Prostate cancer

1. Prof. Bou Sopheap
Members:
1. Chea Montrey 6. Hour Kimly 11. Chhun Sokseyha
2. Chea Kimhak 7. Song Chhomsovanda 12. Khvan Vianan
3. Khim Chhun Eng 8. Phat Phearak 13. Nim Moniroth
4. Sok Pisey 9. Ron Senghong 14. Song Makara
5. Chamroeun Hengny 10. Seng Chandarith 15. Sorn Hokheng
PROSTATE
CANCER
International University MD52, Urology

2. Content
1. Review anatomy
2. Definition
3. Epidemiology
4. Risk factors
5. Etiologies
6. Pathogenesis
7. Classification
8. Clinical signs and symptoms
9. Laboratory investigation
10. Radiology investigation
11. Differential diagnosis
12. Treatment
13. Complication
14. Prognosis
15. Follow-up and education

3. Review Anatomy
1. Location
- Anterior to the rectum
- Posterior to the pubic symphysis
- Superior to the perineal membrane
- Inferior to urinary bladder
● The gland is supported anteriorly by puboprostatic
ligaments and inferiorly by external urethral
sphincter and perineal membrane.
1. Size
- A normal prostate gland is approximately 20g in
volume, 3cm in length, 4cm wide and 2cm in
depth
1. Vessels
- Arterial supply: Inferior vesical artery from
internal iliac (hypogastric) artery
- Venous drainage: Deep dorsal vein
- Nerve: from pelvic plexuses
- Lymphatic: drains to the internal iliac, sacral,
and the obturator lymphatic channels.

4. 4. Prostate has been divided into three zones:
- Transitional zone (5–10%): located between the bladder
neck and the verumontanum.
- Central zone (25%): located posterior to the transition
zone and proximal to the verumontanum
- Peripheral zone (70%): this area most common affected
by chronic prostatitis & adenocarcinoma
4. Lobes
- One anterior
- One posterior
- One median
- Two lateral

5. Definition
- Prostate cancer is a malignant tumor that forms in the tissues of the prostate gland in men.
- It occurs when cells in the prostate grow uncontrollably, forming a tumor. Some prostate cancers grow slowly and
may not cause serious harm, while others can be aggressive and spread (metastasize) to other parts of the body,
such as bones or lymph nodes.

6. Epidemiology
● Prostate cancer is the second most common
cancer in men and the fifth leading cause of death
worldwide. About 1 in 44 men will die of prostate
cancer.
● The number of prostate cancers diagnosed each
year declined sharply from 2007 to 2014. Since
2014, however, the incidence rate has increased by
3% per year.
● Black men continue to have the greatest burden,
with mortality twice that of any other racial.
● Affects men over the age of 50, risk increase with
age
● The American Cancer Society estimates for prostate
cancer in the United States for 2025 are:
+ About 313,780 new cases of prostate cancer
+ About 35,770 deaths from prostate cancer

7. Risk factors
★ Risk factor of prostate cancer include:
❏ Non-modifiable
● Age: > 50 years old.
● Family history: having family members with prostate cancer increase risk, especially at the young age.
● Genetic factors: mutation in genes such as BRCA2 and BRCA1, GST-P1 at chromosome 11.
❏ Modifiable
● Diet: high intake of red meat and high-fat, high intake calcium, low intake of fruits and vegetable may increase
risk.
● Smoking and Alcohol
● Chemical exposure: contain carcinogens or hormones disrupting compounds that can damage prostate cells
● Inflammation and infection: Chronic prostatitis or sexual transmitted infection (STIs).
.

8. Etiologies
1. Age: especially after 50.
2. Ethnicity: African-american white men.
3. Family history: having a father or brother diagnosed with prostate cancer.
4. Genetics: mutation in genes such as BRCA2 and BRCA1, GST-P1 at chromosome 11.
5. Diet: high in red meat, high fat, and low in fruits and vegetables.
6. Obesity: Being overweight or obese.
7. Physical inactivity: Lack of exercise.
8. Lifestyle: chemical exposures, smoking, high dairy and calcium intake.
9. Inflammation: such as prostatitis, or inflammation of the prostate gland.
10. Hormonal factors: high level of androgens (testosterone) can promote prostate cell growth.
11. Vasectomy: elevation of circulating of free testosterone.

