Metastatic castration-resistant prostate cancer

An alpha-emitting radioactive drug built on a PSMA-targeting antibody, rather than the small-molecule ligands used in existing PSMA therapies, was safe enough to move into further testing and shrank PSA in roughly a third to a half of heavily pre-treated men, including some whose cancer had already stopped responding to lutetium-177 PSMA therapy.

For men who still have a working hormone treatment option but whose cancer is progressing, offering the PSMA radioligand therapy sooner - before chemotherapy - delayed disease progression, though it did not clearly extend how long men lived once the very high rate of patients switching over is accounted for.

This guideline tells doctors and insurers exactly which clinical situations justify a PSMA PET scan for prostate cancer - mainly staging higher-risk disease, investigating a PSA rise after treatment, and checking that a patient's cancer will respond to PSMA radioligand therapy - and which situations do not.

For men whose prostate cancer has grown after chemotherapy, a PSMA-targeted radioactive treatment worked at least as well as, and was gentler than, the chemotherapy drug it replaced - provided a PET scan first confirms the cancer takes up the PSMA tracer.

Men with metastatic castration-resistant prostate cancer that has progressed after hormonal therapy and chemotherapy, and whose tumours show PSMA on a PET scan, can now receive lutetium-PSMA, which extends life, controls pain and is usually better tolerated than further chemotherapy. It has established a new treatment class in which a scan decides who gets the matching radioactive drug, and it is now being tested earlier in the disease (PSMAfore, PSMAddition).

In a small early trial, most heavily pre-treated men with advanced prostate cancer responded to the PSMA-targeted radioactive drug, with manageable side effects, supporting the case for testing it in larger randomised trials.

This was the first evidence, in two patients, that attaching a more powerful (alpha-emitting) form of radiation to the same PSMA-seeking molecule used in lutetium-177 PSMA therapy could produce a complete response even in prostate cancer that had already stopped responding to the beta-emitter version.

Radium-223 is an option for symptomatic bone-predominant castration-resistant prostate cancer, now less used since lutetium-PSMA, and should not be combined with abiraterone after the ERA 223 fracture signal.