Active surveillance and PSA kinetics — a UK perspective

Official guidance in the UK recommends conservative management of men with “low-risk,” localized prostate cancer, monitoring the disease using regular PSA tests, kinetics, and re-biopsies. However, there are few clear data supporting changes in PSA level that should alert a physician or his patient to the need for clinical re-assessment.

Metcalfe et al. compared the alerts resulting from PSA kinetics and a novel longitudinal reference range approach, which incorporates age-related changes, during the monitoring of 408 men with localized prostate cancer. In their study, patients originally diagnosed with “low risk,” localized disease were monitored using regular PSA tests over a mean of 2.9 years, recording the following specific measures:

  • When a patient’s PSA doubling time fell below 2 years
  • When his PSA velocity exceeded 2 ng/ml per year
  • When his upper 10 percent reference range was exceeded

The data from this study is reported to have shown the following:

  • PSA doubling time and PSA velocity alerted a high proportion of men initially but became unresponsive to changes with successive tests.
  • Calculating the PSA doubling time using recent PSA measurements reduced the decline in response.
  • The reference range method maintained responsiveness to changes in PSA level throughout the monitoring.

The authors suggest that increasing unresponsiveness of PSA kinetics is a consequence of the underlying model. They suggest that novel methods are needed for evaluation of patients in cohorts currently being managed by active surveillance techniques. And they state that, in the meantime, specific guidance as to the appropriate means for following and assessing the status of patients on active surveillance regimens (and in particular the guidance issued by the National Insdtitute for Clinical Excellence in the UK) needs to be applied with caution.

The “New” Prostate Cancer InfoLink concurs with the conclusions of this paper. The validity of PSA kinetics as a means to assess prostate cancer risk has been extensively questioned. Guidelines based on PSA kinetics are therefore open to considerable question too. Patients on active surveillance, and their physicians, should be aware that there are no defininitive methods yet available to accurately assess when a specific patient should consider switching from active surveillance to invasive treatment based on sound risk guidelines.

3 Responses

  1. Active surveillance (AS) is an important treatment for the disease. The starting point of uncertainty is the biopsy. The biopsy method should be standardized and correlated to gland volume. PSA alone can’t be the alert system. In a localized cancer, as the cancer accumulates mutations and becomes more poorly differentiated, PSA leakage can cease to be informative as these cancers secrete less PSA per unit cell.

    There is no question that better markers of disease progression are needed, but there is room for improvement in the current methods. A less uncertain starting point will not resolve the issue, but will help considerably. Having a more precise mapping of the gland at diagnosis will eliminate some of the uncertainty and improve the value of PSA in alerting a need for action.

    AS has potential for many men. I hope that improvements in current procedures will support the value of this protocol.

  2. Does anyone have the full text of this paper? The abstract refers to “a novel longitudinal reference range approach”, but does not define what that is.

  3. Jon:

    I have not seen this paper either. However, I have e-mailed the lead author to ask for a copy.

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