This document provides an overview of prostate cancer, including its epidemiology, risk factors, anatomy, pathophysiology, staging, diagnosis, treatment, and monitoring. Key points include that prostate cancer incidence increases with age and is higher in African American men. Common treatments involve androgen deprivation therapy using LHRH agonists, anti-androgens or surgery. For advanced disease, options include chemotherapy, immunotherapy, or androgen synthesis inhibitors. Response is monitored mainly through PSA levels and imaging of metastases.

1. Prostate
Cancer
Dr. Alghazali

2. Learning Objectives
✓ Epidemiology
✓ Risk Factors
✓ The basic of anatomy
✓ Pathophysiology
✓ Stages of PC
✓ Diagnosis and grading system
✓ Clinical presentation
✓ Drug therapy plans
✓ Monitoring and evaluation

3. Prostate cancer
➢Prostate cancer is the most commonly diagnosed cancer in men
➢It is the second leading cause of cancer related death in men.
➢The disease course ranges from asymptomatic tumors that may not require
treatment to aggressive tumors that result in distant metastases.

4. Epidemiology
• Prostate cancer incidence increased during the late 1980s and early 1990s, due to widespread prostate
specific antigen (PSA) screening
• the disease is rare among men under age 40, but the incidence sharply increases with each subsequent
decade of life.
• More than 70% of cases are diagnosed in men older than 65 years
• African Americans have a higher incidence and death rate

5. Risk Factors
➢Age
➢Race
➢Genetic: Mutations of DNA repair genes
➢Environmental: Increased risk associated with cadmium exposure
• Hormonal: increased testosterone, decreased 5αreductase activity, Polymorphic
expression of the androgen receptor gene

6. Risk Factors
➢Diet:
-Mediterranean diet associated with reduced risk of prostate cancer
-Increased risk associated with high meat and high fat diets
-Decreased intake of 1,25dihydroxyvitamin D, lycopene, and βcarotene

7. Prostate anatomy
It consist of 5 lobes and 3 zones:
The 5 lobes are:
1- Anterior
2-Middle
3-Posterior
4-Two lateral lobes

8. The 3 zones are:
1- Central
Peripheral
3-Transitional

9. • Benign Prostatic Hyperplasia (PBH): arise form transitional zone in
middle lobe
• Prostate carcinoma (PC): arise from peripheral zone in posterior lobe

10. Hormonal regulation of the prostate gland
• ACTH, adrenocorticotropic hormone
• DHT, dihydrotestosterone
• FSH, follicle stimulating hormone
• GH, growth hormone
• LH, luteinizing hormone;
• LHRH, luteinizing hormone–releasing hormone
• PROL, prolactin.

11. Pathophysiology
✓The types of cell in prostate are : Stromal cell and Epithelial cell.
✓Testosterone metabolized by 5 alpha reductase types 2 into DHT in stromal cell
✓DHT activate the androgen receptors on both cells
✓Results in the overactivation of of growth factors and cause hyperplasia and over
growth
✓Theses cells has the ability to spread out though the blood and lymphatic system

12. Diagram of pathophysiology

13. Hematogenous spread of prostate cancer
• Pelvis
• Lumbar spin
• Lungs
• Kidneys
• Breast
• Brain

14. Stages of PC
• Stage I
• Stage II
• Stage III
• Stage IV

15. Gleason’s Pattern Scale

16. Pattern of tumors
1- Primary grade (1-5)
2- Secondary grade (1-5)
Gleason’s Score = 2-10

17. Grading system

19. Clinical Presentation
Localized Disease
➢Asymptomatic
Locally Invasive Disease
➢Ureteral dysfunction, frequency
➢Hesitancy
➢Dribbling
➢Impotence

20. Advanced Disease
➢Back pain
➢Cord compression
➢Lower extremity edema
➢Pathologic fractures
➢Anemia
➢Weight loss

21. Diagnosis
Initial tests
➢Digital rectal examination – DRE
➢Prostate specific antigen - PSA
➢Trans rectal ultrasonography - TRUS (if either DRE is positive or PSA is elevated)
➢Biopsy

22. Staging tests
➢Gleason score on biopsy specimen
➢Bone scan
➢CBC
➢Liver function tests
➢Serum phosphatases (acid/alkaline)
➢Excretory urography
➢Chest xray

23. Treatment goals
❖ The goal of reducing testosterone to castration levels through surgical or chemical treatment
❖The goal in early-stage prostate cancer is to minimize morbidity and mortality from prostate
cancer.
❖The goal in advanced prostate cancer focus on providing symptom relief and maintaining
quality of life.

