Original Study
PSA Flare With Abiraterone in Patients With Metastatic Castration-Resistant Prostate Cancer

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Abstract

Background

The aim of this study was to assess early serum prostate-specific antigen (PSA) changes in patients treated with abiraterone and to correlate those changes with clinical outcome.

Patients and Methods

We retrospectively evaluated 103 patients with castrate-resistant prostate cancer (CRPC) treated with compassionate use of abiraterone in Romagna, Italy. In these patients, serum PSA levels were monitored every 4 weeks, and a time course of serum PSA levels was obtained. The PSA flare phenomenon was evaluated. The log-rank test was applied to compare survival between groups of patients according to early PSA level changes.

Results

Of 103 patients, 43 (41.7%) had an immediate PSA response, whereas 9 (8.7%) had an initial PSA flare. Of the 9 patients with PSA flare, 5 attained a subsequent PSA response. The temporary PSA flare exceeded baseline values by a median of 19.7% (range, 5%-62.9%). The median PFS of the 9 patients in the PSA-flare group was higher compared with patients without the PSA flare (10.5 vs. 6.4 months; P = .0999) but was similar to the subgroup of patients with immediate PSA response (10.5 vs. 10.7 months; P = .7019). In the multivariate analysis, only the PSA response remained as a predictor of progression-free survival (PFS) (P < .0001) and overall survival (OS) (P = .0003), respectively.

Conclusion

PSA flare occurs not infrequently in patients with CRPC who respond to abiraterone. Patients should be informed of this possible PSA flare phenomenon.

Introduction

Prostate cancer (PC) is the most common noncutaneous cancer in men and the second leading cause of cancer-related deaths for men.1 Castration-resistant prostate cancer (CRPC) is the lethal evolution of the disease that, once it is metastatic, is associated with a median overall survival (OS) of 2 to 3 years despite hormonal manipulations and chemotherapy with docetaxel.2, 3, 4 In recent years, abiraterone has emerged as a standard therapy for patients with metastatic CRPC after docetaxel and, most recently, even before chemotherapy in the predocetaxel space.5, 6, 7

A prostate-specific antigen (PSA) level decline of at least 50%, confirmed 4 weeks after beginning, was consensually regarded as a criterion of response to treatment.8 However, in the phase trial with abiraterone in patients previously treated with docetaxel, the PSA level was monitored every months.5 In the phase randomized trial with abiraterone in patients without previous chemotherapy, the PSA level was monitored every two 28-day cycles in the first months and then every month.7 As a consequence, to date no data have been reported in the literature on early PSA changes in the initial few months of abiraterone treatment. In clinical practice, most oncologists currently monitor PSA levels more frequently before each cycle and then almost every month to assess the efficacy of abiraterone and other new high-cost therapeutic options in individual patients with CRPC. However, no information is available about the kinetics of serum PSA during the first few months after the initiation of abiraterone. This prompted us to study retrospectively the time course of serum PSA in a database of patients with metastatic CRPC receiving abiraterone. We observed an important phenomenon: a small proportion of responders to abiraterone initially experienced a rise in serum PSA (PSA flare). In this retrospective study, we analyzed the PSA flare after abiraterone treatment in patients with CRPC and correlated this phenomenon with PSA declines and clinical outcomes.

Section snippets

Data Collection

From March 2011 to August 2012, 103 consecutive patients with CRPC were included in the abiraterone compassionate use program at Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy; at the time of their inclusion, these patients showed disease progression after having received at least a chemotherapeutic regimen including docetaxel. The compassionate use program was approved by the Romagna Ethics Committee; all patients gave their written informed

Results

From March 2011 to August 2012, a total of 103 patients with CRPC, median age 74 years (range, 48-87 years), received abiraterone after docetaxel alone (n = 61) or after docetaxel and at least 1 more line of therapy (n = 42). The characteristics of all patients are summarized in Table 1. The median follow-up was 16.8 months, with an estimated median PFS of 6.6 months (95% confidence interval [CI], 5.4-8.2 months) and an estimated median OS of 18.6 months (95% CI, 14.4-22.0 months).

Discussion

Serum PSA levels are used in the management of patients with PC to monitor tumor response during hormonal therapy or chemotherapy, or both, in advanced disease.8, 9 For some time, one of the obstacles to developing new therapies in PC was the absence of criteria to assess tumor response, with most patients exhibiting nonmeasurable bone-only disease. Although the debate continues as to whether a decline in the serum PSA level is a surrogate for OS in metastatic PC,10, 11 a PSA level decline of

Conclusion

In this retrospective study, we reported the PSA flare in patients with CRPC treated with abiraterone. The PSA flare after abiraterone occurred in a number of patients (8.7%) treated with abiraterone. The clinical outcome of patients experiencing the PSA flare phenomenon correlated with that of those achieving an immediate PSA response.

We believe that physicians should be aware of this PSA flare phenomenon during the first few months after the initiation of abiraterone treatment for CRPC.

Disclosure

UDG has received consultant fees and had an advisory role with Pfizer, GSK, Bayer, and Novartis.

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    ∗

    These authors contributed equally to this work.

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