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- Van Hemelrijck, Mieke, et al.
(författare)
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Reasons for Discontinuing Active Surveillance : Assessment of 21 Centres in 12 Countries in the Movember GAP3 Consortium
- 2019
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838. ; 75:3, s. 523-531
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Tidskriftsartikel (refereegranskat)abstract
- Background: Careful assessment of the reasons for discontinuation of active surveillance (AS) is required for men with prostate cancer (PCa). Objective: Using Movember's Global Action Plan Prostate Cancer Active Surveillance initiative (GAP3) database, we report on reasons for AS discontinuation. Design, setting, and participants: We compared data from 10 296 men on AS from 21 centres across 12 countries. Outcome measurements and statistical analysis: Cumulative incidence methods were used to estimate the cumulative incidence rates of AS discontinuation. Results and limitations: During 5-yr follow-up, 27.5% (95% confidence interval [CI]: 26.4–28.6%) men showed signs of disease progression, 12.8% (95% CI: 12.0–13.6%) converted to active treatment without evidence of progression, 1.7% (95% CI: 1.5–2.0%) continued to watchful waiting, and 1.7% (95% CI: 1.4–2.1%) died from other causes. Of the 7049 men who remained on AS, 2339 had follow-up for >5 yr, 4561 had follow-up for <5 yr, and 149 were lost to follow-up. Cumulative incidence of progression was 27.5% (95% CI: 26.4–28.6%) at 5 yr and 38.2% (95% CI: 36.7–39.9%) at 10 yr. A limitation is that not all centres were included due to limited information on the reason for discontinuation and limited follow-up. Conclusions: Our descriptive analyses of current AS practices worldwide showed that 43.6% of men drop out of AS during 5-yr follow-up, mainly due to signs of disease progression. Improvements in selection tools for AS are thus needed to correctly allocate men with PCa to AS, which will also reduce discontinuation due to conversion to active treatment without evidence of disease progression. Patient summary: Our assessment of a worldwide database of men with prostate cancer (PCa) on active surveillance (AS) shows that 43.6% drop out of AS within 5 yr, mainly due to signs of disease progression. Better tools are needed to select and monitor men with PCa as part of AS.
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| 2. |
- Beckmann, Kerri, et al.
(författare)
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Androgen Deprivation Therapies and Changes in Comorbidity : A Comparison of Gonadotropin-releasing Hormone Agonists and Antiandrogen Monotherapy as Primary Therapy in Men with High-risk Prostate Cancer
- 2019
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Ingår i: European Urology. - : ELSEVIER SCIENCE BV. - 0302-2838 .- 1873-7560. ; 75:4, s. 676-683
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Tidskriftsartikel (refereegranskat)abstract
- Background: Some studies suggest that gonadotropin-releasing hormone (GnRH) agonists are associated with higher risk of adverse events than antiandrogens (AAs) monotherapy. However, it has been unclear whether this is due to indication bias.Objective: To investigate rates of change in comorbidity for men on GnRH agonists versus AA monotherapy in a population-based register study.Design, setting, and participants: Men with advanced nonmetastatic prostate cancer (PCa) who received primary AA (n = 2078) or GnRH agonists (n = 4878) and age- and area-matched PCa-free men were selected from Prostate Cancer Database Sweden 3.0. Increases in comorbidity were measured using the Charlson Comorbidity Index (CCI), from 5 yr before through to 5 yr after starting androgen deprivation therapy (ADT).Outcome measures and statistical methods: Multivariable linear regression was used to determine differences in excess rate of CCI change before and after ADT initiation. Risk of any incremental change in CCI following ADT was assessed using multivariable Cox regression analyses.Results and limitations: Men on GnRH agonists experienced a greater difference in excess rate of CCI change after starting ADT than men on AA monotherapy (5.6% per yr, p < 0.001). Risk of any new CCI change after ADT was greater for GnRH agonists than for AA (hazard ratio, 1.32; 95% confidence interval, 1.20-144).Conclusions: Impact on comorbidity was lower for men on AA monotherapy than for men on GnRH agonists. Our results should be confirmed through randomised trials of effectiveness and adverse effects, comparing AA monotherapy and GnRH agonists in men with advanced nonmetastatic PCa who are unsuitable for curative treatment.Patient summary: Hormone therapies for advanced prostate cancer can increase the risk of other diseases (eg, heart disease, diabetes). This study compared two common forms of hormone therapy and found that the risk of another serious disease was higher for those on gonadotropin-releasing hormone agonists than for those on antiandrogen monotherapy.
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| 5. |
- Thomsen, Frederik Birkebæk, et al.
