Urological cancers

Question 1

What are the 3 types of androgen deprivation therapy in prostate cancer?

Answer 1

1) GnRH agonist - goserelin, leuprolide
2) GnRH antagonist - degarelix
3) Bilateral orchidectomy

Question 2

What are the initial problems/risks of using GnRH agonists in prostate cancer?

Answer 2

Androgen flare

GnRH agonist –> stimulates pituitary –> stimulates LH production –> transient increase of testosterone –> flare of symptoms especially in extensive mets, urinary retention, bone pain, visceral disease

Question 3

Treatment of metastatic castration-sensitive prostate cancer

Answer 3

ADT AND one of

• Docetaxel chemotherapy
• Abiraterone acetate (only after docetaxel)
• Enzalutamide (only after docetaxel)
• Local radiotherapy
• Apalutamide

Question 4

Treatment of metastatic castration-resistant prostate cancer

Answer 4

Chemotherapy: docetaxel, cabazitaxel

Androgen targeted therapies: abiraterone, enzalutamide (only after docetaxel)

PARP inhibitors

Immunotherapy (modest activity)

Radiopharmaceuticals

Question 5

Toxicities of docetaxel

Answer 5

Motor/sensory peripheral neuropathy**

Cytopenia

Question 6

Toxicities of cabazitaxel

Answer 6

Diarrhoea**
Cytopenia particularly neutropenia
Less sensory/motor peripheral neuropathy

Question 7

MOA of abiraterone acetate

Answer 7

Stops adrenal and autocrine (from tumour) production of testosterone by inhibiting 17-alpha-hydroxylase

Question 8

AEs of abiraterone acetate

Answer 8

Inhibits 17-alpha-hydroxylase in the adrenal so it shifts production to mineralcorticoid

Hypertension
Hypokalaemia
Peripheral oedema

Also transaminitis (unrelated)

Need coadministration of corticosteroids to reduce side effects

Question 9

MOA of enzalutamide

Answer 9

Androgen receptor antagonist

Question 10

AEs of enzalutamide

Answer 10

Cognitive change
Seizures
Fatigue
Hypertension

Question 11

What are the 2 types of RCC?

Answer 11

Clear cell (most common)

Non-clear cell

Question 12

What is the importance of the VHL protein?

Answer 12

Hypoxia –> hypoxia inducible factor (HIF) –> stimulates angiogenesis, cell proliferation

VHL protein keeps HIF in check and prevents unnecessary angiogenesis, cell proliferation

= Mutated VHL protein –> excessive HIF –> cancer

Question 13

Treatment of metastatic clear cell RCC

Answer 13

1) TKIs e.g. sunitinib
= Favourable risk disease

2) PD1 mab e.g. nivolumab, ipilimumab
CTLA4 + PD1 mab
= Intermediate/poor risk disease

3) mTOR inhibitors (small role)

Question 14

How do TKIs work in RCC?

Answer 14

Inhibit VEGF receptors –> stops RCC angiogenesis and cell proliferation

Question 15

How do PD1 mAb work in RCC?

Answer 15

Binds to PD1 on T cell (so it can’t bind to PDL1 on tumour cell) –> stops inhibitory signal –> activates T cell to work

Question 16

AEs of VEGF-R TKIs

Answer 16

GI - mucositis, stomatitis, diarrhoea

Skin - hand-foot syndrome

Hypothyroidism

LFT derangement, transaminitis

Cardiac - CCF, MI, arterial/venous thromboembolism, QT prolongation

Question 17

Does cytoreductive nephrectomy have a role in metastatic RCC?

Answer 17

No
Used to be standard of care
But now we have systemic therapy we rarely do this anymore unless tumour was too bulky and patient was symptomatic of it

Question 18

3 histologic classifications of bladder ca

Answer 18

TCC (most common in developed world)

SCC (most common in the world) due to schistosomiasis

Adenocarcinoma (arises from urachal remnant, treat like GI cancer)

Question 19

What is the gold standard treatment for muscle invasive bladder ca?

Answer 19

Radical cystectomy + neoadjuvant chemotherapy (cisplatin, gemcitabine)

Question 20

Who is ineligible for cisplatin (gold standard for muscle invasive bladder ca)?

Answer 20

ECOG 2 and above
CrCl <60
Grade 2 hearing loss
Grade 2 neuropathy
NYHA class 3 

Which is a lot of old people!

Question 21

What’s 2nd line therapy for muscle invasive bladder ca?

I.e. not eligible for platinum or progression on platinum

Answer 21

Immunotherapy!
However only 20% responsive rate

PD1 mAb: nivolumab, pembrolizumab

Question 22

2 types of testicular ca

Which one produces AFP and BHCG?

Answer 22

Seminoma (50%)
Non-seminoma (50%)

Both make BHCG
Non-seminoma makes AFP

Question 23

Treatment of testicular ca

Answer 23

Orchidectomy + chemotherapy + surveillance (high recurrence)

Question 24

Diagnosis of prostate ca requires

Answer 24

Histology from Biopsy

Question 25

Grading of prostate ca

Answer 25

ISUP

no longer use Gleason score

Question 26

Role of PSMA PET scan

Answer 26

Superior in detecting metastatic disease than whole body bone scan or CTCAP