Medical Therapy for Prostate Cancer

Medical therapy uses drugs and other anti-cancer agents to fight cancer. For prostate cancer, the primary medical therapy is a treatment called androgen deprivation therapy (ADT) which blocks the hormone testosterone. Because testosterone fuels prostate cancer, blocking this hormone is essential for the successful treatment of prostate cancer.

Additional therapies, such as chemotherapy, immunotherapy, targeted therapy, and radiopharmaceuticals are always used in addition to ADT. Medical therapies for prostate cancer are typically used after surgery or radiation to improve cure rates or to treat disease that has:

  • recurred after initial surgery and/or radiation, or
  • spread beyond the prostate gland (metastatic disease)

Androgen deprivation therapy

Androgen deprivation therapy (ADT), also called hormone therapy, typically involves blocking testosterone production from the testes, the primary source of testosterone in the body with drugs called luteinizing hormone-releasing hormone (LHRH) agonists (such as Lupron or Zoladex injections) or LHRH antagonists (such as Degarelix injections). Patients on LHRH therapy will continue this treatment even if additional treatment are added in.

In metastatic disease, it is important to block other sources of testosterone as well, such as the adrenal glands and the cancer itself.

More about hormone therapy

Chemotherapy for prostate cancer

Chemotherapy is an option for patients with metastatic prostate cancer, where the cancer has spread to the lymph nodes and bones.  Chemotherapy is used in conjunction with LHRH therapy when the latter is insufficient to control further spread of the cancer on its own. While chemotherapy is not expected to destroy all the cancer cells, it may shrink the cancer or slow its growth and reduce pain.

Chemotherapy uses drugs that are injected or infused through a vein to kill cancer cells. Unfortunately, these drugs also damage some normal cells. The chemotherapy dose must be high enough to kill the cancer cells but not high enough to destroy too many healthy cells. Your physician team will adjust your chemotherapy to maximize efficacy and minimize toxicity.  The two most commonly used chemotherapy agents in prostate cancer are docetaxel (Taxotere) and cabazitaxel (Jevtana). These two agents are effective against adenocarcinoma of the prostate – the most common type of prostate cancer.  However, 1 to 2% of men can also develop “small cell” cancer of the prostate. This kind of cancer is aggressive, spreads rapidly, and is best treated with other, platinum-based chemotherapy drugs.

Immunotherapy for prostate cancer

Immunotherapy is a type of cancer treatment approach that seeks use the body’s immune system to fight against the cancer. Immunotherapy for prostate cancer may involve:

  • A prostate cancer vaccine. Sipuleucel-T (Provenge), was the first FDA-approved therapeutic cancer vaccine. This treatment vaccine may be part of your prostate cancer therapy if your cancer has metastasized (spread) outside the prostate to other parts of your body, and/or your PSA continues to rise even though you are on hormone therapy, such as LHRH therapy.

How it works

Some of your immune cells are collected in a process called leukapheresis, which is similar to a blood donation. The cells are then sent to a laboratory, where a special antigen, or protein, called prostatic acid phosphatase (PAP), is added to them to help teach your immune cells to recognize and kill cancer cells. PAP is a protein made only by the prostate. Thus these “educated immune cells” creates a personalized vaccine which kills cells that make PAP.  Since PAP is almost exclusive to the prostate, this vaccine kills prostate cancer. Sipuleucel-T (Provenge) is given intravenously (through an IV) in three doses, about two weeks apart and works best in tumors that grow slowly.

  • Checkpoint inhibitors. Recently it has also been recognized that men with Lynch syndrome have a five-fold increased risk of developing prostate cancer. Lynch syndrome is caused by a mutation in one of the mismatch repair (MMR) genes, MLH1, MSH2, MSH6, or PMS2.  Absence and/or lack of function of these proteins leads to lack of MMR function, causing accumulation of mutations.  It is these mutations, however, that make the cancer susceptible to a new class of immunotherapy drugs called checkpoint inhibitors, such as pembrolizumab (Keytruda), which is FDA approved for any cancer with MMR deficiency. Keytruda is effective in 2 to 3% of men with advanced prostate cancer.  Thus, men with advanced prostate cancer should have their tumors tested for a possible benefit from treatment with checkpoint inhibitors.

Targeted therapy for prostate cancer

It is now well recognized that as we treat advanced prostate cancer, the tumor DNA can undergo alterations, which can create further therapeutic opportunities.  The tumor DNA can be tested by doing a tumor biopsy (where possible) or by sampling the blood, a so-called “liquid biopsy.”  In up to 15 to 20% of men with advanced prostate cancer, the above biopsies can reveal an “actionable mutation.” The most commonly recognized mutation is a defect in repairing errors that develop in DNA, also called DNA-deficient repair (DDR). 

Currently, two FDA-approved drugs, olaparib (Lynpraza) and rucaparib (Rubraca) for treatment of patients with DDR. The normal DNA repair apparatus involves a number of different genes and proteins. The most commonly altered proteins include BRCA2, BRCA 1, ATM, and CHEK2. If your tumor has alterations in these DNA repair proteins, both olaparib and rucaparib, which are PARP inhibitors, can assist in killing cancerous cells. Analyzing tumor DNA can reveal other genetic abnormalities for which other targeted therapies, including drugs currently in clinical trials, may be useful against your cancer.

Radiopharmaceuticals for prostate cancer

Radiopharmaceuticals are a growing and promising area of therapeutics in prostate cancer and will likely change prostate cancer treatment over the next decade.  Radiopharmaceuticals are drugs that carry a radioactive substance or isotope. Some of them are able to find and latch onto cancer cells by homing in on a specific protein, receptor or other biomarker, similar to how targeted therapy drugs work. Once the drug finds the targeted cells, the radiation begins to kill the targeted cells.

Currently there are two FDA-approved radiopharmaceuticals for the treatment of prostate cancer:

  • Pluvicto™ (lutetium Lu 177 vipivotide tetraxetan) is a radiopharmaceutical that homes in on prostate cancer cells that have a biomarker called prostate-specific membrane antigen. The drug attaches to and is absorbed by the PSMA-positive cells where the drug then releases radiation that can damage and kill them. Your physician team will determine whether your prostate cancer cells are PSMA-positive with a specialized PSMA-PET scan. Pluvicto is used for patients with metastatic castration-resistant prostate cancer that is PSMA-positive. It is administered as an intravenous infusion, every six weeks for a maximum of six treatments. Pluvicto is considered a theranostic treatment, a rapidly growing type of cancer treatment.
  • Xofigo (radium Ra 223 dichloride) is an injection used to treat prostate cancer that no longer responds to LHRH therapy alone.  This drug goes to the bone and releases radiation there, killing the cancer cells in the bone. This treatment is used in patients whose prostate cancer has spread to the bone with symptoms but not to other parts of the body. The injection is given every 6 weeks for a maximum of 6 doses.

Theranostics — a new frontier in prostate cancer treatment

This promising approach — using new radiopharmaceuticals to target cancer cells and deliver radiation directly to the cell — is a rapidly growing field called Theranostics. Roswell Park is at the forefront of this work and has offered Theranostic treatments to patients for years for the treatment of certain neuroendocrine and adrenal tumors. In addition to Pluvicto, a number of other radiopharmaceuticals to target other prostate-specific proteins are in development.

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