Prostate Cancer 🩺

Overview

Prostate cancer is one of the most common cancers in men. It generally develops in the prostate
gland, a small gland that is part of the male reproductive system. Most cases of prostate cancer grow
slowly and may not cause significant symptoms, especially in older men. However, aggressive types
can spread (metastasize) to other organs such as the bones, lymph nodes, and other tissues.

Key Facts:

Incidence: Prostate cancer is the second most common cancer in men worldwide. It is more
common in older men, particularly those over 65 years of age.
Risk Factors: Age, family history, race (more common in African American men), and diet (high-
fat diets) are significant risk factors.

Pathophysiology

Prostate cancer originates from the prostatic epithelium, often beginning in the peripheral zone of
the prostate, which is the most common site for cancerous transformation.

1. Genetic and Molecular Factors:

Gene Mutations: Mutations in the PTEN gene, TP53, and BRCA1/2 genes are associated
with aggressive forms of prostate cancer.
Androgen Signaling: Prostate cancer cells are often dependent on androgens
(testosterone) for growth. The androgen receptor plays a critical role in the disease's
development, and the majority of prostate cancers show elevated androgen receptor activity.
2. Prostatic Intraepithelial Neoplasia (PIN):
PIN is considered a precursor to prostate cancer. It refers to abnormal growth of epithelial
cells in the prostate, which can transition into carcinoma over time.
3. Adenocarcinoma:
Prostate adenocarcinoma is the most common type, comprising approximately 95% of all
prostate cancers. It originates in the glandular tissue of the prostate and is classified based
on Gleason scoring (discussed below).

Clinical Presentation

Prostate cancer may present asymptomatically, or with signs and symptoms that overlap with benign
prostate diseases. The majority of patients are diagnosed through routine screening.

1. Early-Stage Prostate Cancer (Localized):

Often asymptomatic.
May be detected incidentally during a routine digital rectal exam (DRE) or PSA testing
(Prostate-Specific Antigen).
2. Advanced Disease:
Urinary symptoms (e.g., increased frequency, difficulty urinating, weak stream, hematuria).
Pain: Especially in the lower back, hips, or pelvis due to bone metastasis.
Fatigue: Common in metastatic cases.
 3. Metastasis:
Common sites for prostate cancer metastasis include the bones (vertebrae, pelvis), lymph
nodes, liver, and lungs.

Diagnosis

1. Prostate-Specific Antigen (PSA):

A serum biomarker used for both screening and monitoring prostate cancer.
Elevated levels (>4 ng/mL) can indicate prostate cancer, but also benign prostatic
hyperplasia (BPH) or prostatitis.
PSA velocity (rate of change) and PSA density (adjusted for prostate volume) are used to
improve diagnostic specificity.
2. Digital Rectal Exam (DRE):
Physicians palpate the prostate through the rectum to assess for any irregularities or hard,
nodular areas, which may suggest cancer.
3. Biopsy:
The gold standard for diagnosis is a transrectal ultrasound-guided biopsy (TRUS) with
tissue sampling from suspected areas of the prostate. It is the definitive method for
diagnosing prostate cancer.
4. Imaging:
MRI: Used for local staging and assessing the extent of cancer, particularly in high-risk cases.
Bone Scintigraphy: If metastatic bone disease is suspected.
CT Scan: Useful for detecting metastasis, especially to lymph nodes.
5. Gleason Score:
A grading system that assigns scores based on the architecture and differentiation of prostate
cancer cells. It is used to predict the aggressiveness of the cancer.
The Gleason score is composed of two numbers (e.g., 3+4 or 4+3), reflecting the two most
predominant patterns in the biopsy. A higher score indicates more aggressive cancer:
6 or below: Low-grade
7: Intermediate-grade
8-10: High-grade

Staging and Risk Classification

1. TNM Staging System:

T (Tumor): Describes the size and extent of the primary tumor.
N (Nodes): Describes regional lymph node involvement.
M (Metastasis): Indicates whether there is distant spread to other parts of the body.
2. Risk Groups: Prostate cancer is stratified into risk groups based on clinical and pathological
findings:
Low Risk: PSA <10 ng/mL, Gleason score ≤6, clinical stage T1-T2a.
Intermediate Risk: PSA 10-20 ng/mL, Gleason score 7, clinical stage T2b-T2c.
High Risk: PSA >20 ng/mL, Gleason score ≥8, clinical stage T3-T4.

