EUROPEAN UROLOGY 68 (2015) 372–373

available at www.sciencedirect.com journal homepage: www.europeanurology.com

Platinum Priority – Editorial Referring to the article published on pp. 365–371 of this issue

Prostate-specific Antigen Pox Virus Vaccination for Recurrent Prostate Cancer Manfred P. Wirth *, Michael Froehner Department of Urology, University Hospital ‘‘Carl Gustav Carus,’’ Technische Universita¨t Dresden, Dresden, Germany

Prostate cancer is a suitable target of innovative immunotherapeutic treatment approaches [1,2]. It has been hypothesized that such therapies could be most efficient when used earlier in the course of the disease [1]. In their phase 2 study, reported in this month’s issue of European Urology, DiPaola and coworkers administered prostatespecific antigen (PSA) pox virus vaccine (PROSTVAC-VF) to 40 patients with nonmetastatic PSA recurrence after local treatment for histopathologically confirmed prostate cancer without current hormonal therapy [3]. Of the 50 patients initially enrolled, 10 were excluded because of various violations of predefined study entry criteria. Treatment consisted of two types of fowlpox virus–based vaccine directed against the PSA molecule (a single dose of PROSTVAC-V followed by PROSTVAC-F boosts). Toxicity was mild to moderate with mainly immune response– related side effects. Within 18 mo, most patients experienced disease biochemical or clinical progression. With too few events, survival analysis was not possible. A slower PSA velocity after vaccination treatment was the main finding of this study [3]; however, without a control group available, it is impossible to estimate the size of this effect. Vaccination including PROSTVAC-VF, as used in the study by DiPaola et al [3], represents a promising new approach to treat advanced or recurrent prostate cancer [4,5]. It was found to be associated with improved survival outcome in patients with metastatic castration-resistant prostate cancer, although it was not associated with a measurable impact on disease progression [5]. Major PSA responses were infrequent [6]. Taking these observations [5] into consideration, it is difficult to evaluate the clinical significance of slowing down of the PSA velocity, particularly at this early stage of disease

progression. As mentioned by the authors [3], further uncertainties concern the interpretation of PSA kinetics in such a study. It is not yet sufficiently understood to what degree the anti–PSA-directed vaccination interferes with production and cleavage of this molecule. Data from other immunotherapy studies in prostate cancer let us expect an impact on overall survival rather than on measurable disease progression [5,6]. Patient heterogeneity is another point complicating the interpretation of this study’s results [3]. Considering the multitude of enumerated prior treatments, it is hardly possible to imagine a typical patient to whom the observations of this study may apply. With the variety of options that have become available in recent years [7], treatment of relapsing prostate cancer has become more complex. It is increasingly difficult to measure the impact of an individual new drug on outcome in the presence of various simultaneously or consecutively used substances in this setting. Studies investigating immunotherapy for which the primary aim is survival prolongation should be adequately powered (preferably with a multicentric design) and should contain a control group that enables the identification of a putative survival prolongation. Such a study design is costly but necessary to establish these promising new treatment approaches in daily practice. Conflicts of interest: The authors have nothing to disclose.

References [1] Quinn DI, Shore ND, Egawa S, Gerritsen WR, Fizazi K. Immunotherapy for castration-resistant prostate cancer: progress and new paradigms. Urol Oncol 2015;33:245–60.

DOI of original article: http://dx.doi.org/10.1016/j.eururo.2014.12.010. * Corresponding author. Department of Urology, University Hospital ‘‘Carl Gustav Carus,’’ Technische Universita¨t Dresden, Fetscherstrasse 74, D-01307 Dresden, Germany. Tel. +49 351 4582447; Fax: +49 351 4584333. E-mail address: [email protected] (M.P. Wirth). http://dx.doi.org/10.1016/j.eururo.2015.02.025 0302-2838/# 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

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Prostate-specific antigen pox virus vaccination for recurrent prostate cancer.

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