PSMA and AR-Targeted Therapy — in Prostate Cancer

PSMA stands for prostate-specific membrane antigen, a protein found in high concentrations on the surface of most prostate cancer cells. It matters for two distinct reasons. First, a PSMA PET-CT scan uses a PSMA-targeting tracer to find cancer deposits that conventional scans can miss, which affects staging. Second, PSMA expression on the tumour is the eligibility criterion for radioligand therapy — if the scan shows strong expression, Lu-177 PSMA-617 may be an option in later disease. Low or absent PSMA expression means radioligand therapy is unlikely to help regardless of disease stage.

NCCN and ESMO recommend germline genetic testing for all men with metastatic prostate cancer, and for locally advanced or high-risk disease in many guidelines. The practical reason is that if a BRCA1, BRCA2 or HRR mutation is found, PARP inhibitors become a treatment option that would otherwise not be available. Without the test, that option is invisible. A positive result also has implications for blood relatives. If your oncologist has not mentioned it, ask directly whether it has been ordered and what the result showed.

Standard hormone therapy — also called androgen deprivation therapy or ADT — lowers testosterone using injections and is the foundation of prostate cancer treatment. Androgen receptor pathway inhibitors (ARPIs) are layered on top to block the remaining hormone signalling more precisely at the receptor level. PSMA radioligand therapy and PARP inhibitors work through entirely different mechanisms. In practice, most patients are on ADT plus an ARPI together. The term targeted therapy generally refers to these newer agents added to or replacing basic hormone suppression.

Lu-177 PSMA-617 has received regulatory approval in India and is available at select nuclear medicine centres. It is not available everywhere, and whether there is a centre near you is a practical question to put directly to your oncologist. It requires a positive PSMA PET scan as a prerequisite, and it is currently indicated for patients who have already received an ARPI and taxane chemotherapy. If you meet the criteria, your team can advise on where it can be accessed.

When prostate cancer progresses on one ARPI, switching to another from the same class sometimes helps, though the benefit varies. Your oncologist will review your biomarker results at this point. If a BRCA or HRR mutation was found, PARP inhibitors become the relevant next option. If PSMA expression was confirmed, radioligand therapy may follow. If MSI-H or dMMR is present, immunotherapy enters the picture. Progression on an ARPI is not the end of options — it is the point at which the next layer of testing and treatment becomes most relevant.

Androgen receptor pathway inhibitors are oral medications your CION oncologist prescribes and monitors at outpatient visits. PARP inhibitors are managed the same way. PSMA PET-CT scans are coordinated with partner imaging centres. Lu-177 PSMA radioligand therapy is administered at specialist nuclear medicine centres; your CION team can advise on whether a referral applies in your situation. CION does not provide CAR-T or cell therapy.