| 31. |
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| 32. |
- Gandaglia, Giorgio, et al.
(författare)
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Clinical Characterization of Patients Diagnosed with Prostate Cancer and Undergoing Conservative Management : A PIONEER Analysis Based on Big Data
- 2024
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Ingår i: European Urology. - 0302-2838. ; 85:5, s. 457-465
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Tidskriftsartikel (refereegranskat)abstract
- Background: Conservative management is an option for prostate cancer (PCa) patients either with the objective of delaying or even avoiding curative therapy, or to wait until palliative treatment is needed. PIONEER, funded by the European Commission Innovative Medicines Initiative, aims at improving PCa care across Europe through the application of big data analytics. Objective: To describe the clinical characteristics and long-term outcomes of PCa patients on conservative management by using an international large network of real-world data. Design, setting, and participants: From an initial cohort of >100 000 000 adult individuals included in eight databases evaluated during a virtual study-a-thon hosted by PIONEER, we identified newly diagnosed PCa cases (n = 527 311). Among those, we selected patients who did not receive curative or palliative treatment within 6 mo from diagnosis (n = 123 146). Outcome measurements and statistical analysis: Patient and disease characteristics were reported. The number of patients who experienced the main study outcomes was quantified for each stratum and the overall cohort. Kaplan-Meier analyses were used to estimate the distribution of time to event data. Results and limitations: The most common comorbidities were hypertension (35–73%), obesity (9.2–54%), and type 2 diabetes (11–28%). The rate of PCa-related symptomatic progression ranged between 2.6% and 6.2%. Hospitalization (12–25%) and emergency department visits (10–14%) were common events during the 1st year of follow-up. The probability of being free from both palliative and curative treatments decreased during follow-up. Limitations include a lack of information on patients and disease characteristics and on treatment intent. Conclusions: Our results allow us to better understand the current landscape of patients with PCa managed with conservative treatment. PIONEER offers a unique opportunity to characterize the baseline features and outcomes of PCa patients managed conservatively using real-world data. Patient summary: Up to 25% of men with prostate cancer (PCa) managed conservatively experienced hospitalization and emergency department visits within the 1st year after diagnosis; 6% experienced PCa-related symptoms. The probability of receiving therapies for PCa decreased according to time elapsed after the diagnosis.
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| 33. |
- Hoogland, Agnes Marije, et al.
(författare)
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Cysteine-rich secretory protein 3 and β-microseminoprotein on prostate cancer needle biopsies do not have predictive value for subsequent prostatectomy outcome.
- 2011
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Ingår i: BJU International. - 1464-4096. ; 108:8, s. 1356-1362
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: • To investigate whether cysteine-rich secretory protein 3 (CRISP-3) and/or β-microseminoprotein (β-MSP) expression in diagnostic prostate needle biopsies have predictive value for prostate cancer (PC) on radical prostatecomy (RP). • To evaluate their potential clinical implementation in a preoperative setting. PATIENTS AND METHODS: • In total, 174 participants from the European Randomized Study of Screening for Prostate Cancer, Rotterdam section, treated by RP for PC were included in the present study. • CRISP-3 and β-MSP immunohistochemistry was performed on corresponding diagnostic needle biopsies. • Outcome was correlated with clinicopathological parameters (prostate-specific-antigen, PSA; number of positive biopsies; Gleason score, GS; pT-stage; surgical margins at RP) and significant PC at RP (pT3/4, or GS > 6, or tumour volume ≥0.5 mL) in the total cohort (n= 174) and in a subgroup with low-risk features at biopsy (PSA ≤ 10 ng/ml, cT ≤ 2, PSA density <0.20 ng/mL/g, GS < 7 and ≤2 positive biopsy cores; n= 87). RESULTS: • β-MSP and CRISP-3 expression in PC tissue was heterogeneous, with variable staining intensities occurring in the same tissue specimen. • High expression of β-MSP significantly correlated with GS < 7 at RP; it was not a predictor for significant PC at RP neither in the total group (n= 174; odds ratio, OR, 0.319; 95% confidence interval, CI, 0.060-1.695; P= 0.180), nor in the low-risk group (n= 87; OR, 0.227; 95% CI, 0.040-1.274; P= 0.092). • CRISP-3 expression was not related to clinicopathological parameters, and did not predict significant PC at RP in the total group (n= 174; OR, 1.056; 95% CI, 0.438-2.545; P= 0.904) or the low-risk group (n= 87; OR, 1.856; 95% CI, 0.626-5.506; P= 0.265). CONCLUSIONS: • High β-MSP expression correlated with low GS in subsequent RP specimens, supporting the view that β-MSP exerts a tumour-suppressive effect. • No significant prognostic value of β-MSP or CRISP-3 in prostate needle biopsies for significant PC at RP was found. • β-MSP or CRISP-3 do not have additional value in the therapeutic stratification of patients with PC.