(författare)
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Gonadotropin-releasing Hormone Agonists, Orchiectomy, and Risk of Cardiovascular Disease : Semi-ecologic, Nationwide, Population-based Study
- 2017
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 72:6, s. 920-928
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In observational studies, men with prostate cancer treated with gonadotropin-releasing hormone (GnRH) agonists had a higher risk of cardiovascular disease (CVD) compared to men who had undergone orchiectomy. However, selection bias may have influenced the difference in risk.OBJECTIVE: To investigate the association of type of androgen deprivation therapy (ADT) with risk of CVD while minimising selection bias.DESIGN, SETTING, AND PARTICIPANTS: Semi-ecologic study of 6556 men who received GnRH agonists and 3330 men who underwent orchiectomy as primary treatment during 1992-1999 in the Prostate Cancer Database Sweden 3.0.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We measured the proportion of men who received GnRH agonists as primary treatment in 580 experimental units defined by healthcare provider, diagnostic time period, and age at diagnosis. Incident or fatal CVD events in units with high and units with low use of GnRH agonists were compared. Net and crude probabilities were also analysed.RESULTS AND LIMITATIONS: The risk of CVD was similar between units with the highest and units with the lowest proportion of GnRH agonist use (relative risk 1.01, 95% confidence interval [CI] 0.93-1.11). Accordingly, there was no difference in the net probability of CVD after GnRH agonist compared to orchiectomy (hazard ratio 1.02, 95% CI 0.96-1.09). The 10-yr crude probability of CVD was 0.56 (95% CI 0.55-0.57) for men on GnRH agonists and 0.52 (95% CI 0.50-0.54) for men treated with orchiectomy. The main limitation was the nonrandom allocation to treatment, with younger men with lower comorbidity and less advanced cancer more likely to receive GnRH agonists.CONCLUSION: Our data do not support previous observations that GnRH agonists increase the risk of CVD in comparison to orchiectomy.PATIENT SUMMARY: We found a similar risk of cardiovascular disease between medical and surgical treatment as androgen deprivation therapy for prostate cancer.
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| 6. |
- Van Hemelrijck, Mieke, et al.
(författare)
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Multiple events of fractures and cardiovascular and thromboembolic disease following prostate cancer diagnosis : results from the population-based PCBaSe Sweden
- 2012
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 61:4, s. 690-700
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To date, adverse events of prostate cancer (PCa) treatment have only been studied as a single event, and little is known about the risk of subsequent adverse events. OBJECTIVE: We assessed the frequency of multiple events (fractures, stroke, heart disease [HD], and thromboembolic disease [TED]) following PCa diagnosis. DESIGN, SETTING, AND PARTICIPANTS: PCBaSe Sweden is based on the National Prostate Cancer Register (NPCR) that covers >96% of incident PCa cases in Sweden. MEASUREMENTS: We evaluated the number of events (fractures, stroke, HD, and TED) leading to hospitalisation recorded in the National Hospital Discharge Registry after PCa diagnosis and conducted multivariate age-adjusted Cox proportional hazards regression to estimate the risk of developing multiple events. RESULTS AND LIMITATIONS: Between 1997 and 2007, 30 642 men received primary endocrine treatment, 26 432 curative treatment, and 19 526 surveillance: 75% had no event during follow-up, 17% had one event, and 9% had more than one event. The incidence of any event was 102 in 1000 person-years. Men who already had experienced an event, particularly HD, before or after the date of PCa diagnosis were more likely to have multiple events afterwards. For example, the hazard ratio of developing a third event for those with two or more events of HD before PCa diagnosis was 1.40 (95% confidence interval, 1.28-1.52) compared with those with no events of HD before PCa diagnosis. Events treated without hospitalisation were not included, so the number of adverse events is possibly underestimated. CONCLUSIONS: A third of PCa patients with an adverse event after treatment subsequently experienced another adverse event, but apart from history of HD or stroke before PCa diagnosis, no specific characteristics were found for these men. Thus PCa management needs to take into account the risk of adverse events in all PCa patients, especially those with a history of adverse events before PCa diagnosis.
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| 7. |
- Van Hemelrijck, Mieke, et al.
(författare)
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Quantifying the Transition from Active Surveillance to Watchful Waiting Among Men with Very Low-risk Prostate Cancer
- 2017
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Ingår i: European Urology. - : ELSEVIER SCIENCE BV. - 0302-2838 .- 1873-7560. ; 72:4, s. 534-541
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Tidskriftsartikel (refereegranskat)abstract
- Background: Active surveillance (AS) is commonly used for men with low-risk prostate cancer (PCa). When life expectancy becomes too short for curative treatment to be beneficial, a change from AS to watchful waiting (WW) follows. Little is known about this change since it is rarely documented in medical records.Objective: To model transition from AS to WW and how this is affected by age and comorbidity among men with very low-risk PCa.Design, setting, and participants: National population-based healthcare registers were used for analysis.Outcome measurements and statistical analysis: Using data on PCa characteristics, age, and comorbidity, a state transition model was created to estimate the probability of changes between predefined treatments to estimate transition from AS to WW.Results and limitations: Our estimates indicate that 48% of men with very low-risk PCa starting AS eventually changed to WW over a life course. This proportion increased with age at time of AS initiation. Within 10 yr from start of AS, 10% of men aged 55 yr and 50% of men aged 70 yr with no comorbidity at initiation changed to WW. Our prevalence simulation suggests that the number of men on WW who were previously on AS will eventually stabilise after 30 yr. A limitation is the limited information from clinical follow-up visits (eg, repeat biopsies).Conclusions: We estimated that changes from AS to WW become common among men with very low-risk PCa who are elderly. This potential change to WW should be discussed with men starting on AS. Moreover, our estimates may help in planning health care resources allocated to men on AS, as the transition to WW is associated with lower demands on outpatient resources.Patient summary: Changes from active surveillance to watchful waiting will become more common among men with very low-risk prostate cancer. These observations suggest that patients need to be informed about this potential change before they start on active surveillance.
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