Nonmetastatic castration resistant Prostate cancer

Defined as prostate cancer with rising PSA level in the setting of castrate serum testosterone level of less than 50ng/dL in the absence of visible disease spread, following initial definitive therapy.

Castration resistant prostate cancer (CRPC) defined as a rising level of PSA in the setting of castrate levels of testosterone of less than 50 ng/dL is defined as a level that is more than 2 ng/mL higher than the nadir and 25% of more over the nadir, which is confirmed by a second test at least three weeks after the first one.

If no metastases are apparent on radiologic imaging the designation is nonmetastatic CRPC, MO.

About 1/3 of patients with nmCRPC develop metastatic disease within one year.

A PSA doubling time of less than 10 months puts patients at very high risk for developing metastases.

Only two factors are known  to predict for the time to onset of metastasis and the nonmetastatic castration resistant prostate cancer: PSA doubling time of less than three months has a median time to metastasis of approximately nine months; If PSA doubling time is longer than 15 months the time to metastasis is longer than four years.

Shorter  PSA doubling time is associated with reduced bone metastasis free  survival time among patients with nmPRPC.

Preventing or delaying progression to metastatic CRPC prolongs  patient survival and improved quality of life.

For patients with doubling times greater than 10 months continued monitoring is indicated.

Subsequently the addition of next generation androgen receptor  inhibitors are indicated.

Treatments for nmPRPC include apalutamide enzalutamide, and darolutamide.

These androgen receptor inhibitors act by competitively inhibiting antigen binding, antigen receptor nuclear translocation, and androgen receptor mediated transcription.

These androgen receptor inhibitors approved for nonmetastatic call prostate cancer improve metastasis free survival an overall survival and appear to have similar efficacy.

These androgen receptor inhibitors prolong metastatic free survival by approximately two years.

Approximately 80% will develop metastatic disease within three years.

In this sitting next generation AR inhibitors  approved include apalutamide, enzalutamide, and darolutamide.

The addition of these agents have demonstrated overall survival benefit with approximately one year of life gained, and preserved quality of life.

The studies associated with the  demonstration of AR inhibitors are the SPARTAN, PROSPER, and ARAMIS trails.


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