Treatment for Metastatic Prostate Cancer

For metastatic prostate cancer, commonly used treatments include hormonal therapy, chemotherapy, and novel hormonal agents. However, after using these treatments for a while, prostate cancer may become increasingly uncontrollable.

PARP Inhibitors

For uncontrollable metastatic prostate cancer, PARP inhibitors are the urologist’s new weapon!

PARP inhibitors interfere with cellular DNA repair, causing DNA damage and ultimately leading to cell death.

In normal body cells, even when DNA repair is interfered with by PARP inhibitors, there are other backup DNA repair mechanisms that maintain normal cell function. In contrast, research indicates that the backup DNA repair mechanisms in castration-resistant metastatic prostate cancer cells seem to already be mutated (such as common mutations in the BRCA1/2 tumor suppressor genes). After using PARP inhibitors, further interference with DNA repair in cancer cells ultimately leads to their deaths.

Phase III Clinical Trials in Western Countries:

PARP inhibitors alone (PROfound trial):

1. Metastatic prostate cancer
2. Previously treated with hormonal therapy but now castration-resistant
3. No restriction on whether chemotherapy has been used
4. Previously treated with novel hormonal agents
5. Only patients with mutated DNA repair genes are included.

• Results: For patients who experienced progression after novel hormonal agents, if genetic testing reveals mutations in BRCA1, BRCA2, or ATM genes, using PARP inhibitors can extend survival.

Combination of PARP inhibitors and novel hormonal agents (ASCO GU 2023 PROpel update):

1. Metastatic prostate cancer
2. Previously treated with hormonal therapy but now castration-resistant
3. No restriction on whether chemotherapy has been used
4. Not previously treated with novel hormonal agents
5. Patients with normal or mutated DNA repair genes are included

• Results: With combination of PARP inhibitors and novel hormonal agents, the average survival time was nearly four years (42.1 months), the longest among studies of first line treatment for metastatic castration resistant prostate cancer to date.

Common adverse events:

Patients may experience side effects such as anemia, fatigue, nausea, loss of appetite, diarrhea, and decreased platelet count after using the drug. It is recommended to have regular blood tests to monitor blood cell counts and liver/kidney function, especially during the initial stages of medication use.