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| 34. |
- Lawlor, Ailbhe, et al.
(författare)
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Predictive Models for Assessing Patients’ Response to Treatment in Metastatic Prostate Cancer : A Systematic Review
- 2024
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Ingår i: European Urology Open Science. - 2666-1691. ; 63, s. 126-135
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Forskningsöversikt (refereegranskat)abstract
- Background and objective: The treatment landscape of metastatic prostate cancer (mPCa) has evolved significantly over the past two decades. Despite this, the optimal therapy for patients with mPCa has not been determined. This systematic review identifies available predictive models that assess mPCa patients’ response to treatment. Methods: We critically reviewed MEDLINE and CENTRAL in December 2022 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Only quantitative studies in English were included with no time restrictions. The quality of the included studies was assessed using the PROBAST tool. Data were extracted following the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews criteria. Key findings and limitations: The search identified 616 citations, of which 15 studies were included in our review. Nine of the included studies were validated internally or externally. Only one study had a low risk of bias and a low risk concerning applicability. Many studies failed to detail model performance adequately, resulting in a high risk of bias. Where reported, the models indicated good or excellent performance. Conclusions and clinical implications: Most of the identified predictive models require additional evaluation and validation in properly designed studies before these can be implemented in clinical practice to assist with treatment decision-making for men with mPCa. Patient summary: In this review, we evaluate studies that predict which treatments will work best for which metastatic prostate cancer patients. We found that existing studies need further improvement before these can be used by health care professionals.
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| 35. |
- MacLennan, Steven, et al.
(författare)
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Mapping European Association of Urology Guideline Practice Across Europe : An Audit of Androgen Deprivation Therapy Use Before Prostate Cancer Surgery in 6598 Cases in 187 Hospitals Across 31 European Countries
- 2023
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838. ; 83:5, s. 393-401
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Evidence-practice gaps exist in urology. We previously surveyed European Association of Urology (EAU) guidelines for strong recommendations underpinned by high-certainty evidence that impact patient experience for which practice variations were suspected. The recommendation "Do not offer neoadjuvant androgen deprivation therapy (ADT) before surgery for patients with prostate cancer" was prioritised for further investigation. ADT before surgery is neither clinically effective nor cost effective and has serious side effects. The first step in improving implementation problems is to understand their extent. A clear picture of practice regarding ADT before surgery across Europe is not available.OBJECTIVE: To assess current ADT use before prostate cancer surgery in Europe.DESIGN, SETTING, AND PARTICIPANTS: This was an observational cross-sectional study. We retrospectively audited recent ADT practices in a multicentre international setting. We used nonprobability purposive sampling, aiming for breadth in terms of low- versus high-volume, academic, versus community and public versus private centres.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Our primary outcome was adherence to the ADT recommendation. Descriptive statistics and a multilevel model were used to investigate differences between countries across different factors (volume, centre type, and funding type). Subgroup analyses were performed for patients with low, intermediate, and high risk, and for those with locally advanced prostate cancer. We also collected reasons for nonadherence.RESULTS AND LIMITATIONS: We included 6598 patients with prostate cancer from 187 hospitals in 31 countries from January 1, 2017 to May 1, 2020. Overall, nonadherence was 2%, (range 0-32%). Most of the variability was found in the high-risk subgroup, for which nonadherence was 4% (range 0-43%). Reasons for nonadherence included attempts to improve oncological outcomes or preoperative tumour parameters; attempts to control the cancer because of long waiting lists; and patient preference (changing one's mind from radiotherapy to surgery after neoadjuvant ADT had commenced or feeling that the side effects were intolerable). Although we purposively sampled for variety within countries (public/private, academic/community, high/low-volume), a selection bias toward centres with awareness of guidelines is possible, so adherence rates may be overestimated.CONCLUSIONS: EAU guidelines recommend against ADT use before prostate cancer surgery, yet some guideline-discordant ADT use remains at the cost of patient experience and an additional payer and provider burden. Strategies towards discontinuation of inappropriate preoperative ADT use should be pursued.PATIENT SUMMARY: Androgen deprivation therapy (ADT) is sometimes used in men with prostate cancer who will not benefit from it. ADT causes side effects such as weight gain and emotional changes and increases the risk of cardiovascular disease, diabetes, and osteoporosis. Guidelines strongly recommend that men opting for surgery should not receive ADT, but it is unclear how well the guidance is followed. We asked urologists across Europe how patients in their institutions were treated over the past few years. Most do not use ADT before surgery, but this still happens in some places. More research is needed to help doctors to stop using ADT in patients who will not benefit from it.
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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. ; 134:2, s. 291-299
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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. |
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| 38. |
- van Leeuwen, Pim J, et al.
(författare)
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Toward an Optimal Interval for Prostate Cancer Screening.
