Long-term follow-up of prostate cancer patients randomized to radical prostatectomy or active surveillance (a.k.a. “watchful waiting”) showed a substantial and statistically significant survival advantage for the surgical procedure, Swedish researchers said.
Specifically, among participants in the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) followed for up to 29 years, patients who underwent radical prostatectomy added a mean of 2.9 years to their life expectancy after 23 years, according to Anna Bill-Axelson, MD, PhD, Uppsala University, Uppsala, Sweden, and colleagues.
The researchers found a relative risk of 0.55 (95% CI 0.41-0.74) for prostate cancer death in those undergoing prostatectomy versus active surveillance, they reported in the New England Journal of Medicine.
But a U.S. prostate cancer specialist told MedPage Today that the very length of the study complicates the interpretation, since current diagnosis and treatment is markedly different than when the trial began.
“It would be very difficult for a newly diagnosed patient to determine where he fits in this study,” said James Mohler, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, New York.
In SPCG-4, 695 men with localized prostate cancer were randomly assigned to either radical prostatectomy or watchful waiting in 14 centers in Sweden, Finland, and Iceland from 1989 to 1999. Findings similar to those in the current study were reported in a 2014 follow-up analysis.
Of the 695 men involved in the study, 347 were randomly assigned to the radical prostatectomy group and 348 to the watchful-waiting group. In the new analysis, the maximum potential follow-up time was 29.3 years, and median follow-up was 23.6 years.
As of December 2017, 80% of the men enrolled in the study had died. The cumulative incidence of death from all causes at 23 years was 71.9% in the radical prostatectomy group and 83.8% in the watchful waiting group (difference 12.0 percentage points; 95% CI 5.5-18.4).
Seventy-one deaths in the radical prostatectomy group and 110 in the watchful waiting group were due to prostate cancer, for an absolute difference in risk of 11.7 percentage points (95% CI 5.2-18.2).
Distant metastases were diagnosed in 92 men in the radical prostatectomy group and 150 men in the watchful waiting group. At 23 years the cumulative incidence of metastases was 26.6% in the radical prostatectomy group and 43.3% in the watchful waiting group (difference 16.7 percentage points; 95% CI 9.6-23.7).
Bill-Axelson and her colleagues also found that among men in the radical prostatectomy group, extracapsular extension was associated with a risk of death from prostate cancer that was five times that of men without extracapsular extension. In addition, a high Gleason score (>7) — about 40% of both treatment groups had scores in that range — was associated with a risk of death from prostate cancer that was 10 times higher than a score of 6 or lower.
But the researchers did not report mortality for the two treatment groups stratified by baseline Gleason score. Adverse events such as incontinence and sexual dysfunction were also not addressed in the current report (a 2011 publication indicated similar rates of erectile dysfunction in the two groups but a nearly fourfold higher prevalence of urinary leakage in the prostatectomy patients).
“A mean of 2.9 years of life were gained with radical prostatectomy,” observed the authors. “The mean number of years gained is a crude measure, since any given man who is randomly assigned to undergo the procedure either might not benefit at all or might have a much greater benefit than the mean number for the whole group indicates. However, the measure puts in perspective what is risked by delaying intervention.”
“This remains the best randomized study of radical prostatectomy versus observation ever done,” Mohler told MedPage Today. “Its follow-up is long, it did not have PSA early detection bias, and even with the problems with Gleason grading and the determination of clinical pathologic stage, the group of patients seems to be largely devoid of who we would place on active surveillance today.”
But Mohler, who was not involved in the study, said that because of the way that prostate cancer diagnosis and management has changed since 1989, it’s unclear what the findings mean for current patients.
“The authors raise the concern that diagnosing cancer earlier – like it is done today – might fail to show this gain in life benefit because of contamination of modern-day patients with lots of patients that don’t really need to be treated,” he said. “And that’s a very legitimate concern, so it would be wrong for patients and urologists to say that this study proves that more men should have radical prostatectomy… That’s why this study is so hard to interpret in 2018.”
However, Mohler noted that if a patient does have an aggressive prostate cancer, the study shows that a patient “is better off having radical prostatectomy than observation, in terms of preventing the development of metastasis, dying of prostate cancer, and overall survival.”
One co-author reported relationships with Astellas/Medivation and Orion. Others declared they had no relevant disclosures.