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

If you’ve been treated for prostate cancer and your PSA (prostate-specific antigen) blood level or another test shows that your prostate cancer has not been cured or has come back (recurred), further treatment can often still be helpful.

Follow-up treatment will depend on where the cancer is thought to be, what treatments you’ve already had, and other factors. Imaging tests (such as MRI, PET scans, or bone scans) or biopsies may be done to get a better idea about where the cancer is and which treatments are most likely to be helpful.

Cancer that is thought to still be in or around the prostate (or that isn’t seen on imaging tests)

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

If you’ve had a radical prostatectomy, radiation therapy to the area where the prostate was might be an option, sometimes along with hormone therapy, which might include a newer hormone drug such as abiraterone.

If your first treatment was radiation, treatment options might include surgery (radical prostatectomy) or some type of ablative therapy, such as cryotherapy or high-intensity focused ultrasound (HIFU). However, when these treatments are done after radiation, they carry a higher risk for side effects such as incontinence. Getting radiation therapy again might not be a good option because of the increased risk of serious side effects, although in some cases brachytherapy may be an option as a second treatment after external radiation.

Sometimes when the cancer doesn’t go away (or when it comes back) after the first treatment, it might not be clear exactly where the remaining cancer is in the body. If the only sign of cancer is a biochemical recurrence (a rising PSA level alone, without cancer being seen on imaging tests), another option for some men might be observation instead of 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 rising 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 your PSA is going up very quickly, some doctors might recommend starting treatment even before the cancer can be seen on tests or causes symptoms.

Observation might be more appealing if you are older and your PSA level is rising slowly. Still, not all men might be comfortable with this approach.

If your PSA is rising quickly enough to warrant treatment, but localized treatments, such as surgery, radiation therapy, or ablative therapy, aren’t likely to be helpful, hormone therapy with a drug such as enzalutamide is often the next option. If one type of hormone therapy isn’t helpful, another can be tried. See “Androgen pathway modulation-resistant prostate cancer,” below.

Cancer that has reached nearby areas

If tests show that the cancer has spread to the pelvic area but hasn’t yet spread to other parts of the body, treatment options will likely depend on what type of treatment you’ve had.

If you’ve had a radical prostatectomy, radiation therapy to the pelvic area might be an option, typically along with hormone therapy, which might include a newer hormone drug such as abiraterone.

If your first treatment was radiation, treatment options might include hormone therapy or monitoring the cancer and then treating it with hormone therapy if it becomes necessary. Other options for some men might include surgery to remove the pelvic lymph nodes (pelvic lymph node dissection, or PLND) or radiation to the pelvic lymph nodes, if it hasn’t been done already.

Cancer that has spread to other parts of the body

If the cancer has spread to other parts of the body, it will most likely go to the bones or other lymph nodes outside of the pelvis first. Much less often, the cancer might spread to the liver or other organs.

When prostate cancer has spread to other parts of the body (including the bones), hormone therapy is usually the preferred treatment. Although it’s often very effective for a time, it isn’t likely to cure the cancer, and at some point it might stop working. Usually, the first hormone treatment is a luteinizing hormone-releasing hormone (LHRH) agonist (often along with a first-generation anti-androgen), LHRH antagonist, or orchiectomy. It might be used:

• Along with a newer hormone drug, such as abiraterone, apalutamide, or enzalutamide
• Along with a chemotherapy drug (usually docetaxel) and a newer hormone drug, such as abiraterone or darolutamide
• Along with niraparib (a PARP inhibitor) and abiraterone, for men whose cancer cells have a change in the BRCA2 gene
• Along with capivasertib (an AKT inhibitor) and abiraterone, for men whose cancer cells have lost the PTEN gene
• By itself

For tumors in the bones, other treatments aimed at bone metastases might be used as well.

Androgen pathway modulation-resistant 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.

• Androgen pathway modulation-resistant prostate cancer (APMR), also called castration-resistant prostate cancer (CRPC), is cancer that is still growing even when an orchiectomy or an LHRH agonist or antagonist is keeping the testosterone level in the body at castrate levels (the level that would be expected if the testicles were removed). The cancer might still respond to other forms of hormone therapy, though.

Men with prostate cancer that is still growing despite initial hormone therapy (CRPC) now have many more treatment options than they had in the past.

If the prostate cancer cells haven’t been tested for gene or protein changes that might affect treatment options, that might be done at this time.

If a first-generation anti-androgen (flutamide, bicalutamide, or nilutamide) was not part of the initial hormone therapy, it may be added at this time. If you are already getting an anti-androgen but the cancer is still growing, stopping the anti-androgen (while continuing other hormone treatments) seems to help sometimes.

One of the newer hormone drugs may be added to the existing hormone therapy, especially if the cancer is causing few or no symptoms. These include abiraterone (Zytiga), enzalutamide (Xtandi), apalutamide (Erleada), and darolutamide (Nubeqa). Other, less commonly used options might include ketoconazole, estrogens (female hormones), and corticosteroids.

If the cancer is causing few or no symptoms, the prostate cancer vaccine sipuleucel-T (Provenge) is another option. 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. If it hasn’t been used already, chemotherapy with the drug docetaxel 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, may help.

Depending on which treatments a man has had, other options at some point might include:

• A different type of hormone therapy, such as abiraterone or enzalutamide, 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, typically along with hormone therapy, if the cancer cells have a change (mutation) in a DNA repair gene such as BRCA1 or BRCA2. Options include rucaparib (Rubraca), olaparib (Lynparza), talazoparib (Talzenna), and niraparib plus abiraterone (Akeega).
• Immunotherapy with pembrolizumab (Keytruda) or dostarlimab (Jemperli), if the cancer cells have certain gene changes (MSI-H, dMMR, or high TMB).

Several types of treatment might be helpful if cancer has spread to the bones. These include:

• Drugs that affect bone cells, such as bisphosphonates or denosumab
• External radiation therapy (including stereotactic body radiation therapy, or SBRT), especially if there are only a few bone tumors
• Radiopharmaceutical drugs, which can often be helpful if the cancer is more widespread
• Ablative treatments that focus extreme heat or cold on bone tumors to ablate (destroy) them, if there are only a few tumors, especially if radiation isn’t helpful

Many medicines can also help relieve pain. If you are having pain from prostate cancer, make sure your cancer care team knows about it.

Several promising new medicines are now being tested against androgen pathway modulation-resistant prostate cancer. Because these cancers can become hard to treat, men with these cancers might want to consider exploring new options by taking part in clinical trials.