By David Fiore, MD
Professor of Family Medicine, University of Nevada, Reno
Dr. Fiore reports no financial relationships relevant to this field of study.
SYNOPSIS: In men with prostate cancer diagnosed in the 1990s (primarily by digital rectal exam), researchers found that radical prostatectomy offered an average survival benefit of 2.9 years over watchful waiting.
SOURCE: Bill-Axelson A, et al. Radical prostatectomy or watchful waiting in prostate cancer — 29-year follow-up. N Engl J Med 2018;379:2319-2329.
This was a follow-up of the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4), in which 695 men were assigned randomly to either radical prostatectomy or watchful waiting from 1989 to 1999 and were followed for up to 29 years. As of 2017, 80% of participants had died, with 181 deaths attributed to prostate cancer (71 in the radical prostatectomy group and 110 in the watchful-waiting group). The cumulative incidence of death at a median of 23 years was 71.9% in the radical prostatectomy group and 83.8% in the watchful waiting group, with a relative risk (RR) of 0.74 for the surgical group and number needed to treat (NNT) of 9.2. 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 (RR for the complete follow-up period, 0.55; NNT, 8.5).
Metastases were diagnosed in 92 men in the radical prostatectomy group and 150 men in the watchful waiting group (RR, 0.54 for the radical prostatectomy group; NNT, 6.0). In men who underwent radical prostatectomy, extracapsular extension and higher-grade Gleason scores were associated with a worse prognosis. Thirty-eight men with extracapsular extension died from prostate cancer compared with nine men without extracapsular extension (RR, 5.21). Compared to men with a Gleason score of 6, a score of 7 (4+3) was associated with a five times higher risk of prostate cancer death (RR, 5.73). A Gleason score of 8 or 9 was associated with more than a 10 times higher risk of death (RR, 10.63).
This is an important study offering new insight on the progression of prostate cancer and the effect of treatment on long-term outcomes. However, there are a few major caveats, including when this study started and how diagnosis and management of prostate cancer have changed. Critically, only 18% of cancers were found by screening, and only 12% of patients had nonpalpable T1c tumors at the time of screening. This is in stark contrast to the situation in the United States, where most prostate cancers are detected by screening and 80% of prostate cancers were localized (1999-2006).1
In the United States, the authors of two studies compared radical prostatectomy to observation. Even after 20 years, those researchers failed to find a benefit from surgery.2,3 In addition, “watchful waiting” is distinct from “active surveillance” (also called “active monitoring”), which is now the preferred alternative to immediate surgery for nonaggressive prostate cancers in the United States.
Another major limitation of this study is that the authors did not report harms from treatment. Rates of erectile dysfunction following radical prostatectomy range from 14-85% (too wide a range to be useful in counseling), with best estimates in high-quality studies averaging closer to 75%.4 Rates of incontinence, which can be debilitating for otherwise healthy men, run about 20%.5 Unfortunately, these rates are not much lower after robotic surgery.
The NNT statistics were impressive, and this study received a lot of attention in the lay press. Still, this study does not really change the equation about when or whether to order a PSA for screening purposes, nor does it help much when deciding between active monitoring and radical prostatectomy. What this research does tell us is that in men with advanced prostate cancer and a longer life expectancy, radical prostatectomy offers both survival and disease-free survival benefits.
- Brawley OW. Trends in prostate cancer in the United States. J Natl Cancer Inst Monogr 2012;2012:152-156.
- Hamdy FC, et al. 10-Year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer. N Engl J Med 2016;375:1415-1424.
- Wilt TJ, et al. Follow-up of prostatectomy versus observation for early prostate cancer. N Engl J Med 2017;377:132-142.
- Emanu JC, et al. Erectile dysfunction after radical prostatectomy: Prevalence, medical treatments, and psychosocial interventions. Curr Opin Support Palliat Care 2016;10:102-107.
- Haglind E, et al. Urinary incontinence and erectile dysfunction after robotic versus open radical prostatectomy: A prospective, controlled, nonrandomised trial. Eur Urol 2015;68:216-225.