9. Pathogenesis
Prostatic neoplasms are adenocarcinoma: 95%
● Hormonal:There are associated with hormones testosterone, DHT, and
estrogens in prostate carcinogenesis. But it is controversial, the main issues
includes:
+ The source of androgens:
- Testicular testosterone main source of androgens in prostate
- DHT(Dihydrotestosterone) predominates in prostate tissue and binds to
AR(Androgen receptor)
- Adrenal cortex promotes synthesis of androgens in prostate
+ Estrogens in pathogenesis
- The effect of estrogen is determined by 2 receptors:ER-α, ER-β
.ER-α leads to abnormal proliferation, inflammation, and development of
premalignant lesion
.ER-β leads to anticarcinogenic effects that balance the actions of ER-alpha
and androgens.

10. Pathogenesis (Con’t)
● Androgen Receptor Signaling
- Animal model study found that loss of androgen receptor function prevented prostatic carcinogenesis, malignant
transformation, metastasis.
- Thus stromal androgen receptor used for prostate cancer progression, malignant transformation, and metastasis.
● Prostate Intraepithelial Neoplasia (PIN)
- Direct injury is hypothesized response to infections, autoimmune diseases, circulating carcinogen, from diet, or urine
refluxed into the prostate.
- Biological responses increase proliferation between basal cells and mature luminal cells. In a small subset of cells,
some contain “stem cell” or tumor initiating properties and telomere shortening.
- Subset of PIN cells activate telomerase enzyme, causing cells to become immortal increase genetic instability that
progress to high-grade PIN and early prostate formation.

11. Type of prostate cancer
Common type 90-95%
- Adenocarcinoma: cancer that develops from the epithelial cell
Rare type 5-10%
- Neuroendocrine cancer: cancer that develops from neuroendocrine cell (Ex: Small cell carcinoma)
- Squamous cell cancer: cancer that develops from flat cell that cover prostate
- Transitional cell carcinoma: cancer that develops from cell that lines in the urethra (urothelial carcinoma)
- Lymphoma: cancer of the lymphatic system

12. Small cell carcinoma
Adenocarcinoma Transitional cell carcinoma

13. Grading
Gleason’s grading
Gleason score
- G1:3+3=6
- G2:3+4=7
- G3:4+3=7
- G4:4+4 or 5+3=8
- G5:4+5 or 5+4
Or 5+5= 9 or 10

14. Classification

15. Clinical signs and symptoms
Usually symptoms of Prostate cancer occur late until it far advanced, therefore asymptomatic.
● Large and localized extensive prostate cancer may cause symptoms similar to BPH but it is more progressive and
do not remit :
+ Such as obstructive voiding symptoms
- Weak urinary stream / strain to begin
- Incomplete emptying
- Urinary hesitancy and frequency
- Nocturia and dysuria
+ Erectile dysfunction
+ Hematospermia
+ Hematuria
+ Metastatic advanced stage may cause bone pain, unexplained weight loss, fatigue…
+ Larger localized extensive of Prostate cancer will cause compression to the rectum in which leading to large bowel
obstruction or difficulty in defecation

16. ● Individual early detection
- Age of 50
- Concurring with obstructive voiding symptoms
- High risk factor of Prostate cancer
- Family history of Prostate cancer
- Genetic related
+ Usually Digital Rectal examination and detection of serum PSA (Prostate Specific Antigen) are initial diagnostic work-
up
● Digital Rectal Examination
- Focus on prostate size, consistency, and abnormalities within or beyond the gland
- Carcinoma characteristics are : hard, irregular border, and fixed
- Approximately 20-25% of men with abnormal DRE have prostate cancer

17. Laboratory investigation
1) PSA (Prostate specific antigen):
- PSA > 3 - 4ng/ml
- Other cause of high level Of PSA: BPH(benign prostate hyperplasia),UTI(urinary tract infection),prostatic
trauma.
1) Free PSA(Unbound):
- Low prostate cancer
- High BPH
1) Biomarker
- PCA3(prostate cancer antigen 3) : urine test high level
2) Alkaline Phophate: Elevated if Bone metastasis
3) Prostate Biopsy: Definitive Diagnostic test.

18. Radiology investigation
1. Ultrasound
- Transrectal ultrasonography (TRUS): detected abnormalities and to guide biopsy, usually following an abnormal
PSA level or DRE.
- A hypoechoic lesion (60-70%) in the peripheral zone of the gland but can be hyperechoic or isoechoic (30-40% of
lesions).
1. Magnetic Resonance Imaging (MRI)
- Indication: the evaluation of prostate cancer after an ultrasound-guided prostate biopsy has confirmed cancer.
1. MR spectroscopy: to detect and characterize prostate cancer.
2. Computed Tomography (CT): to detect enlarged pelvic and retroperitoneal lymph nodes, hydronephrosis, and
osteoblastic metastases.

