ERSPC Trials Research Articles

P0990 - Prostate cancer specific mortality in the ERSPC trial: What is the role of screening result and adherence

P0990 - Prostate cancer specific mortality in the ERSPC trial: What is the role of screening result and adherence

Pooled RCTs: Reanalysis accounting for screening intensity suggests that screening reduces prostate cancer mortality.

Source Citation Tsodikov A, Gulati R, Heijnsdijk EAM, et al. Reconciling the effects of screening on prostate cancer mortality in the ERSPC and PLCO Trials. Ann Intern Med. 2017;167:449-55. 28869989

Prostate cancer screening: and yet it moves!

The debate of prostate cancer (PCa) screening has been shaped over decades. There is a plethora of articles in the literature supporting as well as declining prostate-specific antigen (PSA) screening. Does screening decrease PCa mortality? With the long-term results of the European Randomized Study of Screening for Prostate (ERSPC) the answer is clearly YES. It moves! However, in medicine there are no benefits without any harm and thus, screening has to be performed in targeted and smart way-or in other words-in a risk-adapted fashion when compared with the way it was done in the past. Here, we discuss the main findings of the ERSPC trials and provide insights on how the future screening strategies should be implemented.

Long-term treatment with testosterone undecanoate injections and its effect of prostate cancer incidence in hypogonadal men.

119 Background: Concerns regarding the safety of testosterone treatment, particularly regarding prostate cancer in elderly men, still hamper the use of testosterone in hypogonadal men. Methods: Registry studies of 942 men with testosterone levels less than or equal to 12.1 nmol/L from three German centers. Patients received testosterone undecanoate for up to 16 years. Results: In cohort A (mean age: 57.70 ± 6.76 years; Bremerhaven), prostate-specific antigen (PSA) increased from 1.77±0.97 to 2.0±1.01 ng/ml (p=0.0021). Prostate volume increased from 28.34±10.79 to 30.72±14.28 ml (p<0.0001). Five out of 300 patients were diagnosed with prostate cancer. The proportion was 1.7% with an incidence of 39.4 per 10,000 patient-years. In cohort B (mean age: 59.53 ± 8.35 years; Norderstedt), PSA increased from 0.86±0.57 to 1.38±0.49 ng/ml (p<0.0001). Prostate volume increased from 27.9±8.15 to 36.98±7.22 ml (p<0.0001). Six out of 261 patients were diagnosed with prostate cancer. The proportion was 2.3% with an incidence of 54.5 per 10,000 patient-years. One patient in cohort B was treated with external beam radiation, all other patients underwent radical prostatectomy. In cohort C (mean age: 42.6 ± 13.4 years; Muenster), PSA increased from 1.6±0.4 to 1.9±0.4 (p<0.001). Prostate volume increased from 16.9±5.1 to 19.9±5.3 ml (p<0.001). No patient was diagnosed with prostate cancer. Conclusions: The PLCO trial reported an incidence of 116 per 10,000 patient-years (Andriole, NEJM 360(13):1310-9), the ERSPC trial 96.6 (Schröder, NEJM 366(11):981-90). Although these screening trials cannot be directly compared to our registries of hypogonadal men receiving testosterone replacement therapy, the incidence of prostate cancer in our registry studies does not suggest an increased risk in hypogonadal men on long-term testosterone treatment.

1450 THE TRUE BENEFIT OF PSA-SCREENING: MODELING THE IMPACT OF TRIAL SETTING AND PROTOCOL ON MORTALITY

You have accessJournal of UrologyProstate Cancer: Detection and Screening II1 Apr 20121450 THE TRUE BENEFIT OF PSA-SCREENING: MODELING THE IMPACT OF TRIAL SETTING AND PROTOCOL ON MORTALITY Eveline Heijnsdijk, Elisabeth Wever, and Harry de Koning Eveline HeijnsdijkEveline Heijnsdijk Rotterdam, Netherlands More articles by this author , Elisabeth WeverElisabeth Wever Rotterdam, Netherlands More articles by this author , and Harry de KoningHarry de Koning Rotterdam, Netherlands More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.1944AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The ERSPC trial showed a significant prostate cancer mortality reduction for the PSA-screening arm, while the PLCO trial didn't. A number of explanations caused by differences in the trials have been debated, such as contamination in the control arm, differences in compliance after referral to biopsy and screening interval. Still, in meta-analyses, the results of both trials are often, incorrectly, just simply pooled. By modeling, we will show the impact of the trial setting and protocol, to assess the impact of these differences on mortality and to evaluate whether the results of the trials are really contradictory. METHODS Using a micro-simulation modeling calibrated on data of the ERSPC trial, we estimated the cure rate of screen detected cancers leading to a 27% mortality reduction for men screened at least once. We used this cure rate in a model calibrated on published data of the PLCO trial. Using this PLCO model, we predicted what the prostate cancer mortality reduction in the PLCO trial would have been when there was no screening in the control arm. Then, we changed the assumptions for the PLCO trial, by increasing the biopsy compliance to 100%, the screening attendance to 100%, including screening in the control arm and increasing the screening interval to 4 years. RESULTS In the absence of screening in the control arm, the predicted prostate cancer mortality reduction in the PLCO trial is 23%. Using a screening attendance rate of 100%, the mortality reduction would be 25%, and using a biopsy compliance rate of 100% the mortality reduction would be 41%. Including screening in the control arm leads to a mortality reduction of 14% and a 4 year interval to 11%. CONCLUSIONS Differences in biopsy compliance and screening in the control arm between the two trials can explain a large part of the difference in the outcome of the trials. The mortality reductions will also be predicted by two other models of the Cancer Intervention and Surveillance Modeling Network (CISNET) to quantify more robust the contribution of the trial setting and protocol to the mortality reduction. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e588 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Eveline Heijnsdijk Rotterdam, Netherlands More articles by this author Elisabeth Wever Rotterdam, Netherlands More articles by this author Harry de Koning Rotterdam, Netherlands More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

