Table A1:
GRADE Evidence Profile for Randomized Trials of PSA Screening for Prostate Cancer
| Number of Studies (Design) | Risk of Bias | Inconsistency | Indirectness | Imprecision | Publication Bias | Upgrade Considerations | Quality |
|---|---|---|---|---|---|---|---|
| All-cause mortality | |||||||
| 2 RCTs (48;55) | No serious limitations | No serious limitations | No serious limitations | No serious limitations | Not evaluated | None | High |
| Prostate cancer mortality | |||||||
| 2 RCTs (48;55) | Serious limitations (−1)a | Serious limitations (−1)b | No serious limitations | No serious limitations | Not evaluated | Other considerations (+1)c | Moderate |
| Prostate cancer detection | |||||||
| 2 RCTs (48;55) | No serious limitations | No serious limitations | No serious limitations | No serious limitations | Not evaluated | None | High |
| High-risk prostate cancer detection | |||||||
| 2 RCTs (48;55) | Serious limitations (−1)d | Serious limitations (−1)e | No serious limitations | Serious limitations (−1)f | Not evaluated | None | Low |
Abbreviations: ERSPC, European Randomized Study of Screening for Prostate Cancer; GRADE, Grading of Recommendations Assessment, Development, and Evaluation; PC, prostate cancer; PLCO, Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial; PSA, prostate-specific antigen; RCT, randomized controlled trial.
The rate of contamination in the control group was very high in the ERSPC trial, potentially attenuating the mortality risk reductions in the screening group. The treatment differences of screen-detected PCs in the ERSPC trial arms may have decreased mortality in the screen arm or increased mortality in the control arm.
The effect of screening on prostate cancer mortality risk was in opposite directions in the 2 trials: significantly reduced in the ERSPC trial and increased but not significantly in the PLCO trial.
Both trials were large, well-conducted multicentre trials with data monitoring committees, independent cause of death committees, and independent analytical teams.
The trials defined high risk differently and tumour risk measures, particularly metastasis, were generally not consistently evaluated in the trial groups over time.
The detection rates of high-risk tumours were not consistent between countries: significantly reduced in the screen group compared to the control group in some reports and not in others.
The majority of the prostate cancers detected in the trials were low-grade localized tumours, and the low occurrence, variable definition, and incomplete investigations resulted in unreliable estimates of high-risk or aggressive tumours.