Prostate cancer recurrence, PSADT, and patient comorbidities

D’Amico and his colleagues demonstrated some time ago that PSA velocity and PSA doubling time (PSADT) are valuable tools in predicting which patients with recurrent prostate cancer after first-line treatment are at greatest risk of metastatic disease and prostate cancer-specific mortality. But they have now shown that PSADT is less predictive of risk in men with other “comorbid” health problems.

In the new article by Wo et al., the Harvard research team explored whether “time-dependent continuous PSA velocity at recurrence” was associated with all-cause mortality (ACM) in prostate cancer patients who had biochemical recurrence after treatment with definitive radiation therapy (RT) alone with or without androgen deprivation therapy (ADT) in the setting of  a randomized, controlled clinical trial.

Between 1995 to 2001, they enrolled 206 men with localized, unfavorable prostate cancer who were randomly assigned to be treated with RT alone or with RT + ADT. The comorbidities (other significant clinical conditions) of all patients were carefully recorded. The results of the study can be summarized as follows:

  • The median patient follow-up was 8.4 years.
  • Within the follow-up period, 89 patients had a biochemical recurrence and 74 patients died from any cause.
  • For all patients in the trial, a higher PSA velocity was significantly associated with increased ACM after adjusting for age, treatment arm, comorbidity score, and use of salvage ADT.
  • For the 89 patients who had a biochemical recurrence, an increasing PSA velocity at recurrence and a moderate to severe comorbidity score were both significantly associated with increased ACM.
  • PSA velocity at recurrence was associated with significantly higher risk of ACM among the patients with no or minimal comorbidity, but was not among the patients with moderate to severe comorbidity.

In other words, a rapid PSA velocity or PSADT at recurrence is clearly associated with an increased risk of ACM among patients with no or minimal comorbidity, but for those patients with moderate to severe comorbidities there is no clear indication that their PSA velocity at recurrence is predictive of their ACM.

Wo et al. accurately suggest that their study can be used to support the “judicious use of salvage [ADT], particularly in men with moderate to severe comorbidities,” in situations where careful monitoring of patients should be used to assess exactly when it is best to initiate hormone therapy for men who have a biochemical recurrence after prior radiation.

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