Dataset Information

Intervention-related Deaths in the European Randomized Study of Screening for Prostate Cancer.

ABSTRACT:

Background

Identification of intervention-related deaths is important for an accurate assessment of the ratio of benefit to harm in screening trials.

Objective

To investigate intervention-related deaths by study arm in the European Randomized Study of Prostate Cancer Screening (ERSPC).

Design setting and participants

ERSPC is a multicenter trial initiated in the 1990s to investigate whether screening on the basis of prostate-specific antigen (PSA) can decrease prostate cancer mortality. The present study included men in the core age group (55-69 yr: screening group n = 112 553, control group n = 128 681) with 16-yr follow-up.

Outcome measurements and statistical analysis

Causes of death among men with prostate cancer in ERSPC were predominantly evaluated by independent national committees via review of medical records according to a predefined algorithm. Intervention-related deaths were defined as deaths caused by complications during the screening procedure, treatment, or follow-up. Descriptive statistics were used for the results.

Results and limitations

In total, 34 deaths were determined to be intervention-related, of which 21 were in the screening arm and 13 in the control arm. The overall risk of intervention-related death was 1.41 (95% confidence interval 0.99-1.99) per 10 000 randomized men for both arms combined and varied among centers from 0 to 7.0 per 10 000 randomized men. A limitation of this study is that differences in procedures among centers decreased the comparability of the results.

Conclusions

Intervention-related deaths were rare in ERSPC. Monitoring of intervention-related deaths in screening trials is important for assessment of harms.

Patient summary

We investigated deaths due to screening or treatment to assess harm in a trial of prostate cancer screening. Few such deaths were identified.

SUBMITTER: Godtman RA

PROVIDER: S-EPMC8655382 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Differential treatment between trial arms has been suggested to bias prostate cancer (PC) mortality in the European Randomized Study of Screening for Prostate Cancer (ERSPC). OBJECTIVE:To quantify the contribution of treatment differences to the observed PC mortality reduction between the screening arm (SA) and the control arm (CA). DESIGN, SETTING, AND PARTICIPANTS:A total of 14 136 men with PC (SA: 7310; CA: 6826) in the core age group (55-69yr) at 16yr of follow-up. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:The outcomes measurements were observed and estimated numbers of PC deaths by treatment allocation in the SA and CA, respectively. Primary treatment allocation was modeled using multinomial logistic regression adjusting for center, age, year, prostate-specific antigen, grade group, and tumor-node-metastasis stage. For each treatment, logistic regression models were fitted for risk of PC death, separately for the SA and CA, and using the same covariates as for the treatment allocation model. Treatment probabilities were multiplied by estimated PC death risks for each treatment based on one arm, and then summed and compared with the observed number of deaths. RESULTS AND LIMITATIONS:The difference between the observed and estimated treatment distributions (hormonal therapy, radical prostatectomy, radiotherapy, and active surveillance/watchful waiting) in the two arms ranged from -3.3% to 3.3%. These figures, which represent the part of the treatment differences between arms that cannot be explained by clinicopathological differences, are small compared with the observed differences between arms that ranged between 7.2% and 10.1%. The difference between the observed and estimated numbers of PC deaths among men with PC was 0.05% (95% confidence interval [CI] -0.1%, 0.2%) when applying the CA model to the SA, had the two groups received identical primary treatment, given their clinical characteristics. When instead applying the SA model to the CA, the difference was, as expected, very similar-0.01% (95% CI -0.3%, 0.2%). Consistency of the results of the models demonstrates the robustness of the modeling approach. As the observed difference between trial arms was 4.2%, our findings suggest that differential treatment explains only a trivial proportion of the main findings of ERSPC. A limitation of the study is that only data on primary treatment were available. CONCLUSIONS:Use of prostate-specific antigen remains the predominant explanation for the reduction in PC mortality seen in the ERSPC trial and is not attributable to differential treatment between trial arms. PATIENT SUMMARY:This study shows that prostate cancer deaths in the European screening trial (European Randomized Study of Screening for Prostate Cancer) were prevented because men were diagnosed and treated earlier through prostate-specific antigen screening, and not because of different, or better, treatment in the screening arm compared with the control arm.

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