Urological Cancer

Question 1

Where in the kidney do RCCs (Renal Cell Carcinomas) originate?

Answer 1

Proximal tubule epithelial cells

Question 2

Epidemiology of RCCs?

Answer 2

1-2% of malignancies

F:M = 2:1

Usually after 50 years of age, rarely before 40

Question 3

Presentation of RCCs?

Answer 3

Generally asymptomatic
Generalised symptoms
Can have haematuria, loin pain/ mass

Polycythaemia (5%)
HTN (30%)
Pyrexia (20%)

Question 4

Genetic Condition associated with RCCs?

Some details about it

Answer 4

Von Hippel–Lindau (VHL) disease

Autosomal dominant

presenting with:
- bilateral RCCs,
- retinal and cerebellar haemangioblastomas,
- phaeochromocytomas,
- pancreatic neuroendocrine tumours
- renal cysts.

VHL protein acts as a tumour suppressor by tagging hypoxia-inducible gene products (VEGF, TGF) for degradation. Inactivating mutations of the VHL gene lead to uncontrolled angiogenesis and neoplasia.

Aberrations in the von Hippel-Lindau (vHL) gene are observed in 50-90% of ccRCC

Collegen

Question 5

Management of RCC

Answer 5

Nephrectomy
- if VHL disease consider partial nephrectomy
- still consider nephrectomy if there are Mets (they can get better after it’s removed)

Question 6

Prognosis in RCC?

Answer 6

Calculated using: International Metastatic renal cell carcinoma Database Consortium (IMDC or Heng) criteria

1 point for each of:
• impaired fitness (<80% on the Karnofsky performance status score)
• haemoglobin below the lower limit of normal
• neutrophils above the upper limit of normal
• platelets above the upper limit of normal
• serum calcium above the upper limit of normal
• <12 months from diagnosis to the requirement for systemic chemotherapy.

Those with no adverse prognostic factors have a 2-year survival of more than 75% and are considered to have a good prognosis;
Those with one or two factors are regarded as having an intermediate prognosis and have an approximately 50% chance of surviving for 2 years;
Those with three factors or more have a poor prognosis and a 2-year survival of 7%.

Question 7

Systemic therapy in RCC?

Answer 7

Tyrosine Kinase inhbitoris:
- sunitinib or pazopanib
+/- pembrolizumab OR ipilimumab+nivolumab

+/- mTOR inhibitors

Question 8

Common AE of VEGF-R TKIs?

Answer 8

GI: mucositis, stomatosis, diarrhoa (all TKIs)

Skin: dry, rash, hand-food syndrome

Thyroid: hypothyroid (risk increases with time)

LFT derangement (trans-aminitis +/- bili)

Question 9

Most common bladder cancer? (in developed countries)

Answer 9

Urethelial Carcinoma/ Transitional Cell Carcinoma (TCC, 90%)

Non-urothelial carcinoma
- squamous carcinoma (more common worldwide - schistosomiasis)
- adenocarcinoma

Question 10

Risk factors for bladder/ ureteric cancers?

Answer 10

Transitional Cell Carcinomas (TCCs):
- Smoking
- Chemical exposure: petroleum/ chemical/ rubber/ cable industry workers (benzidine, beta naphthylamine)
- aristolochic acid (weight loss herbs)
- drug exposure (cyclophosphamide, phenacetin)
- male (4:1)
- age (uncommon < 40)

• schistosomiasis/ chronic inflammation (more squamous cell carcinomas)

Question 11

Which parts of the urinary system are lined with transitional cell epithelium?

Answer 11

calyces, renal pelvis, ureter, bladder, urethra

Question 12

Presentation urothelial tumours?

Answer 12

painless haematuria (80%)
clots/ obstruction
UTI symptoms (no bacteria)
Flank pain (concerning for mets)

Question 13

Treatment for urothelial cancers?

Answer 13

Superficial
- resection / diathermy
- bladder infusion of mycobacterium BCG (bacille Calmette-Guerin) or cytotoxic meds (gemcitabine or mitomycin)

Invasive urothelial cancer
- neoadjuvant chemo (cisplatin-based)
- cystectomy etc
- bladder conserving chemo radio

Metastatic
- palliative chemo (cisplatin-based)
- PD-1/ PDL-1 inhibitor

Upper tract tumours:
- surgery (nephro-ureterectomy)
- adjuvant chemo (cispaltinum/ gemcitabine)

Question 14

Treatment for locally invasive Prostate Cancer?

(without distant Mets - T3, N0)

Answer 14

combined androgen deprivation and radiotherapy;

improves 10-year survival, compared with endocrine treatment alone, from 61% to 71%.

