Prostate Cancer
BY ZAIN RIZVI
Case #1
A 60-year-old black man presents to his primary care physician with
complaints of difficulty with urination. He describes a weak stream and
a sense of incomplete voiding. He describes nocturia (5 episodes per
night) and has been taking an alpha-blocker for this with minimal
improvement. He says he can last about 60 to 90 minutes without
urinating. He denies any suprapubic tenderness, dysuria, or hematuria.
He further denies any back pain or gastrointestinal complaints.
Rectal exam reveals his prostate to be approximately 60 mL,
asymmetrical, with a large 2-cm nodule at the right base.
Differential Diagnosis
Prostatic Carcinoma
Benign Prostatic Hyperplasia
Pathophysiology
Develops when the rates of cell division and cell death are no longer equal, leading to uncontrolled tumor growth
Most commonly diagnosed male cancer
Mutation
p53, RB genes
Types of carcinomas
Adenocarcinoma – 95%
Transitional cell morphology – 4%
Location of carcinomas
Peripheral zone – 70%
Central zone – 20%
Transitional zone – 10%
Risk factors
Age
Race
Diet
Family History
Genetics
Hormones
Premalignant Lesions
Prostatic intraepithelial neoplasia
Confined within the epithelium
Most likely precursor of prostatic adenocarcinoma
Two grades – low and high
Atypical small acinar proliferation
Suspicious for malignancy is not a specific pathologic entity
Morphological spectrum for normal prostate to high-grade prostatic intraepithelial neoplasia.
(A) Normal prostate. (B) Low-grade prostatic intraepithelial neoplasia. The nuclei are enlarged,
vary in size, have normal or slightly increased chromatin content, and possess small or
inconspicuous nucleoli. (C) High-grade prostatic intraepithelial neoplasia. Cells are
characterized by large nuclei of fairly uniform size, an increased chromatin content (which might
be irregularly distributed) and prominent nucleoli that are similar to those of carcinoma cells.
Screening
Ideally, physicians should consider a number factors
Especially age, family history
Early detection and treatment
PSA
DRE
The American Urological Association (AUA) 2009 guideline
recommends that early detection and risk assessment of prostate cancer
be offered to asymptomatic men 40 years of age or older who wish to be
screened and have an estimated life expectancy of more than 10 years.
Digital Rectal Examination (DRE)
Most cancers lie in the
peripheral, posterior part of
the prostate
Asymmetry, nodule, or a fixed,
“rock hard” mass
Less than 50% of abnormal
DREs are associated with
prostate cancer
Prostate Specific Antigen (PSA)
Glycoprotein produced by the prostatic acini
PSA elevations may help in staging, counseling, and monitoring prostate cancer patients
Free-to-Total PSA ratio has increased specificity
>50% of patients have extraprostatic disease if PSA >10 ng/mL
<5% of patients have lymph node metastases and only 1% have bone
metastases if PSA <20 ng/mL
66% of patients have lymphatic involvement and 90% have seminal vesicle
involvement if PSA >50 ng/mL
Clinical Features
Asymptomatic - Majority
Urinary complaints - LUTS
Retention, urgency, frequency, nocturia
Hematuria
Systemic complaints
Weight loss or loss of appetite
Anemia
Bone pain
Neurological deficits
Investigations
Prostate Cancer Screening
Digital rectal examination (DRE)
Prostate-specific antigen (PSA)
If screening is positive
Core needle biopsy is indicated
Gleason Score
TRUS
Not helpful for screening – common diagnostic modality
Transrectal Ultrasound Scanning (TRUS)
Most common diagnostic modality
With guided biopsies (10 to 12 biopsy regimen):
Lateral peripheral zone in initial biopsy
Transitional zone in repeat biopsy
Also measures the volume of prostate
Hyperechoic areas are indicative of cancers
Staging
T stage:
DRE
MRI or TRUS
N stage:
CT/MRI or biopsy as necessary
Pelvic lymph node dissection is the gold-standard assessment of N stage.
M stage:
Physical examination
Imaging (MRI or isotope bone scan, chest radiology)
Biochemical investigations (e.g., alkaline phosphatase)
Gleason score
Gleason Scores range from 6-10
Scores of 6 or less - cancer cells that
look similar to normal cells, slow
growing
A score of 7 - intermediate risk for
aggressive cancer.
Scores of 8 or higher - cancers that
are likely to spread more rapidly,
these cancers are often referred to as
poorly differentiated or high grade
Prediction models
Prostate Nomogram
[Link]
PSA is a driving variable
Partin Tables
Recently updated
Management
The patient’s overall life expectancy (as determined by age and
comorbidities) and overall health status
The biologic characteristics of the tumor, together with its predicted
aggressiveness and behaviour
Localized Prostate Cancer
Watchful Waiting
Palliative care
Not all men need to be treated
Co-morbids
Repeat biopsy in 1 year and follow PSA
PSA doubling times
Progressing Localized Cancer
Active surveillance
Advantages
Avoidance of possible side effects and costs of definitive therapy that may be
unnecessary, and maintaining quality of life
Disadvantages
Possibly missing an opportunity for cure, the risk of progression and/or metastases,
increased anxiety, increased physician visits and tests, and causing subsequent
treatment to be more aggressive
Patients must have clinically localized disease and be candidates for
definitive treatment and choose observation
DRE, PSA
Core needle biospy
Localized Cancer - Curative
Radical Prostatectomy
Indicated for the treatment of men in good health with localized
prostate cancer
Life expectancy exceeds 10 years, with curative intent
Procedure types
Open retropubic procedure
Laparoscopic
Robotically assisted
High-Risk Cancer
Radical External Beam Radiotherapy
Often accompanied by neoadjuvant and adjuvant hormone therapy in
high-risk disease
Indication
Life expectancy >5 years
Contraindication
Severe LUTS, IBD, previous pelvic irradiation
Raised PSA Post-EBRT (Relapse)
Salvage Radical Prostatectomy
Best suited to younger patients in good health; demanding and has poor outcome
Cryotherapy
Long-term results are promising but appear inferior to other standard therapies and
are not endorsed by the AUA in their 2007 treatment guidelines for localized disease.
High-intensity Focused Ultrasound
Potential of selective destruction of tissues at depth without damaging intervening
structures
For locally advanced nonmetastatic prostate cancer
Watchful waiting or active surveillance
Palliative treatment of locally advanced disease
Hormone therapy
EBRT with hormone therapy
Hormone therapy
In elderly patients or those
unwilling to consider radiotherapy
Blocks production and use of
androgens
Androgen suppression therapy
Androgen deprivation therapy
Adverse Effects of Hormone Therapy
Loss of interest in sex (lowered libido)
Erectile dysfunction
Loss of bone density
Bone fractures
Loss of muscle mass and physical strength
Changes in blood lipids
Insulin resistance
Weight gain
Mood swings
Fatigue
Growth of breast tissue (gynecomastia)
Thank You
