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Increase in PSA Levels 5 to 10 Years After Prostatectomy May Not Signify Subsequent Development of Metastasis in Patient's Lifetime

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Key Points

  • Study findings show that at least 9.1% and 15.6% of patients with prostate cancer whose PSA levels increase after 5 years and 10 years of initial treatment, respectively, may not develop metastatic disease in their lifetime.
  • The side effects from salvage therapy for patients with prostate cancer are considerable and can lead to bowel and urinary problems, loss of libido, hot flashes, and fatigue.
  • Just as in the case of PSA screening, any benefits of early detection of recurrent disease must be weighed against the potential harms of overtreatment.

While early treatment of prostate cancer recurrence after a radical prostatectomy based on detectable or rising prostate-specific antigen (PSA) levels may reduce the risk of disease metastasis, even without salvage treatment, many patients will die of other causes before metastatic disease manifests clinically, according to a new study. The study found that at least 9.1% and 15.6% of patients with prostate cancer whose PSA levels increase after 5 and 10 years of initial treatment, respectively, may not develop metastatic disease in their lifetime. Therefore, overdetection and overtreatment for recurrence may not be beneficial to some men. Just as in the case of PSA screening, any benefits of early detection of recurrent disease must be weighed against the potential harms of overtreatment, according to the study authors. The study by Xia et al is published in Clinical Cancer Research.

Study Methodology

Times from PSA recurrence were estimated from data from 441 patients with radical prostatectomy treated at Johns Hopkins University in Baltimore who did not receive salvage treatment. Times to other-cause death were based on U.S. life tables adjusted to reflect other-cause survival among radical prostatectomy cases in the Surveillance, Epidemiology, and End Results (SEER) registry. Competing-risks simulation was used to estimate lower bounds on the chance that other-cause death would precede clinical metastasis for patients with disease characteristics at diagnosis based on data from 4,455 patients from the UCSF Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) database.

Using this information, the researchers then created a simulation model generating a virtual population of 1 million patients with different age and disease characteristics and computed the fraction of patients with PSA recurrence for whom the time from PSA recurrence to another cause of death was less than the time from PSA recurrence to metastasis in the absence of salvage therapy.

Study Findings

The researchers found that at least 9.1% and 15.6% of patients with prostate cancer whose PSA levels increased after 5 and 10 years of initial treatment, respectively, were overdetected. Among those patients older than 70 with a PSA recurrence within 10 years of first diagnosis, the model projected that at least 31.4% were overdetected.

“Salvage therapy for prostate cancer patients includes radiation therapy, which has side effects, such as bowel problems and urinary symptoms, and hormone therapy, which can cause hot flashes, fatigue, loss of libido, and … has been linked with osteoporosis, heart disease, and even diabetes,” Ruth Etzioni, PhD, of the Division of Public Health Sciences at the Fred Hutchinson Cancer Research Center in Seattle, and a coauthor of the study, said in a statement. “Our findings are in line with treatment studies showing that immediate salvage therapy following detection of rising PSA levels is not the right thing for everyone. We need to develop ways to determine who needs salvage therapy and when to give it.”

Dr. Etzioni is the corresponding author for the Clinical Cancer Research article.

The study was funded by the National Cancer Institute and the Centers for Disease Control and Prevention.

Bruce J. Trock, PhD, reported receiving a commercial research grant from Myriad Genetics and has provided expert testimony on diabetes treatment for SonaCare Medical, LLC. The other study authors reported no potential conflicts of interest.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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