Articles

Natural History of Early, Localized Prostate Cancer: A Final Report from Three Decades of Follow-up eulogo1

By: Marcin Popioleka , Jennifer R. Riderb c lowast , Ove Andréna, Sven-Olof Anderssona, Lars Holmbergd e, Hans-Olov Adamic f and Jan-Erik Johanssona

Published online: 01 March 2013

Keywords: Natural history, Localized prostate cancer, Mortality

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Abstract

Background

Most localized prostate cancers are believed to have an indolent course. Within 15 yr of diagnosis, most deaths among men with prostate cancer (PCa) can be attributed to other competing causes. However, data from studies with extended follow-up are insufficient to determine appropriate treatment for men with localized disease.

Objective

To investigate the long-term natural history of untreated, early-stage PCa.

Design, setting, and participants

We conducted a population-based, prospective-cohort study using a consecutive sample of 223 patients with untreated, localized PCa from a regionally well-defined catchment area in central Sweden. All subjects were initially managed with observation. Androgen deprivation therapy was administered when symptomatic tumor progression occurred.

Outcome measurements and statistical analysis

Based on >30 yr of follow-up, the main outcome measures were: progression-free, cause-specific, and overall survival, and rates of progression and mortality per 1000 person-years.

Results and limitations

After 32 yr of follow-up, all but 3 (1%) of the 223 men had died. We observed 90 (41.4%) local progression events and 41 (18.4%) cases of progression to distant metastasis. In total, 38 (17%) men died of PCa. Cause-specific survival decreased between 15 and 20 yr, but stabilized with further follow-up. All nine men with Gleason grade 8–10 disease died within the first 10 yr of follow-up, five (55%) from PCa. Survival for men with well-differentiated, nonpalpable tumors declined slowly through 20 yr, and more rapidly between 20 and 25 yr (from 75.2% [95% confidence interval, 48.4–89.3] to 25% [95% confidence interval, 22.0–72.5]). It is unclear whether these data are relevant for tumors detected by elevated prostate-specific antigen levels.

Conclusions

Although localized PCa most often has an indolent course, local progression and distant metastasis can develop over the long term, even among patients considered low risk at diagnosis.

Take Home Message

The probability of prostate cancer progression stabilizes beyond 20 yr following diagnosis. Nonetheless, metastases may occur over extended follow-up, even in some patients initially considered low risk.

Keywords: Natural history, Localized prostate cancer, Mortality.

Footnotes

a School of Health and Medical Sciences, Örebro University; and Department of Urology, Örebro University Hospital, Örebro, Sweden

b Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA

c Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA

d Regional Oncologic Center, University Hospital, Uppsala, Sweden

e King's College London, Medical School, Division of Cancer Studies, London, UK

f Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

lowast Corresponding author. Department of Epidemiology, Harvard School of Public Health, 677 Huntington Ave., Boston, MA 02115, USA. Tel. +1 617 470 1880.

Authors contributed equally.

z.star Please visit www.eu-acme.org/europeanurology to read and answer questions on-line. The EU-ACME credits will then be attributed automatically.