- 2012
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Ingår i: European urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 61:1, s. 171-176
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The rate of decrease in advanced cancers is an estimate for determining prostate cancer (PCa) screening program effectiveness. OBJECTIVE: Assess the effectiveness of PCa screening programs using a 2- or 4-yr screening interval. DESIGN, SETTING, AND PARTICIPANTS: Men aged 55-64 yr were participants at two centers of the European Randomized Study of Screening for Prostate Cancer: Gothenburg, Sweden (2-yr screening interval, n=4202), and Rotterdam, the Netherlands (4-yr screening interval, n=13 301). We followed participants until the date of PCa, the date of death, or the last follow-up at December 31, 2008, or up to a maximum of 12 yr after initial screening. Potentially life-threatening (advanced) cancer was defined as cancer with at least one of following characteristics: clinical stage ≥T3a, M1, or N1; serum prostate-specific antigen (PSA) >20.0 ng/ml; or Gleason score ≥8 at biopsy. INTERVENTION: We compared the proportional total (advanced) cancer incidence (screen-detected and interval cases), defined as the ratio of the observed number of (advanced) cancers to the expected numbers of (advanced) cancers based on the control arm of the study. MEASUREMENTS: The proportional cancer incidence from the second screening round until the end of observation was compared using a 2- or 4-yr screening interval. RESULTS AND LIMITATIONS: From screening round 2 until the end of observation, the proportional cancer incidence was 3.64 in Gothenburg and 3.08 in Rotterdam (relative risk [RR]: 1.18; 95% confidence interval [CI], 1.04-1.33; p=0.009). The proportional advanced cancer incidence was 0.40 in Gothenburg and 0.69 in Rotterdam (RR: 0.57; 95% CI, 0.33-0.99; p=0.048); the RR for detection of low-risk PCa was 1.46 (95% CI, 1.25-1.71; p<0.001). This study was limited by the assumption that PSA testing in the control arm was similar in both centers. CONCLUSIONS: A 2-yr screening interval significantly reduced the incidence of advanced PCa; however, the 2-yr interval increased the overall risk of being diagnosed with (low-risk) PCa compared with a 4-yr interval in men aged 55-64 yr. Individualized screening algorithms must be improved to provide the strategy for this issue.
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| 39. |
- Vickers, Andrew J., et al.
(författare)
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Empirical estimates of prostate cancer overdiagnosis by age and prostate-specific antigen
- 2014
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Ingår i: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prostate cancer screening depends on a careful balance of benefits, in terms of reduced prostate cancer mortality, and harms, in terms of overdiagnosis and overtreatment. We aimed to estimate the effect on overdiagnosis of restricting prostate specific antigen (PSA) testing by age and baseline PSA. Methods: Estimates of the effects of age on overdiagnosis were based on population based incidence data from the US Surveillance, Epidemiology and End Results database. To investigate the relationship between PSA and overdiagnosis, we used two separate cohorts subject to PSA testing in clinical trials (n = 1,577 and n = 1,197) and a population-based cohort of Swedish men not subject to PSA-screening followed for 25 years (n = 1,162). Results: If PSA testing had been restricted to younger men, the number of excess cases associated with the introduction of PSA in the US would have been reduced by 85%, 68% and 42% for age cut-offs of 60, 65 and 70, respectively. The risk that a man with screen-detected cancer at age 60 would not subsequently lead to prostate cancer morbidity or mortality decreased exponentially as PSA approached conventional biopsy thresholds. For PSAs below 1 ng/ml, the risk of a positive biopsy is 65 (95% CI 18.2, 72.9) times greater than subsequent prostate cancer mortality. Conclusions: Prostate cancer overdiagnosis has a strong relationship to age and PSA level. Restricting screening in men over 60 to those with PSA above median (>1 ng/ml) and screening men over 70 only in selected circumstances would importantly reduce overdiagnosis and change the ratio of benefits to harms of PSA-screening.
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| 40. |
- Vickers, Andrew J., et al.
(författare)
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Screening for Prostate Cancer: Early Detection or Overdetection?
- 2012
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Ingår i: Annual Review of Medicine. - : Annual Reviews. - 0066-4219 .- 1545-326X. ; 63, s. 161-170
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Forskningsöversikt (refereegranskat)abstract
- A sophisticated reading of the randomized trial evidence suggests that, although screening for prostate cancer with prostate-specific antigen (PSA) can reduce cancer-specific mortality, it does so at considerable cost in terms of the number of men who need to be screened, biopsied, and treated to prevent one death. The challenge is to design screening programs that maximize benefits (reducing prostate cancer mortality) and minimize costs (overtreatment). Recent research has suggested that this can be achieved by risk-stratifying screening and biopsy; increasing reliance on active surveillance for low-risk cancer; restricting radical prostatectomy to high-volume surgeons; and using appropriately high-dose radiotherapy. In current U. S. practice, however, many men who are screened are unlikely to benefit, most men found to have low-risk cancers are referred for unnecessary curative treatment, and much treatment is given at low-volume centers.
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