24. Types of surgery therapy
➢Bilateral orchiectomy:
Surgical removal of the testes
➢Prostatectomy: ???
➢Lumpectomy: ???

25. Drug Therapy
The initial treatment for prostate cancer depends on the disease stage, Gleason score,
presence of symptoms, and life expectancy of the patient
❑Initial treatment
➢Androgen ablation (orchiectomy or LHRH agonist with or without anti-androgens)
➢Hormonal manipulations
➢Cytotoxic chemotherapy / Radiation
➢Supportive care

26. No pharmacologic Therapy
➢Observation/Active Surveillance (PSA and DRE testing are performed every 6 to 12
months)
➢Orchiectomy (for patients with impending spinal cord compression or ureteral obstruction)
➢Radiation
➢Radical Prostatectomy

28. Pharmacotherapy classes for early-stage disease (ADT)
➢Luteinizing Hormone Releasing Hormone Agonists
➢Gonadotropin Releasing Hormone Antagonists
➢Anti-androgens
➢Combined Androgen Blockade

29. Pharmacotherapy classes for metastatic stage disease
➢Chemotherapy
➢Immunotherapy
➢Bone Protective Therapies

30. Luteinizing Hormone Releasing Hormone Agonists
LHRH agonists are a reversible method of ADT and are as effective as orchiectomy
in treating prostate cancer.
The list of approved LHRH agonists include:
• leuprolide, leuprolide depot, leuprolide implant
• Triptorelin depot, triptorelin implant
• Histrelin LA, and goserelin acetate implant.

31. • Disease flare within the first week of therapy can be caused by an
initial induction of LH and FSH that is induced by the LHRH agonist,
leading to an initial period of increased testosterone production.
The reaction usually resolves after 2 weeks

32. Adverse effects
The most common adverse effects:
• Vasomotor symptoms, such as hot flashes, erectile dysfunction
• Decreased libido, and injection site reactions.
Long term adverse effects:
• Decreased bone mineral density and metabolic syndrome.
• Disease flare within the first week of therapy

33. Cautions
➢Caution should be exercised if initiating LHRH agonists in patients with the
potential for ureteral obstruction or spinal cord impingement because
irreversible complications may occur.
➢Men initiated on long term ADT should generally have a baseline bone
mineral density test, and be initiated on calcium and vitamin D
supplementation.

34. Gonadotropin Releasing Hormone Antagonists (Degarelix )
• GnRH is an alternative to LHRH agonists
• Degarelix reversibly binds to GnRH receptors on cells in the pituitary
gland, reducing the production of testosterone to castration levels.
The major advantage of direct GnRH antagonists:

35. Anti-androgens
First generation nonsteroidal anti-androgens are:
• Flutamide, bicalutamide, and nilutamide.
➢Monotherapy with first generation is less effective than LHRH agonist therapy,
therefore indicated only in combination with ADT.
➢Flutamide and bicalutamide are indicated in combination with an LHRH agonist,
while nilutamide is indicated after orchiectomy.

36. Side effect:
➢Gynecomastia
➢Hot flushes
➢Gastrointestinal disturbances (diarrhea)
➢Liver function test abnormalities
➢Breast tenderness

37. Second Generation Anti-androgen
❖Enzalutamide is a second-generation anti-androgen that is effective in mCRPC,
even when first generation anti-androgens have failed.
❖mCRPC: Metastatic castration resistant prostate cancer
❖Enzalutamide prevents the AR from trans locating into the cell nucleus

38. Androgen Synthesis Inhibitors
✓Androgen synthesis can continue to occur in the periphery (eg, adrenal
glands)
✓Cytochrome P450 enzymes play a critical role in androgen synthesis.
✓CYP17A1 inhibition prevents the conversion of pregnenolone to DHEA, a
requisite precursor for testosterone.

39. Androgen Synthesis Inhibitors
✓Abiraterone acetate is a potent and specific
inhibitor of CYP17A1.
✓Abiraterone has benefit in combination with
ADT in hormone sensitive prostate cancer
✓Abiraterone used in the treatment of mCRPC

40. Chemotherapy
➢Docetaxel is an antimicrotubule taxane, which has been shown to improve survival in mCRPC
patients when administered at 75 mg/m2 every 3 weeks.
➢More recently, docetaxel in combination with ADT has demonstrated improved overall survival
in hormone sensitive prostate cancer.
The most common adverse effects include:
• Nausea, alopecia, bone marrow suppression, fluid retention, and peripheral neuropathy.
• increased risk of liver toxicity

41. Immunotherapy
• Sipuleucel-T (Provenge) : is an autologous immunotherapy that was approved
for patients with asymptomatic or minimally symptomatic mCRPC.
Side effects:
• Hypersensitivity, chills, fever, fatigue, headache, and myalgias

42. Immune cells collected
Antigen Presenting cells (APC)
PAP-GM-CSF

45. Monitoring and evaluation process
➢Monitor PSA and circulating androgens for castration level of testosterone.
➢Monitor symptoms for improvement or worsening.
➢Obtain imaging studies to evaluate response of distant metastases.
➢Monitor for any new signs or symptoms of progression, and adverse effects from
therapy.
➢Evaluate adherence to ADT.