Men with early-stage, initially untreated prostate cancer face an increasing risk over time for progression to more aggressive and lethal disease, according to an article in the June 9th issue of The Journal of the American Medical Association.

According to background information in the article, physicians of patients with early, localized stage disease have the challenge of maximizing the possibilities for survival without extensively overtreating the patient. Even without initial treatment, only a small proportion of all patients with cancer diagnosed at an early clinical stage die from prostate cancer within 10 to 15 years following diagnosis. However, little is known about disease progression and risk of death beyond 10 to 15 years of watchful waiting.

Jan-Erik Johansson, MD, PhD, and his Swedish colleagues analyzed survival following “watchful waiting” in 223 patients from central Sweden with early-stage, initially untreated prostate cancer. The mean observation period was 21 years.

The researchers found that after complete follow-up, 39 (17 percent) of all patients developed generalized disease. “Most cancers had an indolent course during the first 10 to 15 years,” the authors wrote. “However, further follow-up from 15 (when 49 patients were still alive) to 20 years revealed a substantial decrease in cumulative progression-free survival (from 45.0 percent to 36.0 percent), survival without metastases (from 76.9 percent to 51.2 percent) and prostate cancer?specific survival (from 78.7 percent to 54.4 percent). The prostate cancer mortality rate increased from 15 per 1000 person-years during the first 15 years to 44 per 1000 person-years beyond 15 years of follow-up.”

“Our data may be important for counseling and clinical management of individual patients. Postponement of death is not the only treatment objective because local progression may create substantial suffering,” the researchers added. “In conclusion, our data indicate that the probability of progression to a more aggressive and lethal phenotype may increase after long-term follow-up of prostate cancers that are diagnosed at an early stage and initially left without treatment. These findings argue for early radical treatment of patients with long life expectancy.”

In an accompanying editorial, Alfred I. Neugut, M.D., Ph.D., and Victor R. Grann, M.D., M.P.H., wrote that the study by Johansson et al shows that long follow-up may be necessary to observe the full benefits of earlier diagnosis and treatment of prostate cancer.

“A major question has been whether the use of radical prostatectomy improves survival, a question addressed by the recent radical prostatectomy randomized trial from Sweden and by the Prostate Cancer Intervention Versus Observation Trial (PIVOT), now in progress. But perhaps one of the key problems is the one raised in this study, i.e., the length of follow-up necessary to demonstrate a survival benefit. It is difficult to think in terms of conducting a randomized trial for screening with a horizon of 15 to 20 years, but perhaps that is exactly what will be necessary to really observe the impact of prostate-specific antigen (PSA) screening on prostate cancer.”