SUMMARY: Prostate cancer is the most common cancer in American men with the exclusion of skin cancer, and 1 in 9 men will be diagnosed with prostate cancer during their lifetime. It is estimated that in the United States, about 174,650 new cases of Prostate cancer will be diagnosed in 2019 and 31,620 men will die of the disease. The widespread use of PSA testing in the recent years has resulted in a dramatic increase in the diagnosis and treatment of prostate cancer. The management of clinically localized prostate cancer that is detected based on Prostate Specific Antigen (PSA) levels remains controversial and management strategies for these patients have included Surgery, Radiotherapy or Active Monitoring. However, it has been proposed that given the indolent nature of prostate cancer in general, majority of the patients do not benefit from treatment intervention and many patients die of competing causes. Further, treatment intervention can result in adverse effects on sexual, urinary, or bowel function. The U.S. Preventive Services Task Force (USPSTF) has recommended that population screening for prostate cancer should not be adopted as a public health policy, because the risks appeared to outweigh benefits, from detecting and treating PSA-detected prostate cancer.
In the Prostate Testing for Cancer and Treatment (ProtecT) study which is a prospective, randomized trial, management with Active Monitoring, Radical Prostatectomy, and External Beam Radiotherapy were compared, among patients with PSA-detected clinically localized prostate cancer. This study at a median follow up of 10 yrs concluded that prostate cancer-specific mortality was low, irrespective of the treatment given, with similar efficacy outcomes, but with a variable impact on quality of life. In this study, it was noted that patients assigned to Active Monitoring were significantly more likely to have metastatic disease than those assigned to treatment. This in turn would warrant salvage treatment, which could result in toxicities as well. Long term survival results are not mature. In the Prostate Cancer Intervention versus Observation Trial (PIVOT), at 19 years of follow up, the relative risk of death from prostate cancer was 0.65 (65% lower with intervention) but the absolute difference in risk was only 4%. However, long term follow up results are not mature. These data suggested that Radical Prostatectomy reduces mortality among men with clinically detected localized prostate cancer, but evidence from long-term follow-up is lacking.
The Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) is a randomized trial in which 695 men with localized prostate cancer were randomly assigned to the Radical Prostatectomy group (N=347) and to the watchful-waiting group (N=348), between 1989 and 1999. This trial opened before the era of Prostate Specific Antigen (PSA) testing. Enrolled patients were younger than 75 years of age and had localized tumor Stage T1, or T2. Tumors had to be well differentiated to moderately well differentiated according to the WHO classification, and were required to have a serum PSA level of less than 50 ng/ml and a negative bone scan. The baseline characteristics were similar in both groups. The mean age was 65 years, the mean PSA level was approximately 13 ng/ml, and only 12% of the patients had nonpalpable stage T1c tumors. Patients were followed up every 6 months for the first 2 years and then annually. The Primary end points were death from any cause, death from prostate cancer, and the risk of metastases. Secondary end points included the initiation of Androgen Deprivation Therapy. The median follow up time was 23.6 years.
The cumulative incidence of death from prostate cancer at 23 years was 19.6% in the Radical Prostatectomy group and 31.3% in the watchful-waiting group (difference of 11.7%) and the relative risk for the complete follow up period was 0.55, meaning 55% lower risk of death with Radical Prostatectomy (P<0.001). The mean years of life gained, in the Radical Prostatectomy group at 23 years of follow up was 2.9 years. The cumulative incidence of distant metastases at 23 years was 26.6% in the Radical Prostatectomy group and 43.3% in the watchful-waiting group (difference of 16.7%) and the relative risk based on data from the complete follow up period was 0.54, meaning 54% lower risk of distant metastases (P<0.001). Among those who underwent Radical Prostatectomy, extracapsular extension was associated with a risk of death from prostate cancer that was 5 times as high as that among men without extracapsular extension. A Gleason score higher than 7 was associated with a risk, that was 10 times as high as that with a score of 6 or lower.
It was concluded that among men with clinically detected localized prostate cancer, Radical Prostatectomy resulted in a mean gain of almost 3 years of life after 23 years of follow up, and a high Gleason score and the presence of extracapsular extension in the Radical Prostatectomy specimens were highly predictive of death from prostate cancer. In the current day clinical practice however, with widespread PSA testing and PSA-detected tumors utilizing multiparametric Magnetic Resonance Imaging with targeted biopsies, the lead time induced by screening and definition of risk groups becomes increasing relevant when recommending treatment. Radical Prostatectomy or Watchful Waiting in Prostate Cancer – 29-Year Follow-up. Bill-Axelson A, Holmberg L, Garmo H, et al. N Engl J Med 2018; 379:2319-2329