Management

1. Active Surveillance:
 Recommended for low-risk, localized prostate cancer in older men or those with significant
comorbidities.
Involves regular monitoring with PSA testing, DRE, and biopsy.
2. Surgical Treatment:
Radical Prostatectomy: The removal of the prostate gland. It is indicated for localized
prostate cancer with curative intent. The procedure may include lymph node dissection if
there's concern for metastasis.
Robotic-Assisted Surgery: Minimally invasive surgery that has become the standard of
care.
3. Radiation Therapy:
External Beam Radiation Therapy (EBRT): Commonly used for localized or locally
advanced prostate cancer.
Brachytherapy: Placement of radioactive seeds directly into the prostate. Suitable for early-
stage prostate cancer.
Stereotactic Body Radiation Therapy (SBRT): A newer, more targeted form of radiation.
4. Hormonal Therapy (Androgen Deprivation Therapy):
Used to lower androgen levels, which prostate cancer cells depend on for growth.
Includes LHRH agonists/antagonists (e.g., Leuprolide, Goserelin) and anti-androgens
(e.g., Flutamide, Bicalutamide).
Castration-resistant prostate cancer (CRPC) occurs when cancer becomes resistant to
androgen deprivation.
5. Chemotherapy:
Used for metastatic or castration-resistant prostate cancer.
Drugs like Docetaxel and Cabazitaxel are commonly used.
6. Immunotherapy:
Sipuleucel-T: An autologous dendritic cell vaccine for castration-resistant prostate cancer.
Immune checkpoint inhibitors (e.g., Pembrolizumab) are also under investigation for
advanced prostate cancer.
7. Bone-targeted Therapies:
Bisphosphonates (e.g., Zoledronic acid) or RANK-L inhibitors (e.g., Denosumab) are
used to manage bone metastasis and prevent skeletal-related events.

Prognosis

Prostate cancer has a relatively favorable prognosis, particularly for low-risk cases. The prognosis
depends on factors such as the stage of cancer, Gleason score, and PSA levels at diagnosis.

Survival Rates: The 5-year survival rate for localized prostate cancer is close to 100%, while for
metastatic prostate cancer, it can drop significantly.
Castration-Resistant Prostate Cancer (CRPC): When the cancer becomes resistant to
androgen deprivation, the prognosis worsens, but newer treatments are improving survival.

Prevention and Screening

1. Screening:
PSA Testing: The role of PSA testing in prostate cancer screening is controversial. Many
guidelines recommend shared decision-making between the physician and patient,
especially in those aged 55–69 years.
 Digital Rectal Exam (DRE): Although still used, DRE is less sensitive than PSA testing.
2. Diet and Lifestyle:
Diets rich in fruits, vegetables, and low in red meat and fat have been associated with a
lower risk of prostate cancer.
Exercise and maintaining a healthy weight may reduce risk and improve overall health
outcomes.

Conclusion

Prostate cancer is a complex and heterogeneous disease with a wide range of clinical presentations
and outcomes. Early detection, effective risk stratification, and individualized treatment plans are
essential for improving prognosis and survival. Regular screening, especially for high-risk groups,
continues to be a key element in the management of prostate cancer.

