When Enzalutamide Stops Working: — Resistance and What Comes Next

Abiraterone and enzalutamide work on the same pathway — both ultimately suppress androgen receptor activity, though at different points in the process. When enzalutamide resistance is driven by AR-V7 or a similar receptor change, abiraterone is unlikely to help for the same reason. Your oncologist may still consider it in specific situations, particularly if the mechanism of resistance has not been confirmed by testing. Ask directly whether your AR-V7 result or other findings suggest cross-resistance before this option is pursued.

PARP inhibitors such as olaparib and rucaparib block a DNA repair process that some cancers depend on to survive. They are effective when the cancer has a fault in its own DNA repair machinery — most often a mutation in BRCA1 or BRCA2, though other genes in the HRR pathway also count. They do not work without this fault. ASCO and ESMO guidance recommends testing all patients with metastatic castration-resistant prostate cancer for HRR mutations. The test is done on tumour tissue or, in some cases, a blood sample. If this testing has not been done, ask for it now.

Lutetium-177 PSMA is a targeted treatment that attaches a radioactive particle to a molecule designed to seek out PSMA — a protein expressed on the surface of many prostate cancer cells. When the molecule binds to a cancer cell, the particle damages it from inside. To be eligible, your tumour must show adequate PSMA expression on a PSMA PET scan, and most clinical protocols require prior treatment with both an androgen receptor pathway inhibitor and taxane chemotherapy. Regulatory approvals from the US FDA and EMA are based on the VISION trial. Availability varies by centre.

Yes. Docetaxel and cabazitaxel work independently of the androgen receptor changes that cause enzalutamide resistance, which means they can remain effective even after enzalutamide has stopped working. If you have not yet had chemotherapy, docetaxel is commonly the first chemotherapy option considered. Cabazitaxel is used where docetaxel has already been given and the cancer has progressed. ASCO and ESMO guidance supports both as standard options. Whether you are fit enough for chemotherapy is something your oncologist will assess based on your overall health and other conditions.

Yes, especially if your standard options are limited or you want access to emerging treatments. Clinical trials for prostate cancer after enzalutamide are ongoing across several treatment types, including novel androgen receptor targeting agents, radioligand therapies, bispecific antibodies, and combinations. Being in a trial does not mean receiving an unproven treatment — many trials compare a new approach against the current standard of care, with close monitoring throughout. Ask your oncologist whether an open trial currently matches your profile and test results.

If your cancer has spread to bones and not to internal organs, radium-223 is an option to discuss. It is a radioactive element that concentrates naturally in bone and delivers localised radiation to bone metastases. It is not a treatment for soft-tissue disease, and it is distinct from chemotherapy. ASCO guidance supports its use in patients with symptomatic bone metastases and no known visceral metastases. It can be used alongside some systemic treatments, though your oncologist will advise what combination is appropriate for your situation and how it fits into the overall plan.