© The Author 2007. Published by Oxford University Press.
ARTICLES |
Prostate-Specific Antigen Levels as a Predictor of Lethal Prostate Cancer
For the Scandinavian Prostate Cancer Group Study No. 4
Affiliations of authors: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (KF, HOA); Regional Oncological Center at Uppsala University, Uppsala, Sweden (HG, LH); Department of Urology, Örebro University Hospital, Örebro, Sweden (OA, JEJ); Department of Urology, Uppsala University Hospital, Uppsala, Sweden (ABA); Regional Oncological Center, Karolinska University Hospital, Stockholm, Sweden (JA)
Correspondence to: Katja Fall, MD, PhD, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Box 281, S-171 77 Stockholm, Sweden (e-mail: Katja.Fall{at}ki.se).
Background: Rates of long-term survival among patients with untreated localized prostate cancer are high. To avoid unnecessary treatment, tools are needed to identify the small proportion of patients who are destined to develop lethal prostate cancer.
Methods: To evaluate the accuracy of early changes in prostate-specific antigen (PSA) levels as predictors of prostate cancer outcome, we assessed serial measurements of PSA level among 267 men with localized prostate cancer in a Scandinavian cohort of men who were diagnosed between 1989 and 1999 and who were managed by watchful waiting. We then 1) fitted individual regression lines to the PSA values assessed for each patient during the first 2 years of follow-up by using three different models, 2) evaluated early PSA curve characteristics as determinants of the cumulative incidence of lethal prostate cancer and calculated hazard ratios for baseline PSA value and rate of change in PSA level to prostate cancer outcome, and 3) plotted time-dependent receiver operating characteristic (ROC) curves. All P values are two-sided.
Results: During complete follow-up for a mean of 8.5 years, 34 patients (13%) died from prostate cancer, and 18 (7%) developed metastases but were still alive at end of follow-up. In a log-linear model, both PSA value at baseline (P = .05) and the rate of PSA change (P<.001) were associated with the development of lethal prostate cancer. In the ROC analysis, however, the accuracy of classifying the disease as either indolent or destined to progress was low, regardless of the cut point chosen for initial PSA level or rate of change in PSA level.
Conclusions: Although baseline PSA value and rate of PSA change are prognostic factors for lethal prostate cancer, they are poor predictors of lethal prostate cancer among patients with localized prostate cancer who are managed by watchful waiting.
| CONTEXT AND CAVEATS Prior knowledge Although patients with untreated localized prostate cancer may have high rates of long-term survival, many undergo treatment. Study design Prospective analysis to determine the specificity and sensitivity of prostate-specific antigen (PSA) level and its rate of change per year (PSA velocity) in predicting lethal prostate cancer among a cohort of men who were diagnosed with localized prostate cancer and underwent watchful waiting rather than treatment. Contributions Although PSA value at the time of prostate cancer diagnosis and its rate of change were associated with the development of lethal disease after an average of 8.5 years after diagnosis, the accuracy of predicting aggressive disease was low. Implications Baseline PSA value and its rate of change were poor predictors of lethal prostate cancer in this cohort. Limitations There is variability in PSA measurements due to physiologic factors and differences in testing methods and the number of measurements taken.
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Manuscript received September 20, 2006; revised January 19, 2007; accepted February 15, 2007.
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J Natl Cancer Inst 2007 99: 496-497.
J Natl Cancer Inst 2007 99: 493.
J Natl Cancer Inst 2007 99: 493.
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