Authors Hamdy FC, Donovan JL, Lane JA, et al. (ProtecT Study Group)

Review Date September 2016

Citation The New England Journal of Medicine 2016; DOI: 10.1056/NEJMoa1606220 (online)



The management of clinically localised prostate cancer diagnosed after a PSA test remains controversial. Active surveillance (here called ‘active monitoring’) is an option that can help ameliorate the negative effects of over-treatment of PSA-detected prostate cancer. The longer term outcomes of this approach compared to active treatment after diagnosis (surgery and/or radiotherapy) are still uncertain, with concerns about worse outcomes for men undergoing active surveillance.



This UK trial (ProtecT) compared active monitoring, radical prostatectomy and external beam radiotherapy with respect to prostate-cancer mortality at a median of 10 years of follow-up. Groups were also compared for rates of disease progression, metastases, and all-cause mortality.



Between 1999 and 2009, 82,429 men aged between 50 and 69 years received a PSA test. From these, 2664 were diagnosed with localised prostate cancer. Treatment options were discussed with the men and 62% of those diagnosed (n=1643) agreed to be randomised to one of 3 treatment options: 545 to the active monitoring arm, 553 to the surgery arm and 545 to radiotherapy. After randomisation, clinicians and patients were aware of the treatment assignment. Those in the active monitoring arm were regularly monitored for PSA level (every 3 months in the 1st year, 6-monthly in the 2nd year and yearly thereafter) to detect disease progression; active treatment with curative intent was implemented as necessary.

The primary outcome was prostate-cancer mortality (deaths definitely or probably due to prostate cancer or its treatment) at a median of 10 years follow-up. Secondary outcomes included the rates of disease progression, metastases, and all-cause mortality. Statistical analysis was done on an intention-to-treat basis with Cox proportional hazards regression.



Fourteen (1%) of the 1643 randomised men were lost to follow-up for secondary outcomes but the primary outcome was ascertained for all participants. 88% of the active monitoring group, 71% of the surgery group and 74% of the radiotherapy group received treatment within 9 months of randomisation (>85% of the latter 2 groups received treatment by the end of the follow-up period). Of the 545 men in the active monitoring group, 55% had received active treatment by the end of the follow-up. Of the men in the radiotherapy group, 3 had salvage prostatectomy, 14 received long-term ADT and 1 high-intensity focused U/S therapy. Of the surgical group, 18 had primary treatment failure (5 had salvage radiotherapy) and another 9 men had adjuvant radiotherapy within a year of surgery.

Prostate-cancer-specific survival was 99% and did not differ significantly between groups. There were 17 prostate-cancer-specific deaths overall: 8 in the active-monitoring group (1.5/1000 person-years (PY); 95% CI: 0.7 to 3.0), 5 in the surgery group (0.9/1000 PY; 95% CI: 0.4 to 2.2), and 4 in the radiotherapy group (0.7/1000 PY; 95% CI: 0.3 to 2.0); the difference across groups was not significant (P=0.48 for the overall comparison).

No significant difference was seen across the groups for all-cause mortality (169 deaths; P=0.87 for the comparison across three groups). Metastases developed in more men in the active-monitoring group (33 men; 6.3/1000 PY; 95% CI: 4.5 to 8.8) than in the surgery group (13 men; 2.4/1000 PY; 95% CI, 1.4 to 4.2) or the radiotherapy group (16 men; 3.0/1000 PY; 95% CI: 1.9 to 4.9) (P=0.004 for the overall comparison).

Higher rates of disease progression were seen in the active-monitoring group (112 men; 22.9/1000 PY; 95% CI: 19.0 to 27.5) than in the surgery group (46 men; 8.9/1000 PY; 95% CI: 6.7 to 11.9) or the radiotherapy group (46 men; 9.0/1000 PY; 95% CI: 6.7 to 12.0) (P



At a median follow-up of 10 years, prostate-cancer-specific mortality was low irrespective of the treatment assigned, with no significant difference among treatments. This mortality rate was lower than expected at the beginning of the trial. Surgery and radiotherapy were associated with lower incidences of disease progression and metastases than was active monitoring. However, nearly half the men in the active monitoring group did not receive active treatment and thus avoided the side effects of treatment.


Points to Note
  1. Prostate-cancer-specific mortality within 10 years of diagnosis of clinically localised prostate cancer (after PSA testing) was low (1%) irrespective of the type of treatment.
  2. A quarter of men in the active monitoring arm of the trial received active treatment within 3 years, noting that a change to active treatment may have been due to reasons other than disease progression.
  3. Given the small numbers of events at 10 years follow-up, data on the longer-term survival of the ProtecT participants are needed to evaluate the trade-off between side-effects of active treatments and the higher risk of disease progression with active monitoring, so that men and their doctors can make fully informed decisions.
  4. A companion paper from this study (Donovan et al) on patient-reported outcomes shows that surgery was associated with worse effects on sexual function and urinary continence than radiotherapy or active monitoring, factors that need to be considered along with survival when deciding on treatment.
  5. Limitations of the study include: the trial protocol was developed 2 decades ago and much has changed in prostate cancer diagnosis and treatment since then; the participants were mostly white men (<1% Afro-Caribbean).