and statistical analysis: We assessed the actuarial probability for any PCa and for clinically significant (cs)PCa (Gleason >7). Cox proportional-hazards regression was performed to assess whether the association between baseline PSA andPCSM was comparable for all age groups. A Lorenz curve was computed to assess the association between baseline PSA and PCSM for men aged 60-61 yr.Results and limitations: The overall actuarial probability at 16 yr ranged from 12% to 16% for any PCa and from 3.7% to 5.7% for csPCa across the age groups. The actuarial proba-bility of csPCa at 16 yr ranged from 1.2-1.5% for men with PSA <1.0 ng/ml to 13.3-13.8% for men with PSA >3.0 ng/ml. The association between baseline PSA and PCSM differed marginally among the three age groups. A Lorenz curve for men aged 60-61 yr showed that 92% of lethal PCa cases occurred among those with PSA above the median (1.21 ng/ ml). In addition, for men initially screened at age 60-61 yr with baseline PSA <2 ng/ml, further continuation of screening is unlikely to be beneficial after the age of 68-70 yr if PSA is still <2 ng/ml. No case of PCSM emerged in the subsequent 8 yr (up to age 76-78 yr). A limitation is that these results may not be generalizable to an opportunistic screening setting or to contemporary clinical practice. Conclusions: In all age groups, baseline PSA can guide decisions on the repeat screening interval. Baseline PSA of <1.0 ng/ml for men aged 55-69 yr is a strong indicator to delay or stop further screening. Patient summary: In prostate cancer screening, the patient's baseline PSA (prostate-specific antigen) level can be used to guide decisions on when to repeat screening. The PSA test when used according to current knowledge is valuable in helping to reduce the burden of prostate cancer.
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| 38. |
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| 39. |
- Stinesen-Kollberg, Karin, et al.
(författare)
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Prostate Specific Antigen and Biopsy Contamination in the Goteborg-1 Randomized, Population-Based, Prostate Cancer Screening Trial
- 2022
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Ingår i: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5347 .- 1527-3792. ; 208:5, s. 1018-1027
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Tidskriftsartikel (refereegranskat)abstract
- Purpose:Even when a screening study has demonstrated a mortality reduction, the degree of pre-testing and contamination is of importance as it can dilute the "true" effect of screening. Our object was to describe the level of pre-testing and contamination in the Goteborg-1 prostate cancer screening trial.Materials and Methods:A total of 20,000 men, 50-64 years old, were invited in 1994 and randomized to either a screening group (offered prostate specific antigen testing every 2 years) or to a control group. Follow-up was through December 31, 2014. Outcome measurement was overall testing in the screening group and control group. A positive prostate specific antigen test was defined as a prostate specific antigen >= 3 ng/ml.Results:In the study, 4.2% in the screening group and 4.6% men in the control group were tested before study start. During follow-up, 72% in the control group took at least 1 prostate specific antigen test (contamination) compared to 87% of men in the screening group. Of all prostate specific antigens, 24% in the screening group and 39% in the control group were above threshold. In total, 66% of the men underwent prostate biopsy within 12 months from a raised prostate specific antigen in the screening group and 28% in the control group.Conclusions:Similar proportions of men were prostate specific antigen-tested in both the screening group and control group, yet only a minority of contamination prostate specific antigens led to biopsy. Also, men in the screening group started screening at a younger age. These could both be explanations for our result that organized screening is more effective in reducing prostate cancer mortality than non-organized testing. When carried out properly and compared to an unscreened population, the effects of organized screening are likely even greater than previously shown in the Goteborg screening trial.
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| 40. |
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| 41. |
- Wallström, Jonas, et al.
