ESMO 2017: Management of M0 Patient with Rising PSA: How can PET imaging help?

Madrid, Spain ( Dr. Haberkorn from Germany provided a discussion assessing how PET imaging can assist with monitoring and treating the M0 patient at the symposium on the Management of the M0 patient with rising PSA at ESMO 2017. The rationale for PSMA targeting prostate cancer is that PSMA expression increases progressively in higher grade tumors, metastatic disease, and hormone-refractory prostate cancer, while at the same time maintaining normal expression patterns in normal tissue. These molecules have high specificity for receptors, fast circulation through the body, are easy to produce and label, and have high stability, and no host immune response. 

In 2017, PSMA PET is able to detect >50% of PSMA positive lymph nodes with a short axis diameter <8mm. When comparing 18F-fluoromethylcholine and 68Ga-PSMA at various PSA levels, the head-to-head detection level at various cut-points favors 68Ga-PSMA: PSA <0.5 ng/mL – 50% vs 12.5%; PSA 0.5-2.0 ng/mL – 71% vs 36%; PSA >2.0 ng/mL – 88% vs 63% [1]. However, as Dr. Haberkorn notes, even though 68Ga-PSMA PET outperforms conventional CT imaging for detection of lymph node metastases, what do we do when planning for IMRT regarding the lesions that we don’t see? Importantly, if 68Ga-PSMA PET increases detection of lesions, does it change treatment planning? In a small study assessing primary prostate cancer recurrences (n=44; n=15 initial diagnoses), 63% of patients had overall management changed after 68Ga-PSMA PET imaging [1].

The quest for improved PSMA radiotracers is ongoing. A new radiofluorinated molecule resembling the structure of therapeutic PSMA-617 has been developed in pre-clinical models, 18F-PSMA-1007. This radiotracer has no plasma binding and no metabolism in human plasma, as well as little radioactivity in the bladder and cleavage of the tracer in the kidneys [2]. 18F-PSMA-1007 is now undergoing initial clinical validation in humans. Finally, Dr. Haberkorn’s group is at the cutting edge of PSMA therapeutics, concluding his presentation with impressive images of a patient with multiple bone metastases receiving 225-Actinium-PSMA (225-Ac-PSMA) and experiencing a complete durable radiographic/PSA response after three treatments of 225-Ac-PSMA.

Speaker: Uwe Haberkorn, University Hospital Heidelberg and DKFZ Heidelberg, Heidelberg, Germany

Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md at the European Society for Medical Oncology Annual Congress - September 8 - 12, 2017 - Madrid, Spain

1. Morigi JJ, Stricker PD, van Leeuwen PJ, et al. Prospective comparison of 18F-Fluromethylcholine versus 68GA-PSMA PET/CT in prostate cancer patients who have rising PSA after curative treatment and are being considered for targeted therapy. J Nucl Med 2015;56(8):1185-1190.

2. Cardinale J, Schafer M, Benesova M, et al. Preclinical evaluation of 18F-PSMA-1007, a new prostate-specific membrane antigen ligand for prostate cancer imaging. J Nucl Med 2017;58(3):425-431.

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