EAU 2021: Is Nuclear Medicine Taking over the Treatment of Metastatic Prostate Cancer? PRLT Is Only a Tessera in the Treatment of CRPC

(UroToday.com) The European Association of Urology (EAU) 2021 Virtual Annual Meeting included a joint session of the EAU and the Canadian Urological Association and a presentation by Dr. Frederic Pouliot suggesting that prostate radioligand therapy is only a tessera in the treatment of CRPC. Dr. Pouliot notes that theranostics is the combination of imaging and therapy, most commonly 177Lu-PSMA radioligand therapy. Radioligand therapy is promising, but Dr. Pouliot poses: is it really as simple as PSMA PET positive disease = PSMA radioligand targetable = PSA response = clinical benefits?


Dr. Pouliot highlighted that based on the last several years of research we have been able to discern the evolution and plasticity of metastatic prostate cancer, and the multitudes of available treatment for each disease space (as highlighted in the following figure):


PSMA PET positive.jpg

Dr. Pouliot suggests that radioligand therapy may not be the be-all end-all treatment for all patients. For example, in patients with advanced prostate cancer with neuroendocrine liver metastasis, there may be a lack of PSMA expression, thus underestimating the burden of disease:

Pouliot.jpg

Dr. Pouliot then briefly highlighted the TheraP trial,1 which randomized men with mCRPC in a 1:1 fashion to 177Lu-PSMA-617 or cabazitaxel. Importantly, as Dr. Pouliot notes, all patients had to undergo both Ga-68-PSMA-PET/CT and F-18-FDG-PET/CT prior to randomization. In order to be eligible for inclusion, patients must have had a high avidity lesion on PSMA PET/CT (SUV max >20 at any site) with measurable disease with SUV max of 10 or greater. Further, there could be no sites of disease which were FDG positive but PSMA negative. As such, 28% of patients in the 177Lu-PSMA-617 were ineligible, highlighting that perhaps not everyone may benefit from radioligand therapy.

An alternative for assessing advanced prostate cancer patients is by using molecular imaging to image polyclonality in metastatic prostate cancer. In work from Dr. Pouliot’s group, they assessed the metabolic response for each individual metastatic lesion (n=165) among 15 patients with metastatic prostate cancer who underwent 18F-FDG PET/CT before and at least three months after initiation of a systemic therapy that did not change in that period.2 They defined intermetastasis heterogeneity was defined as opposite metabolic responses for at least two metastases from the same compartment (bone or soft tissue) between the two-time points. They found that there was intrapatient intermetastasis response heterogeneity in 40% of cases, suggesting that systemic therapies can induce heterogeneous responses among individual metastases in patients with prostate cancer and supporting the polyclonal evolution of prostate cancer in advanced disease:

Pouliot EAU.jpg

As follows is a schematic for redefining tumor biology after ARAT in M0 CRPC or M1 HSPC:

tumor biology.jpg

It goes without question that, beyond PSMA, we have many advanced prostate cancer therapeutic options in the second and third-line settings, including docetaxel, radium-223, abiraterone, enzalutamide, olaparib, and cabazitaxel.

Dr. Pouliot concluded his presentation highlighting again the PSMA radioligand therapy is only a tessera for the treatment of mCRPC. The true optimal position for radioligand therapy remains to be determined and may be in combination with PARP inhibitors and/or immunotherapy, which will be assessed in ongoing clinical trials:

beyond PSMA.jpg

Presented by: Frederic Pouliot, MD, Universite Laval, Centre de recherce CHU de Quebec-Universite Laval, Quebec City, Quebec, Canada

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2021 European Association of Urology, EAU 2021- Virtual Meeting, July 8-12, 2021.

References:

  1. Hofman MS, Emmett L, Sandhu S, et al. [(177)Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): A randomized, open-label, phase 2 trial. Lancet. 2021 Feb 27;397(10276):797-804.
  2. Morin F, Beauregard JM, Bergeron M, et al. Metabolic imaging of prostate cancer reveals intrapatient intermetastasis response heterogeneity to systemic therapy. Eur Urol Focus. 2017 Dec;3(6):639-642.
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