Oncological aspects of urological cancer Flashcards
1
Q
Name the types of urological cancer
A
- prostate - most common
- renal cancer
- testicular
- bladder
- penile - least common
2
Q
What is screening for
A
- To detect cancer in its early stages
- Often patient may be asymptomatic
- Early detection leads to better cure rates
3
Q
What is adjuvant therapy for
A
- to remove as much of the tumour as possible
4
Q
Name types of adjuvant therapy
A
- chemotherapy
- Endocrine treatments
- biological therapy
5
Q
What is the risk factors for prostate cancer
A
- high fat diet
- smoking
- family history
- high testosterone
- afro-caribbean
6
Q
What is the screening that is used in prostate cancer
A
- PSA
- DRE in combination with PSA is more useful
7
Q
why is PSA not necessarily a good screening test
A
- not an adequate screening test as there are significant numbers of false negative and positives
8
Q
What is PSA more useful in measuring
A
- monitoring response to treatment
9
Q
How do you confirm diagnosis in prostate cancer
A
- TRUS - transurethral ultrasound biopsy which is used to confirm diagnosis
10
Q
what are the symptoms of prostate cancer
A
- majority are asymptomatic
- LUTs - nocturia, frequency, poor stream, hesitancy, terminal dribbling
- haematospermia
- haematuria
- perineal discomfort
- leg oedema
- anorexia and weight loss
11
Q
What are the symptoms of metastatic prostate disease
A
- bone pain and anaemia
12
Q
what can locally advanced prostate cancer lead to
A
- rectal symptoms and renal failure due to urinary tract outflow obstruction
13
Q
What investigations would you use in prostate cancer
A
- DRE
- Blood
- Biopsy
- imaging
14
Q
What does a DRE fill like in prostate cancer
A
- hard
- irregular
15
Q
What does bloods look like in prostate blood
A
- raised PSA (normal in 30% of cancer cases)
16
Q
What biopsy do you do in prostate cancer
A
- transurethral ultrasound biopsy - this confirms diagnosis after raised PSA and abnormal DRE
17
Q
What imaging do you use in prostate cancer
A
- X rays
- CT/MRI (used for staging)
- bone scan (only in high risk of bony mets)
18
Q
What type of cancer is prostate cancer
A
- adrenocarcinoma - 95%
19
Q
what area does prostate cancer tend to be in
A
- peripheral zone - 75%
- transition zone - 20%
- central zone - 5%
20
Q
Where do tumours spread in prostate cancer
A
Local
- seminal vesicles
- bladder
- rectum
lymph or haematogenous
- sclerotic bony lesions
21
Q
What do you need to warn patients of prior to treatment in prostate cancer
A
- warn prior to radical treatment for potential of loss of sexual function as well as effects on urinary system
- warn of potential loss of ejaculation and fertility
22
Q
What score is used to grade prostate cancer
A
Gleason score
23
Q
Describe how the Gleason score works
A
this is a score of the most common histological pattern seen + the highest grade of tumour histology seen
- a lower Gleason score is a better prognosis
24
Q
What are the options for treatment of prostate cancer
A
- Surgery - often a transurethral resection of the prostate (TURP)
- Radiotherapy
- cryotherapy
25
According to the Gleason score what is well differentiated versus a poor differentiated tumour
= 6-7 - well differentiated
= 7-8 - moderately differentiated
= 9-10 - poorly differentiated
26
what is the removal of the prostate gland called
- Prostactomy
27
Who is a prostactomy considered in
- considered with patients for a life expectancy of 15 years
- PSA <15
- under 75 years old
- no co-morbidities
28
What are the types of radiotherapy that can be used in prostate cancer
- External bean
- Brachytherapy = implanting radioactive seeds into the prostate - causes LUTs and can make patients go into urinary obstruction (confined to small tumours)
29
most prostate cancer is responsible to the withdrawal....
most prostate cancer is responsible to the withdrawal of androgens
30
name the types of endocrine therapy that is used in prostate cancer
- medical castration
- androgen receptor antagonists in castrate resistant patients
- inhibition of CYP12
31
How is medial castration achieved in prostate cancer
- GNRH analogues such as goseralin
32
a rapid fall of PSA...
