Prostate Cancer

Question 1

Risk factors for prostate ca? (4)

Answer 1

Age >50

FH

High-levels of dietary fat

Ethnicity: Black, North American, Northwestern European

Question 2

Symptoms of prostate Ca (diagnosis)? (5)

Answer 2

Any urinary symptoms: nocturia, frequency, hesitancy, dysuria, haematuria

UTIs

Constitutional

Bone pain

Palpable lymphadenopathy

DRE

Question 3

Key exam findings to ask for? (5)

Answer 3

Weight & BMI

Pallor

Bony tenderness (metastatic disease)

Lymphadenopathy (metastatic disease)

DRE - asymmetrical, nodular.

Question 4

Would you use PSA for prostate cancer screening?

Answer 4

The best available evidence suggests that screening for prostate Ca has at most small benefit

For example, NNTS was 1,400 to prevent 1 cancer-related death in a big RCT

Furthermore, there are risk associated with prostate biopsy (2%), concern of overdiagnosis with unnecessary anxiety.

Generally, no benefit unless the life-expectancy is at least 10 years

In this regard, I would not routinely screen this patient with an average risk

However, I will discuss the pros & cons of pursuing screening.

Exception is of course when the patient has high-risk of prostate Ca (e.g. FH, Black men, suspected BRCA…etc).

Question 5

What investigations would you like to review for this patient with prostate Ca?

Answer 5

T: confirm Dx - histopathology (abnormal cells in 2 different samples) and radiology (XR/CT - lytic or sclerotic lesions, bone scan?mets) for staging. MRI is useful: T2WI - intra-prostatic lesion, TIWI - lymph node or bone lesions.

E: r/v urine MCS to rule out coexisting infection, nephrotic/nephritic syndrome

S: PSA level (>4 mcg/L)

Treatment baseline: testosterone (androgen deprivation therapy), FBC, EUC, LFTs (for ADT - hepatitis)

Screen for complications: EUC (renal impairment), USS (obstructive uropathy/atrophy from chronic damage, hydronephrosis), VQ scan (PE)

Question 6

What would you do about his prostate cancer (local disease)? (you are keen on wait and see - 3 facts)

Answer 6

I would be more inclined to monitor/conservatively Mx since…

1. There are no high-risk features (advanced stage or high-grade) and PSA is <10
2. No signs of complications: symptoms, renal failure
3. Patient’s expected survival is <10 (if so more argument for doing nothing)

Overall, the chance of this localisede prostate cancer affecting patient’s mortality is unlikely to be high.

Question 7

What are the treatment options for localised prostate Ca? (3)

Answer 7

EBRT + neoadjuvant ADT

Brachytherapy

Radical prostatectomy

Question 8

Approach (specific pharmacology) to managing metastatic prostate cancer?

Answer 8

1st line = upfront ADT +/- chemo (docetaxel) if can tolerate = SOC.

ADT requires castration (i.e. inactivating testes - bilateral orchidectomy or GnRH agonist or GnRH antagonist) → then commence Anti-androgens (Enzalutamide, Abiraterone - if so need to give prednisolone)

Zolendronate or denosumab if bone mets (no effects on OS but decreases skeletal events)

if progresses - options include Cabazitaxel

Question 9

What is the risk associated with castration (i.e. GnRH agonist or bilateral orchidectomy)?

Answer 9

Risk of flare-up due to sudden increase in LH/FSH → testosterone → worsening disease, epidural/spinal cord compression or urinary outflow obstruction. Anti-androgens can prevent this flare phenomenon.

Question 10

What is the major side effect of Abiraterone? Why do you think this patient is on steroid?

Answer 10

It is a Cyp-17 blocker → blocks cortisol synthesis → excess ACTH production → mineralocorticoid excess

This results in aldosterone excess → Hypokalaemia and HTN

So must give Prednisolone with it

Question 11

Side effect of Enzalutamide? (1)

Answer 11

Lowers seizure threshold.

Question 12

Gleeson score meaning and range

Answer 12

Higher - more aggressive

Ranges from 2-10.

Question 13

What is Castration? 2 methods?

Answer 13

Castration is a process of removing/inactivating the testicles, where Androgens are synthesized in men.

1. Surgical orchidectomy
2. Chemical castration - GnRH agonist or antagonist (Leuprorelin, Goserelin, Buserilin…etc)

Question 14

The rationale for Anti-Androgen therapy even after castration?

Answer 14

Adrenal glands still is a source of Androgen production even after the castration process.

Thus, we need either androgen receptor blocker (hence blocking testosterone binding to prostate Cancer cells which promotes it’s growth) or impair testosterone synthesis.

Question 15

2 main classes of anti-androgen therapy and how do they work? Give drug examples

Answer 15

1. Androgen receptor blockers: Cyproterone acetate, Bicalutamide, Enzalutamide
2. Testosterone synthesis blocker (e.g. 17-alpha hydroxylase inhibitor) - Abiraterone