Novel Hormonal Agents for Metastatic Castration-Resistant Prostate Cancer

First-line Treatment Options

For patients with recurrent metastatic castration-resistant prostate cancer (mCRPC), the most effective treatment approach is to use novel hormonal agents such as abiraterone acetate with prednisone, enzalutamide, or apalutamide, depending on prior therapy received. 1, 2, 3
The National Comprehensive Cancer Network (NCCN) recommends abiraterone acetate 1,000 mg daily with prednisone 5 mg twice daily until disease progression as a Category 1 recommendation for patients who have not received prior novel hormonal therapy. 3, 4
Enzalutamide 160 mg daily is an alternative first-line option for mCRPC patients who have not received prior novel hormonal therapy. 2, 5
Both abiraterone and enzalutamide have demonstrated significant improvement in overall survival and radiographic progression-free survival in high-quality evidence from randomized controlled trials. 2, 3

The NCCN guidelines recommend continuing androgen deprivation therapy (ADT) indefinitely to maintain castrate levels of testosterone (<50 ng/dL) even during disease progression. 1, 3
For patients with bone-predominant symptomatic disease who have progressed on both novel hormonal agents and docetaxel, Radium-223 is recommended as a treatment option. 3
When using abiraterone, clinicians should monitor blood pressure, potassium levels, liver function, and cardiac status due to risk of hypertension, hypokalemia, hepatotoxicity, and cardiac disorders. 3
For patients on enzalutamide, monitoring should include assessment for fatigue, diarrhea, hot flashes, and seizure risk (reported in 0.9% of patients). 1
A common pitfall to avoid is failing to continue ADT during progression and subsequent therapies. 1, 3

The European Society for Medical Oncology (ESMO) guidelines recommend adding an androgen receptor inhibitor (anti-androgen) as a second-line hormonal manipulation for patients progressing on castration 6, 7, 8, 9
The American Urological Association and other major guidelines also support continuing androgen deprivation therapy (ADT) indefinitely, even when adding additional therapies, to maintain castrate testosterone levels 6, 7, 8, 9

The ESMO guidelines specifically state that subsequent hormonal manipulation options include addition of an androgen receptor inhibitor (anti-androgen) 6, estrogen 8, ketoconazole 6, and steroids 6, 7, 8, 9
The National Comprehensive Cancer Network (NCCN) recommends verifying castrate testosterone levels (<50 ng/dL) before labeling as castration-resistant prostate cancer (CRPC) and proceeding with treatment intensification 6, 7, 8

Regular monitoring of serum testosterone, PSA levels, and imaging is essential to assess response to treatment and adjust the treatment plan as needed 6, 7, 8
The ESMO guidelines recommend considering an anti-androgen withdrawal trial if PSA rises despite adding an anti-androgen, as some patients may experience PSA reduction and clinical improvement from this phenomenon 6, 7

For non-metastatic CRPC, traditional anti-androgens like bicalutamide 50 mg daily can be added to ongoing ADT 6, 7
Bicalutamide competitively inhibits androgen receptors and is well-established in combination with LHRH agonists, with common side effects including gynecomastia and breast pain 6, 7