Treating Prostate Cancer That Doesn’t Go Away or Comes Back After Treatment

If your prostate-specific antigen (PSA) blood level or another test shows that your prostate cancer has not been cured or has come back (recurred) after the initial treatment, further treatment can often still be helpful. Follow-up treatment will depend on where the cancer is thought to be and what treatment(s) you've already had. Imaging tests such as CT, MRI, or bone scans may be done to get a better idea about where the cancer is.

Cancer that is thought to still be in or around the prostate

If the cancer is still thought to be just in the area of the prostate, a second attempt to cure it might be possible.

After surgery: If you’ve had a radical prostatectomy, radiation therapy might be an option, sometimes along with hormone therapy.

After radiation therapy: If your first treatment was radiation, treatment options might include cryotherapy or radical prostatectomy, but when these treatments are done after radiation, they carry a higher risk for side effects such as incontinence. Having radiation therapy again is usually not an option because of the increased potential for serious side effects, although in some cases brachytherapy may be an option as a second treatment after external radiation.

Sometimes it might not be clear exactly where the remaining cancer is in the body. If the only sign of cancer recurrence is a rising PSA level (as opposed to the cancer being seen on imaging tests), another option for some men might be active surveillance instead of active treatment. Prostate cancer often grows slowly, so even if it does come back, it might not cause problems for many years, at which time further treatment could then be considered.

Factors such as how quickly the PSA is going up and the original Gleason score of the cancer can help predict how soon the cancer might show up in distant parts of the body and cause problems. If the PSA is going up very quickly, some doctors might recommend that you start treatment even before the cancer can be seen on tests or causes symptoms.

Observation might be a more appealing option to certain groups of men, such as those who are older and in whom the PSA level is rising slowly. Still, not all men might be comfortable with this approach.

If the PSA is rising quickly enough to warrant treatment, but localized treatments (such as surgery, radiation therapy, or cryotherapy) aren’t likely to be helpful, hormone therapy is often the next option. If one type of hormone therapy isn’t helpful, another can be tried (see castrate-resistant prostate cancer, below). 

Cancer that clearly has spread

If the cancer has spread outside the prostate, it will most likely go to nearby lymph nodes first, and then to bones. Much less often the cancer will spread to the liver or other organs.

When prostate cancer has spread to other parts of the body (including the bones), hormone therapy is probably the most effective treatment. But it isn’t likely to cure the cancer, and at some point it might stop working. Usually the first treatment is a luteinizing hormone-releasing hormone (LHRH) agonist, LHRH antagonist, or orchiectomy, sometimes along with an anti-androgen drug or abiraterone. Another option might be to get chemotherapy, most often along with the hormone therapy. Other treatments for bone metastases  might be used as well.

Castrate-resistant and hormone-refractory prostate cancer

Hormone therapy is often very effective at shrinking or slowing the growth of prostate cancer that has spread, but it usually becomes less effective over time. Doctors use different terms to describe cancers that are no longer responding to hormones.

• Castrate-resistant prostate cancer (CRPC) is cancer that is still growing despite the fact that hormone therapy (an orchiectomy or an LHRH agonist or antagonist) is keeping the testosterone level in the body as low as what would be expected if the testicles were removed (called castrate levels). The cancer might still respond to other forms of hormone therapy, though.
• Hormone-refractory prostate cancer (HRPC) is cancer that is no longer helped by any form of hormone therapy.

Men whose prostate cancer is still growing despite initial hormone therapy now have many more treatment options than they had even a few years ago.

If an anti-androgen drug was not part of the initial hormone therapy, it is often added at this time. If a man is already getting an anti-androgen but the cancer is still growing, stopping the anti-androgen (while continuing other hormone treatments) seems to help sometimes.

Other forms of hormone therapy may also be helpful for a while, especially if the cancer is causing few or no symptoms. These include abiraterone (Zytiga), enzalutamide (Xtandi), apalutamide (Erleada), darolutamide (Nubeqa), ketoconazole, estrogens (female hormones), and corticosteroids.

The prostate cancer vaccine sipuleucel-T (Provenge) is another option for men whose cancer is causing few or no symptoms. This might not lower PSA levels, but it can often help men live longer.

For cancers that are no longer responding to initial hormone therapy and are causing symptoms, several options might be available. Chemotherapy with the drug docetaxel (Taxotere) is often the first choice because it has been shown to help men live longer, as well as to reduce pain. If docetaxel doesn’t work or stops working, other chemo drugs, such as cabazitaxel (Jevtana), may help.

Other options at some point might include:

• Immunotherapy with pembrolizumab (Keytruda), if the cancer is has certain gene changes (MSI-H or dMMR)
• A different type of hormone therapy, such as abiraterone, enzalutamide, or apalutamide (if they haven’t been tried yet)
• The radiopharmaceutical lutetium Lu 177 vipivotide tetraxetan (Pluvicto), if the cancer cells have the PSMA protein
• A targeted therapy drug, such as rucaparib (Rubraca) or olaparib (Lynparza), possibly along with hormone therapy, if the cancer cells have a BRCA gene mutation

Bisphosphonates or denosumab can often help if the cancer has spread to the bones. These drugs can reduce pain and even slow cancer growth in many men. Other medicines and methods can also help keep pain and other symptoms under control. External radiation therapy can help treat bone pain if it’s only in a few spots. Radiopharmaceutical drugs can often reduce pain if it’s more widespread, and may also slow the growth of the cancer.

If you are having pain from prostate cancer, make sure your doctor and health care team know about it. 

Several promising new medicines are now being tested against prostate cancer, including vaccines, monoclonal antibodies, and other new types of drugs. Because the ability to treat hormone-refractory prostate cancer is still not good enough, men are encouraged to explore new options by taking part in clinical trials.