A long-term follow-up of a study conducted by researchers from Uppsala University Hospital, Sweden and colleagues found a substantial long-term reduction in mortality for patients with localised prostate cancer who undergo a radical prostatectomy vs. watchful waiting. While the benefit on mortality appears to be limited to patients under 65, surgery did reduce the risk of metastases and the need for additional treatment in older men. The article was published in the March 6, 2014 edition of New England Journal of Medicine.
The researchers used data from the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4), which randomised 695 patients with localised prostate cancer to surgery or watchful waiting, with follow-up for up to 24 years. In the SPCG-4 study patients were randomly assigned to above treatments between 1989 and 1999, therefore before the prostate-specific antigen era.
The primary endpoints were death from any cause, death from prostate cancer, and risk of metastases, and secondary endpoints included initiation of androgen-deprivation therapy.
Radical prostatectomy vs. watchful waiting for localised prostate cancer
Over the course of the study, 200 of 347 patients in the surgery group and 247 of the 348 patients in the watchful waiting group died. Of the deaths, 63 in the surgery group and 99 in the watchful waiting group were due to prostate cancer. Patients in the radical prostatectomy group had significantly reduced risk of death from any cause (p < 0.001), death from prostate cancer (p = 0.001), and distant metastases (p < 0.001) and less frequently required androgen-deprivation therapy (p < 0.001).
In a subgroup analyses, reductions in any-cause mortality for radical prostatectomy were significant in patients aged < 65 years (p < 0.001) and in patients with low-risk (p = 0.002) and intermediate-risk disease (p = 0.02). Reductions in risk for prostate cancer–specific mortality were significant in patients aged < 65 years (p = 0.002) and patients with intermediate-risk disease (p < 0.001).
Reduced risk of distant metastasis was significant both in patients aged < 65 years (p < 0.001) and in those aged ≥ 65 years (p = 0.04) and in patients with low-risk (p = 0.006) and intermediate-risk disease (p < 0.001). Patients in the radical prostatectomy group were significantly less likely to receive androgen-deprivation therapy in both age categories and all three risk categories.
Between 10 and 18 years of follow-up, the number needed to treat to prevent one death from any cause decreased from 20 to 8 in the whole cohort and from 8 to 4 in patients aged < 65 years. One patient died after surgery in the radical prostatectomy group. For prostate cancer–specific mortality, the difference favoring the radical prostatectomy group continued to increase from 9.6 deaths per 1,000 person-years during 5 to 10 years of follow-up to 24.5 deaths during 15 to 20 years of follow-up.
At 18 years of follow-up, approximately 40% of patients in the radical prostatectomy group and 60% in the watchful waiting group had disease progression with or without confirmed metastases and received androgen-deprivation therapy or other palliative treatments.
"The latest results from the SPCG-4 trial indicate that surgery can not only improve survival, especially in men diagnosed at a younger age or with intermediate-risk disease, but also that surgery can reduce the burden of disease in terms of development of metastases and the need for palliative treatment," said co-author Jennifer Rider, assistant professor in the Department of Epidemiology at Harvard School of Public Health and assistant professor of medicine, Channing Division of Network Medicine, Brigham and Women's Hospital. "However, a large proportion of men in the trial still alive at 18 years did not require initial surgery or any subsequent therapy, pointing to the potential benefits of active surveillance strategies to limit overtreatment."
The investigators found that androgen-deprivation therapy was used in fewer patients who underwent radical prostatectomy. The benefit of surgery with respect to death from prostate cancer was largest in men younger than 65 years of age and in those with intermediate-risk prostate cancer. However, radical prostatectomy was associated with a reduced risk of metastases among older men. They concluded that extended follow-up confirmed a substantial reduction in mortality after radical prostatectomy; the number needed to treat to prevent one death continued to decrease when the treatment was modified according to age at diagnosis and tumour risk. A large proportion of long-term survivors in the watchful-waiting group have not required any palliative treatment.
The study was supported by the Swedish Cancer Society, National Institutes of Health, Karolinska Institute, Prostate Cancer Foundation, and Percy Falk Foundation.
The authors reported no potential conflicts of interest.
Bill-Axelson A, Holmberg L, Garmo H, et al. Radical Prostatectomy versus Watchful Waiting in Early Prostate Cancer. New England Journal of Medicine 2014; 370(10):932-42.