Biomarkers, targeted and immunotherapies for prostate cancer

This section covers the following topics:

• Genetic testing for inherited mutations for treatment selection
• Tumor biomarker testing for treatment selection 
• Immunotherapy
• Targeted therapy

Genetic tests for inherited mutations for treatment selection

Any person diagnosed with mCRPC meets national guidelines for genetic testing for an inherited mutation. Genetic testing may be used to guide treatment selection.  

• Men with mCRPC who test positive for an inherited mutation in BRCA1, BRCA2, ATM, CHEK2, PALB2 or other gene linked to a certain type of DNA damage repair may benefit from a type of targeted therapy known as a PARP inhibitor. 
• Men who test positive for an inherited mutation linked to Lynch syndrome, may benefit from the immunotherapy pembrolizumab (Keytruda). 

Biomarker tests

Biomarker tests look at samples of blood, tumor or other tissue for changes or abnormalities caused by cancer. These tests can give doctors clues about the cancer, including:

• how fast the cancer is growing
• which treatments are most likely to work
• whether or not the cancer is responding to treatment or growing
• whether or not the cancer has come back after remission

Biomarkers for treatment selection

Biomarker tests may be used to select treatments, and help patients avoid side effects from treatments that will not work for them. Biomarker tests used to select a specific treatment are sometimes called "companion diagnostic tests." These tests may be done on tumor tissue or (in many cases) on blood. See our Biomarker Testing section for more information. 

Experts recommend biomarker testing for prostate cancer based on risk groups.

• Men with low and favorable-intermediate-risk prostate cancer and a life expectancy of > 10 years should consider multi-gene tumor testing. Multi-gene tumor testing can help predict how aggressive the prostate cancer is and guide treatment.
  • Prostate multi-gene tumor tests include Decipher, Oncotype DX Prostate, Prolaris and ProMark.
• Men with regional or metastic prostate cancer should consider tumor testing for:
  • An abnormality known as homologous recombination deficiency (HRD).
    • If tumor mutations in BRCA1, BRCA2, PALB2, ATM or CHEK2 are found, patients should be considered for referral for genetic counseling and testing for an inherited mutation. 
  • An abnormality known as “microsatellite instability" (MSI-H or MSI-high) also known as "mismatch repair deficiency" (dMMR or MMR-D).
    • MSI-high cancers are common in people with a Lynch syndrome gene mutations. People with advanced/metastatic MSI-high prostate cancer may respond well to an immunotherapy agent. 
• Additional biomarker tests that may be used for metastic castration-resistant prostate cancer (mCRPC) include AR-V7 testing. AR-V7 stands for Androgen Receptor Variant 7.  AR-V7 is a blood test that looks for a form of the androgen receptor that makes androgen therapy less effective. AR-V7 testing can help identify patients who would not benefit from androgen receptor therapies.

Immunotherapies 

Immunotherapies are cancer treatments that help the body’s immune system detect and attack cancer cells. 

• Immune checkpoint inhibitors are a type of immunotherapy most often used to treat advanced/metastatic prostate cancer that have MSI-H or dMMR; usually after other treatments have been tried.
  • Keytruda (pembrolizumab) may be used to treat patients with castration resistant prostate cancer that is MSI-H or dMMR and have had one line of therapy affecting the whole body.
• Cancer treatment vaccines are a type of immunotherapy that uses a patient’s own cancer cells to boost their immune system.
  • Provenge (sipuleucel-T) may be used to treat patients with metastatic prostate cancer whose disease has progressed aftger hormonal treatment who have either no or very minimal symptoms related to the prostate cancer.

Targeted therapies

The PARP inhibitor, Lynparza (olaparib) has received FDA-approval to treat mCRPC after the cancer has progressed on the drugs enzalutamide (Xtandi) or abiraterone (Zytiga) in people with a mutation in BRCA1, BRCA2, ATM or other gene linked to a certain type of DNA damage repair.

The PARP inhibitor, Rubraca (rucaparib) has received FDA-approval to treat mCRPC, in people who have an inherited mutation in BRCA1 or BRCA2 (found through genetic testing) or a tumor mutation in BRCA1 or BRCA2 (found through tumor testing or liquid biopsy). 

Table of targeted and immunotherapies for prostate cancer