What effect does ADT have on PSMA expression by prostate cancer cells?

Arguably the molecule of the year in the prostate cancer world is prostate-specific membrane antigen (PSMA). Prostate cancer cells variously express this protein on their cell surfaces. An antibody to PSMA can attach to the cancer cells by binding to this protein. When the PSMA antibody is also bound to a radioactive molecule that gives off gamma radiation, the cells can be located with the same gamma cameras traditionally used to find bone metastases. But by using the PSMA molecule as a link to the prostate cancer cells, those cells can be located anywhere in the body and not just in the bones. If PSMA is bound to a radioisotope that gives off alpha or beta radiation, the radiation can be used to kill the cancer cells.

This all sounds very promising from both a diagnostic and therapeutic perspective. However, there is a catch. Not all prostate cells highly express PSMA (whether they are cancerous or not). 

One might suppose that, when ADT suppresses prostate cell growth, it also suppresses PSMA expression on those same cells. It turns out, though, that the effect of ADT on PSMA expression is more complicated than that, as a recent editorial by Vaz et al. in the European Journal of Nuclear Medicine and Molecular Imaging demonstrates.  

Short-term ADT actually upregulates PSMA expression, whereas long-term ADT suppresses PSMA expression. Here “short term” appears to be in the order of just a few weeks. Long term appears to be in the order of three months or more.

It is clear from the Vaz et al. review that there are many other factors that can influence PSMA expression. As such, there is no simple formula that fits all patients as to whether they should start (or stop) ADT, if they are planning to get PSMA imaging and hope to maximize its effectiveness. At a minimum, though, patients who are candidates for PSMA diagnostics should be aware of the complex relationship that ADT can have to PSMA expression.  

The decision to start or stop ADT should always be made in consult with one’s oncologist.

For access to the article see:  

https://link.springer.com/article/10.1007%2Fs00259-019-04529-8    

Vaz S, Hadaschik B, Gabriel M, Herrmann K, Eiber M, Costa D. (2019). Influence of androgen deprivation therapy on PSMA expression and PSMA-ligand PET imaging of prostate cancer patients. Eur J Nucl Med Mol Imaging. 2019 Oct 25. doi: 10.1007/s00259-019-04529-8. [Epub ahead of print]