| 1. |
- Rannikko, Antti, et al.
(författare)
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Population-based randomized trial of screening for clinically significant prostate cancer ProScreen : a pilot study
- 2022
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Ingår i: BJU International. - : Wiley. - 1464-4096 .- 1464-410X. ; 130:2, s. 193-199
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To evaluate the feasibility of a population-based screening trial using prostate-specific antigen (PSA), a kallikrein panel and multiparametric magnetic resonance imaging (MRI) aimed at minimizing overdiagnosis, while retaining mortality benefit. Patients and Methods: Feasibility of the screening algorithm was evaluated in terms of participation, screening test results and cancer detection. A random sample of 400 men aged 65 years was identified from the population registry and invited for screening with three stepwise tests (PSA, kallikrein panel and MRI). Men with PSA levels ≥3 ng/mL were further tested with the kallikrein panel, and those with positive findings (risk >7.5%) were referred for prostate MRI. Men with positive MRI (Prostate Imaging Reporting and Data System [PI-RADS] score 3–5) had targeted biopsies only. Men with negative MRI, but PSA density ≥0.15 underwent systematic biopsies. Results: Of the 399 men invited, 158 (40%) participated and 27 had PSA levels ≥3 ng/mL (7% of the invited and 17% of the participants). Of these, 22 had a positive kallikrein panel (6% of the invited and 81% of the PSA-positive men). Finally, 10 men (3% of the invited and 45% of 4Kscore [kallikrein panel]-positive) had a suspicious MRI finding (PI-RADS score ≥3) and five were diagnosed with a clinically significant prostate cancer (Gleason Grade Group [GG] ≥2) at fusion biopsy (3% of the participants), with two GG 1 cases (1%). Additional testing (kallikrein panel and MRI) after PSA reduced biopsies by 56%. Conclusion: The findings constitute proof of principle for our screening protocol, as we achieved a substantial detection rate for clinically significant cancer with few clinically insignificant cases. Participation, however, was suboptimal.
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| 2. |
- Auvinen, Anssi, et al.
(författare)
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Prostate Cancer Screening With PSA, Kallikrein Panel, and MRI : The ProScreen Randomized Trial
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Ingår i: JAMA. - 0098-7484. ; , s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: Prostate-specific antigen (PSA) screening has potential to reduce prostate cancer mortality but frequently detects prostate cancer that is not clinically important.OBJECTIVE: To describe rates of low-grade (grade group 1) and high-grade (grade groups 2-5) prostate cancer identified among men invited to participate in a prostate cancer screening protocol consisting of a PSA test, a 4-kallikrein panel, and a magnetic resonance imaging (MRI) scan.DESIGN, SETTING, AND PARTICIPANTS: The ProScreen trial is a clinical trial conducted in Helsinki and Tampere, Finland, that randomized 61 193 men aged 50 through 63 years who were free of prostate cancer in a 1:3 ratio to either be invited or not be invited to undergo screening for prostate cancer between February 2018 and July 2020.INTERVENTIONS: Participating men randomized to the intervention underwent PSA testing. Those with a PSA level of 3.0 ng/mL or higher underwent additional testing for high-grade prostate cancer with a 4-kallikrein panel risk score. Those with a kallikrein panel score of 7.5% or higher underwent an MRI of the prostate gland, followed by targeted biopsies for those with abnormal prostate gland MRI findings. Final data collection occurred through June 31, 2023.MAIN OUTCOMES AND MEASURES: In descriptive exploratory analyses, the cumulative incidence of low-grade and high-grade prostate cancer after the first screening round were compared between the group invited to undergo prostate cancer screening and the control group.RESULTS: Of 60 745 eligible men (mean [SD] age, 57.2 [4.0] years), 15 201 were randomized to be invited and 45 544 were randomized not to be invited to undergo prostate cancer screening. Of 15 201 eligible males invited to undergo screening, 7744 (51%) participated. Among them, 32 low-grade prostate cancers (cumulative incidence, 0.41%) and 128 high-grade prostate cancers (cumulative incidence, 1.65%) were detected, with 1 cancer grade group result missing. Among the 7457 invited men (49%) who refused participation, 7 low-grade prostate cancers (cumulative incidence, 0.1%) and 44 high-grade prostate cancers (cumulative incidence, 0.6%) were detected, with 7 cancer grade groups missing. For the entire invited screening group, 39 low-grade prostate cancers (cumulative incidence, 0.26%) and 