He began his discussion by explaining how theranostics works. A target cell (in this case a prostate cancer cell) has specific membrane receptors which can be bound to by binding molecules. These binding molecules can then be attached to a radionuclide through a linking molecule. The radionuclide can then deliver its energy to the cancer cell, thereby causing cell death. This treatment method has been employed for decades in the treatment of thyroid cancer, with radioactive iodide being used to target thyroid cells, however, it has been rarely employed in other malignancies until recently.
Prostate-specific membrane antigen (PSMA) is a transmembrane protein expressed in prostate cancer cells. It has been utilized recently as a target for imaging modalities such as a PSMA PET/CT. There has been emerging data that PSMA PET/CT is the most specific imaging modality to detect metastatic or nodal disease that may have been missed by a conventional bone scan or CT scan. Recently the use of PSMA PET/CT has been recommended by the EAU for men with a rising PSA after radical prostatectomy in order to determine if there is metastatic or nodal disease, as this may influence treatment decisions.
Dr. Fanti discussed that while utilization of PSMA as a diagnostic imaging tool is fairly well established at this point, it has even more potential as a therapeutic treatment for advanced prostate cancer. In 2014 the first patient was treated with Lutetium linked to PSMA (177Lu-PSMA-617) in a small case series of patients with metastatic prostate cancer. Patients showed a dramatic response in terms of decrease of visible lesions on PSMA scan, as well as a significant decrease in PSA values. More recent work out of Australia has confirmed the therapeutic efficacy of 177Lu-PSMA-617 in a separate cohort of men. Fanti acknowledges, however, that its use is still in its infancy, but results appear promising. This currently is being considered as a third line treatment in men with metastatic castrate-resistant prostate cancer who have already failed standard therapy, including docetaxel-based chemotherapy, and a second-generation antiandrogen.
He concluded by discussing the future of theranostics. He believes that they can become even more efficacious if we are able to link alpha-emitting particles to cancer-specific molecules, as alpha-emitting particles are higher energy and travel shorter distances. In theory, this could lead to more effective cancer cell destruction and less residual side-effects to healthy tissue. Fanti believes that we will start hearing about theranostics much more commonly in the literature in the coming years, and he is excited to see emerging research in the field. He stressed that in order to advance this field, it is important for him and his nuclear medicine colleagues to collaborate with other clinicians such as urologic oncologists and medical oncologists in order to develop clinical trials in order to change the standards of care.
Presented by: Stefano Fanti, MD, Professor Department of Experimental, Diagnostic and Specialty Medicine - DIMES at the University of Bologna. He is Director of Nuclear Medicine Division of the PET Unit at the Policlinico S. Orsola and Director of Speciality School of Nuclear Medicine at the University of Bologna.
Written by: Brian Kadow, MD, Society of Urologic Oncology Fellow, Fox Chase Cancer Center at the 34th European Association of Urology (EAU 2019) #EAU19 conference in Barcelona, Spain, March 15-19, 2019.