To be screened or not to be screened? Modeling the consequences of PSA screening for the individual

Wever, Elisabeth M.; Hugosson, Jonas; Heijnsdijk, Eveline A.M.; Bangma, Chris H.; Draisma, Gerrit; Koning, Harry J. de

doi:10.1038/bjc.2012.317

Cited by 22 publications

(18 citation statements)

References 26 publications

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“…Additionally, there is considerable uncertainty regarding the benefit of screening. Nonetheless, our results seem to be consistent with previous literature …”

Section: Discussionsupporting

confidence: 94%

“…This is the case since the comorbidity lifetables were based on Medicare data. While this can be considered a serious limitation, it was already shown that a large proportion of overdiagnosis occurs in men older than 60 …”

Section: Discussionmentioning

confidence: 99%

“…Additionally, no study has yet modeled the association between overdiagnosis and comorbidity in prostate cancer for screen‐detected men. This association could have a critical impact on the estimates of, specially for men with significant comorbidities.…”

mentioning

confidence: 99%

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Estimating the individual benefit of immediate treatment or active surveillance for prostate cancer after screen‐detection in older (65+) men

Carvalho

Heijnsdijk

Koning

2016

Intl Journal of Cancer

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A significant proportion of screen-detected men with prostate cancer is likely to be overtreated, especially in older age groups. We aim to find which groups of screen-detected older men (651) benefit the most from Immediate Radical Treatment or Active Surveillance (AS) for prostate cancer, depending on age, screening history, health status and prostate cancer stage at detection. We used a microsimulation model (MISCAN) of the natural history of prostate cancer based on ERSPC data. Individual life histories are simulated with US comorbidity lifetables based on a random sample of MEDICARE data. Different screening histories are simulated and we count outcomes for men screen-detected from ages 66 to 72. For immediately treated men with low-risk disease ( T2a, Gleason 6) the probability of overtreatment ranges from 61% to 86% decreasing to between 37 and 46%, if they are assigned to AS. For intermediate risk men ( T2, Gleason 3 1 4) overtreatment ranges from 23 to 60%, which reduces to between 16 and 31% for AS. For high risk men (T3, or ! Gleason 4 1 3), overtreatment ranges from 11 to 51%. The disease stage at screen-detection is a critical risk factor for overtreatment. For low risk men, AS seems to significantly reduce overtreatment at a modest cost. For intermediate risk men, the decision between immediate treatment or AS depends on age and comorbidity status. Men screen-detected in a high risk disease stage may benefit from immediate treatment even beyond age 69.Overdiagnosis consists of the detection of cancer that would not develop into clinical cancer in absence of screening, or eventually be life-threatening. If an overdiagnosed man is referred for radical treatment then he is considered to be overtreated. In a context of limited healthcare resources, it is crucial to identify which patients are at risk of overtreatment and therefore could be better handled by Active Surveillance (AS) or be left untreated.Estimates of overdiagnosis in prostate cancer can vary considerably. Depending on, whether an excess incidence approach is used or, on the specific microsimulation model, estimates range between 23 and 60% of screen-detected men.

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“…Additionally, there is considerable uncertainty regarding the benefit of screening. Nonetheless, our results seem to be consistent with previous literature …”

Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

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Estimating the individual benefit of immediate treatment or active surveillance for prostate cancer after screen‐detection in older (65+) men

Carvalho

Heijnsdijk

Koning

2016

Intl Journal of Cancer

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“…However, in the appendix of Heijnsdijk et al (2012), it is shown that the incidence of prostate cancer in the screen arm of all centres of the ERSPC is predicted well by the model. Also, in the United States, the estimated lifetime risk of prostate cancer diagnosis is 16.22% and of prostate cancer death is 2.79% (SEER, 2010), which are close to lifetime risks of this model (Wever et al , 2012). Therefore, the results can also be applied in the US population.…”

