Are changes in PSA kinetics potentially indicative of metastasis-free survival?

Researchers at Johns Hopkins have provided data to support the hypothesis that, in men being treated with novel, non-hormonal agents for non-metastatic, non-castrate, biochemically recurrent prostate cancer after first-line therapy, changes in PSA kinetics may be indicative of metastasis-free survival.

To provide the initial data in support of this hypothesis, Antonarakis et al. carried out a retrospective analysis of data from 146 patients enrolled in four Phase II trials of investigational agents: marimastat (n = 39), imatinib (n = 25), ATN-224 (n = 22), and lenalidomide (n = 60).

They looked at data on several different factors that held the potential to influence metastasis-free survival, including within-subject changes in PSA slope, PSA doubling time, and PSA velocity before and after initiation of treatment.

The results of their analysis showed the following:

  • The average (median) follow-up of the 146 men was 16.8 months.
  • At the time of median follow-up, 70/146 patients (47.9 percent) had developed metastases.
  • After adjusting for age and other clinical prognostic variables, four factors were independently predictive of metastasis-free survival.
    • Baseline PSA doubling time (PSADT) (P =0.05)
    • Baseline PSA slope (P = 0.01)
    • On-study change in PSADT (P = 0.02)
    • On-study change in PSA slope (P = 0.03)
  • According to a landmark Kaplan-Meier analysis
    • Average (median) metastasis-free survival was 63.5 months for men with a decrease in PSA slope within 6 months of treatment.
    •  Average (median) metastasis-free survival was 28.9 months for men with no decrease in PSA slope within 6 months of treatment.

The analysis effectively “suggests that within-subject changes in PSADT and PSA slope after initiation of experimental therapy may correlate with MFS in men with biochemically recurrent prostate cancer.”

Clearly this hypothesis would need to be validated in larger, prospective trials before changes in PSA kinetics could be used as an intermediate endpoint for screening new agents in this category of patients.

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