Editorial Imaging in prostate cancer with multiparametric magnetic resonance imaging and gallium positron emission tomography-computed tomography: ‘the real deal’? Prostate cancer imaging has undergone monumental change over the past few years with the rise of multiparametric MRI (mp-MRI) in targeting lesions [1], but also the establishment of newer radiopharmaceuticals for positron emission tomography-CT (PET-CT) and re-staging of patients with a rising PSA after primary treatment [2]. These developments are welcomed. However, are these imaging modalities ‘the real deal’? Due to the lack of great imaging modalities for prostate cancer we have been quick to jump on almost anything that is better than what we have had at our disposal. But is this the correct pathway when evidence is lacking? Particularly that the results achieved at centres of excellence may be translated to local and even non-tertiary centres? In metropolitan Melbourne (≈4.3 million people) the number of radiology facilities conducting mp-MRI has gone from around three to >20 in a short space of time, and regional centres have come on board in the rest of the state, surely not all of the reporting radiologists are expert in this complex area? What implications will this have on the quality, and will it ultimately lead to a lessening of specificity and sensitivity? There are also costs at ≈$500 and upwards, so they are not cheap to consumers. A rebate number has been applied for and will almost certainly come along in time but high-quality data must be maintained lest MRI again be pushed aside as a fad that could not last or deliver on its ‘promises’. An alternative is that better uro-radiologists will retain the majority of the studies and hence maintain the quality. This has not always been the case with other imaging tools and will be difficult to contain. PET-CT has long been hailed as a type of ‘holy grail’ in many urological malignancies. The most common radiopharmaceutical being fluorodeoxyglucose and this method has the advantage of being anatomical but also functional. Put simply cells that turnover more glucose retain more fluorine-(radio)labelled metabolites and this appears on the scan. The specificity is lacking, so more refined targets than general cell metabolism are required. Thus a new agent was developed based on prostate-specific membrane antigen (PSMA). PSMA is a cell surface protein with high expression © 2015 The Author BJU International © 2015 BJU International | doi:10.1111/bju.13094 Published by John Wiley & Sons Ltd. www.bjui.org

in prostate cancer cells [3]. The radioactivity of this radiopharmaceutical is provided by gallium-68 (68Ga) that has a short half-life of 68 min. In particular, PSMA levels are directly related to androgen independence, metastasis and progression [4]. Hence, 68Ga-labelled PSMA PET-CT (68Ga-PSMA PET-CT) was created. Ultimately cells producing PSMA will only retain the radiolabel and therefore it will be far more specific than glucose (Figure 1). To date there is only one large study of ≈300 prostate cancer patients [2] examining this radiopharmaceutical in prostate cancer but it is being used by clinicians passionately and almost without question. Certainly the specificity has been excellent but what of the sensitivity? Further, specificity may reduce, as more data is available, particularly data comparing uptake to tissue. 68Ga-PSMA PET-CT may yet rise above all others (as choline PET-CT was supposed to do!) but we desperately need more data. Urologists and other specialists and even generalists involved with prostate cancer management must understand the limitations of the new imaging techniques and also keep a close eye on the literature. The timeframe from development of modalities and release to practice has shrunk meaning the typical larger bodies of research and concomitant training are not occurring. We hope both mp-MRI and 68Ga-PSMA PET-CT are ‘the real deal’. However, let us reflect that assumptions about imaging techniques made by individuals and at multidisciplinary meetings [5] that impact upon patient decisions and management need to be balanced against what is known. Further, any data on these imaging techniques should be prospectively collected thus assisting us in answering these important questions.

Conflicts of Interest None declared. Nathan Lawrentschuk Department of Surgery, Austin Hospital and Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Vic., Australia Olivia Newton-John Cancer Research Institute, Austin Hospital

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Editorial

Fig. 1 Positive gallium-68 prostate-specific membrane antigen (PSMA) PET-CT with a large right iliac node in the top views and a bony metastasis not easily visible in the vertabra on the lower views. This gentleman had biochemical recurrence after failed high dose brachytherapy.

References 1

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Thompson J, Lawrentschuk N, Frydenberg M, Thompson L, Stricker P, USANZ. The role of magnetic resonance imaging in the diagnosis and management of prostate cancer. BJU Int 2013; 112 (Suppl. 2): 6–20 Afshar-Oromieh A, Avtzi E, Giesel FL et al. The diagnostic value of PET/CT imaging with the (68)Ga-labelled PSMA ligand HBED-CC in the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging 2015; 42: 197–209 Afshar-Oromieh A, Malcher A, Eder M et al. PET imaging with a [68Ga]gallium-labelled psma ligand for the diagnosis of prostate cancer:

© 2015 The Author 2 BJU International © 2015 BJU International

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biodistribution in humans and first evaluation of tumour lesions. Eur J Nucl Med Mol Imaging 2013; 40: 486–95 Mease RC, Foss CA, Pomper MG. PET imaging in prostate cancer: focus on prostate-specific membrane antigen. Curr Top Med Chem 2013; 13: 951–62 Rao K, Manya K, Azad A et al. Uro-oncology multidisciplinary meetings at an australian tertiary referral centre – impact on clinical decision-making and implications for patient inclusion. BJU Int 2014; 114 (Suppl. 1): 50–4