PSA kinetics and prediction of outcomes of untreated patients

There has been an on-going difference of opinion within sections of the urology community regarding the value of PSA velocity and/or PSA doubling times in predicting outcomes to first-line prostate cancer treatment.

On the one hand, Vickers and colleagues have been arguing that PSA kinetics make no difference to the accuracy of outcomes as predicted using the PCPT Calculator. In the opposite corner, Catalona and colleagues have been arguing that use of PSA velocity does improve the accuracy of the prediction. For an earlier summary of this topic, please see the article “PSA velocity: is it important to prostate cancer risk?

Vickers et al. have now published a detailed literature review and use this review to further suggest that the calculation of PSA velocity or PSA doubling do nothing to improve the predictive accuracy of the PCPT Calculator.

They conducted a systematic review of studies published before March 2007 in which a PSA dynamic (velocity or doubling time) was calculated in patients before definitive treatment, a subsequent event (such as biopsy or recurrence) was ascertained, and the association between the two was analyzed. Their principal end point was the type of analysis reported, particularly whether the predictive accuracy of a statistical model that included both absolute PSA level and a PSA dynamic was compared with that of a model that included only PSA.

The results of this review are given as follows:

  • 87 articles were eligible for analysis.
  • The most common end points were biopsy (42 articles), and either recurrence (14 articles) or metastases or death (14 articles) after definitive therapy.
  • Although PSA dynamics were generally found to be associated with outcome, only one article compared predictive accuracy of models with and without a PSA dynamic: this article reported that PSA velocity improved prediction slightly (from 0.81 to 0.83), but was subject to verification bias.
  • No article used decision analytic methods to examine the clinical impact of PSA dynamics.

Vickers et al. conclude that there is little evidence that calculation of PSA velocity or PSA doubling time in untreated patients provides predictive information beyond that provided by absolute PSA level alone, and state that  “We see no justification for the use of PSA dynamics in clinical decision making before treatment in early-stage prostate cancer.”

2 Responses

  1. Hello, I have a few questions there seems no answer to. Please help.

    Many patients will have prostate cancer recurrence after primary radiation therapy (RT). Some will choose watchful waiting (or be given a placebo in a clinical trial).

    (1) How many of these patients would see their PSA go up (analogous to PSADT decreasing) at 2, 4, and 6 months after recurrence?

    (2) How many patients would see there PSA go down (analogous to PSADT increasing) at 2, 4, and 6 months after recurrence?

    (3) Also, what are the pros and cons of measuring PSA doubling time (PSADT) versus measuring PSA response (PSAR) in the first 6 months after recurrence?

    I am looking for hard data and explanations why some placebo patient’s PSA variables improve, at certain time points.

    Any assistance would be greatly appreciated!

    Thank you very much,

    Brian, MD, MBA

  2. Dear Brian:

    I don’t think any of the regular commentators on this site can answer that question. One would need access to the sorts of databases available to people who are heavily involved in clinical trials of one type or the other.

    I can think of two people you might want to approach who might be able to help you get answers to these questions. The first is Dr. Mack Roach at UCSF, who has been significantly involved for years in many of the trials conducted by the RTOG. The other is someone like Dr. Ian Thompson at the University of Texas at San Antonio, who has had extensive clinical trial experience in prostate cancer, including placebo therapy, surgery, and radiation trials. Each of these researchers provides academic contact information on the links I have given you. If they can’t answer your questions themselves, they would most certainly be able to help you find someone who could.

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