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. 2012 Mar 15;118(6):1533-42.
doi: 10.1002/cncr.26437.

Changes in PSA kinetics predict metastasis- free survival in men with PSA-recurrent prostate cancer treated with nonhormonal agents: combined analysis of 4 phase II trials

Emmanuel S Antonarakis  1 , Marianna L Zahurak, Jianqing Lin, Daniel Keizman, Michael A Carducci, Mario A Eisenberger
Affiliations

Changes in PSA kinetics predict metastasis- free survival in men with PSA-recurrent prostate cancer treated with nonhormonal agents: combined analysis of 4 phase II trials

Emmanuel S Antonarakis et al. Cancer. .

Abstract

Background: Several phase II trials in men with noncastrate PSA-recurrent prostate cancer have assessed the impact of novel nonhormonal agents on PSA kinetics. However, it is unknown whether changes in PSA kinetics influence metastasis-free survival (MFS).

Methods: We performed a retrospective post hoc analysis of 146 men treated in 4 phase II trials examining the investigational agents marimastat (a matrix metalloproteinase inhibitor; n = 39), imatinib (a tyrosine kinase inhibitor; n = 25), ATN-224 (a copper/zinc-superoxide dismutase inhibitor; n = 22), and lenalidomide (an antiangiogenic/immunomodulatory drug; n = 60). We investigated factors influencing MFS, including within-subject changes in PSA kinetics (PSA slope, doubling time, and velocity) before and after treatment initiation.

Results: After a median follow-up of 16.8 months, 70 patients (47.9%) developed metastases. In multivariable Cox regression models, factors that were independently predictive of MFS after adjusting for age and other clinical prognostic variables were baseline PSA doubling time (PSADT) (P = .05), baseline PSA slope (P = .01), on-study change in PSADT (P = .02), and on-study change in PSA slope (P = .03). In a landmark Kaplan-Meier analysis, median MFS was 63.5 months (95% confidence interval [CI], 34.6-not reached) and 28.9 months (95% CI, 13.5-68.0) for men with or without any decrease in PSA slope by 6 months after treatment, respectively.

Conclusions: This hypothesis generating analysis 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. If validated in prospective trials, changes in PSA kinetics may represent a reasonable intermediate end point for screening new agents in these patients.

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Conflict of interest statement

Authors’ disclosures: The authors indicate no potential conflicts of interest.

Figures

Fig 1
Fig 1
Metastasis-free survival stratified by (A) changes in PSA doubling time, (B) changes in PSA velocity, and (C) changes in log PSA slope.
Fig 1
Fig 1
Metastasis-free survival stratified by (A) changes in PSA doubling time, (B) changes in PSA velocity, and (C) changes in log PSA slope.
Fig 1
Fig 1
Metastasis-free survival stratified by (A) changes in PSA doubling time, (B) changes in PSA velocity, and (C) changes in log PSA slope.
Fig 2
Fig 2
(A) Model showing theoretical changes in PSA slope after initiation of a non-hormonal experimental therapy. (B) Metastasis-free survival stratified by these three categories of PSA slope change
Fig 2
Fig 2
(A) Model showing theoretical changes in PSA slope after initiation of a non-hormonal experimental therapy. (B) Metastasis-free survival stratified by these three categories of PSA slope change
See this image and copyright information in PMC

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