Prostate cancer

Introduction
Prostate cancer is a malignant neoplasm originating in the prostate gland, a male reproductive organ located below the bladder and in front of the rectum. It is one of the most commonly diagnosed cancers in men worldwide and a significant cause of cancer-related mortality. Most prostate cancers are adenocarcinomas arising from the glandular epithelial cells. The disease can range from indolent, localized tumors to aggressive forms with rapid progression and metastasis.

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Epidemiology

• Incidence: Prostate cancer is the second most common cancer in men after skin cancer.

• Age: Rare before age 40; incidence rises sharply after age 50.

• Geographic variation: High incidence in North America, Northern Europe, Australia, and the Caribbean; lower in Asia and Africa, partly due to differences in screening and dietary/lifestyle factors.

• Risk factors:

  • Age (most significant risk factor).

  • Family history (especially first-degree relatives).

  • Genetic mutations (e.g., BRCA1, BRCA2, HOXB13).

  • African ancestry (associated with higher incidence and aggressiveness).

  • Diets high in saturated fats and low in fruits/vegetables.

  • Obesity and sedentary lifestyle.

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Pathophysiology
Prostate cancer develops from the transformation of normal glandular epithelial cells into malignant ones through a multistep process involving genetic and epigenetic changes. Key features include:

• Mutations in tumor suppressor genes (e.g., PTEN, TP53).

• Androgen receptor signaling promoting tumor growth.

• Activation of oncogenes and deregulation of cell cycle control.

• Histologically, most cases are acinar adenocarcinomas; less common types include ductal adenocarcinoma, neuroendocrine carcinoma, and mucinous carcinoma.

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Clinical Presentation
Early-stage prostate cancer is often asymptomatic. Symptoms, when present, are related to local tumor growth, urethral obstruction, or metastatic spread.

• Local disease:

  • Urinary frequency, urgency, hesitancy, weak stream.

  • Nocturia.

  • Hematuria (less common).

• Locally advanced disease:

  • Urinary retention.

  • Erectile dysfunction.

  • Hematospermia.

• Metastatic disease:

  • Bone pain (especially spine, pelvis, ribs).

  • Pathological fractures.

  • Lower limb edema due to lymphatic obstruction.

  • Weight loss, fatigue.

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Diagnosis

1. Screening

• Prostate-specific antigen (PSA): Elevated levels may indicate cancer, but also rise in benign prostatic hyperplasia (BPH) and prostatitis.

• Digital rectal examination (DRE): Palpation for nodules, asymmetry, or firmness.

• Screening guidelines vary; many recommend shared decision-making for men aged 50–69, earlier for high-risk groups.

2. Diagnostic Workup

• Multiparametric MRI: Helps detect suspicious lesions and guide biopsies.

• Prostate biopsy: Transrectal or transperineal ultrasound-guided biopsy for histologic confirmation.

• Histological grading: Gleason score/Grade Group classification for prognosis.

• Staging:

  • Localized: Confined to prostate.

  • Locally advanced: Extension beyond capsule/seminal vesicle invasion.

  • Metastatic: Spread to lymph nodes, bones, or other organs.

• Imaging for metastases: Bone scan, CT, PSMA PET-CT.

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Management
Treatment is determined by disease stage, tumor grade, PSA level, patient age, comorbidities, and preferences.

1. Active Surveillance (Low-risk Localized Disease)

• Suitable for men with low-grade, low-volume cancer.

• Regular monitoring with PSA, DRE, MRI, and repeat biopsies.

2. Definitive Local Therapies

a. Surgery

• Radical prostatectomy: Removal of the entire prostate and seminal vesicles, with or without pelvic lymph node dissection.

  • Open, laparoscopic, or robot-assisted approaches.

  • Side effects: Urinary incontinence, erectile dysfunction, infertility.

b. Radiation Therapy

• External beam radiation therapy (EBRT): High-energy beams to prostate ± pelvic nodes.

• Brachytherapy: Radioactive seed implantation into prostate.

• Side effects: Radiation cystitis, proctitis, erectile dysfunction.

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3. Androgen Deprivation Therapy (ADT)
Prostate cancer growth is androgen-dependent; reducing testosterone suppresses tumor growth.

a. Luteinizing hormone-releasing hormone (LHRH) agonists

• Leuprolide: 7.5 mg intramuscularly every month, or longer-acting formulations (e.g., 22.5 mg every 3 months).

• Goserelin: 3.6 mg subcutaneously every 28 days, or 10.8 mg every 12 weeks.

b. LHRH antagonists

• Degarelix: 240 mg subcutaneously as a loading dose, then 80 mg monthly.

• Relugolix: 120 mg orally once daily (after 360 mg loading dose).

c. Surgical castration

• Bilateral orchiectomy – rapid testosterone reduction.

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4. Advanced/Metastatic Disease

a. Androgen receptor pathway inhibitors

• Abiraterone acetate: 1000 mg orally once daily on empty stomach + prednisone 5 mg twice daily.

• Enzalutamide: 160 mg orally once daily.

• Apalutamide: 240 mg orally once daily.

• Darolutamide: 600 mg orally twice daily.

b. Chemotherapy

• Docetaxel: 75 mg/m² IV every 3 weeks + prednisone.

• Cabazitaxel: 20–25 mg/m² IV every 3 weeks + prednisone.

c. Radiopharmaceuticals

• Radium-223 dichloride: 55 kBq/kg IV every 4 weeks for 6 doses (bone metastases).

d. Immunotherapy

• Sipuleucel-T: Autologous cellular immunotherapy, given IV in 3 doses at 2-week intervals.

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5. Supportive and Palliative Care

• Bisphosphonates (zoledronic acid 4 mg IV every 3–4 weeks) or denosumab (120 mg SC every 4 weeks) to reduce skeletal-related events in metastatic bone disease.

• Analgesia for bone pain.

• Management of ADT side effects (osteoporosis prevention, metabolic monitoring).

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Prognosis

• Localized low-grade disease: Excellent prognosis; 10-year survival >95%.

• High-grade or metastatic disease: Prognosis depends on treatment response; median survival reduced but improving with modern therapies.