Urological Cancer Flashcards
Where in the kidney do RCCs (Renal Cell Carcinomas) originate?
Proximal tubule epithelial cells
Epidemiology of RCCs?
1-2% of malignancies
F:M = 2:1
Usually after 50 years of age, rarely before 40
Presentation of RCCs?
Generally asymptomatic
Generalised symptoms
Can have haematuria, loin pain/ mass
Polycythaemia (5%)
HTN (30%)
Pyrexia (20%)
Genetic Condition associated with RCCs?
Some details about it
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
Management of RCC
Nephrectomy
- if VHL disease consider partial nephrectomy
- still consider nephrectomy if there are Mets (they can get better after it’s removed)
Prognosis in RCC?
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%.
Systemic therapy in RCC?
Tyrosine Kinase inhbitoris:
- sunitinib or pazopanib
+/- pembrolizumab OR ipilimumab+nivolumab
+/- mTOR inhibitors
Common AE of VEGF-R TKIs?
GI: mucositis, stomatosis, diarrhoa (all TKIs)
Skin: dry, rash, hand-food syndrome
Thyroid: hypothyroid (risk increases with time)
LFT derangement (trans-aminitis +/- bili)
Most common bladder cancer? (in developed countries)
Urethelial Carcinoma/ Transitional Cell Carcinoma (TCC, 90%)
Non-urothelial carcinoma
- squamous carcinoma (more common worldwide - schistosomiasis)
- adenocarcinoma
Risk factors for bladder/ ureteric cancers?
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)
Which parts of the urinary system are lined with transitional cell epithelium?
calyces, renal pelvis, ureter, bladder, urethra
Presentation urothelial tumours?
painless haematuria (80%)
clots/ obstruction
UTI symptoms (no bacteria)
Flank pain (concerning for mets)
Treatment for urothelial cancers?
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)
Treatment for locally invasive Prostate Cancer?
(without distant Mets - T3, N0)
combined androgen deprivation and radiotherapy;
improves 10-year survival, compared with endocrine treatment alone, from 61% to 71%.
Treatment for Metastatic Prostate Cancer?
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,
How does prostate Cx become ‘castrate resistant’?
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.
GnRH agonist example(s)
goserelin and leuprorelin
GnRH antagonist example(s)
degarelix
Androgen deprivation strategies for prostate Cancer
Surgical orchidectomy
GnRH agonist (goserelin or leuprolin)
GnRH antagonist (degarelix)
Androgen receptor blocker (bicalutimode, enzalutamide)
Androgen synthesis inhibitor (abiraterone)
Corticosteroids/ oestrogens
Examples of androgen receptor blockers
bicalutamide
enzalutamide (more powerful)
Androgen synthesis blocker in Prostate Cancer, and MOA?
abiraterone
CYP17 inhibitor
Issue with GnRH agonists
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.
Chemo for prostate Cancer?
Docetaxel - increasing evidence to use earlier in METASTATIC prostate Cx
Targeted therapy in Prostate Cx
• 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.
Epidemiology Germ Cell tumours
1–2% of all cancers.
much less common in women.
most common cancers in men aged 15–35
Aetiology Germ Cell Tumours
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
Extra-gonadal sites of Germ Cell Tumours?
rarely occur in extragonadal sites in the midline,
- pituitary,
- mediastinum
- retroperitoneum
Ix for Germ Cell tumours
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.
Which tumours have raised AFP/ beta-HCG??
Non-seminomas
Seminomas:
- raised serum LDH
- only rarely a mildly raised β-hC
- never a raised AFP
Treatment for seminomas
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
Chemo in Seminomas
- 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.
Meds in BEP
cisplatin, etoposide and bleomycin
Fertility and Non-seminomatous Gem Cell tumours
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.
