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Original Contribution
June 9, 2004

Natural History of Early, Localized Prostate Cancer

Author Affiliations

Author Affiliations: Departments of Urology and Clinical Medicine (Drs Johansson, Andrén, and Andersson) and Statistical Unit, Center for Clinical Research (Mr Magnuson), Örebro University Hospital, and Center for Assessment of Medical Technology (Drs Johansson and Andersson), Örebro, Sweden; Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden (Drs Dickman and Adami); Regional Oncologic Center, University Hospital, Uppsala, Sweden (Dr Holmberg); and Department of Epidemiology and the Harvard Center for Cancer Prevention, Harvard School of Public Health, Boston, Mass (Dr Adami).

JAMA. 2004;291(22):2713-2719. doi:10.1001/jama.291.22.2713

Context Among men with early prostate cancer, the natural history without initial therapy determines the potential for survival benefit following radical local treatment. However, little is known about disease progression and mortality beyond 10 to 15 years of watchful waiting.

Objective To examine the long-term natural history of untreated, early stage prostatic cancer.

Design Population-based, cohort study with a mean observation period of 21 years.

Setting Regionally well-defined catchment area in central Sweden (recruitment March 1977 through February 1984).

Patients A consecutive sample of 223 patients (98% of all eligible) with early-stage (T0-T2 NX M0 classification), initially untreated prostatic cancer. Patients with tumor progression were hormonally treated (either by orchiectomy or estrogens) if they had symptoms.

Main Outcome Measures Progression-free, cause-specific, and overall survival.

Results After complete follow-up, 39 (17%) of all patients experienced generalized disease. Most cancers had an indolent course during the first 10 to 15 years. 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% to 36.0%), survival without metastases (from 76.9% to 51.2%), and prostate cancer–specific survival (from 78.7% to 54.4%). The prostate cancer mortality rate increased from 15 per 1000 person-years (95% confidence interval, 10-21) during the first 15 years to 44 per 1000 person-years (95% confidence interval, 22-88) beyond 15 years of follow-up (P = .01).

Conclusion Although most prostate cancers diagnosed at an early stage have an indolent course, local tumor progression and aggressive metastatic disease may develop in the long term. These findings would support early radical treatment, notably among patients with an estimated life expectancy exceeding 15 years.