Section: Discussionsupporting

confidence: 66%

Treatment of local–regional prostate cancer detected by PSA screening: benefits and harms according to prognostic factors

et al. 2013

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Background:Men with screen-detected prostate cancer can choose to undergo immediate curative treatment or enter into an expectant management programme. We quantified how the benefits and harms of immediate treatment vary according to the prognostic factors of clinical T-stage, Gleason score, and patient age.Methods:A microsimulation model based on European Randomized Study of Screening for Prostate Cancer data was used to predict the benefits and harms of immediate treatment versus delayed treatment of local–regional prostate cancer in men aged 55–74 years. Benefits included life-years gained and reduced probability of death from prostate cancer. Harms included lead time and probability of overdiagnosis.Results:The ratio of mean lead time to mean life-years gained ranged from 1.8 to 31.2, and the additional number of treatments required per prostate cancer death prevented ranged from 0.3 to 11.6 across the different prognostic groups. Both harm–benefit ratios were lowest, most favourable, for men aged 55–59 years and diagnosed with moderate-risk prostate cancer. Ratios were high for men aged 70–74 years regardless of clinical T-stage and Gleason score.Conclusion:Men aged 55–59 years with moderate-risk prostate cancer are predicted to derive greatest benefit from immediate curative treatment. Immediate treatment is least favourable for men aged 70–74 years with either low-risk or high-risk prostate cancer.

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“…It is an excellent marker in the follow-up of PC patients managed medically or surgically. However, there are significant issues with PSA’s diagnostic, screening,31 and predictive/prognostic value 32…”

Section: Current Markersmentioning

confidence: 99%

The genetics of neuroendocrine prostate cancers: a review of current and emerging candidates

Ather¹,

Siddiqui²

2012

TACG

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Prostate cancer (PC) displays a strong familial link and genetic factors; genes regulating inflammation may have a pivotal role in the disease. Epigenetic changes control chromosomal integrity, gene functions, and, ultimately, carcinogenesis. The most widely studied epigenetic event in PC is aberrant DNA methylation (hypo- and hypermethylation); besides this, chromatin remodeling and micro RNA (miRNA) are other studied alterations in PC. These all lead to genomic instability and inappropriate gene expression. Causative dysfunction of histone modifying enzymes results in generic and locus-specific changes in chromatin remodeling. miRNA deregulation also contributes to prostate carcinogenesis, including interference with androgen-receptor signaling and apoptosis. These epigenetic alterations have the potential to act as biomarkers for PC for screening and diagnosis as well as prognosis and follow-up. The variable biological potential for a newly diagnosed PC is one of the biggest challenges. The other major clinical problem is in the management of castration-resistant PC. Neuroendocrine (NE) differentiation is one of the putative explanations for the development of castration-resistant disease. Most advanced and poorly differentiated cancer does not produce prostate-specific antigen (PSA) in response to disease progression. Circulating and tissue biomarkers like chromogranin A (CgA) thus become important tools. There is the potential to use various genetic and epigenetic alterations and NE differentiation as therapeutic targets in the management of PC. However, we are still some distance from developing clinically effective tools. Valuable insights into the nature of NE differentiation in PC have been gained in the last decades, but additional understanding of its pathogenetic mechanisms is needed. This will help in devising novel therapeutic strategies to develop targeted therapies. CgA has the potential to become an important marker of advanced castration-resistant PC in cases where prostate-specific antigen can no longer be relied upon. Aberrant androgen-receptor signaling at various levels provides evidence of the importance of this pathway for the development of castration-resistant PC. Many epigenetic influences – in particular, the role of changing miRNA expression – provide valuable insights. Currently, massive sequencing efforts are underway to define important somatic genetic alterations (amplifications, deletions, point mutations, translocations) in PC, and these alterations hold great promise as prognostic markers and for predicting response to therapy.

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To be screened or not to be screened? Modeling the consequences of PSA screening for the individual

Cited by 22 publications

References 26 publications

Estimating the individual benefit of immediate treatment or active surveillance for prostate cancer after screen‐detection in older (65+) men

Estimating the individual benefit of immediate treatment or active surveillance for prostate cancer after screen‐detection in older (65+) men

Treatment of local–regional prostate cancer detected by PSA screening: benefits and harms according to prognostic factors

The genetics of neuroendocrine prostate cancers: a review of current and emerging candidates

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