Urological cancers Flashcards
What are the 3 types of androgen deprivation therapy in prostate cancer?
1) GnRH agonist - goserelin, leuprolide
2) GnRH antagonist - degarelix
3) Bilateral orchidectomy
What are the initial problems/risks of using GnRH agonists in prostate cancer?
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
Treatment of metastatic castration-sensitive prostate cancer
ADT AND one of
- Docetaxel chemotherapy
- Abiraterone acetate (only after docetaxel)
- Enzalutamide (only after docetaxel)
- Local radiotherapy
- Apalutamide
Treatment of metastatic castration-resistant prostate cancer
Chemotherapy: docetaxel, cabazitaxel
Androgen targeted therapies: abiraterone, enzalutamide (only after docetaxel)
PARP inhibitors
Immunotherapy (modest activity)
Radiopharmaceuticals
Toxicities of docetaxel
Motor/sensory peripheral neuropathy**
Cytopenia
Toxicities of cabazitaxel
Diarrhoea**
Cytopenia particularly neutropenia
Less sensory/motor peripheral neuropathy
MOA of abiraterone acetate
Stops adrenal and autocrine (from tumour) production of testosterone by inhibiting 17-alpha-hydroxylase
AEs of abiraterone acetate
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
MOA of enzalutamide
Androgen receptor antagonist
AEs of enzalutamide
Cognitive change
Seizures
Fatigue
Hypertension
What are the 2 types of RCC?
Clear cell (most common)
Non-clear cell
What is the importance of the VHL protein?
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
Treatment of metastatic clear cell RCC
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)
How do TKIs work in RCC?
Inhibit VEGF receptors –> stops RCC angiogenesis and cell proliferation
How do PD1 mAb work in RCC?
Binds to PD1 on T cell (so it can’t bind to PDL1 on tumour cell) –> stops inhibitory signal –> activates T cell to work
AEs of VEGF-R TKIs
GI - mucositis, stomatitis, diarrhoea
Skin - hand-foot syndrome
Hypothyroidism
LFT derangement, transaminitis
Cardiac - CCF, MI, arterial/venous thromboembolism, QT prolongation
Does cytoreductive nephrectomy have a role in metastatic RCC?
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
3 histologic classifications of bladder ca
TCC (most common in developed world)
SCC (most common in the world) due to schistosomiasis
Adenocarcinoma (arises from urachal remnant, treat like GI cancer)
What is the gold standard treatment for muscle invasive bladder ca?
Radical cystectomy + neoadjuvant chemotherapy (cisplatin, gemcitabine)
Who is ineligible for cisplatin (gold standard for muscle invasive bladder ca)?
ECOG 2 and above CrCl <60 Grade 2 hearing loss Grade 2 neuropathy NYHA class 3
Which is a lot of old people!
What’s 2nd line therapy for muscle invasive bladder ca?
I.e. not eligible for platinum or progression on platinum
Immunotherapy!
However only 20% responsive rate
PD1 mAb: nivolumab, pembrolizumab
2 types of testicular ca
Which one produces AFP and BHCG?
Seminoma (50%)
Non-seminoma (50%)
Both make BHCG
Non-seminoma makes AFP
Treatment of testicular ca
Orchidectomy + chemotherapy + surveillance (high recurrence)
Diagnosis of prostate ca requires
Histology from Biopsy
Grading of prostate ca
ISUP
no longer use Gleason score
Role of PSMA PET scan
Superior in detecting metastatic disease than whole body bone scan or CTCAP
