Prostate Cancer Flashcards
Androgens
- Normal growth and differentiation of the
prostate depends on the presence of
androgens - Prostate CANCER depends on androgens for
growth - LHRH is released from the hypothalamus
stimulating release of LH and FSH from
anterior pituitary gland - LH stimulates production of testosterone
in testes - Testosterone makes up 95% of circulating
androgens - Testicular androgens are the major driver of
prostate cancer growth
Steroidogenesis – Androgen creation
- Androgen biosynthesis pathway can
exist in any tissue but for men, it’s
primarily in testes (90-95%) and
adrenal gland (5-10%) - Cholesterol is the foundational
molecule for creating other hormones
including testosterone,
glucocorticoids, & mineralocorticoids - CYP17 is a critical enzyme for
conversion of pregnenolone/
progesterone to androgens or cortisol.
Androgens in Prostate Cancer
- Testosterone from testes is
converted to Dihydrotestosterone
(DHT) within the prostate cell - Activation of Androgen Receptor
(AR) by DHT in prostate cancer
cells: - Signals cell growth and proliferation
- Prevents apoptosis
- Drive an increase in Prostate Specific
Antigen (PSA)
Prostate Specific Antigen (PSA)
- PSA is a protein produced by cancerous and non-cancerous prostate
tissue - PSA can be measured through a blood test
- Normal 0-4 ng/mL
- Normal rising of PSA occurs with aging
- PSA of >10ng/mL can be suggestive of prostate cancer
Normal PSA can still have cancer
Using PSA for Prostate Cancer Screening
- Limitations:
- No PSA value completely excludes prostate cancer
- Low PSA thresholds for further investigations increases the probability of false positive
(overdiagnosis) - Low specificity – PSA can be elevated for several different reasons (not just in cancer)
- PSA can be used for screening but is controversial
- Men should discuss with their physician starting at age 50
- MyHealth.Alberta offers a patient discussion aid to facilitate shared decision making regarding PSA
- PSA screening is more likely to be considered in those at higher risk (but is still not
recommended by guidelines) - African ancestry
- Father or brother that had prostate cancer before age 65
- Genetic disposition (such as BRCA mutation)
Prostate Cancer Screening
pros and cons
Prostate cancer is more likely to be found with PSA testing than
without PSA testing (10% who are screened will be diagnosed
vs 7% who are not screened
help find some prostate cancers early
cons
High PSA level is not specific to cancer. It can be high due to
several reasons (BPH, infection).
Overdiagnosis (can identify a cancer that would not have
caused a problem) and lead to unnecessary treatment
(estimated about 27 out of 1,000 men may get treatment they
don’t need).
without PSA testing (10% who are screened will be diagnosed
vs 7% who are not screened
Only a small proportion of prostate cancer causes symptomatic
disease or death. Most prostate cancers progress slowly and
are not life threatening
Harms such as false positives, overdiagnosis, and complications
with follow up tests (bleeding, infection, urinary incontinence)
commonly occur with PSA screening
- Digital Rectal Examination (DRE)
- Palpation of the prostate through
the rectum - Canadian Task Force on
Preventative Health Care no
longer recommends as a method
of screening (as of 2014) - No evidence that DRE reduces
prostate cancer mortality - DRE can help support a suspected
diagnosis of Prostate Cancer
risk factors
Age
* Over 70% of cases are diagnosed in men over 65
years old
* Ethnicity:
* African decent have higher incidence and mortality rate
* Low rate in Japan and other Asian countries
Higher testosterone in African populations
Data is coming out to say it is due to social determinants of health, later access to health care for African population
Warning signs are ignored
- Family history (brother or father)
- Risk increases two fold
- Germline genetic mutations (about 12% of men
with metastatic prostate cancer have a germline
mutations known to increase cancer risk) - BRCA 1 or 2
- Lynch syndrome
- Various others
- Diet/Supplements
- Mediterranean diet reduces risk
- Increased risk with high meat or high fat diet
- Vitamin E (SELECT trial found Vitamin E increased
risk by 17%) Vitamin E supplementation actually has higher incidence of prostate cancer - Hormonal
- Not present in castrated men
- Up to 80% are hormone-dependent
- African decent have 15% increased testosterone
- Japanese decent have lower 5-alpha-reductase
activity - Smoking increases risk and mortality\
- Benign Prostatic Hypertrophy (BPH)
- Does not appear to increase prostate cancer risk
- Has similar symptoms and hence can complicate the
diagnosis of prostate cancer
Symptoms could be masked by thinking it is BPH
Prostate Cancer – Clinical Presentation
- Local Disease
- Asymptomatic
- Ureteral dysfunction
- Frequency, hesitancy, dribbling
- Impotence
- Advanced Disease
- Back pain, cord compression,
fractures (bone is the most
common site of metastases) - Anemia
- Weight Loss
Prostate Cancer Diagnosis and Workup
- Diagnosis:
- Diagnosis done via ultrasound guided needle biopsy
- Transrectal biopsy or transperineal biopsy
- Elevated PSA and/or abnormal DRE are NOT diagnostic for prostate cancer
although they do serve to risk stratify patients - Workup
- History & physical exam
- Laboratory tests (CBC, SCr, urinalysis)
- PSA – likely done before biopsy
- Bone scan or CT scan if high risk (assessment for mets)
- MRI
Factors to Consider for Developing Treatment Plan
- Disease Factors:
- Stage
- TNM
- Localized vs Regional vs Metastatic
- Risk Category
- Grading
- Pathology or Histologic Stage
- Gleason Score or Grade Group
- Prostate Specific Antigen (PSA)
- Patient Factors:
- Life expectancy:
- ≥ 20 years, 10-20 years, < 10 years
- Symptoms
- Is patient symptomatic??
staging?
slide 17
Prostate Cancer Grading (determining “risk”)
- Grading is based on histologic
appearance - Rated on a scale of 1 (well differentiated)
to 5 (poorly differentiated) - “Gleason score”
- Two score from two samples added
together (sum out of ten) - “Grade Group”
- Two scores written separately “3+4”
- Poorly differentiated tumours typically
grow more rapidly and carry a poorer
prognosis.
Look at 2 samples taken from biopsy
How far wawy from good looking prostate cells are we?
What is the most prominent cell and pattern seen?
PSA (determining “risk”)
based on PSA level
- PSA level in Prostate Cancer Patient
- <10 ng/mL – low risk indicator
- 10-20 ng/mL – intermediate risk indicator
- > 20 ng/mL – high risk indicator
- How fast a PSA is rising can also be a clue to disease
aggression (PSA doubling time)
Treatment Modalities
- Active Surveillance
- Ongoing close monitoring (symptom monitoring & scheduled monitoring of PSA and DRE, with repeat biopsies if clinically indicated)
- Surgery
- Radical prostatectomy (RP)
- Surgical removal of prostate gland and surrounding tissues (including seminal vesicles)
- Adverse effects include urinary incontinence and/or erectile dysfunction
- If “nerve sparing”, then 50-80% regain sexual potency within the first year
- Pelvic Lymph Node Biopsy (PLNB)
- Done with RP if patient is deemed high risk of developing lymph node metastases
- Orchiectomy (surgical castration)
- Rarely done
- Radiation
- External beam radiation therapy (EBRT) and/or Brachytherapy - Refer to Radiotherapy lecture (Dr Debenham)
- Pharmacotherapy
- Androgen Deprivation Therapy (“Medical Castration”)
- “Novel” hormonal manipulation therapies (enzalutamide/apalutamide or abiraterone)
- Chemotherapy
