Most prostate cancer is caught while it is still in the prostate, and that is the situation I cover in Treatment Options for Prostate Cancer. This one is about the harder case, where the cancer has spread beyond the gland.
Two terms come up constantly and it helps to have them straight.
Hormone sensitive disease means the cancer still responds to lowering testosterone. Castration resistant disease means it has found a way to keep growing even after testosterone has been driven down. Both can be metastatic, meaning the cancer has spread to bone or lymph nodes or elsewhere.
The change that mattered most
For a long time the approach was sequential. Start with hormonal therapy, wait for it to fail, then add the next thing, wait for that to fail, and so on down the list.
We do not do that anymore. For men presenting with metastatic hormone sensitive disease, the standard now is to combine treatments up front. Hormonal therapy plus a second agent, and in selected men hormonal therapy plus a second agent plus chemotherapy. People call these doublet and triplet therapy.
Treating harder at the start, rather than holding drugs in reserve, produced real gains in survival. If I had to name the single most important shift in advanced prostate cancer over the past decade, that would be it.
Blocking testosterone better
Prostate cancer grows in response to testosterone, so most treatment starts by taking testosterone away. That can be done by stopping production or by blocking the receptor the testosterone acts on. Surgical removal of the testicles accomplished this for decades and still works, but injections and pills have largely replaced it.
The newer agents do the same job more completely.
Abiraterone blocks an enzyme the body needs to make testosterone precursors, and it works on sources outside the testicles as well. It is given with prednisone.
Enzalutamide, apalutamide and darolutamide block the androgen receptor itself, and they do it more thoroughly than the older antiandrogens did. They differ mainly in side effect profile, and darolutamide in particular crosses into the brain less, which matters for fatigue and cognitive complaints.
Chemotherapy
Docetaxel remains the workhorse. It is now often given early, alongside hormonal therapy, rather than held back until hormones fail. Cabazitaxel is used after docetaxel.
Chemotherapy is not curative in this setting. It buys time, and for many men it buys good time.
Targeted radiation
Radium-223 is given as an injection but behaves like radiation. It is an alpha emitter, which means it releases its energy over a very short distance. Bone affected by prostate cancer takes it up preferentially, so it delivers radiation to the cancer while sparing normal bone. It is for men whose metastatic disease is in bone.
Lutetium-177 PSMA is newer and works on a related principle. PSMA is a protein sitting on the surface of most prostate cancer cells. Attach a radioactive isotope to a molecule that seeks out PSMA and you deliver radiation to cancer cells wherever they are. A PSMA PET scan confirms the cancer actually expresses the target before treatment goes ahead.
Treatment aimed at your specific cancer
This is where genetic testing earns its keep.
Some men carry mutations in BRCA1, BRCA2 or related DNA repair genes. In those men, PARP inhibitors such as olaparib and rucaparib can be effective, because they exploit a repair pathway the cancer has already lost. You cannot know whether that applies to you without testing for it, which is why men with metastatic disease should be offered germline genetic testing.
That testing matters for your family as well. A BRCA mutation carries implications for your children and your siblings, including risks that have nothing to do with the prostate.
Immunotherapy
Sipuleucel-T is a therapeutic vaccine, made individually for each patient from their own blood cells, and given over about a month. It is for men with metastatic castration resistant disease who have few or no symptoms. It was the first FDA approved therapeutic cancer vaccine and it does improve survival. It now sits among a lot more options than it did when it arrived.
The question that is still open
Sequencing. We have more effective treatments than we have good evidence about what order to use them in, or which combinations suit which patients, or how to weigh cost against benefit for a given man. Those questions were unsettled when I first wrote about this and a fair number of them are unsettled still.
What has changed is the starting point. A man diagnosed with metastatic prostate cancer today has considerably better odds than a man diagnosed with the same disease fifteen years ago. That was not something I could say for most of my career.
References for this article need updating. The 2013 to 2014 studies cited in the original version no longer support the current text.