Elsevier

The Lancet Oncology

Volume 19, Issue 12, December 2018, Pages e696-e708
The Lancet Oncology

Review
Consensus on molecular imaging and theranostics in prostate cancer

https://doi.org/10.1016/S1470-2045(18)30604-1Get rights and content

Summary

Rapid developments in imaging and treatment with radiopharmaceuticals targeting prostate cancer pose issues for the development of guidelines for their appropriate use. To tackle this problem, international experts representing medical oncologists, urologists, radiation oncologists, radiologists, and nuclear medicine specialists convened at the European Association of Nuclear Medicine Focus 1 meeting to deliver a balanced perspective on available data and clinical experience of imaging in prostate cancer, which had been supported by a systematic review of the literature and a modified Delphi process. Relevant conclusions included the following: diphosphonate bone scanning and contrast-enhanced CT are mentioned but rarely recommended for most patients in clinical guidelines; MRI (whole-body or multiparametric) and prostate cancer-targeted PET are frequently suggested, but the specific contexts in which these methods affect practice are not established; sodium fluoride-18 for PET-CT bone scanning is not widely advocated, whereas gallium-68 or fluorine-18 prostate-specific membrane antigen gain acceptance; and, palliative treatment with bone targeting radiopharmaceuticals (rhenium-186, samarium-153, or strontium-89) have largely been replaced by radium-223 on the basis of the survival benefit that was reported in prospective trials, and by other systemic therapies with proven survival benefits. Although the advances in MRI and PET-CT have improved the accuracy of imaging, the effects of these new methods on clinical outcomes remains to be established. Improved communication between imagers and clinicians and more multidisciplinary input in clinical trial design are essential to encourage imaging insights into clinical decision making.

Introduction

Worldwide, more than 1 000 000 men are diagnosed with prostate cancer and over 300 000 men die from it annually,1, 2 with an increasing incidence as a result of greater life expectancy.3, 4, 5 Developments in diagnosis and treatment of prostate cancer are evolving very rapidly, and the 5-year relative survival for patients has increased from 73·4% (95% CI 72·9–73·9) in 1999–2001 to 81·7% (81·3–82·1) in 2005–07. With several clinical trials showing improved overall survival with new drugs, it is likely to further improve in the coming years.4, 6

The costs of prostate cancer management are also increasing, with an overall cost in the EU of €8·43 billion for 2009.7 High costs underscore the need for improved communication and cooperation among the medical specialties involved in the diagnosis and treatment of patients with prostate cancer to generate pertinent data in clinical trials to facilitate the rational integration of imaging into clinical decision making.

Several imaging methods for the evaluation of prostate cancer have been suggested, and these include methods that have been available for decades (eg, CT, bone scintigraphy, and transrectal ultrasound), as well as those that were introduced more recently (eg, whole-body MRI [WB-MRI], multiparametric MRI, and PET). However, there has been little consensus about the usefulness of these approaches.8, 9, 10, 11

Promotion of the use of the most appropriate diagnostic and therapeutic interventions in clinical practice, guidelines, and consensus statements, are of paramount importance for the medical community, although they cannot replace scientific evidence. The availability of an increasing number of therapeutic and diagnostic options requires more careful choices. Evidence-based data (eg, meta-analyses) are often unable to inform the appropriate use of available medical options, and most guidelines that are promoted by professional organisations tend to lead to bias because experts are usually selected from within the same specialty. In the area of prostate cancer, most clinical guidelines have been promoted by urological societies (including the European Association of Urology [EAU] and American Urological Association [AUA]), oncological societies (including the European Society for Medical Oncology [ESMO], Society of Urologic Oncology [SUO], American Society for Clinical Oncology, International Society of Geriatric Oncology [SIOG], and National Comprehensive Cancer Network [NCCN]), and radiation oncology societies (including the American Society for Radiation Oncology [ASTRO], and the European Society for Radiotherapy and Oncology [ESTRO]), and attempts at producing collaborative guidelines have been made recently (eg, AUA with ASTRO and SUO,12 and EAU with ESTRO and SIOG13, 14). The Advanced Prostate Cancer Consensus Conference is the sole attempt to obtain consensus globally on areas of diagnostic and treatment uncertainty, including imaging.11

Representing nuclear medicine specialists who have led advances in novel molecular imaging techniques for prostate cancer, the European Association of Nuclear Medicine (EANM) decided to promote a project named Focus 1 to develop consensus statements in prostate cancer with a well-balanced and structured methodology. For this purpose, a multidisciplinary panel of international experts was established with representation from all involved specialties that included a balanced number of oncologists, urologists, radiation oncologists, radiologists, and nuclear medicine specialists, to achieve a less biased consensus than those conducted with more restrictive representation of specialties; patient advocates were also involved.

Section snippets

Panellist selection

Panellists were selected on the basis of their expertise and publication record in the diagnosis or treatment of prostate cancer as well as on their involvement in the development of guidelines. We sought representation of all core clinical disciplines listed previously, and panellists were actively involved in all stages of a modified Delphi consensus process (figure). Preference was given to candidates already involved in similar guideline projects. Availability for the modified Delphi

Questionnaire

With the results of the literature review (appendix) used as a basis to tackle the most pertinent questions relating to prostate cancer imaging, a questionnaire was proposed and agreed upon among the panellists. A modified Delphi process was then used to gain a structured consensus on each of these identified and researched topics.32 Anonymised summaries of the first two rounds of the modified Delphi process served as the basis for live presentations and further discussions during the EANM

Findings

Four clinical topics were identified from the systematic review that informed the subsequent modified Delphi process. These were imaging for staging of prostate cancer, imaging at biochemical recurrence of prostate cancer, imaging of advanced prostate cancer, and therapy of metastatic castration-resistant prostate cancer with radiopharmaceuticals. Findings that were asked in the questionnaire can be found in the table.

Guidelines and consensus

Development of guidelines and consensus statements is of paramount importance for the medical community to guide clinical decision making. The availability of an increasing number of diagnostic and therapeutic options for prostate cancer requires careful decision making to optimise the use of resources, while appreciating that evidence-based data, such as systematic reviews and meta-analyses, are not always sufficient to inform appropriate use of medical options.55

To address the clinical need

Conclusion

EANM Focus 1 constitutes the efforts of a multidisciplinary panel of international experts to produce a comprehensive series of statements on prostate cancer imaging and therapy with radiopharmaceuticals. This approach can be regarded as a useful method to build consensus on topics of relevant clinical value, in which differing views might exist. Consensus was achieved for many questions, and clear preferences were expressed for the remainder. The most relevant conclusions drawn regarding the

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