Background
Phase III RCT (ProtecT Trial). 1,643 patients with PSA-detected localized prostate cancer (largely T1c-T2a, PSA ≤20 ng/mL) from 9 UK centers, enrolled 1999–2009. Randomized 1:1:1 to: active monitoring (AM), radical prostatectomy (RP), or radical radiotherapy (RT: 74 Gy/37 fx 3D-CRT or IMRT + 3–6 months neoadjuvant/concurrent ADT). This is the largest randomized trial of the three primary management strategies for localized prostate cancer. The Hamdy NEJM 2016 paper reported clinical outcomes; the Donovan NEJM 2016 paper (same issue) reported patient-reported outcomes.
Interventions and follow up
Arm A: Active monitoring (PSA-based, with intervention on progression)
Arm B: Radical prostatectomy
Arm C: Radical radiotherapy (74 Gy + 3–6 months ADT)
Primary endpoint: Prostate cancer mortality at 10 year
mFollow up: Median 10 year
Arm B: Radical prostatectomy
Arm C: Radical radiotherapy (74 Gy + 3–6 months ADT)
Primary endpoint: Prostate cancer mortality at 10 year
mFollow up: Median 10 year
Results
10-year prostate cancer mortality: AM: 1.5%, RP: 0.9%, RT: 0.7% — no significant difference between arms (p=.48)
10-year metastases: AM: 6.3%, RP: 2.4%, RT: 3.0% — AM significantly higher (p=.004)
10-year disease progression: AM: 33.0%, RP: 13.4%, RT: 16.0%
Patient-reported QoL (Donovan 2016): Erectile dysfunction highest after RP; bowel dysfunction highest after RT; urinary incontinence highest after RP; urinary irritation/obstruction highest after RT
10-year metastases: AM: 6.3%, RP: 2.4%, RT: 3.0% — AM significantly higher (p=.004)
10-year disease progression: AM: 33.0%, RP: 13.4%, RT: 16.0%
Patient-reported QoL (Donovan 2016): Erectile dysfunction highest after RP; bowel dysfunction highest after RT; urinary incontinence highest after RP; urinary irritation/obstruction highest after RT
Adverse events
Main adverse events: RP: urinary incontinence (66% affected at 6 months, improving to 46% at 12 months vs 15% RT); erectile dysfunction: 67% RP vs 36% RT vs 30% AM at 12 months. RT: bowel dysfunction (57% rectal bleeding at 6 months, 50% at 12 months vs 7% RP and 10% AM). No treatment-related deaths.
Conclusions
All three management strategies produce equivalently low prostate cancer mortality at 10 years for PSA-detected localized prostate cancer. However, active monitoring is associated with substantially higher rates of local progression and distant metastases compared with immediate radical treatment. Treatment choice must balance oncologic outcomes against distinctive adverse effect profiles, with RP causing more urinary and erectile dysfunction and RT causing more bowel and urinary symptoms.
Key Limitations
Key Limitations: RT dose (74 Gy) is lower than current standard (78+ Gy or hypofractionated), and no brachytherapy boost was used; modern RT may produce even better oncologic outcomes. Active monitoring protocol differs from modern active surveillance (biopsy-directed, MRI-guided). Most patients had low-risk disease (Gleason ≤6 in 76%); results may not apply to intermediate/high-risk disease. 15-year follow-up data (published 2023) show continued separation of the metastases curves.
Clinical Context
ProtecT is the landmark randomized trial providing Level 1 evidence that active surveillance, radical prostatectomy, and radiotherapy produce equivalent prostate cancer mortality at 10 years in PSA-screen-detected localized disease. It has profoundly influenced shared decision-making for localized prostate cancer. The 15-year follow-up (2023, Hamdy/Lane) showed persistent OS equivalence but significantly higher metastases with active monitoring, reinforcing the need for careful monitoring with intervention on progression. Treatment choice remains individualized based on tumor risk, patient comorbidity, and quality-of-life priorities.