Case Report Prostate-Specific Antigen Flare Phenomenon During 223 Ra-Dichloride Treatment for Bone Metastatic Castration-Resistant Prostate Cancer: A Case Report Giuseppe De Vincentis, 1 Giulia Anna Follacchio, 1 Viviana Frantellizzi, 1 Mauro Liberatore, 1 Francesco Monteleone, 1 Enrico Cortesi 2 Clinical Genitourinary Cancer, Vol. 14, No. 5, e529-33 ª 2016 Elsevier Inc. All rights reserved. Keywords: Bone metastases, mCRPC, PSA, Radionuclide therapy, Radium-223 Introduction Castration-resistant prostate cancer (CRPC) has a poor prognosis with a median survival of 2 years. 1 In CRPC patients, bone metastases are the leading cause of pain and disability, and are independently associated with increased mortality. 2,3 223 Ra-dichloride is a first-in- class alpha-emitting radionuclide currently indicated in CRPC pa- tients with symptomatic bone metastases and no known visceral me- tastases. Thanks to its analogy to calcium, 223 Ra targets areas of high osteoblastic activity such as bone metastases, delivering high-energy short-range alpha particle radiation. 4 The phase III ALpharadin in SYMptomatic Prostate CAncer Patients (ALSYMPCA) trial showed a significant effect of 223 Ra on overall survival and a delay in median time to the first symptomatic skeletal event, associated with a relevant bone pain palliation. In addition, 223 Ra treatment was characterized by a low toxicity profile in terms of hematologic and nonhematologic adverse events, which were mild to moderate in intensity. 5 223 Ra therapy is gaining widespread use in the United States and Europe. In this specific therapeutic setting, prostate-specific antigen (PSA) is not an objective biomarker in assessing 223 Ra efficacy. 5 To our knowledge, few articles in the literature examined the clinical role of an increase in PSA level during 223 Ra treatment. 6,7 This event, indeed, could be either due to disease progression or to a “PSA flare” phenomenon as a result of tumoral cell damage. In CRPC patients, PSA flare is a well known phenomenon consisting of a transient rise in serum PSA levels followed by a decrease described in the course of hormonal therapy with luteinizing hormone-releasing hormone Clinical Practice Points  223 Ra-dichloride is an alpha-emitting radionuclide recently approved for treatment of castration-resistant prostate cancer (CRPC) patients with symptomatic bone metastases.  In this specific therapeutic setting, prostate-specific antigen (PSA) is not an objective biomarker in assessing 223 Ra efficacy. We present a 79-year-old patient who was affected by CRPC and symptomatic bone metastases enrolled in the 223 Ra-dichloride Early Access Program who presented a relevant rise in PSA levels after the fifth 223 Ra administration.  No radiological signs of disease progression were found, so this event was recognized as a PSA flare phenomenon and the last 223 Ra infusion was administered.  In clinical practice, PSA flare in the course of 223 Ra treatment can be misinterpreted as a therapeutic failure with early withdrawal from a potentially effec- tive therapy.  During 223 Ra treatment, PSA flare can be explained as a direct consequence of 223 Ra cytotoxic effect on cancer cells.  Further analysis should be conducted on large cohort to evaluate the clinical significance of PSA flare phe- nomenon during 223 Ra treatment. 1 Department of Radiological Sciences, Oncology and Human Pathology, Nuclear Medicine Unit, Sapienza University of Rome, Rome, Italy 2 Department of Radiological Sciences, Oncology and Human Pathology, Medical Oncology Unit, Sapienza University of Rome, Rome, Italy Submitted: Mar 18, 2016; Revised: Apr 12, 2016; Accepted: Apr 16, 2016; Epub: Apr 27, 2016 Address for correspondence: Giulia Anna Follacchio, MD, Department of Radiological Sciences, Oncology and Human Pathology, Nuclear Medicine Unit, 324, Viale Regina Elena, 00161 Rome, Italy Fax: þ390649978592; e-mail contact: giuliaanna.follacchio@uniroma1.it 1558-7673/$ - see frontmatter ª 2016 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.clgc.2016.04.014 Clinical Genitourinary Cancer October 2016 - e529