Fifteen-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer
- Study type
- Clinical trial
- Study name
- ProtecT
- Phase
- Phase 3
- Design
- Three-arm, multicentre randomised trial (United Kingdom)
- Sample size
- 1643 men
- Source
- N Engl J Med · 2023
- Trial registration
- NCT02044172
In plain words
This UK study compared three approaches in men with prostate cancer confined to the gland: regular monitoring, surgery or radiotherapy. After 15 years, the chance of dying from prostate cancer was very low and similar in all three groups (about 3%). In the monitoring group the disease spread more often, but about a quarter of the men in this group never needed treatment and were spared its side effects.
Key results
Treatment arms and regimens
Active monitoring (a care strategy without a drug): regular PSA testing with clinical review, with the option of switching to radical treatment if the disease progressed. The frequency of PSA testing and the referral threshold are not stated in the sources reviewed.
Radical prostatectomy; most operations were open retropubic nerve-sparing procedures. No protocol drug treatment.
Three-dimensional conformal external-beam radiotherapy to a total dose of 74 Gy in 37 fractions, with neoadjuvant hormone therapy (androgen deprivation); the hormonal drug, dose and duration are not stated in the sources reviewed.
Source of the regimen details: Patient-reported outcomes report of the same trial (Donovan et al, NEJM 2016; PMC5134995) and ClinicalTrials.gov NCT02044172; trial without a protocol drug regimen except neoadjuvant hormone therapy, whose drug, dose and duration are not stated in these sources
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Men aged 50 to 69 diagnosed with localised prostate cancer through population PSA testing in the UK between 1999 and 2009 (of 82,429 men tested, 2896 had prostate cancer and 2664 clinically localised cancer); 1643 (62%) were randomised. More than a third had intermediate- or high-risk disease at diagnosis.
Endpoints
Primary outcome: death from prostate cancer. Secondary outcomes: death from any cause, metastasis, disease progression and initiation of long-term hormone therapy.
Safety and side effects
In this 15-year report, no new treatment complications were reported after the 10-year analysis. In the patient-reported outcomes report (NEJM 2016): pad use rose from 1% at baseline to 46% at 6 months after prostatectomy (4% with active monitoring and 5% with radiotherapy) and was 17% versus 8% and 4% at 6 years. Erections firm enough for intercourse fell from 67% at baseline to 52% (active monitoring), 22% (radiotherapy) and 12% (prostatectomy) at 6 months, and to 30%, 27% and 17% at 6 years. Bowel function was worse in the radiotherapy group, especially at 6 months, and bloody stools were more frequent in this group from year 2 onwards (P<0.001). No significant differences between groups were seen in anxiety, depression or overall quality of life.
Clinical significance and place in guidelines
ProtecT is the main basis for accepting active surveillance as a standard option for low-risk cancer in the EAU, NCCN and ESMO guidelines, and it emphasises shared decision-making that takes treatment side effects into account. However, the "active monitoring" protocol of this study (mainly PSA-based) was less intensive than today's active surveillance with MRI and repeat biopsy.
Limitations
Most patients had low-risk cancer; monitoring in this trial was done without regular MRI; surgical and radiotherapy techniques have changed since patients were enrolled; the small number of deaths limits the statistical power of the comparisons.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.