Prostate cancer

Question 1

Chemotherapy in prostate cancer

Answer 1

Taxels - docitaxel and cabazataxel - microtubule inhibitors

Question 2

First line treatment for prostate cancer

Answer 2

ADT + docetaxel + abiraterone

Question 3

Treatment for castrate resistant prostate cancer

Answer 3

Abiraterone and enzalutamide

Question 4

Side effects of abiraterone and enzalutamide

Answer 4

HTN , hot flushes, arthralgias, cognitive impairment

Question 5

First line for RCC

Answer 5

Levatinib and pembroluzimab - only for clear cell renal carcinoma

Question 6

Post nephrectomy management

Answer 6

pembrolizumab

Question 6

Management of bladder cancer - non muscle invasive

Answer 6

TURBT + intravesical BCG

Question 7

Definition of castrate sensitive and castrate resistant prostate cancer

Answer 7

Castrate sensitive: responsive to ADT
Castrate resistant: cancer grows despite ADT, rise in PSA or mets
Aggressive if PSA doubling < 8 months

Question 8

Risk factors for prostate cancer

Answer 8

AGE (esp >65 years old)
Family history (double the risk with one first degree relative)
Genetics (BRCA 1 or 2, MLH1, MSH 2/6)

Note: BPH and sexual activity has no association with prostate cancer

Question 9

Screening for prostate cancer

Answer 9

Controversial - only done in asymptomatic patients
Done by checking PSA levels
High levels can occur with urethritis, ejaculation, riding a bike, cancer etc

Question 10

Staging of prostate cancer

Answer 10

Stage I: confined to one lobe
Stage II: both lobes
Stage III: spread to seminal vesicles, lymph nodes, bladder or rectum
Stage IV: distant spread

Question 11

Symptoms of prostate cancer

Answer 11

Usually asymptomatic until disease has progressed to atleast stage 2 as cancer is usually peripheral and away from the urethra
When symptoms occur, it is usually due to urethral compression
Hesitancy, poor stream , urinary retention
Urinary incontinence if urethral sphincter infiltrated
Hematuria
Constitutional symptoms
Metastases
- Bone pain
- Neurological signs from cord compression sec to vertebral mets
Lymphoedema from LN infiltration

Question 12

Diagnosis of prostate cancer

Answer 12

PSA persistently elevated 1 month apart PSA > 4
DRE
DRE: Hard and indurated
Lobar asymmetry
Sulcus obliteration
Nodules
Biopsy: Transrectal guided biopsy
Take 5-7 samples as cancer is often in the peripheries
tumor localisation is poor with TRUS and have upto 46% false negative rate
Evaluate the histology to give Gleason score
Staging imaging: bone scan, CT, PET

Question 13

What is the Gleason score?

Answer 13

Gleason grade/pattern: depending on the degree of differentiation of tumor cells and stromal invasion, tumors are graded from 1 (well differentiated) to 5 (poorly differentiated)
Gleason score: the sum of the two most prevalent Gleason’s grades

Question 14

Management of non metastatic prostate cancer

Answer 14

Stage 1: active surveillance: Checking PSA 6 monthly, and DRE annually. Biopsy done at one year (then based on risk thereafter) or PSA doubling time < 3 years

Stage 2: Definitive management: Radical prostatectomy or
RTx (EBRT or brachytherapy)
Stage 3: Combined RTx (brachytherapy + EBRT) plus ADT OR
Radical prostatectomy +/- lymphadenectomy
Darolutamide - best evidence for prevention of metastases

Question 15

Pharmacological options for ADT or ARPI (androgen receptor pathway inhibitors)

Answer 15

ADT
GnRH agonists (- relins) e.g. gosrelin - cause surge of LH and FSH followed by suppression
GnRH antagonists (- lix) e.g. degarelix - cause suppression of LH and FSH

ARPI
1st gen anti-androgen - bicalutamide, flutamide - competitive antagonist of androgen receptor
2nd gen - enzalutamide - competitive antagonist of androgen receptor
3rd gen - darulutamide

CYP17 inhibitor - abiraterone and prednisone - blocks 17 alpha hydroxylase and prevents conversion of testosterone to DHT

Question 16

Side effects of abiraterone

Answer 16

Increased aldosterone synthesis - HTN, hypokalaemia, hyperNa, arrhythmias
Cortisol deficiency - needs to be given with prednisone

Question 17

Side effects of brachytherapy and EBRT

Answer 17

Proctitis, urethritis, cystitis
Erectile dysfunction

Question 18

Side effects ADT

Answer 18

Reduced oestrogen: increased CV risk, osteoporosis
Reduced testosterone : decreased libido, gynaecomastia, smaller penis and testis
Reduced cortisol - Addison’s crisis in ARPI

Question 19

Management of metastatic prostate cancer

Answer 19

Castrate sensitive:
ADT + docetaxel + darolutamide OR
ADT + docetaxel + abiraterone/ pred

Castrate resistant:
ADT + cabazitaxel +/- PARPi

BPP/ denusomab for bone disease

Question 20

Follow up for prostate cancer

Answer 20

PSA every 6 months for 5 years then annually for patients who have definitive local therapy
PSA every 3-6 months if on ADT

Question 21

Moa of taxels

Answer 21

Inhibition of microtubule assembly
Need to give GSCF to reduce risk of neutropenia

Question 22

Other newer non PBS approved treatments for prostate cancer

Answer 22

Pembrolizumab - if dMMR/ MSI -H)
PARPi - olaparib (BRCA 1/2) - diarrhoea main SE
Radiopharmaceuticals - 177-Leutitium PSMA and Radium 223 - xerostomia (Leu -17 as PSMA also present on salivary gland)