Radical prostatectomy significantly reduced the risk of death compared with watchful waiting in men under 65 with early prostate cancer, in a large study from Sweden. However, in older men although surgery was associated with a reduced risk of metastases there was no effect on mortality.

Between 1989 and 1999, 695 men with early prostate cancer were randomised to either watchful waiting (WW) or radical prostatectomy (RP) and followed up to the end of 2012. Primary endpoints were death from any cause, death from prostate cancer and risk of metastases, at 18 years from diagnosis. There were 348 and 347 men in the WW and RP groups respectively. Mean age was 65 years and mean PSA 13 ng/ml.

It is important to remember that watchful waiting is different from active surveillance for prostate cancer. The watchful waiting group received symptomatic treatment rather than definitive treatment if disease progression was identified, usually in the form of hormone therapy. In active surveillance the aim is to detect disease progression in time to offer definitive radical treatment.

By the end of 2012, 447 of the 695 men enrolled in the study had died (64%). The cumulative incidence of death from all causes at 18 years was 56.1% in the RP group and 68.9% in the WW group. This represents a relative risk (RR) of death of 0.71 (95% CI:0.59-0.86, P < 0.001) for RP. The number needed to treat (NNT) to prevent one death was eight.

In terms of prostate cancer specific deaths, at 18 years the cumulative incidence was 17.7% in the RP group versus 28.7% in the WW group. RR of prostate cancer specific death in the RP group was 0.56 (95% CI:0.41-0.77, P = 0.001). Distant metastases occurred in 26.1% of the RP patients and 38.3% of the WW patients during the 18 years of follow-up.

The greatest reductions in risk of prostate cancer death were in patients diagnosed under the age of 65, RR 0.45 (95% CI:0.29-0.69, P = 0.002). The NNT to prevent one death from prostate cancer was four.

Among men diagnosed over the age of 65, there was no significant reduction in mortality but a significant reduction in risk of developing distant metastases: RR 0.68 (95% CI:0.46-1.0, P = 0.04).

Urologists continue to grapple with the question of whether radical treatment improves outcomes in men with early prostate cancer.

The PIVOT trial, published in 2012, showed that radical prostatectomy did not improve outcomes over watchful waiting at 15 years of follow-up. 1

However, this large Swedish study has one important difference: the study began with men diagnosed with early prostate cancer between 1989 and 1999, before the era of PSA screening. In PIVOT, the additional lead time produced by screening means that much longer follow-up is required to assess the effect of radical intervention.

This paper is important, but difficult to interpret given the changes in management of prostate cancer during the long time period of the study.

PSA screening has changed the picture, and the development of intensive active surveillance programmes rather than simple watchful waiting has improved outcomes for men who elect not to embark on radical treatment at the time of diagnosis.

This study randomised some men with higher risk prostate cancer, i.e. Gleason grade > 7 or PSA > 20 ng/ml, and therefore many men with much more significant risk of disease progression would have been placed under watchful waiting. However, despite this, in men 65 and over the study failed to demonstrate a benefit for early radical prostatectomy,

in terms of death, although the risk

of distant metastases was reduced. This may therefore add weight to the argument for active surveillance for older men with low-risk disease.

Dr Jonathan Rees