Study design
RCT
Population
- Number of patients studied: 1643
- Inclusion criteria: Men aged 50-69 with localized prostate cancer, diagnosed through PSA testing
- Exclusion criteria: Not specified
Interventions
- Experimental groups: Active monitoring, prostatectomy, radiotherapy
Primary outcome: % Metastasis at 15 years
Secondary outcomes
| Outcome | Active-monitoring | Prostatectomy | Radiotherapy |
|---|---|---|---|
| Metastases | 51 | 26 | 27 |
| Long-term ADT initiation | 69 | 40 | 42 |
| Clinical progression | 141 | 58 | 60 |
Potential Issues and Biases
Since the trial's inception, treatments and diagnostic methods have evolved. Investigators were not using contemporary multiparametric MRI or positron-emission tomography with prostate-specific membrane antigen, and biopsies were not image-targeted.
Strengths
The strengths of the trial include the randomized comparison of findings in men with PSA-detected, clinically localized, low- or intermediate-risk prostate cancer, along with generalizable population-based recruitment with high levels of randomization, standardized treatment pathways, and sustained high rates of follow-up.
Conclusion
After 15 years of follow-up, prostate cancer-specific mortality was low regardless of the treatment assigned. The choice of therapy involves weighing trade-offs between benefits and harms associated with treatments for localized prostate cancer.
Hamdy, F. C., Donovan, J. L., Lane, J. A., Metcalfe, C., Davis, M., Turner, E. L., ... Neal, D. E. (2023). Fifteen-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer. New England Journal of Medicine, 388(17), 1547-1558.
Editorial - Localized Prostate Cancer: Then and Now
ProtecT Trial Outcomes
Between 1999-2009, 82,429 men aged 50-69 underwent PSA testing in the UK as part of the ProtecT trial. 15-year follow-up data showed a 21.7% mortality rate from any cause and 2.7% from prostate cancer. Metastasis incidence was 9.4% in the active-monitoring group and roughly half in the prostatectomy and radiotherapy groups.
| Safety Outcomes | Active Monitoring | Prostatectomy | Radiotherapy |
|---|---|---|---|
| Metastasis | 9.4% | ~4.7% | ~4.7% |
| Mortality (Any Cause) | 21.7% | 21.7% | 21.7% |
| Mortality (Prostate Cancer) | 2.7% | 2.7% | 2.7% |
Treatment Choice & Side Effects
Treatment choice for localized prostate cancer involves weighing trade-offs between benefits and harms. Radical prostatectomy and radiation therapy are associated with substantial sexual or urinary dysfunction.
PSA Testing Evolution
PSA testing has dramatically changed since 1999, with many clinics no longer performing the test. Multiparametric MRI and PI-RADS scoring have emerged for better-targeted biopsies. Additional risk-stratification methods, transcriptomic assays, germline genomic assessments, and PSMA PET scans are now available.
ProtecT Trial Limitations
The trial predominantly included low-risk or favorable intermediate-risk patients, and conclusions for underpowered subgroups are not appropriate. Active monitoring from the trial should not be used today, as active surveillance protocols have improved.
Modern Prostate Cancer Management
The management of localized prostate cancer has changed significantly since 1999. The ProtecT trial provides valuable data for decision making in low- or intermediate-risk prostate cancer patients.
Sartor, O. (2023). Localized Prostate Cancer — Then and Now. New England Journal of Medicine, 388(17), 1617-1618.