Extended follow-up of the Scandinavian Prostate Cancer Group-4 trial (SPCG-4) has confirmed that radical prostatectomy is associated with a substantial reduction in mortality among men with early prostate cancer. These results were published in the New England Journal of Medicine.
Each year in the United States, more than 192,000 men are diagnosed with prostate cancer and more than 27,000 die of the disease. Prostate cancer is typically a disease of aging. It may persist undetected for many years without causing symptoms. In fact, most men die with prostate cancer not from prostate cancer. Approximately 20 percent of men will develop prostate cancer during their lifetime, yet only 3 percent will actually die of the disease.
Historically, the treatment of early-stage prostate cancer has been controversial because thus far there is no clear proof that aggressive treatment prolongs survival compared with deferred treatment. Furthermore, treatment can cause lasting side effects, such as impotence and incontinence. As a result, some men opt for a more conservative approach, called active surveillance or watchful waiting—which defers treatment until symptoms appear and/or there is evidence of progression.
SPCG-4 was designed to evaluate the long-term benefits of radical prostatectomy in men with early prostate cancer. The study included 695 men with early prostate cancer who were randomly assigned to radical prostatectomy or watchful waiting between 1989 and 1999. The men were followed through the end of 2012. The primary endpoints of the study were death from any cause, death from prostate cancer, and risk of metastases. Secondary endpoints included initiation of androgen-deprivation therapy.
During 23.2 years of follow-up, 200 of 347 men in the surgery group and 247 of 348 men in the watchful-waiting group died. Of these deaths, 63 in the surgery group and 99 in the watchful-waiting group were due to prostate cancer.
Patients in the radical prostatectomy group were 12.7 percent less likely to die from any cause, 11.0 percent less likely to die from prostate cancer, and 12.2 percent less likely to have distant metastases. They were also 25.0 percent less likely to need androgen-deprivation therapy.
Subgroup analyses indicated that the benefit of surgery (in terms of mortality from prostate cancer) was largest among men younger than age 65 and those with intermediate-risk prostate cancer. Radical prostatectomy was associated with a reduced risk of metastases among both older and younger men. Patients who underwent radical prostatectomy were significantly less likely to receive androgen-deprivation therapy—regardless of age or risk category.
Between 10 and 18 years of follow-up, the number needed to treat to prevent one death continued to decrease. At 18 years of follow-up, approximately 40 percent of men in the prostatectomy group and 60 percent in the watchful-waiting group had disease progression with or without confirmed metastases and received androgen-deprivation therapy or other palliative treatments.
The researchers concluded that long-term follow up confirmed that radical prostatectomy is associated with a substantial reduction in mortality compared to watchful waiting in men with early prostate cancer.
Bill-Axelson A, Holmberg L, Garmo H, et al. Radical prostatectomy or watchful waiting in early prostate cancer. New England Journal of Medicine. 2014; 370:932-942.