Epidemiology and Prognosis – In 2021, prostate cancer accounted for 26% of new non-cutaneous cancer cases and 11% of cancer-related deaths in the United States.
It is the most common malignancy in men and the second leading cause of cancer mortality.
Following diagnosis of metastatic disease, prostate cancer is uniformly fatal with a five-year survival of about 30%.
About 10% of prostate cancer patients present with de novo metastatic disease with a five-year survival rate near 37%.
Five-year survival varies: – 30% with testosterone suppression for patients with ≥4 bone or liver metastases. – 70% for metachronous low-volume disease.
The incidence of metastatic prostate cancer has increased across all races and age groups in the past decade.
Treatment Foundations Androgen deprivation therapy (ADT), surgical or pharmaceutical, is the cornerstone treatment for prostate cancer and typically lifelong for metastatic disease.
ADT monotherapy has been replaced by combination treatment (ADT *plus* additional agents such as docetaxel, abiraterone, enzalutamide, or darolutamide) for metastatic castrate-sensitive prostate cancer (mCSPC).
Common adverse effects: sexual dysfunction, cardiovascular disease, diabetes, cognitive decline, and bone density loss.
Evidence from Clinical Trials CHAARTED and STAMPEDE trials demonstrated improved overall survival adding docetaxel to ADT in high-volume mCSPC.
Long-term ADT combined with external beam radiation therapy (EBRT) improves disease-free and 15-year overall survival versus short-term ADT.
Disease Progression – 90% of men with metastatic prostate cancer initially respond to ADT; median response duration: 18–24 months. – 10% exhibit primary ADT resistance. – Most eventually develop castration-resistant prostate cancer (mCRPC). – In non-metastatic castrate-resistant prostate cancer (nmCRPC), PSA rises without radiographic metastases.
Metastasis-free survival ≈ 30 months. 33% develop metastases within 2 years.
Patients with higher degree of circulating tumor cells have shorter survival.
Advanced and Combination Therapies Treatment categories:
Androgen Deprivation Therapy (ADT): Agents: Leuprolide, Goserelin, Degarelix, Histrelin, Triptorelin.
Chemotherapy: Docetaxel, Cabazitaxel, Mitoxantrone. Androgen Receptor Pathway Inhibitors (ARPIs):** – Abiraterone, Enzalutamide, Apalutamide, Darolutamide.
PARP Inhibitors:** Used with ARPIs in patients with homologous recombination repair mutations.
Immunotherapy:** Sipuleucel-T (autologous cellular therapy).
Radiopharmaceuticals: – Radium-223, Lutetium Lu-177 (PSMA-targeted).
Key Drug Profiles | Class | Drug | Dose
| GnRH agonist | Leuprolide acetate (Lupron Depot) | 7.5–45 mg IM/SC depending on formulation | | GnRH antagonist | Degarelix (Firmagon) | 240 mg loading, then 80 mg monthly SC | | ARPI | Abiraterone (Zytiga) | 1 g daily + prednisone 5 mg bid | | ARPI | Enzalutamide (Xtandi) | 160 mg daily | | ARPI | Apalutamide (Erleada) | 240 mg daily | | Chemotherapy | Docetaxel (Taxotere) | 75 mg/m² q3wk | | Chemotherapy | Cabazitaxel (Jevtana) | 25 mg/m² q3wk + prednisone | | Radiotherapy Agent | Radium-223 dichloride | IV for mCRPC post-ARPI/taxane | | Immunotherapy | Sipuleucel-T (Provenge) | 3 infusions every 2 weeks |
Combination or triplet therapy (ADT + ARPI + Docetaxel) yields the best survival outcomes in high-volume, high-risk, or de novo metastatic disease.
-The *Arensas trial showed significant overall survival benefit with darolutamide + ADT + docetaxel versus placebo.
– For high-risk localized disease, combining ADT with radiation improves mortality outcomes.
NM-CRPC patients are commonly managed with ARPIs to delay metastasis.
Complications – Urinary: incontinence, obstruction. – Sexual: impotence, loss of ejaculation. – Radiation-related: cystitis, proctitis, secondary bladder or colorectal cancer. – Long-term radiotherapy increases bladder cancer risk 3-fold and radiation cystitis/proctitis risk over 100-fold.