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ASCO 2019 Annual Meeting

ASCO 2019: Rational Approaches to Integrating Novel Imaging Into Clinical Trial Design

Chicago, IL (UroToday.com) Oliver Sartor, MD gave a talk at ASCO 2019 on the role of PET imaging in advanced prostate cancer. There have been many tracers used for PET imaging, all showing benefit in the detection of prostate cancer at various stages and different settings. PSMA-PET imaging has shown benefit in the diagnosis of bone and soft tissue disease, although it is not FDA approved yet. Choline PET has been FDA approved at Mayo Clinic, Fluciclovine has been FDA approved but less sensitive than PSMA. Lastly, FDG-PET has been FDA approved but not in prostate cancer, although it has shown some benefit in this entity as well. Dr. Sartor continued by providing some technical data regarding the various gamma emitters used in PET imaging (Table 1). According to Dr. Sartor, special attention should be paid to Cu-64 and Zr-89, which will clinically be used more often in the near future.

Table 1 – Gamma emitters used in PET imaging:
GammaEmitters_PET_Imaging_ASCO_OliverSartor.png

Many local therapy failures are secondary to a poor understanding of disease localization. Prostate cancer imaging is especially challenging given bone involvement because conventional imaging assesses bone stroma and not the tumor. 

The investigation of PET in “localized therapies” is now actively being explored. It is important to acknowledge that PSMA-PET is likely more than ten times better than conventional imaging, but no imaging will ever be perfect. The localization of disease is just the beginning of imaging, and many other factors need to be considered:

  1. Microenvironment assessment – (Hypoxia, immune infiltrates, and stromal integrins). For example, there has been published data1 on the usage of 89Zr-atezolizumab imaging as a non-invasive approach to assess clinical response to immunotherapy (PD-L1 blockade in cancer), as shown in Figure 1. These data show that clinical responses correlated better with PD-L1 imaging than with immunohistochemistry or RNA sequencing.
  2. Predictive and prognostic biomarker – Patient selection for treatment
  3. Linkage to underlying genotype
Figure 1 - 89Zr-atezolizumab imaging as a non-invasive approach to assess clinical response to immunotherapy:
89Zr-atezolizumab_Imaging_NonInvasive_Approach.png
Dr. Sartor moved on to discuss the role PET imaging plays in relationship to systemic therapies. PET has a potential role as a predictive biomarker in this setting. Also, the role of PET in radiopharmaceuticals, hormonal therapy, and chemotherapy needs to be assessed. Some patients have demonstrated very rapid PSMA-PET response (9 days after androgen deprivation therapy initiation), (Figure 2). FDG-PET has even been used to predict the time of hormonal treatment failure in metastatic castrate-sensitive prostate cancer patients.2

Figure 2 - Rapid PSMA-PET response after initiating androgen deprivation therapy:
Rapid_PSMA-PET_response_postADT.png
Next, Dr. Sartor discussed the combination of PETS allowing us access to some interesting information. Recently, there has been a published study examining the role of PET in assessing androgen receptor expression and glycolytic activity as a prognostic biomarker for metastatic castrate-resistant prostate cancer.3 This study demonstrated that the prognosis of patients with metastatic castration-resistant prostate cancer is adversely affected by easily observed positron emission tomography–based molecular imaging biomarkers, such as total lesion numbers detected per patient, high 2-fluoro-2-D-deoxyglucose F 18 uptake of individual lesions, and the pattern of androgen receptor and glycolysis lesion phenotypes within individual patients.

Dr. Sartor ended his discussion asking a very important question: While there is no doubt that significant advances have been made in novel PET imaging, enabling us to see the disease better and more of it, does it really matter in the long run? Does it change patient outcomes? Unfortunately, to date, we cannot answer this.

Presented by: A. Oliver Sartor, MD, Professor of Medicine, Medical Director, Tulane Cancer Center, New Orleans, Louisiana

Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, @GoldbergHanan at the 2019 ASCO Annual Meeting #ASCO19, May 31- June 4, 2019, Chicago, IL USA

References:
  1. Bensch F. et al. 89Zr-atezolizumab imaging as a non-invasive approach to assess clinical response to PD-L1 blockade in cancer. Nat Med. 2018 Dec;24(12):1852-1858
  2. Jadvar H. et al. Prediction of time to hormonal treatment failure in metastatic castrate-sensitive prostate cancer with 18F-FDG PET/CT. J Nucl Med. 2019 Mar 29.
  3. Fox JJ. et al. Positron Emission Tomography/Computed Tomography-Based Assessments of Androgen Receptor Expression and Glycolytic Activity as a Prognostic Biomarker for Metastatic Castration-Resistant Prostate Cancer. JAMA Oncol. 2018 Feb 1;4(2):217-224.