Prostate Cancer

1. Definition

• Prostate cancer is a malignant tumor of the prostate gland, arising primarily from prostate epithelial cells (most often adenocarcinoma).
• It is the most common non-cutaneous cancer in men and a leading cause of cancer-related death.

2. Risk Factors

• Age: Incidence rises after 50 years.
• Race/Ethnicity: Higher risk in African-Caribbean men; lower in Asian men.
• Family history: BRCA1/2, HOXB13 mutations.
• Genetics: gBRCA2 especially linked to aggressive disease.
• Lifestyle: High-fat diet, obesity, low physical activity.

3. Pathophysiology

• Driven by androgen signaling (testosterone → dihydrotestosterone → androgen receptor activation).
• Disease progression:
  1. Localized (organ-confined).
  2. Locally advanced (capsular penetration, seminal vesicle involvement).
  3. Metastatic (bone is the most common site, especially axial skeleton).
  4. Castration-resistant prostate cancer (CRPC): Tumor grows despite castrate levels of testosterone (<50 ng/dL).

4. Clinical Features

• Early stages often asymptomatic (detected via PSA screening or digital rectal exam).
• Later: urinary obstruction, hematuria, bone pain (metastasis), weight loss.

5. Diagnosis & Staging

• PSA (Prostate Specific Antigen): Used for screening, monitoring, recurrence.
• Biopsy: Confirmatory, graded with Gleason Score / ISUP Grade Groups.
• Staging: TNM system + PSA + Gleason score.
• Imaging: MRI, bone scan, PSMA PET-CT (in advanced cases).

6. Pharmacologic Management

a. Hormonal Therapy (Androgen Deprivation Therapy – ADT)

• LHRH agonists: leuprolide, goserelin.
• LHRH antagonists: degarelix, relugolix (oral).
• Antiandrogens: bicalutamide, flutamide, nilutamide (used less often now).
• Next-generation androgen receptor inhibitors (ARIs): enzalutamide, apalutamide, darolutamide.
• CYP17 inhibitor: abiraterone (blocks androgen synthesis, given with prednisone).

b. Chemotherapy

• Docetaxel: Standard in metastatic hormone-sensitive & castration-resistant disease.
• Cabazitaxel: Second-line after docetaxel.

c. Targeted / Radiopharmaceuticals

• PARP inhibitors: olaparib, rucaparib (for BRCA-mutated disease).
• Radium-223: Alpha-emitter for bone-predominant metastatic CRPC (not for visceral mets).
• PSMA-directed therapy: Lutetium-177-PSMA (recently approved).

d. Immunotherapy

• Sipuleucel-T: Autologous cellular vaccine (limited use).
• Checkpoint inhibitors: Pembrolizumab (MSI-H/dMMR tumors).

7. Supportive & Palliative Considerations

• Bone health: ADT → osteoporosis → denosumab or zoledronic acid for bone metastases.
• Hot flashes, metabolic syndrome, CV risk: Associated with ADT.
• Pain management: Opioids, bisphosphonates, palliative RT.

8. Monitoring & Pharmacist Role

• PSA & Testosterone levels (treatment response, progression).
• Adherence to oral agents (e.g., abiraterone, enzalutamide, relugolix).
• Drug interactions:
  • Abiraterone: CYP3A4 substrate, requires prednisone.
  • Enzalutamide/apalutamide: strong CYP inducers (affects anticoagulants, anticonvulsants).
• Toxicity monitoring:
  • Docetaxel → neutropenia, neuropathy.
  • Abiraterone → hypertension, hypokalemia, liver toxicity.
  • Enzalutamide/apalutamide → seizures, fatigue, hypertension.
• Patient education: Oral drug timing (e.g., abiraterone taken fasting), side-effect management.

Key Takeaway for Oncology Pharmacists:

Prostate cancer management centers on androgen suppression and evolves with resistance. Pharmacists play a crucial role in monitoring hormone therapy, managing toxicities, preventing bone complications, and ensuring safe use of next-generation oral targeted therapies.

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