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Impact of 68Ga-PSMA PET on the Management of Patients with Prostate Cancer - Beyond the Abstract

Prostate cancer is one of the most common cancers in men1. Various imaging modalities have been used to assess the presence and extent of primary or recurrent tumors, however, at least partly due to prostate cancer’s predilection for metastatic spread to bone, their suboptimal diagnostic capability has been well documented. The prostate-specific membrane antigen (PSMA), which is a protein expressed on dysplastic prostate cells, has been a target of interest to cancer biologists and imagers for several decades. Novel positron emission tomography (PET) imaging probes targeting the internal epitope of the PSMA receptor have shown great potential to overcome some of the difficulties in this field. PSMA is expressed in prostate cancer cells at 100–1000 times higher levels than that of normal prostate cells and with an even greater degree in tumors with higher stages and grades2. Studies have shown that 68Ga-PSMA PET has excellent ability to detect lesions, even in patients with low serum PSA levels, and that this may affect patient management. In this study, the authors aimed to summarize the recently published studies by performing a meta-analysis dealing with the research question of “What is the proportion of patients who experience change in their management when 68Ga-PSMA PET is used as compared with conventional imaging modalities (computed tomography, magnetic resonance imaging, and/or bone scintigraphy) in patients with prostate cancer?”3.

In this meta-analysis, which included 15 studies, the authors found that PSMA PET changed the management plan in 54% (95% confidence interval 47–60%) of the patients and that the degree of change was significantly associated with PET positivity (%) (p = 0.0486). One of the major strengths of this study is that it touches on the actual “impact” PSMA PET had on patient care in contrary to simply evaluating the detection rate or diagnostic test accuracy of this modality 6. The next step for PSMA PET to be integrated into routine clinical practice would be to show that it translates into true clinical outcomes. For instance, future studies could focus on whether using PSMA PET (and/or management changes followed by it) could potentially predict biochemical recurrence or prostate cancer-specific mortality4.

One of the main limitations of this meta-analysis is that the included 15 studies were heterogeneous in nature, especially with regard to the clinical state of prostate cancer. However, as most studies focused on intermediate-to-high risk patients in the clinical setting of biochemical failure, it seems plausible that this “impact” in management change can be applied to such patients. However, future studies will be needed to find out whether this “impact” is applicable to low-risk patients with newly diagnosed prostate cancer. Also, a change in management is not necessarily a surrogate for improved outcomes (eg, theoretically management can be changed to an alternative strategy which could ultimately result in a worse outcome). Furthermore, rather than simply pooling the results of several studies, well-designed studies that address a specific clinical question could provide more useful information that can be used in real life practice.

Finally, we would like to touch on the fact that this meta-analysis only assessed the impact of that 68Ga-PSMA PET. The detectability of PSMA PET could be influenced by several pharmaceutical and technical factors, and therefore using other radiotracers (i.e., 18F-DCFBC) could lead to different results5. We should keep in mind that clinical factors such as usage of concurrent hormone therapy and prostate-specific antigen values can affect PSMA PET positivity [6]. Studies in the future should investigate the diagnostic capability and their impact on clinically-relevant outcomes in prostate cancer patients using radiotracers other than PSMA keeping in mind the effects of clinical variables.

References:
  1. Torre LA, Bray F, Siegel, RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015; 65: 87–108
  2. Silver DA, Pellicer I, Fair WR, Heston WD, Cordon-Cardo C. Prostate-specific membrane antigen expression in normal and malignant human tissues. Clin Cancer Res. 1997; 3: 81–85
  3. Han S, Woo S, Kim YJ, Suh CH. Impact of 68Ga-PSMA PET on the Management of Patients with Prostate Cancer: A Systematic Review and Meta-analysis. Eur Urol. 2018 Apr 18. pii: S0302-2838(18)30248-3. doi: 10.1016/j.eururo.2018.03.030. [Epub ahead of print]
  4. Woo S, Cho JY, Ku JH, Kim SY, Kim SH. Prostate cancer-specific mortality after radical prostatectomy: value of preoperative MRI. Acta Radiol.2016;57:1006-13
  5. Turkbey B, Mena E, Lindenberg L, Adler S, Bednarova S, Berman R, et al. 18F-DCFBC Prostate-Specific Membrane Antigen-Targeted PET/CT Imaging in Localized Prostate Cancer: Correlation With Multiparametric MRI and Histopathology. Clin Nucl Med.2017;42:735-740
  6. Rauscher I, Düwel C, Haller B, Rischpler C, Heck MM, Gschwend JE, et al. Efficacy, Predictive Factors, and Prediction Nomograms for 68Ga-labeled Prostate-specific Membrane Antigen-ligand Positron-emission Tomography/Computed Tomography in Early Biochemical Recurrent Prostate Cancer After Radical Prostatectomy. Eur Urol.2018;73:656-661
Written by: Sungmin Woo, MD, Department of Radiology, Seoul National University College of Medicine, Seoul, Republic of Korea; Sangwon Han, MD, Department of Nuclear Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea; and Herbert Alberto Vargas, MD, Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.

Authors disclose no conflict of interest on the topic of this paper.

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