19. Differential diagnosis
1. PSA elevated (Probably diagnosis)
- BPH
- Urethral instrumentation
- Chronic prostatitis
1. Prostate induration(Sclerotic lesion) (Probably diagnosis)
- Chronic granulomatous prostatitis
- Previous TURP or needle biopsy
- Prostatic calculi

20. Treatment
Five modality of treatment:
- Active surveillance
- Radiation therapy
- Immunotherapy
- Prostatectomy
- Hormonotherapy
*For localized prostate cancer, radical prostatectomy remains the gold standard treatment.

21. ● Active surveillance: digital rectal exam, PSA blood test, prostate biopsy
● Radiation therapy: 70 Gy in 40 sessions, for 8 weeks oftreatment ( 5 day/
week) for external radiation.
○ External beam radiation
○ Internal beam radiation
● Immunotherapy: helps your immune system fight cancer
● Prostatectomy:
○ Total prostatectomy (prostate, vas deferens and seminal vesicle in
preserving the external sphincter and, if possible erection nerve),
○ Vesico-urethral anastomosis.
● Hormonotherapy: drugs can block or reduce action amount of hormone.
e.g.,LH-RH agonist, anti-androgen

22. Complications
- Patients either treated for prostate cancer or left untreated, both had risk of complications, including urinary and sexual
issues. The complications are divided into:
1. Local complication (Primary tumor)
2. Regional metastasis
3. Distant metastasis
4. Systemic or Paraneoplastic effects
5. Treatment-related complications

23. 1. Local complications: as tumor enlarges within the prostate or invades nearby structures.
- urinary tract obstruction, hematuria, infection, pain
2. Regional metastasis: involve with pelvic and lymphatic within pelvic region.
- seminal vesicle invasion, bladder and rectal invasion, lymph nodes metastasis
3. Distant metastasis: it commonly metastases through hematogenous or lymphatic routes.
- skeletal metastasis, bone marrow infiltration, visceral metastasis (lungs, liver)
4. Paraneoplastic effects: weight loss, fatigue, anemia, coagulopathies
5. Treatment-related complications: it still has some complications even with management of tumor.
- Surgical (radical prostatectomy): erectile dysfunction, urinary incontinence, urethral stricture
- Radiotherapy: hematuria, urinary frequency, diarrhea, rectal bleeding, infertility
- Androgen deprivation therapy (ADT): hot flashes, gynecomastia, osteoporosis & fracture, metabolic
syndrome,
CVS risk, loss of libido, erectile dysfunction.

24. Prognosis
Factors affecting prognosis
- Stage of the cancer
- Gleason score
- PSA level
- Age and general health
Good Prognosis
- Localized, confined to the prostate.
- low serum PSA level at diagnosis
- Gleason score = 6
- 5-year relative survival rate: ~100%
Intermediate Prognosis
- Regional: Cancer has spread outside the prostate but not to distant sites.
- Gleason score = 7
- 5-year relative survival rate: ~95–100%
Poor Prognosis
- Distant: Cancer has spread to distant lymph nodes, bones, or other organs.
- After prostatectomy or radiotherapy, those who quickly rising in PSA levels < 0.2 ng/ml
- Gleason score > 8
- 5-year relative survival rate: ~30%

25. Follow-up and education
Follow-up schedule:
• Every 3–6 months for the first 2 years
• Every 6–12 months for years 3–5
• Annually after 5 years (lifelong serum PSA monitoring)
Patient education:
• Explain disease, PSA meaning, and follow-up process
• Promote healthy lifestyle (diet, exercise, no smoking)
• Manage side effects with counseling and rehabilitation
• Provide psychological and emotional support

26. Reference
1. https://emedicine.medscape.com/article/1923122-overview#showall
2. FRANK H. NETTER, MD, ATLAS OF HUMAN ANATOMY, 7th EDITION
3. Harrison’s Principles of Internal Medicine, 21st Edition
4. https://emedicine.medscape.com/article/1967731-overview?form=fpf
5. https://www.cancer.org/cancer/types/prostate-cancer/about/key-statistics.html
6. https://acsjournals.onlinelibrary.wiley.com/doi/full/10.3322/caac.70028
7. https://www.cancer.org.au/cancer-information/types-of-cancer/prostate-cancer
8. https://www.healthline.com/health/prostate-cancer-risk-factors#:~:text=Key%20takeaways%20*%20Prostate%20canc
er%20development%20is,alcohol%20consumption%20are%20not%20considered%20risk%20factors
.
9. Internal Medicine Current Medical Diagnosis and Treatment 2024 McGraw
10. Pathophysiology The Biologic Basis for Disease in Adults and Children
11. European association of urology : https://uroweb.org/