Question 15

Treatment for Metastatic Prostate Cancer?

Answer 15

initially with androgen deprivation to achieve medical castration

Once this fails, the disease is termed ‘castration-resistant’;
- further palliative options are more potent hormonal drugs (such as androgen receptor blockers; see later) or conventional chemotherapy.

Targeted therapies
- PARP inhibitors
- Bone-targeted therapy - alpharadin (223radium), zoledronic acid, denosumab, palliative radiotherapy,

Question 16

How does prostate Cx become ‘castrate resistant’?

Answer 16

prostate cancer tissue is able to trap circulating androgens so that tissue levels of androgens are maintained, even despite very low levels of circulating androgens.

receptor super-sensitivity

altered ligand binding, allowing other steroids to act as agonists and eventually bypassing the androgen receptor.

Question 17

GnRH agonist example(s)

Answer 17

goserelin and leuprorelin

Question 18

GnRH antagonist example(s)

Answer 18

degarelix

Question 19

Androgen deprivation strategies for prostate Cancer

Answer 19

Surgical orchidectomy

GnRH agonist (goserelin or leuprolin)

GnRH antagonist (degarelix)

Androgen receptor blocker (bicalutimode, enzalutamide)

Androgen synthesis inhibitor (abiraterone)

Corticosteroids/ oestrogens

Question 20

Examples of androgen receptor blockers

Answer 20

bicalutamide

enzalutamide (more powerful)

Question 21

Androgen synthesis blocker in Prostate Cancer, and MOA?

Answer 21

abiraterone

CYP17 inhibitor

Question 22

Issue with GnRH agonists

Answer 22

in the first week, GnRH agonists produce a rise in luteinizing hormone (LH) and testosterone, which can result in a tumour flare in metastatic disease; they must therefore be combined with an antiandrogen, e.g. flutamide, in the initial phases.

Question 23

Chemo for prostate Cancer?

Answer 23

Docetaxel - increasing evidence to use earlier in METASTATIC prostate Cx

Question 24

Targeted therapy in Prostate Cx

Answer 24

• PARP inhibitors.
- if deficits in DNA repair, associated w BRCA2 gene. e.g. olaparib,

• Bone-targeted therapy.
- alpharadin (223 radium),
- zoledronic acid and denosumab
- palliative radiotherapy - used to target painful metastases.

Question 25

Epidemiology Germ Cell tumours

Answer 25

1–2% of all cancers.
much less common in women.
most common cancers in men aged 15–35

Question 26

Aetiology Germ Cell Tumours

Answer 26

Seminoma (termed ‘dysgerminoma’ in women)

non-seminoma
- varying proportions of mature and immature elements; mature elements are now known as teratoma (previously referred to all non-seminomas)
• Embryonal carcinoma
• Choriocarcinoma
• Yolk sac tumour
• Teratoma

Question 27

Extra-gonadal sites of Germ Cell Tumours?

Answer 27

rarely occur in extragonadal sites in the midline,
- pituitary,
- mediastinum
- retroperitoneum

Question 28

Ix for Germ Cell tumours

Answer 28

Assay of serum tumour markers
- α-fetoprotein (AFP),
- β-human chorionic gonadotrophin (β-hCG)
- lactate dehydrogenase (LDH).

Ultrasound or MRI scanning of the testicle or ovary

CT or MRI scanning is performed to seek distant metastases.

Question 29

Which tumours have raised AFP/ beta-HCG??

Answer 29

Non-seminomas

Seminomas:
- raised serum LDH
- only rarely a mildly raised β-hC
- never a raised AFP

Question 30

Treatment for seminomas

Answer 30

Surgery
- inguinal orchidectomy, to avoid spillage of highly metastatic tumour in the scrotum
- surgery for diagnosis and staging should always be conservative in women

Chemo
- depends on seminoma vs non-seminom and mets or no
- generally carboplatin or BEP

Question 31

Chemo in Seminomas

Answer 31

• Carboplatin is the first choice because of convenience, reduced acute side-effects in seminomas (surveillance legit option also)
• combination chemotherapy (e.g. cisplatin, etoposide and bleomycin, BEP) will cure over 90% of those with visible metastatic disease.

Question 32

Meds in BEP

Answer 32

cisplatin, etoposide and bleomycin

Question 33

Fertility and Non-seminomatous Gem Cell tumours

Answer 33

Although approximately 20% of men will be infertile due to azoospermia at the time of diagnosis, the majority of the remainder will retain their fertility after chemotherapy and be able to father children normally.

Similarly, most women retain their fertility.