Updated NCCN guidelines for the treatment of advanced prostate cancer

This study reviewed the current NCCN guidelines for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC).

Metastatic castration-resistant prostate cancer (mCRPC) is an aggressive form of PC that has spread and is no longer responsive to hormonal therapy such as androgen deprivation therapy (ADT). mCRPC is associated with poor outcomes. Testosterone is a male sex hormone (androgen) that triggers PC growth. A reduction in testosterone levels usually results in decreased PCa growth. However, mCRPC continues growing despite a drastic reduction of testosterone levels.

This review by the National Comprehensive Cancer Network (NCCN) was conducted to update guidelines and recommendations for the treatment of mCRPC.

Men with metastatic castration-naïve prostate cancer (mCNPC) are the ones without prior ADT and are responsive to ADT. For such patients, ADT can be given in combination with either abiraterone (Zytiga), prednisone (Deltasone), apalutamide (Erleada), or enzalutamide (Xtandi). For men with mHNPC who are unfit for the aforementioned drugs, ADT can be given alone. These anti-androgen drugs reduce the levels of androgens in the body and showed improved overall survival, progression-free survival, and metastasis-free survival.

CRPC defines cancer which is unresponsive to ADT. In men with CRPC that has not spread (non-metastatic), apalutamide, darolutamide (Nubeqa), or enzalutamide are recommended. Patients with mCRPC can benefit from cabazitaxel (Jevtana) treatment as it improved outcomes compared to abiraterone or enzalutamide.

Tumors found in mCRPC often have mixed genetic abnormalities. BRCA1/BRCA2 genes block the rapid and uncontrolled growth of cells, therefore the formation of tumors. The ATM gene sends signals to cells to control the rhythm they grow and divide. Abnormalities in these genes lead to the formation of tumors. Olaparib (Lynparza) is a targeted therapy that blocks a protein called PARP, which helps damaged cells to repair themselves. Therefore, olaparib keeps cancer cells from repairing themselves which eventually causes them to die.

It is now also recommended to use olaparib (Lynparza) as an option for men with mCRPC, and certain genetic abnormalities in at least 1 of 14 genes (BRCA1, BRCA2, ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, RAD51B, RAD51C, RAD51D, or RAD54L) and who had previously received treatment with enzalutamide or abiraterone.

Rucaparib (Rubraca) is another PARP inhibitor approved for the treatment of mCRPC. It may be recommended for men with mCRPC with prior exposure to abiraterone or enzalutamide and a BRCA1 or BRCA2 mutation. Rucaparib should not be used in patients with gene abnormalities other than BRCA1/2.

This review provided updates to the NCCN guidelines for the treatment of mCRPC.