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Assessing Metastatic Disease in Advanced Prostate Cancer: It's Time to Change Imaging

Eur Urol.<https://www.ncbi.nlm.nih.gov/pubmed/27595376> 2016 Aug 29 doi: 10.1016/j.eururo.2016.08.045 [Epub ahead of print]

Refers to article:

METastasis Reporting and Data System for Prostate Cancer: Practical Guidelines for Acquisition, Interpretation, and Reporting of Whole-body Magnetic Resonance Imaging-based Evaluations of Multiorgan Involvement in Advanced Prostate Cancer

Anwar R. Padhani, Frederic E. Lecouvet, Nina Tunariu, Dow-Mu Koh, Frederik De Keyzer, David J. Collins, Evis Sala, Heinz Peter Schlemmer, Giuseppe Petralia, H. Alberto Vargas, Stefano Fanti, H. Bertrand Tombal and Johann de Bono

Accepted 25 May 2016

Two articles on imaging of advanced prostate cancer (APC) were published recently, one in European Urology Focus[1] and one in European Urology[2]. Both were produced by an international panel (United Kingdom, Belgium, Germany, Italy, and the United States) with the most experience in whole-body magnetic resonance imaging (WB-MRI) of APC. This was done under the scientific direction of two key clinical opinion leaders: urologist Bertrand Tombal (Belgium) and clinical trials oncologist Johann de Bono (United Kingdom). These two papers need to be read in tandem.

These articles were prepared in response to recommendations for standardisation of modern imaging made at the Advanced Prostate Cancer Consensus Conference 2015 (APCCC; St. Gallen, Switzerland). The Prostate Cancer Working Group (PCWG3; 2016) also pointed out the limitations of current imaging for direction of patient management and for clinical trials of therapeutics.

These articles are aimed at urologists and oncologists who treat patients with APC, and they cover aspects of current practice and emerging evidence for changes in practice based on clinical trials [1] and [2].

A critical review was written about currently used imaging technologies, such as bone scans and computed tomography (CT) scans, and how current limitations can be addressed by functional imaging methods including positron emission tomography (PET) with CT and WB-MRI [1]. The critical review recognises the central role of imaging in directing clinical care, but it is critical of current reliance on bone and CT scans for directing patient care. The authors provide cogent arguments for the need for change and application of new imaging modalities.

In particular, the review paper addresses the need for more accurate imaging in APC when metastatic disease can be concluded as definitively present or absent and subsequently can guide patient management [1]. These papers do not address the issues of detecting microscopic or minimal metastatic disease [1] and [2].

The promotion of modern imaging methods is framed in light of new data on the potential benefits of more accurate imaging detection of metastases and potential impacts for therapy monitoring. This summary of the impacts of imaging cannot be found elsewhere in the literature—this is a highlight.

The paper assesses imaging methods that have potential clinical utility today rather than the promise of better imaging tomorrow [1]. That is why there is a focus on the potential utility of fluorocholine-PET/CT and on the emerging role of WB-MRI. Prostate-specific membrane antigen–PET scanning is not mentioned in this review but is increasingly used in different parts of Europe and the United States.

Imaging techniques, including WB-MRI and PET/CT, demonstrate capabilities that go beyond current practise and will be unfamiliar to many readers; as such, they require explanation. The illustrations (in the review, supplementary figures, and appendix) demonstrate the power of new technology for multiregional evaluations, for metastasis detection, and for response assessment (in bone and soft tissues).

The METastasis Reporting and Data System for Prostate Cancer (MET-RADS-P) standards paper sets out its objectives focusing on WB-MRI only [2]:

  • Establish minimum technical parameters for data acquisition.
  • Establish standardised data collection that enables detailed reporting of the disease phenotype based on anatomic patterns of metastatic spread.
  • Develop response methods to separately assess bone, soft tissue, and local disease.
  • Provide methods to record presence, location, and extent of discordant responses.
  • Summarise likelihood of response in bone, soft tissues, and local disease.
  • Enable data collection for outcomes monitoring in clinical trials.
  • Allow the education of radiologists to reduce variability in interpretations.
  • Enhance communication with referring clinicians.

Unlike the Prostate Imaging–Reporting and Data System (PI-RADS), which focusses on the detection of (minimal) significant diseases [3], the MET-RADS-P standard uniquely addresses the likelihood of response criteria on a scale of 1–5. Providing guidance borrowed from the Response Evaluation Criteria in Solid Tumors and PCWG3 for soft tissue disease, MET-RADS-P provides new guidance for the assessment of bone disease (there are no internationally recognised criteria). This guidance is based on literature reviews and the personal experiences of the authors. It must be emphasised that MET-RADS-P is not meant to address soft tissue diseases like nodal metastases.

