ProtectT - 10-year outcomes after monitoring, surgery, or radiotherapy for localised prostate cancer
- 1 Clinical Question
- 2 Bottom Line
- 3 Major Points
- 4 Guidelines
- 5 Design
- 6 Population
- 7 Interventions
- 8 Outcomes
- 9 Criticisms
- 10 Funding
- 11 Further Reading
In men with PSA screening detected prostate cancer, how do survival and progression outcomes compare ten years after monitoring, surgery or radiotherapy?
After a median of ten years, prostate cancer specific mortality (PCSM) is low irrespective of the treatment assigned. There were no significant differences in PCSM between the treatment groups. surgery and radiotherapy had lower rates of progression that active monitoring
- In this cohort, prostate cancer specific survival was similar between observation, surgery and radiotherapy
- Men managed under monitoring appeared to have a higher rate of progression and metastases
- Localised prostate cancer is assigned to a risk grouping and then treatment recommended based on the grouping. The patients included in this trial fall across the spectrum of risk groups (low-risk, intermediate-risk and high-risk), meaning that many treatment options are available including Active surveillance, radical prostatectomy and radiotherapy.
- Similar in concept to the EAU guidelines, NCCN uses a risk stratification to group patients for treatment recommendations. The patients included in this trial fall across a series of strata and could be recommended for many treatment types.
In both guidelines, patients included in this trial with Gleason >7 would not be eligible for active surveillance (monitoring).
- Trial type: randomised, multicentre
- N=number of patients randomized (often different from number of patients enrolled)
- Radical prostatectomy : n= 553
- Active monitoring: n=545
- Radiotherapy: n= 545
- Setting: UK, nine sites
- Enrolment: 1999-2009
- Median follow-up: 10 years
- Analysis: intention to treat, cox proportional hazards model with adjustment for confounders
- Primary outcome: prostate cancer specific mortality
- Men aged 50-69 years, diagnosed with localised prostate cancer after a PSA screening test, agreed to undergo randomisation.
- Advanced disease.
From the active monitoring group.
- Age: 62 years
- White ethnic origin: 99%
- Married or living with partner: 84%
- Managerial/professional occupation: 43%
- Known family history of prostate cancer: 8%
- Median PSA in ng/mL: 4.7
- PSA 10+: 10%
- Gleason 6: 77%
- Gleason 7: 20%
- Gleason 8-10: 2%
- Missing Gleason: 0%
- Clinical stage – T1c: 75%
- Clinical stage T2: 25%
- Patients were randomized to a group:
- Active monitoring: PSA measured 3 monthly for the first year and then every 6-12 months thereafter. A change of 50% in a 12 month period triggered a review, with continued monitoring or radical intervention possible.
- Radical prostatectomy: PSA monitoring every 3 months after surgery for 12 months, 6 monthly for two years and then annually. Adjuvant or salvage radiotherapy for those with positive surgical margins, extracapsular disease or a postoperative PSA 0.2ng or higher.
- Radiotherapy: neoadjuvant ADT for 3-6 months, then 3D confocal radiotherapy, 74Gy, 37 fractions.
- Prostate cancer specific mortality
- RP vs AM – HR 0.63 (95% CI 0.21-1.93)
- RT vs AM – HR 0.51 (95% CI 0.15-1.69)
- Log rank test between three groups – p=0.48
- Clinical progression of prostate cancer
- RP vs AM - HR 0.39 (95% CI 0.27-0.54)
- RT vs AM - HR 0.39 (95% CI 0.27-0.55)
- Log rank test between three groups – p<0.001
- All cause mortality
- RP vs AM - HR 0.93 (95% CI 0.65-1.35)
- RT vs AM - HR 0.94 (95% CI 0.65-1.36)
- Log rank test between three groups – p=0.92
- Sensitivity analysis using competing risks regression showed similar results to the Cox proportional hazards model.
- The sister paper describing the PROMS of the same cohort includes detailed descriptions of the Patient Reported Outcomes Measures for each arm of this trial.
- Additional complications
- Surgery – Nine men had thromboembolic or cardiac events, 14 required transfusion of more than three units of blood, one had rectal injury, nine required intervention for anastomotic problems.
- Radiotherapy – three deaths within 90 days, unrelated to prostate cancer.
- Allocation to Active Monitoring was higher risk than recommended in current guidelines
- MRI and transperineal biopsy are now standard of care for monitoring
- The mortality in was low
- There is a low rate of men agreeing to be randomised from the initial cohort
- The average man randomised is somewhat younger than the typical man diagnosed with prostate cancer
- While prostate cancer specific mortality rates are comparable between the groups, this is likely to change given further follow-up, based on the increased observation of metastases in the active monitoring group
- It is now accepted that localised disease is not always low risk disease
Supported by the U.K. National Institute for Health Research Health Technology Assessment Programme (NIHR HTA: projects 96/20/06, 96/20/99, with the University of Oxford as sponsor). Dr. Donovan is supported by the NIHR Collaboration for Leadership in Applied Health Research and Care West, hosted by University Hospitals Bristol NHS Foundation Trust, and Dr. Hamdy is supported by the Oxford NIHR Biomedical Research Centre Surgical Innovation and Evaluation Theme and the Cancer Research U.K. Oxford Centre.
- Wilt TJ et al. Radical prostatectomy versus observation for localized prostate cancer. N. Engl. J. Med. 2012. 367:203-13.
- Bill-Axelson A et al. Radical prostatectomy or watchful waiting in early prostate cancer. N. Engl. J. Med. 2014. 370:932-42.
- Donovan JL et al. Patient-Reported Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer. N. Engl. J. Med. 2016. 375:1425-1437.