1213 COST-EFFECTIVENESS OF PROSTATE CANCER SCREENING BASED ON THE EUROPEAN RANDOMISED STUDY OF SCREENING FOR PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Detection and Screening I1 Apr 20121213 COST-EFFECTIVENESS OF PROSTATE CANCER SCREENING BASED ON THE EUROPEAN RANDOMISED STUDY OF SCREENING FOR PROSTATE CANCER Eveline Heijnsdijk, Elisabeth Wever, and Harry de Koning Eveline HeijnsdijkEveline Heijnsdijk Rotterdam, Netherlands More articles by this author , Elisabeth WeverElisabeth Wever Rotterdam, Netherlands More articles by this author , and Harry de KoningHarry de Koning Rotterdam, Netherlands More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.1502AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The results of the ERSPC trial showed a significant prostate cancer mortality reduction for the PSA-screening arm. However, before screening for prostate cancer can be implemented for the population, the effects on quality of life, overdiagnosis, costs and cost-effectiveness should be assessed. METHODS Using a micro-simulation modeling, based on data of the ERSPC trial and the Dutch population, we predicted the cancers diagnosed, prostate cancer deaths, quality adjusted life years gained, costs and cost-effectiveness of various screening strategies when implemented in the Dutch population. Screening was applied for 1000 men, starting at age 55. The attendance rate for each screen was 80%. Results were calculated for various screening intervals (once in a life time screen and 1-10 year intervals), various true benefits of prostate cancer mortality reductions (27%-39%) and various utilities for correcting for quality of life. No discount was used. RESULTS Compared with a situation without screening, screening from age 55-69 with 4-year intervals leads to a reduction of 8 prostate cancer deaths per 1000 men. In addition, 34 cancers are overdiagnosed, resulting in 20 quality adjusted life years (QALYs) gained. The cost-effectiveness of this strategy is € 28,078 per QALY gained. Screening at one-year intervals from age 55-64 resulted in the highest QALYs gained (26). In this strategy also 8 prostate cancer deaths are prevented, but only 28 cancers are overdiagnosed. The cost-effectiveness is € 22,169 per QALY gained. Screening at ages above 70 results in considerable more overdiagnosis (for example 79 overdiagnosed cases for screening at 1-year intervals from age 55-74). One screen at age 55 results in 2 less prostate cancer deaths, 4 overdiagnosed cases and € 6,967 per QALY gained. With varying assumptions, the cost-effectiveness varied between € 8,590 and € 260,479 per QALY gained. CONCLUSIONS Screening from age 55 to 64 with short (1 to 3 years) intervals was more cost-effective than continuing screening to higher ages or screening with longer intervals (4 to 10 years). Screening at higher ages leads to more overdiagnosis, higher costs and less QALYs gained. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e491 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Eveline Heijnsdijk Rotterdam, Netherlands More articles by this author Elisabeth Wever Rotterdam, Netherlands More articles by this author Harry de Koning Rotterdam, Netherlands More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

New Analyses of Data from the Prostate Cancer Screening Trials

In 2009, results of the two large randomized trials of prostate cancer screening were published (JW Gen Med Mar 18 2009). In the PLCO (U.S.) trial, screening failed to lower prostate cancer–specific mortality, but the trial was criticized because many men in the control group were screened outside the trial. In the ERSPC (European) trial, the lower incidence of prostate cancer–specific mortality in the screening group reached statistical significance ( P= 0.04), but 1410 men were screened and 48 were …

Serum Prostate-Specific Antigen for the Early Detection of Prostate Cancer: Always, Never, or Only Sometimes?

Serum Prostate-Specific Antigen for the Early Detection of Prostate Cancer: Always, Never, or Only Sometimes?

