1. Among men under 75 years of age with localized prostate cancer, radical prostatectomy was associated with a significant survival benefit compared to watchful waiting.
2. In patients who underwent radical prostatectomy, extracapsular extension and a Gleason score of 8 or 9 were strong indicators of poor prognosis.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Though radical prostatectomy is a standard option for the management of localized prostate cancer, the optimal role is debated given the surgical morbidity and low mortality rate from prostate cancer. To assess the long-term mortality benefit of radical prostatectomy in this cohort, the landmark Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) trial randomized men with localized prostate cancer to radical prostatectomy or watchful waiting from 1989 to 1999 and published the annually collected follow-up data in three-year intervals since 2002. This study reports outcomes through 2017 and includes histopathologic associations with long-term prognosis. The results demonstrated that patients randomized to radical prostatectomy had a significantly lower rate of all three components of the primary endpoint ( all-cause mortality, prostate cancer mortality, and distant metastatic disease) compared to the watchful waiting group. Additionally, the authors found a strong association between extracapsular extension and Gleason score of 8 or 9 with death from prostate cancer. While a clear mortality benefit from radical prostatectomy in localized prostate cancer was demonstrated, the impact on clinical practice is limited by current differences in prostate cancer detection and treatment.
This trial was strengthened by the long duration of follow-up data and trial initiation prior to routine prostate-specific antigen (PSA) screening, which adds lead time and necessitates additional follow-up to determine treatment effects. This significantly limits generalizability, however, as most patients enrolled had palpable tumors and represent a population different than that seen in modern practice. Furthermore, the mortality benefit from radical prostatectomy still must be balanced with surgical morbidity and cost.
Relevant Reading: Radical prostatectomy versus observation for localized prostate cancer
In-Depth [randomized controlled trial]: This was a multicenter trial that randomized 695 men with localized prostate cancer to radical prostatectomy (n=347) or watchful waiting (n=348) between 1989 and 1999. Eligibility required age younger than 75 years, a life expectancy more than 10 years and no other known cancer, PSA level <50 ng/mL, and a localized tumor. The histopathologic margins, extracapsular tumor growth, and Gleason grade were reviewed for available biopsy and surgical specimens of patients in the radical prostatectomy group and assessed for prognostic value. The primary end points were death from any cause, death from prostate cancer, and metastasis.
With follow-up through 2017, 553 (80%) of the 695 men in the study had died and the median follow-up time was 23.6 years. For radical prostatectomy vs. watchful waiting, respectively: the cumulative incidence of death at 23 years was 71.9% vs. 83.8% with a corresponding relative risk [RR] of 0.74 (95% CI, 0.62 to 0.87; P<0.001), the cumulative incidence of death from prostate cancer was 19.6% vs. 31.3% with RR of 0.55 (95% CI, 0.41 to 0.74; P<0.001), and the cumulative incidence of distant metastases was 26.6% vs. 43.3% with RR of 0.54 (95% CI, 0.42 to 0.70; P<0.001). At 23 years, a mean of 2.9 additional years of life was gained from radical prostatectomy. The effect of radical prostatectomy among men younger than 65 years was greater with respect to all three primary endpoints. Regarding histopathologic associations with long-term prognosis in the radical prostatectomy group, extracapsular extension (RR, 5.21; 95% CI, 2.42 to 11.22) and Gleason score of 8 or 9 (RR, 10.63; 95% CI, 3.03 to 37.30) had the greatest association with poor prognosis.
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