(författare)
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Bi- or multiparametric MRI in a sequential screening program for prostate cancer with PSA followed by MRI? Results from the Goteborg prostate cancer screening 2 trial
- 2021
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Ingår i: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 31, s. 8692-8702
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Tidskriftsartikel (refereegranskat)abstract
- Objectives The PIRADS Steering Committee has called for "higher quality data before making evidence-based recommendations on MRI without contrast enhancement as an initial diagnostic work up," however, recognizing biparametric (bp) MRI as a reasonable option in a low-risk setting such as screening. With bpMRI, more men can undergo MRI at a lower cost and they can be spared the invasiveness of intravenous access. The aim of this study was to assess cancer detection in bpMRI vs mpMRI in sequential screening for prostate cancer (PCa). Methods Within the ongoing Goteborg PCa screening 2 trial, we assessed cancer detection in 551 consecutive participants undergoing prostate MRI. In the same session, readers first assessed bpMRI and then mpMRI. Four targeted biopsies were performed for lesions scored PIRADS 3-5 with bpMRI and/or mpMRI. Results Cancer was detected in 84/551 cases (15.2%; 95% CI: 12.4-18.4) with mpMRI and in 83/551 cases (15.1%; 95% CI: 12.3-18.2%) with bpMRI. The relative risk (RR) for cancer detection with bpMRI compared to mpMRI was 0.99 (95% one-sided CI: > 94.8); bpMRI was non-inferior to mpMRI (10% non-inferiority margin). bpMRI resulted in fewer false positives, 45/128 (35.2%), compared to mpMRI, 52/136 (38.2%), RR = 0.92; 95% CI: 0.84-0.98. Of 8 lesions scored positive only with mpMRI, 7 were false positives. The PPV for MRI and targeted biopsy was 83/128 (64.8%) for bpMRI and 84/136 (61.8%) for mpMRI, RR = 1.05, 95% CI: 1.01-1.10. Conclusions In a PSA-screened population, bpMRI was non-inferior to mpMRI for cancer detection and resulted in fewer false positives.
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| 42. |
- Wallström, Jonas, et al.
(författare)
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Prostate Cancer Screening with Magnetic Resonance Imaging: Results from the Second Round of the Göteborg Prostate Cancer Screening 2 Trial.
- 2022
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Ingår i: European urology oncology. - : Elsevier BV. - 2588-9311. ; 5:1, s. 54-60
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Tidskriftsartikel (refereegranskat)abstract
- The Göteborg 2 prostate cancer (PC) screening (G2) trial evaluates screening with prostate-specific antigen (PSA) followed by magnetic resonance imaging (MRI) in case of elevated PSA levels.To assess the safety of using a 2-yr interval in men who were previously screened positive with PSA but had negative MRI or positive MRI with a negative biopsy.A total of 61 201 men aged 50-60 yr were randomized and 38 366 were invited for screening (years 2015-2020). Men with positive MRI (Prostate Imaging Reporting and Data System [PI-RADS] score ≥3) were scheduled for targeted biopsies. Men with negative MRI or negative biopsies were reinvited after 2yr. Round 1 and 2 MRI scans (PI-RADS ≥3) of men not diagnosed with PC in round 1 were re-read and classified according to Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) by two radiologists. Interval PCs (detected outside the program before invitation to round 2) were identified by linking to the Regional PC Registry.Tabulation of overall detection of PC was done.Between October 2017 and June 2020, 474 men with round 1 elevated PSA and MRI underwent a second screening. Of those, 19% had nonelevated PSA in round 2 and were not examined further. Of the remaining 376 men, 89% had negative MRI. Targeted biopsies yielded 14 PCs: nine grade group (GG) 1 and five GG 2-3. In men with PI-RADS ≥3 and PC diagnosed in round 2, only two (GG 1) progressed according to the PRECISE criteria and the remainder were stable. Ten interval PCs were diagnosed: seven GG 1, one GG 2, and two GG 5. The two GG 5 PCs were PI-RADS 4 and 5 with negative round 1 biopsy.A 2-yr interval seems to be safe in men with negative MRI, while men with PI-RADS 4 and 5 lesions with negative biopsies should have a closer follow-up.In prostate cancer screening, a 2-yr follow-up seems to be safe if magnetic resonance imaging did not show highly suspicious findings.
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