Questions

1. Which of the following is the most common histological type of prostate cancer?
A) Squamous cell carcinoma
B) Transitional cell carcinoma
C) Urothelial carcinoma
D) Adenocarcinoma
2. What is the most significant risk factor for prostate cancer?
A) Family history
B) Advanced age
C) Obesity
D) Smoking
3. The Gleason score is used to assess the ____.
A) Size of the tumor
B) Degree of histological differentiation of the tumor
C) Stage of prostate cancer
D) Presence of metastasis
4. What is the primary diagnostic test for prostate cancer?
A) Prostate-specific antigen (PSA) blood test
B) MRI of the pelvis
C) Digital rectal exam (DRE)
D) Prostate biopsy
5. Which PSA level is commonly considered a red flag for prostate cancer in men over 50
years old?
A) 1 ng/mL
B) 2.5 ng/mL
C) 4 ng/mL
D) 10 ng/mL
6. Which of the following is the most common site of metastasis for prostate cancer?
A) Liver
B) Bones
C) Lungs
D) Brain
7. Which of the following treatments is the most commonly used for localized prostate
cancer?
A) Radical prostatectomy
B) Radiation therapy
C) Hormonal therapy
D) Chemotherapy
8. Which of the following is a common side effect of androgen deprivation therapy (ADT)?
A) Osteoporosis
B) Hyperglycemia
C) Weight loss
D) Hyperkalemia
9. What is the purpose of performing a pelvic MRI in the evaluation of prostate cancer?
A) To identify distant metastases
B) To evaluate the extent of local invasion
C) To detect regional lymph node involvement
D) To monitor PSA levels
10. Which of the following molecular markers is commonly elevated in patients with prostate
cancer?
A) BRCA1
B) PSA (Prostate-Specific Antigen)
C) HER2
D) CA-125
11. Which of the following genetic mutations is associated with an increased risk of prostate
cancer?
A) BRCA2 mutation
B) TP53 mutation
C) KRAS mutation
D) EGFR mutation
12. Which of the following is a common finding on digital rectal examination (DRE) in a
patient with prostate cancer?
A) A smooth, symmetrical prostate
B) An indurated, asymmetrical prostate with a nodule
C) A tender, enlarged prostate
D) No abnormal findings
13. Which of the following factors most strongly influences the decision to initiate active
surveillance in prostate cancer?
A) Age of the patient
B) Gleason score of 3+3
C) Serum PSA levels >10 ng/mL
D) Presence of metastatic disease
14. The main goal of hormonal therapy in prostate cancer is to ____.
A) Cure the disease
B) Decrease testosterone levels to slow tumor growth
C) Prevent metastasis
D) Enhance the immune response
15. Which of the following is considered a contraindication for radical prostatectomy in
prostate cancer?
A) Gleason score of 7
B) Age older than 75 years
C) Metastatic disease
D) PSA level <10 ng/mL
16. Which treatment is most appropriate for a patient with prostate cancer who has a low
Gleason score and a low PSA level?
A) Radical prostatectomy
B) Active surveillance
C) Chemotherapy
D) Palliative care
17. A 65-year-old man presents with a PSA of 8 ng/mL and a palpable hard nodule on digital
rectal exam. What is the next best step in his management?
A) MRI of the pelvis
B) Transrectal ultrasound-guided biopsy of the prostate
C) Begin androgen deprivation therapy
D) Start radiation therapy
18. A 70-year-old male with prostate cancer undergoes a radical prostatectomy. Post-
operatively, he develops a pelvic lymphocele. What is the most appropriate next step in
management?
A) Percutaneous drainage
B) Immediate chemotherapy
C) Observation without intervention
D) Repeat prostate biopsy
19. A 58-year-old male with a family history of prostate cancer presents with a PSA of 6.5
ng/mL. His digital rectal exam is normal. What is the next best step in management?
A) MRI of the prostate
B) Transrectal ultrasound-guided biopsy
C) Repeat PSA after 6 months
D) Start chemotherapy
20. A 50-year-old male presents with symptoms of urinary frequency, nocturia, and a PSA of 3
ng/mL. His family history is positive for prostate cancer. Which of the following is the
most appropriate management strategy?
A) Repeat PSA testing in 6 months
B) Begin treatment with finasteride
C) Proceed with prostate biopsy
D) Perform digital rectal exam (DRE) only
21. A 75-year-old man with newly diagnosed prostate cancer has a Gleason score of 4+3 and
a PSA of 20 ng/mL. Which treatment option is most appropriate for this patient?
A) Radical prostatectomy
B) Radiation therapy with hormonal therapy
C) Active surveillance
D) Palliative care
22. A 68-year-old male with advanced prostate cancer presents with bone pain, particularly in
the spine and hips. His PSA is elevated to 35 ng/mL. What is the most appropriate next
 step in management?
A) Start androgen deprivation therapy (ADT)
B) Perform a bone scan to assess for metastasis
C) Begin radiation therapy for pain management
D) Start chemotherapy immediately
23. A 62-year-old male with prostate cancer has been receiving androgen deprivation therapy
for 12 months. He now complains of decreased libido, hot flashes, and muscle weakness.
What is the most likely cause of his symptoms?
A) Chemotherapy side effects
B) Metastatic disease progression
C) Side effects of androgen deprivation therapy
D) Anemia from chronic disease
24. A 70-year-old male with newly diagnosed prostate cancer and a Gleason score of 3+3 and
a PSA of 4.5 ng/mL is asymptomatic. What is the most appropriate next step?
A) Radical prostatectomy
B) Active surveillance
C) Radiation therapy
D) Start androgen deprivation therapy
25. A 59-year-old male with a history of prostate cancer presents with back pain, fatigue, and
weight loss. His PSA is 60 ng/mL. What is the next step in management?
A) Start palliative radiation therapy
B) Perform a CT scan to check for metastasis
C) Begin chemotherapy with docetaxel
D) Perform a bone scan