Prostate Cancer

Prostate cancer is a malignant tumor that develops from cells in the prostate gland, a walnut-sized organ located below the bladder that produces seminal fluid. While it often grows slowly, more aggressive forms do exist. Many men die with prostate cancer rather than as a direct result of it.

1. Symptoms (Often absent in early stages; appear as cancer grows or spreads):

• • Urinary Problems: Weak/interrupted flow, frequent urination (especially at night), difficulty starting/stopping, pain/burning, blood in urine/semen.
  • Erectile Dysfunction (ED): Difficulty getting/maintaining an erection.
  • Pain: In the back, hips, pelvis (if spread to bones).
  • Advanced Disease: Leg swelling (lymphedema), weight loss, fatigue, bone fractures

2. Risk Factors:

• • Age: Risk increases dramatically after 50. Most cases are diagnosed in men over 65.
  • Race/Ethnicity: Higher incidence and mortality in Black men compared to White, Asian, or Hispanic men. The reasons are complex (genetic, social, and access).
  • Family History: Having a father or brother with prostate cancer doubles the risk. Risk is higher with early-onset relatives or multiple affected relatives.
  • Inherited Gene Mutations: Mutations in genes like BRCA1, BRCA2, HOXB13, Lynch syndrome genes increase risk.
  • Geography: More common in North America, Northwestern Europe, Australia, and the Caribbean than in Asia or Africa (lifestyle/environment likely play roles).
  • Diet: Potential links to diets high in red/processed meats, high-fat dairy, and low in fruits/vegetables. Obesity may increase the risk of aggressive forms.

3. Screening & Early Detection (Controversial – involves weighing benefits vs. harms):

• • Prostate-Specific Antigen (PSA) Blood Test: Measures PSA protein produced by prostate cells. Elevated levels can indicate cancer, but also occur in BPH (benign enlargement), prostatitis, or after procedures. Not a perfect test.
  • Digital Rectal Exam (DRE): The Doctor feels the prostate for lumps/hardness through the rectum.
  • Guidelines (Vary by Organization – Shared Decision-Making is Key):
    • USPSTF (2023 Draft): Recommends discussing PSA screening:
      • Ages 55-69: Individualized decision based on risk factors/preferences.
      • Age 70+: Routine screening not recommended.
    • American Cancer Society: Discuss screening starting at:
      • Age 50 for average-risk men with >10-15 years of life expectancy.
      • Age 45 for high-risk men (Black men, family history before 65).
      • Age 40 for very high-risk men (multiple relatives with early-onset).
  • Harms of Screening: Overdiagnosis (finding slow-growing cancers that wouldn’t cause harm), Overtreatment (side effects from treating insignificant cancers), False positives (leading to unnecessary biopsies).

4. Diagnosis:

• • Abnormal PSA/DRE: Triggers further investigation.
  • Multiparametric MRI (mpMRI): Increasingly used before biopsy to identify suspicious areas and guide biopsy.
  • Prostate Biopsy: Core needle biopsy guided by ultrasound (often now fused with MRI images). Tissue is examined under a microscope.
  • Pathology Report: Includes:
    • Gleason Score/Grade Group: Measures how aggressive the cancer looks (how abnormal the cells/tissue patterns are). Higher score/group = more aggressive.
    • TNM Staging: Describes tumor size/location (T), lymph node involvement (N), metastasis (M).
    • PSA Level: At diagnosis.
  • Genomic Testing: On biopsy tissue (e.g., Decipher, Oncotype DX GPS) may be used for some localized cancers to better predict aggressiveness and guide treatment decisions.

5. Treatment (Highly personalized based on stage, grade, PSA, age, health, side effect concerns):

• • Active Surveillance: For low-risk, very low-risk, or some favorable intermediate-risk cancers. Close monitoring (PSA, DRE, repeat biopsies, mpMRI) with treatment if signs of progression. Avoids immediate treatment side effects.
  • Watchful Waiting: Less intensive monitoring than AS; for older men/less healthy; aims to manage symptoms if they develop, not necessarily cure.
  • Surgery:
    • Radical Prostatectomy: Removal of the entire prostate and seminal vesicles +/- lymph nodes. Approaches: Open, Laparoscopic, Robot-assisted (common).
    • Side Effects: Erectile dysfunction, urinary incontinence (usually improves over months), infertility.
  • Radiation Therapy:
    • External Beam Radiation Therapy (EBRT): Delivered over weeks (IMRT, IGRT, SBRT). Often combined with ADT for intermediate/high risk.
    • Brachytherapy: Radioactive seeds implanted directly into the prostate (low-dose rate – LDR) or temporary high-dose catheters (high-dose rate – HDR). Often for low/intermediate risk.
    • Side Effects: Urinary/rectal irritation, ED (often delayed), fatigue.
  • Focal Therapy: Experimental techniques (HIFU, Cryotherapy, Laser) targeting only the tumor within the prostate. Not standard; long-term data limited.
  • Androgen Deprivation Therapy (ADT) / Hormone Therapy:
    • LHRH Agonists/Antagonists: Stop testicles from making testosterone (e.g., Leuprolide, Goserelin, Degarelix).
    • Anti-Androgens: Block testosterone from reaching cancer cells (e.g., Bicalutamide, Enzalutamide, Apalutamide, Darolutamide).
    • CYP17 Inhibitors: Block testosterone production throughout body (e.g., Abiraterone).
    • Used for advanced/metastatic disease, or combined with radiation for high-risk localized disease.
    • Side Effects: Hot flashes, loss of libido, ED, fatigue, bone thinning, muscle loss, weight gain, mood changes, increased CV risk.
  • Chemotherapy: Used for metastatic castration-resistant prostate cancer (mCRPC) that stops responding to ADT (e.g., Docetaxel, Cabazitaxel).
  • Immunotherapy:
    • Sipuleucel-T (Provenge): Vaccine for asymptomatic/minimally symptomatic mCRPC.
    • Pembrolizumab: For rare tumors with specific genetic features (MSI-H/dMMR).
  • Targeted Therapy:
    • PARP Inhibitors (Olaparib, Rucaparib): For mCRPC with specific DNA repair gene mutations (e.g., BRCA1/2).
    • Radium-223 (Xofigo): Targets bone metastases with radiation.
  • Radiopharmaceuticals:
    • Lutetium Lu 177 vipivotide tetraxetan (Pluvicto): Targets PSMA-positive mCRPC.
    • Radium-223: See above.
  • Bone Health Management: Bisphosphonates (Zoledronic acid) or Denosumab to prevent fractures in men on ADT or with bone mets.

7. Prevention (No guaranteed way, but may reduce risk):

• • Healthy Diet: Rich in fruits, vegetables (especially cruciferous), whole grains; limit red/processed meats, high-fat dairy.
  • Healthy Weight: Maintain a healthy BMI.
  • Regular Exercise.
  • Discuss Risks: With doctor, especially if high-risk (family history, Black race). Make informed decisions about screening.

8. Prognosis (Generally very good if caught early):

• • Localized/Low Risk: Near 100% 5-year survival. Often curable.
  • Regional Spread: High 5-year survival (>95%), but higher chance of recurrence.
  • Distant Metastases (Stage IV): 5-year survival is approximately 32% (US data), though improving with newer therapies. Treatable but generally not curable; focus shifts to managing disease and quality of life.

Key Factors: Stage at diagnosis, Gleason Score/Grade Group, PSA level, response to treatment.