Editorial Comment

The US Preventive Services Task Force (USPSTF), with no urology representative, reviewed what it considered the relevant published data and concluded that available evidence is insufficient to assess the balance between potential benefits and harms of using PSA to screen men aged < 75 years old for prostate cancer and has recommended against screening men aged > 75 years old (even those at high risk). 1 U.S. Preventive Services Task ForceScreening for prostate cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2008; 149: 185-191 Crossref PubMed Scopus (484) Google Scholar Public Survey and Survival Data Do Not Support Recommendations to Discontinue Prostate-specific Antigen Screening in Men at Age 75UrologyVol. 75Issue 5PreviewTo evaluate the US Preventative Services Task Force (USPSTF) recommendation to discontinue prostate-specific antigen (PSA) screening at age 75. Full-Text PDF ReplyUrologyVol. 75Issue 5PreviewWe sincerely appreciate Dr Catalona's Editorial Comment regarding our article and agree completely with his comments. Over the last year, prostate cancer seems to have been the “whipping boy” of the press. In August 2008, as Dr Catalona notes, the USPSTF recommended against PSA testing in men aged ≥75 years. This was front-page news in USA Today and other papers as it hinted of health care rationing and age discrimination. In the spring of 2009, the press had a field day with the ERSPC and PLCO trial results, generally headlining that screening is not beneficial and ignoring the positive findings from the ERSPC study that showed a 20% reduction in mortality and a 41% reduction in metastatic disease rates in screened men. Full-Text PDF

333 COST EFFECTIVENESS OF PSA SCREENING IN THE US: EXTRAPOLATING FROM THE ERSPC TRIAL

You have accessJournal of UrologyGeneral & Epidemiological Trends & Socioeconomics: Practice Patterns, Cost Effectiveness I1 Apr 2010333 COST EFFECTIVENESS OF PSA SCREENING IN THE US: EXTRAPOLATING FROM THE ERSPC TRIAL Alex Shteynshlyuger and Gerald L. Andriole Alex ShteynshlyugerAlex Shteynshlyuger More articles by this author and Gerald L. AndrioleGerald L. Andriole More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.399AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The objective of population screening for prostate cancer is to decrease morbidity, mortality and costs associated with prostate cancer. Preliminary results of the ERSPC study demonstrated decrease in prostate cancer specific mortality associated with PSA screening. We evaluated the cost effectiveness of PSA screening using data from the ERSPC study protocol when extrapolated to the US. METHODS We used the previously reported SEER-Medicare data and nationwide sample of employer provided estimates of costs of care for patients with diagnosis of prostate cancer. Resource allocation costs that include clinical service costs and test costs of PSA screening in the US were used to determine the costs of population based screening. The data from the ERSPC trial, in accordance with the study protocol, was used to determine the costs and cost-effectiveness of PSA screening. A model incorporating age at diagnosis, life expectancy and estimate of benefits from PSA screening was created that predicts cost effectiveness of screening intervention using alternative outcome scenarios. A sensitivity analysis was performed to test the robustness of results. RESULTS The lifetime cost of screening with PSA, evaluation of abnormal PSA and treatment of identified prostate cancers to prevent one mortality from prostate cancer is $6,950,983 based on the findings from the ERSPC study and extrapolated to the US community patterns of care. If screening achieves similar decrease in overall mortality (by 0.6%) as the reduction in prostate cancer specific mortality observed in the ERSPC study, such intervention would cost $347,549 per life year saved. The screening as reported in the ERSPC study is not cost effective in the US based on the $50,000 per life-year saved cost-effectiveness threshold. The threshold for cost effectiveness of PSA screening is reached when the number needed to treat (NNT) is lowered to 7 or fewer men. The lifelong costs of screening protocols are determined by the cost of treatment with insignificant contribution from the costs of screening. PSA screening becomes cost effective if the average lifelong treatment costs are below $861 per year. CONCLUSIONS PSA screening becomes cost-effective with NNT of 7 or fewer men with little dependence on life expectancy. This suggests that both older and younger men can be treated cost effectively with equally beneficial treatments. We established a model that predicts the minimal requirements including the NNT and improvement in mortality that would make PSA screening a cost-effective public health measure for population based implementation. St. Louis, MO© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e132 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alex Shteynshlyuger More articles by this author Gerald L. Andriole More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

To screen or not to screen?

Unfortunately, interim analyses of the long-awaited ERSPC and PLCO trial data have generated conflicting conclusions. Here, two European authors speculate as to the reasons underlying this contradiction, while highlighting clinically relevant points that are supported by both studies. Particular attention is paid to the potential consequences of overdiagnosis and overtreatment.

Monitoring the ERSPC trial.

Monitoring the ERSPC trial.

The rationale for the ERSPC trial: will it improve the knowledge base on prostate cancer screening?

The rationale for the ERSPC trial: will it improve the knowledge base on prostate cancer screening?