Continued Survival Benefits With Radical Prostatectomy in Longer-Term Follow-up in Scandinavian Prostate Cancer Group-4 Trial
As reported in The New England Journal of Medicine by Bill-Axelson et al, additional long-term follow-up in the Scandinavian Prostate Cancer Group-4 trial (SPCG-4) continues to show significant benefits of radical prostatectomy vs watchful waiting in early prostate cancer, including reduced risk of all-cause mortality, prostate cancer–specific mortality, and distant metastases and reduced need for androgen-deprivation therapy. Survival benefits have increased over time.
Study Details
In SPCG-4, 695 men with early prostate cancer were randomly assigned between 1989 and 1999 (ie, before the prostate-specific antigen [PSA] era) to radical prostatectomy or watchful waiting. 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. Patients in both groups had a mean age of 65 years, only 12% had nonpalpable T1c tumors at baseline, and mean PSA level was approximately 13 ng/mL.
Cumulative Mortality
By December 31, 2012, after median follow-up of 13.4 years (range, 3 weeks to 23.2 years), a total of 294 men in the radical prostatectomy group had undergone a radical prostatectomy (23 with node-positive disease did not undergo the procedure), and 294 men in the watchful waiting group had not received curative treatment. Totals of 200 men in the radical prostatectomy group and 247 in the watchful waiting group had died (18-year cumulative incidence = 56.1% vs 68.9%) and totals of 63 and 99 had died from prostate cancer (18-year cumulative incidence = 17.7% vs 28.7%).
Survival Benefits
Patients in the radical prostatectomy group had significantly reduced risk of death from any cause (absolute 12.7% reduction, relative risk [RR] = 0.71, P < .001), death from prostate cancer (absolute reduction of 11.0%, RR = 0.56, P = .001), and distant metastases (absolute reduction of 12.2%, RR = 0.57, P < .001) and less frequently required androgen-deprivation therapy (absolute reduction of 25.0%, RR = 0.49, P < .001).
Effect of Age and Tumor Risk
In subgroup analyses, reductions in any-cause mortality for prostatectomy were significant in patients aged < 65 years (RR = 0.50, P < .001) and in patients with low-risk (RR = 0.57, P = .002) and intermediate-risk disease (HR = 0.71, P = .02). Reductions in risk for prostate cancer–specific mortality were significant in patients aged < 65 years (RR = 0.45, P = .002) and patients with intermediate-risk disease (RR = 0.38, P < .001).
Reduced risk of distant metastasis was significant both in patients aged < 65 years (RR = 0.49, P < .001) and in those aged ≥ 65 years (RR = 0.68, P = .04) and in patients with low-risk (RR = 0.40, P = .006) and intermediate-risk disease (HR = 0.49, P < .001). Patients in the prostatectomy group were significantly less likely to receive androgen-deprivation therapy in both age categories and all three risk categories.
Increased Benefit Over Time
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 prostatectomy group. For prostate cancer–specific mortality, the difference favoring the 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 men in the 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 investigators concluded, “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 tumor risk. A large proportion of long-term survivors in the watchful-waiting group have not required any palliative treatment.”
Anna Bill-Axelson, MD, PhD, and Lars Holmberg, MD, PhD, of Uppsala University Hospital, contributed equally to the New England Journal of Medicine article.
The study was supported by the Swedish Cancer Society, National Institutes of Health, Karolinska Institute, Prostate Cancer Foundation, and Percy Falk Foundation. The study authors reported no potential conflicts of interest.
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