Establishing risk and prognosis in men with biochemical recurrence after first-line therapy for early stage disease

There are some things we know and some things we don’t know about establishing the risk of rapid progression and the prognosis for men who have a biochemical recurrence after first-line treatment for prostate cancer:

In general, we know that:

  • PSA kinetics (e.g, PSA doubling time and PSA velocity) are valuable in defining a man’s risk for rapid progression
  • The presence of micrometastatic prostate cancer is a serious issue (but usually we can’t tell whether it’s there or not)
  • The ability to actually identify any groups of living cancer cells helps us to treat the patient most effectively

By contrast, we don’t really know (in any detail) :

  • How relevant the patient’s original Gleason score may be to his risk for further progression
  • How relevant the patient’s original PSA level may be to his risk for further progression
  • Whether the amount of tumor in his prostate at the time of first-line treatment is of any significance at all
  • Whether the time from initial treatment to biochemical recurrence is important
  • Whether other specific biological indicators may be able to clearly help us to assess risk for rapid progression

Having said that, Moul et al. have noted that some of these issues may be “academic,” because the PSA doubling time or PSADT is actually a reasonably good identifier of risk for rapid progression in men with PSA recurrence.

Would it help us to know more about some of the other factors? Of course it would, but don’t get the idea that your doctor can’t give you some good guidance about your risks.

Understanding PSA Doubling Time and How it Affects Risk

Since the early 1990s, we have known that PSADT could be used to categorize men who had biochemical failure following first-line therapy into those at higher and lower levels of risk for rapid progression. However, as yet, the degree of accuracy with which we have been able to do this is limited.

The first problem is one associated with the actual calculation of the PSA doubling time. How many PSA measurements should be used? And how far apart should those measurements be? There are no absolute guidelines as to the “right” way to calculate a PSA doubling time. However, there is a growing consensus that if you have two PSA measurements that are sufficiently far apart, you can use these two measurements alone to calculate the PSA doubling time. In their widely read review of the management of patients with non-metastic prostate cancer and a rising PSA, Moul et al. state that (at the Duke Prostate Center):

It is our practice to use the first two PSA measurements after recurrence (i.e., ≥ 0.2 ng/ml) separated by at least 3 months before calculating a PSADT

However, they add that they may make exceptions in the cases of patients who clearly have a very rapidly rising PSA, and use a briefer separation time between the two PSA measurements.

The Definition of High Risk and Risk Categories

The first attempts to use PSADT to define patients who are at high risk following biochemical failure were made by D’Amico and colleagues. In their earliest studies they showed clearly that, in men who had biochemical failure following either radical prostatectomy or radiation therapy, a PSADT of < 3 months placed a patient at significant risk of death from prostate cancer.

In later studies, D’Amico and his colleagues proceeded to show that, in men with a PSADT > 3 months, there was a continuum of risk, with higher PSADT values being associated with lower risks of death from prostate cancer.  And in 2005, Freedland et al. divided men with biochemical failure into four risk groups, based on their PSADT.

Our ability to project a prognosis for men who have biochemical failure based on their PSADT and other factors is still evolving. Current clinical trials of men being treated with investigational therapies for biochemical failure after first-line therapy now tend to stratify the patients (sort them into sets) according to the Freedland et al. PSADT risk groups (< 3.0; 3.0-8.9; 9.0-15.0; and ≥ 15.0 months). Theoretically, this should allow us to get greater understanding of the effectiveness of individual therapies in the treatment of men with prior first-line biochemical failure.

A recent report by Antonarakis et al. from Johns Hopkins (not yet published in full, but presented at a major cancer meeting in 2009) would seem to further support the validity of the Freedland et al. PSADT risk groups.

The Kattan Nomograms and the Prognosis of Salvage Radiotherapy

There is one (and only one) specific situation in which a well-validated nomogram has been developed that permits a man and his doctor to assess the prognostic potential of a specific form of salvage therapy. This is for men who have biochemical recurrence after having had radical surgery as first-line treatment for presumed localized disease, and who are considering external beam radiotherapy as their preferred form of salvage treatment.

For detailed information about the use of this nomogram, and for case examples, please see the section on salvage radiotherapy.

Content on this page last reviewed and updated July 3, 2009.
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