172 high-grade prostate cancers (cumulative incidence, 1.13%) were detected. During a median follow-up of 3.2 years, in the group not invited to undergo screening, 65 low-grade prostate cancers (cumulative incidence, 0.14%) and 282 high-grade prostate cancers (cumulative incidence, 0.62%) were detected. The risk difference for the entire group randomized to the screening invitation vs the control group was 0.11% (95% CI, 0.03%-0.20%) for low-grade and 0.51% (95% CI, 0.33%-0.70%) for high-grade cancer.CONCLUSIONS AND RELEVANCE: In this preliminary descriptive report from an ongoing randomized clinical trial, 1 additional high-grade cancer per 196 men and 1 low-grade cancer per 909 men were detected among those randomized to be invited to undergo a single prostate cancer screening intervention compared with those not invited to undergo screening. These preliminary findings from a single round of screening should be interpreted cautiously, pending results of the study's primary mortality outcome.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03423303.
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| 3. |
- Conti, David, V, et al.
(författare)
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Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
- 2021
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
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| 4. |
- Schröder, Fritz H, et al.
(författare)
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Screening and prostate-cancer mortality in a randomized European study.
- 2009
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Ingår i: The New England journal of medicine. - 1533-4406 .- 0028-4793. ; 360:13, s. 1320-8
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The European Randomized Study of Screening for Prostate Cancer was initiated in the early 1990s to evaluate the effect of screening with prostate-specific-antigen (PSA) testing on death rates from prostate cancer.
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| 5. |
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| 6. |
- Wang, Anqi, et al.
(författare)
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Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
- 2023
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
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Tidskriftsartikel (refereegranskat)abstract
- The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
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| 7. |
- Auvinen, Anssi, et al.
(författare)
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Test sensitivity in the European prostate cancer screening trial: results from Finland, Sweden, and the Netherlands.
- 2009
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Ingår i: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. - 1538-7755. ; 18:7, s. 2000-5
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Tidskriftsartikel (refereegranskat)abstract
- Test sensitivity pertains to the ability of a test to identify subjects with the target disorder. In cancer screening, test sensitivity can be estimated using interval cancer incidence as an indicator of false-negative result. A randomized trial provides the optimal approach for estimating test sensitivity, as the control arm provides the expected rates. We estimated the sensitivity of the prostate-specific antigen test using incidence method, i.e., based on incidence of interval cancer among subjects with negative screening results, compared with that in the control arm. Data from three centers in the European randomized screening trial were used to estimate interval cancer incidence (I(I)) among 39,389 men with negative screening tests. This was compared with incidence among the 79,525 men in the control arm of the trial (I(c)) to estimate test sensitivity (S = 1 - I(I) / I(C)). Confidence intervals were calculated using simulations, assuming that the number of cases follows a Poisson distribution. The estimated test sensitivity following the first screen was 0.87 (0.83-0.92) in Finland, 0.87 (0.62-1.00) in Sweden, and 0.93 (95% confidence interval, 0.90-0.96) in the Netherlands. There was some indication of a higher test sensitivity for aggressive cancers (0.85-0.98 for non-organ-confined cases or Gleason 8-10) and for the second screening round (approximately 0.85-0.95). Test sensitivity varied to some extent between the three centers in the European trial, probably reflecting variation in screening protocols, but was acceptable in the first screening round, and may be better for aggressive cancers and in the second screening round.
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| 8. |
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| 9. |
- 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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