Individualized benefit from radical prostatectomy varies widely
MedWire News: The expected patient benefit from radical prostatectomy deviates significantly from estimates resulting from randomized trials, suggest findings from a US study.
"The results call for changes in the way in which randomized trials are interpreted," say Andrew Vickers (Memorial Sloan-Kettering Cancer Center, New York) and colleagues.
The team analyzed data from the Scandinavian Prostate Cancer Group 4 trial to create statistical models for surgery benefit that allowed individualized estimation of patients' absolute risk reduction, based on age and tumor characteristics.
The trial included 695 men with T1 or T2 prostate cancer, prostate specific antigen (PSA) levels of less than 50 ng/mL, and a negative bone scan. The men were randomly allocated to receive either radical prostatectomy (n=347) or watchful waiting (n=348). Patients were recruited between October 1989 and February 1999 and followed up over a median of 10.8 years.
"Our modeling approach was to create a risk score using Gleason grade, stage, and PSA, based on an analysis of the entire cohort and then include the risk score along with age in separate models for each treatment group," explains the team.
The researchers report that 137 (39.5%) men in the radical prostatectomy group and 156 (44.8%) in the watchful waiting group died.
The cumulative incidence of death due to prostate cancer at 10 years was 9.5% in the radical prostatectomy group and 14.1% in the watchful waiting group, giving an absolute difference in cumulative incidence of 4.6%.
As reported in European Urology, there was a dramatic variation in the expected benefit of radical prostatectomy between patients, depending on age and tumor sensitivity.
Overall, younger men with more aggressive disease experienced a larger reduction in risk for prostate cancer death with radical prostatectomy than older men with lower-risk cancer. The 10-year risk for death from prostate cancer decreased from 24% to 9% for a man aged 60 years with Gleason 7, stage T2 disease, while it decreased from 4% to 3% for a man aged 70 years with Gleason 6, T1 disease.
There was little benefit associated with surgery for those aged more than 70 years, even in cases of aggressive disease. At younger ages, the risk reduction associated with surgery was highly dependent on tumor characteristics. Among men aged 65 years, the risk ranged from 4% with Gleason 6, stage T1 disease to 17% with Gleason 8, stage T2 disease.
Given the wide variation in risk by baseline features, the team assessed what proportion of men were at "average" risk and therefore for whom the overall absolute risk reduction estimate of 4.6% would have been appropriate.
"The absolute risk reduction suggests that about 21 patients need to be treated by radical prostatectomy to avert 1 death; the number needed to treat based on individualized prediction varies from 4 to infinity," report the authors.
"Where it is possible to predict risk, it can be clearly seen that overall results of a trial are an average of very different levels of patient benefit," remark Visker et al.
The researchers suggest their findings could be used to counsel individual patients who are considering treatment options for localized prostate cancer.
The results should also prompt further statistical prediction modeling for randomized trial data, they conclude.
By Sally Robertson