ASCO GU 2020: Defining Extent of Disease Using Novel Approaches - Beyond Standard Imaging

San Francisco, California (UroToday.com) Advanced imaging is increasingly being used across all stages of prostate cancer. Dr. Richard Lee from the Massachusetts General Hospital Cancer Center discussed the data supporting the use of various advanced imaging modalities across the prostate cancer disease spectrum.

Conventional imaging (defined as CT/MRI and bone scan) is widely available and their test characteristics are well-defined. CT and MRI show high resolution anatomic detail, but do not show disease activity. As a reference to compare with advanced imaging modalities, when evaluating for nodal metastatic disease, CT and MRI both have a sensitivity of approximately 40% and specificity of approximately 80%. Rates of positive bone scan for PSA post-radical prostatectomy are 4% for patients with PSA less than 10 ng/ml. A limitation of bone scan is that often times multi-modality imaging with CT or MRI is needed to inform treatment decisions.

Next generation imaging modalities utilize novel molecules for identifying prostate cancer and tracers (positron-emitting radioisotopes) for imaging. Molecules in use include fluciclovine, sodium fluoride, choline, acetate, and prostate specific membrane antigen (PSMA). Tracers include 18F, 11C, and 68Ga.

18F-Fluciclovine PET/CT was FDA approved in 2016 and is widely available at >1000 centers in the United States. Reported PSA detection is 68% overall with the following sensitivity at various PSA thresholds: 41% at PSA < 0.80, 58% at PSA 0.8-2.0, 75% at PSA 2.0 to 6.0, and 87% at PSA > 6.0. When compared head-to-head to 18F-Fluciclovine had significantly better test characteristics than CT and bone scan as outlined below:

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Further, prospective data from the LOCATE study demonstrated that the use of 18F-Fluciclovine PET/CT in men with biochemical recurrence (median PSA 1.0) found that 57% had a lesion detected and the 18F-Fluciclovine PET/CT changed management in 59% of cases.

An important consideration in determining when to use next generation imaging is the likelihood of a positive result at different PSA thresholds. The slide below summarizes 18F-Fluciclovine PET/CT detection rates at various PSA thresholds:

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PSMA is a cell surface protein that is specific to prostate cancer and is over-expressed in 90-95% of prostate cancer cells making it an ideal imaging target. Of note, at this time it is not commercially available in the United States. A comparative study found that PSMA PET/CT had higher rates of similar or higher rates of detection in all stages of disease than conventional imaging. Notably, conventional imaging had higher false-positive rates in patients who did not have disease.

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The slide below summarizes PSMA PET/CT detection rates at various PSA thresholds.

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With both 18F-Fluciclovine PET/CT and PSMA PET/CT demonstrating better test characteristics than conventional imaging, Calais et al prospectively compared PSMA and Fluciclovine PET in 50 men with PSA between 0.2 and 2.0 Detection rates in this single institution study favored PSMA detection overall and especially in pelvic lymph node and extra-pelvic (M1) disease.

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Given the data supporting improved detection compared to conventional imaging, advanced imaging modalities have been recommended by both the NCCN and ASCO guidelines.

Presented by: Richard J. Lee, MD Professor of Stem Cell and Regenerative Biology at Harvard Medical School, Boston, Massachusetts

Written by: Jacob Berchuck, MD, Medical Oncology Fellow at the Dana-Farber Cancer Institute (Twitter: @jberchuck) at the 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California

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