Radioligands used against prostate cancer

PSMA as a new target structure for PCa

Radioligand therapy is still a new experimental form of treatment in urooncology. But now the first successes with PSMA-Lutetium-177 have been achieved in prostate cancer. Time to take a closer look at the method.

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The prostate-specific membrane antigen (PSMA) protein is another tissue marker of the prostate besides the prostate-specific antigen (PSA). Similar to PSA, PSMA is expressed more strongly on cancer cells, but also on healthy prostate cells.

PSMA has always been interesting in studies as a diagnostic tracer, but the protein also appears to be well suited for the treatment of prostate cancer. Of course, PSMA alone is not effective, since it serves only as a target structure, e.g. to guide drugs or radioactive substances to their destination.

Researchers at the German Cancer Research Centre (German acronym: DKFZ) in Heidelberg recently succeeded in binding radioactive lutetium-177 to a PSMA ligand (PSMA-617). This is internalized together with lutetium-177 into the prostate cancer cells and then irradiated from the inside.

In a recent study, researchers used the procedure to test the efficacy in prostate cancer patients. All subjects were pretreated with Docetaxel or Cabazitaxel and a corresponding androgen deprivation therapy (ADT). In addition, about 97% of men already suffered from bone metastases.

As a result, the median overall survival of patients receiving PSMA-617 lutetium-177 was 56 weeks. A biochemical response (PSA decrease > 50%) was not prognostic for overall survival. However, any decrease in PSA after the first treatment cycle was associated with better overall survival (62.9 vs. 47.0 weeks; p = 0.005).

For the time being, however, radioligand therapy remains a remedy in salvage therapy for men who no longer have access to any of the established therapy lines. The current S3 guideline of the German Society of Urology (German acronym: DGU) formulates a first sufficient necessity for the patient's metastatic castration-resistant prostate cancer (mCRPC) to show PSMA-positive lesions in PSMA imaging. Otherwise, this approach is not applicable either.

Source: Rahbar K et al., PSMA targeted radioligand therapy in metastatic castration-resistant prostate cancer after chemotherapy, abiraterone and/or enzalutamide. A retrospective analysis of overall survival. Eur J Nucl Med Mol Imaging 2018; 45(1): 12-19 

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