ProtecT At 10 Years Shows Risk–Benefit Ratio For Active Monitoring in Localised Prostate Cancer

Active monitoring achieves comparable prostate cancer-related mortality to radical treatment for localised prostate cancer but at a cost of increased progression risk

medwireNews: Ten-year findings of the ProtecT study of men with localised prostate cancer detected by prostate-specific antigen (PSA) testing show that disease specific-mortality is low regardless of whether patients receive active monitoring, radical surgery or radiotherapy.

However, disease progression was significantly more common with active monitoring than radical prostatectomy or radical radiotherapy, as demonstrated by a significantly higher combined rate of metastases, clinical T3 or T4 disease, rectal fistula, ureteric obstruction, tumour growth resulting in requirement for a permanent catheter and use of long-term androgen-deprivation therapy.

“For today, we can conclude on the basis of level 1 evidence that PSA monitoring, as compared with treatment of early prostate cancer, leads to increased metastasis”, writes editorialist Anthony D’Amico, from Brigham and Women’s Hospital and the Dana–Farber Cancer Institute in Boston, Massachusetts, USA, in The New England Journal of Medicine.

“Therefore, if a man wishes to avoid metastatic prostate cancer and the side effects of its treatment, monitoring should be considered only if he has life-shortening coexisting disease such that his life expectancy is less than the 10-year median follow-up of the current study”, he recommends.

The study included 2664 men, aged 50 to 69 years (median 62 years), with a median baseline PSA level of 4.6 ng/mL. The majority (77%) had tumours with a Gleason score of 6 and 76% had stage T1c disease.

The primary endpoint of prostate cancer-specific mortality was 1.5 deaths per 1000 person–years for the 545 men who were randomly assigned to undergo active monitoring, consisting of serum PSA measurements every 3 months for the first year and every 6–12 months thereafter, with a review on a rise of 50% or greater.

This was comparable to the rates of 0.9 and 0.7 cases per 1000 person–years for the 553 men who were assigned to undergo radical prostatectomy and the 545 who were given radical radiotherapy, respectively, say Freddie Hamdy, from the University of Oxford in the UK, and co-investigators.

Further analysis suggested that prostate cancer-specific mortality did not differ between the treatment groups with patient age, PSA level, Gleason score or clinical stage, and there was no significant difference in the rate of death from any cause between the arms.

But active monitoring was associated with a significantly higher rate of clinical progression than either surgery or radiotherapy (22.9 vs 8.9 and 9.0 events per 1000 person–years) and a significantly greater likelihood of metastatic disease (6.3 vs 2.4 and 3.0 events per 1000 person–years).

“On the basis of our results, we estimated that 27 men would need to be treated with prostatectomy rather than receive active monitoring to avoid 1 patient having metastatic disease, and 33 men would need to be treated with radiotherapy rather than receive active monitoring to avoid 1 patient having metastatic disease”, the authors summarise, adding that nine patients would undergo active treatment to avoid one case of clinical progression.

Noting that 44% of patients who received active monitoring avoided radical treatment and its associated side effects, Freddie Hamdy and team conclude: “Men with newly diagnosed, localized prostate cancer need to consider the critical trade-off between the short-term and long-term effects of radical treatments on urinary, bowel, and sexual function and the higher risks of disease progression with active monitoring, as well as the effects of each of these options on quality of life.

“Further follow-up of the ProtecT participants with longer-term survival data will be crucial to evaluate this trade-off in order to fully inform decision making for physicians and patients considering PSA testing and treatment options for clinically localized prostate cancer.” 


Hamdy FC, Donovan JL, Lane JA, et al. 10-year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer. N Engl J Med; Advance online publication 14 September 2016. doi: 10.1056/NEJMoa1606220

D’Amico AV. Treatment or monitoring for early prostate cancer. N Engl J Med; Advance online publication 14 September 2016. doi: 10.1056/NEJMe1610395

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