New research published in the New England Journal of Medicine demonstrates that early diagnosis and treatment of prostate cancer reduces suffering and death in men younger than 65 years and the rate of metastatic cancer in older men. The findings come from The Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4), a 23-year study funded by the Swedish Cancer Society and the U.S. National Institutes of Health.
Between 1989 and 1999, researchers randomly assigned 695 men with prostate cancer to either watchful waiting or radical prostatectomy. The men had been diagnosed with localized prostate cancer before the era of PSA testing. Researchers followed the men through the end of 2012 to observe the prevalence of death from prostate cancer or other causes, metastatic cancer and palliative treatments such as hormone therapy, radiation or chemotherapy.
Men Under 65
The study found that men younger than 65 who had a radical prostatectomy had a 15.8% lower risk of dying from prostatecancer than men who did not have surgery. These men also had a 15.8% lower risk of the cancer spreading to other organs and a 25.5% lower risk of overall mortality. Men in this group were also less likely to need palliative treatment.
Men 65 and Older
There was only a 1.9% reduction in overall mortality for men 65 years and older assigned to the radical prostatectomy group, and a 6.6% reduced risk of death from prostate cancer. However, the risk of metastases was reduced by 8.9% among men in this group compared to men in the watchful waiting group.
This is the first study to demonstrate that a radical prostatectomy could reduce metastatic prostate cancer in older men, and thus prevent suffering from advanced disease. The researchers wrote that “the overall long-term disease burden is also a reminder that factors other than survival should be considered when counseling men with localized prostate cancer; the risk of metastases and ensuing palliative treatments also affect quality of life.”
Bill-Axelson, A. et al. Radical Prostatectomy or Watchful Waiting in Early Prostate Cancer. NEJM. 2014; 370(10);932-42
What We Can Learn from the SPCG-4 Study
Active Surveillance for Older Men
The results from this Scandinavian study should affect the current practice of knee-jerk recommendation of active surveillance for all men over 65 years with low-risk prostate cancer. According to the Social Security tables, a 70-year- old man has a life expectancy of 14 years, and a 76-year-old man has a life expectancy of more than 10 years. It is well established that older men are far more likely to harbor aggressive prostate cancer and to suffer metastases and death from this disease. Men should give serious consideration to other options, as well as to active surveillance. Current evidence shows that delayed treatment in men who have been in active surveillance programs is unsuccessful in up to half of patients.
I tell my patients that active surveillance is an option, but it has drawbacks:
- Repeated biopsies are associated with increased risks of serious, sometimes life-threatening infections, erectile dysfunction and scarring around the prostate gland that can make surgery (especially nerve-sparing surgery) more difficult if it is necessary later.
- Up to 30-40% of patients selected for active surveillance have more aggressive cancer in their prostate that has been “missed” by the diagnostic biopsy, but it will show up later.
- Delayed treatment is unsuccessful in a substantial percentage of patients who then risk the development of metastases—and require multiple treatments with significant associated side effects—or death from prostate cancer. Patients with low-risk disease and a long life expectancy are significantly more likely to avoid suffering from prostate cancer if they have early surgery.
Metastatic Prostate Cancer in Older Men
This study shows that radical prostatectomy could reduce metastases in older men. We already knew that men over 70 have higher-grade tumors, a higher rate of metastases and a higher prostate cancer mortality rate. There are many “guidelines” stating that men over 70 should not be screened for prostate cancer, period. In fact, there are proposed quality-of-medicine measurements that state it is an absolute indicator of poor medical practice if a physician orders a PSA test on a man over 70.
Eventually the truth will come out. But unfortunately, countless men will unnecessarily suffer and die of metastatic prostate cancer because of promulgated misinformation.
More Credible than the PIVOT Study
The Scandinavian study and the Prostate Cancer Intervention Versus Observation Trial (PIVOT) both compared radical prostatectomy with watchful waiting. However, they came William J. Catalona, M.D. up with opposite results. The Scandinavian study showed that surgery was better than watchful waiting, and the PIVOT Trial reported that watchful waiting was as good as surgery, except for patients with the more aggressive tumors. Some have claimed that PIVOT is more relevant because it started in the PSA screening era.
However, PIVOT is flawed because it involved many older, less healthy patients who died of other causes before the prostate cancer could kill them. An entry requirement was a 10- year life expectancy. However, half of the PIVOT patients died, most from causes other than prostate cancer, before 10 years. Thus, they were not appropriate candidates for radical prostatectomy. PIVOT was also statistically underpowered and had only an approximately 10-year median follow-up. Thus, PIVOT could show a survival benefit from radical prostatectomy only in the men with the fastest-progressing tumors.
The Scandinavian study has a low- risk group comparable to PSA-screen- detected cancer, and it also has much longer follow-up. Thus, it provides an opportunity to compare patients with low-risk disease. This is a high-quality study by excellent clinical researchers, and the results are more credible than those reported in the PIVOT trial.