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Prostate-specific antigen flare induced by 223RaCl2 in patients with metastatic castration-resistant prostate cancer

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Prostate-specific antigen (PSA) flare is a well-known phenomenon in patients with prostate cancer, but its impact during radium-223 dichloride (223RaCl2) therapy is still unclear. This radioisotope has shown to improve overall survival in metastatic castration-resistant prostate cancer (mCRPC). We sought to evaluate the impact of PSA flare on survival and its relation with metabolic parameters on 18F-labeled sodium fluoride PET/CT.

Methods

We conducted a retrospective study of 168 patients with mCRPC (median age 69; median PSA 29.7) receiving 223RaCl2. Overall survival (OS) and progression-free survival (PFS), estimated by the Kaplan–Meier method and compared using a log-rank test, were evaluated for patient groups corresponding to different definitions of PSA flare. Metabolic 18F-fluoride PET/CT data were analyzed as well.

Results

Immediate PSA decline was observed in 49 patients (29.2%), whereas no PSA response was observed in 59 patients (35.1%). PSA flare (defined as rise after the first cycle followed by decrease below the baseline) was observed in 20 patients (11.9%) and PSA flare followed by a decrease from peak but not below baseline was observed in 40 (23.8%). The first flare subgroup had a median PFS and OS of 20.8 and 23.9 months, respectively. These outcomes were not significantly different from patients with immediate PSA decrease, but were significantly better than in patients with persistent PSA elevation (3.1 months for PFS and 11.5 months for OS, p < 0.001). Moreover, the PSA flare group showed an alkaline phosphatase (ALP) decrease significantly greater than non-responders (p = 0.003). Metabolic 18F-fluoride PET/CT data were available in 35 patients at baseline and during 233RaCl2 therapy. The tumor burden reduction, expressed by ΔTLF10 and ΔFTV10, was more evident within PSA flare group below baseline than non-responders (p = 0.005 and 0.001, respectively).

Conclusions

This report suggests that a flare does not necessarily indicate lack of response to 223RaCl2 therapy.

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Acknowledgements

Prof. Elba C. Etchebehere and Dr. Dong Dai are acknowledged for their valuable contribution.

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Authors and Affiliations

  1. Department of Nuclear Medicine, Humanitas Clinical and Research Hospital, Via Manzoni 56, 20089, Rozzano, MI, Italy

    Angelo Castello & E. Lopci

  2. Department of Nuclear Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Angelo Castello, H. A. Macapinlac & E. B. Santos

Authors
  1. Angelo Castello
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  2. H. A. Macapinlac
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  3. E. Lopci
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  4. E. B. Santos
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Corresponding author

Correspondence to Angelo Castello.

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The study herein presented was approved by the local review board and performed in accordance with the principles of good clinical practice, with the Declaration of Helsinki, and with the national regulations regarding clinical trials. Waivers of informed consent and authorization were granted for the retrospective analysis.

Conflicts of interest

The authors have declared no conflicts of interest.

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Castello, A., Macapinlac, H.A., Lopci, E. et al. Prostate-specific antigen flare induced by 223RaCl2 in patients with metastatic castration-resistant prostate cancer. Eur J Nucl Med Mol Imaging 45, 2256–2263 (2018). https://doi.org/10.1007/s00259-018-4051-y

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  • DOI: https://doi.org/10.1007/s00259-018-4051-y

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