The authors attempt, for the first time, to assess bone disease response in three categories—progressive disease, stable disease, and response (both partial and complete)—rather than the currently used categories of progression and no progression, thus mirroring disease assessments in soft tissue disease [2]. They assert that this new way of assessing the response of bone disease could positively affect physician thinking and actions regarding patient care.

The MET-RADS-P paper [2] specifically provides a recipe for imagers (in appendices only, covering the technical aspects of data acquisition, quality assurance, image analysis, response assessments, heterogeneity analysis, template reporting, and so forth) so that urologists and oncologists can go to their imaging departments and ask for appropriate compliant scanning to be performed for their patients with immediate effect.

Although these papers have an important message [1] and [2], there are still some challenges. WB-MRI is a stable technique, but it requires significant expertise, training, and quality control. Furthermore, the standard tries to address the clinical community as well as clinical trials, which can lead to confusion on first reading. The authors introduced the concept of spatial heterogeneity in therapy response based on their observations about documented differential outcomes on the basis of disease distribution, stating that spatially heterogeneous responses to targeted therapies may be used to guide selective sampling for “actionable mutations”; whether this knowledge will affect patient outcomes remains debated.

Quantitative WB-MRI biomarkers such as ADC histogram descriptors, tumour volume, bone tissue subclassification, and heterogeneity metrics are not addressed in these papers. That is not surprising because these still need to be developed.

We are now at a point at which the WB-MRI technology is stable and available and ready to be validated. The authors show that WB-MRI has crossed the first translational gap for imaging biomarker development [4]. The next challenges include multicentre reproducibility, biological and clinical validation, and qualification. The authors suggest a number of clinical scenarios in which validation could be undertaken, including tumour detection studies using oligorecurrence (M0) and oligometastatic protocols and response assessment studies of established and novel treatments including androgen axis inhibitors, chemotherapy, radium 223, immunotherapies, and poly(ADP-ribose) polymerase inhibitors. Only once these studies are undertaken can the adaptive therapy studies for imaging-depicted heterogeneous response be done.

Finally, the fundamental point not addressed by these papers, as raised by the 2015 APCCC panellists, is whether the earlier detection of metastatic disease using highly sensitive imaging methods will have significant clinical benefits. Will the earlier detection of treatment failure by more sensitive methods, and subsequent modifications in life-prolonging treatments, have benefits for maintaining quality of life (QoL)? These questions are worth investigating, but few data currently exist on the benefits of treatment modifications based on the detection of early treatment failure and on the negative QoL effects of continued treatments with ineffective drugs.

It can be concluded that it is likely that the MET-RADS-P paper will be widely read and quoted in future literature, but most important, it requires validation in clinical trials of established novel treatment approaches in APC and incorporation into clinical practise. MET-RADS-P is not yet at the stage at which it can support the development of novel clinical therapeutics. Radiologic responses and the radiologic definition of progression of disease recently became the standard of care instead of prostate-specific antigen velocity. This new method should be incorporated into new clinical trials because it can help validate this method for early response monitoring of new drugs and treatments.

Conflicts of interest

The authors have nothing to disclose.

References

  • [1] Padhani AR, Lecouvet FE, Tunariu N, et al. Rationale for modernising imaging in advanced prostate cancer. Eur Urol Focus. In press. http://dx.doi.org/10.1016/j.euf.2016.06.018.
  • [2] Padhani AR, Lecouvet FE, Tunariu N, et al. METastasis Reporting and Data System for Prostate Cancer: practical guidelines for acquisition, interpretation, and reporting of whole-body magnetic resonance imaging-based evaluations of multiorgan involvement in advanced prostate cancer. Eur Urol. In press. http://dx.doi.org/10.1016/j.eururo.2016.05.033.
  • [3] J.C. Weinreb, J.O. Barentsz, P.L. Choyke, et al. PI-RADS Prostate Imaging - Reporting and Data System: 2015, Version 2. Eur Urol. 2016;69:16-40 10.1016/j.eururo.2015.08.052
  • [4] O’Connor JPB, Aboagye EO, Adams JE, et al. Imaging biomarker roadmap for cancer studies. Nat Rev Clin Oncol. In press.

Footnotes

Radboud University Medical Centre, Nijmegen, The Netherlands

Corresponding author. Radboud University Medical Centre, PO Box 9101, Nijmegen, 6500 HB, The Netherlands.