- A rapid fall in PSA and a nadir of <1 suggests a good long term outcome
33
what happens in prostate cancer when the cancer is castrate resistant
- it is named androgen independent
- Blockade of adrenal androgens using a peripheral androgen receptor antagonist drug (eg bicalutamide) is effective in around 20% of these castrate resistant patients
34
Name the drugs that are used in castrate resistance prostate cancer
- Androgen receptor antagonists – bicalutamide, enzalutamide
- Corticosteroids – prednisolone and dexamethasone
- Oestrogens – oestradiol
- CYP 17 inhibitors – Abiraterone – very high response rate recorded but suggestion of lower response after corticosteroids
35
Describe what happens in the inhibition of CYP17 in prostate cancer
- The enzyme complex blocks a hydroxylation of pregnenolone and removes the carbon chain on the steroid ring converting a C21 steroid to a C17 steroid – androgen precursors reduce and pregnenolone rises
- If dexamethasone given as well then this suppresses ACTH and therefore pregnenolone will fall
36
What is enzalutaminde (prostate cancer treatment)
* Androgen receptor antagonist ( 5x affinity of bicalutamide)
* Also prevents androgen receptor binding DNA and co-activator proteins
* Able to overcome bicalutamide resistance
* 67% response rate in chemo-naïve and 50% in chemotherapy treated patients
37
What type of chemotherapy drugs is used in prostate cancer
Taxanes
38
name some example of taxanes that is used to treat prostate cancer
- docetaxel
| - cabazetaxel - modified taxane to overcome docetaxel resistance
39
What are the side effects of docetaxel
- infection
- tiredness
- hair loss
40
What palliative care do you use in prostate cancer
- Palliative radiotherapy
- Bisphopshonates for bone disease – zoledronate
- RANKL inhibitor for metastatic disease – denosumab
- Analgesics
- Blood transfusion for anaemia
41
What is the management for localised prostate cancer
Low risk: active surveillance, if signs of disease progression opt for radical treatment
Moderate to high risk:
- Offer active surveillance if moderate risk and they don’t want radical treatment
- Radical prostatectomy or TURP OR radical radiotherapy (radical external beam ± brachytherapy)
- Offer adjuvant hormonal therapy
42
What is the management of locally advanced prostate cancer
- pelvic radiotherapy
- neoadjuvant hormonal and radiotherapy
- radical prostatectomy
43
What is the symptomatic management of metastatic disease
- analgesia
- management of hypercalcaemia and bone disease - bisphosphonates, RANKL inhibition (denosumab)
- radiotherapy for bony mets and SC compression
- blood transfusion for anaemia
44
What are the risk factors for renal adenocarcinoma
- Men>women (×1.5)
- Smoking (×1.4-2.3)
- Renal failure and dialysis (×30)
- Hypertension (1.4-2.0)
- Obesity
- Genetic factors – von Hippel Lindau (VHL) syndrome (around 50% develop RCC)
45
what is the classical triad of symptoms for renal adenocarcinoma
- macroscopic haematuria
- palpable mass
- flank pain (<10%)
46
What are the other presentations of renal adenocarcinoma
- microscopic haematuria
- abdominal pain
- malaise, anorexia, weight loss
- polycythaemia (5%) due to increased EPO by tumour
- hypertension (30%) - due to increased renin by tumour
- anaemia (30%) in case of decreased EPO
- fever
- varicocele with L sided tumours that have infiltrated the renal vein
- paraneoplastic syndrome
47
How does renal adenocarcinoma spread
- via lymph, haematogenous or direct routes to bone, liver and lung
48
What is the histology and genetics of renal adenocarcinoma
- Clear cell carcinoma (80%) – Von-hippel lindau mutation
- Papillary type 2 (10%) – fumarate/hydratase mutation
- Papillary type 1 (5%) – C-met activation
- Chromophobe (5%) – C-kit
49
What are the investigation of renal cell carcinoma
- BP - increased due to increased renin secretion
- Blood - FBC (polycythaemia), ESR (usually increased), U&Es, LFTs, Calcium
- urine - blood cells, cytology for malignant cells of no value
- Imaging
50
What imaging is used in renal adenocarcinoma
- US renal and tract - may show solid lesion
- CT abdomen with contrast - used to identify renal lesion and involvement of renal vein or IVC
- MRI - better than CT for cancer staging
Looking for metastases
- CT chest (lung)
- Bone/DEXA scan (bone)
51
What is the management of renal adenocarcinoma
- localised
- locally advanced
- metastasis
- Localised – radical or partial nephrectomy (open or laparoscopic)
- Locally advanced – radical nephrectomy + adjuvant treatment
- Metastasis – immunotherapy
52
What is the surgical management of renal adenocarcinoma
- radical nephrectomy - unless bilateral tumours are present or contralateral kidney functions poorly = partial nephrectomy
53
What is the medical management for renal cell carcinoma
- overreaction of various protein kinases is thought to be a major factor in many cancers
- blocking these pathways may lead to reduced progression/cure
- Tyrosine kinase inhibitors
- immunotherapy
- mTOR inhibitors
- VEGF inhibitors
54
Name some tyrosine kinase inhibitors in renal cell carcinoma
sunitinib, sorafenib, pazopanib
55
Name some immunotherapy used in renal cell carcinoma
high-dose IL-2
56
Name some mTOR inhibitor
- Sirolimus
| - Everolimus
57
Name VEGF inhibitors
- bevacizumab
58
Describe when high dose IL2 is used in renal cell carcinoma treatment
- For fit patients not anaemic, normal WBC and platelets
- IL-2 response rate is 3-40%
- 10% cure rate – often durable
- Requires in patient admission – very toxic whilst being administered
59
How does wills tumour present
- seen within ages 1-3
| - presents as abdominal mass
60
How do you detect an Wlims tumour
- US
- CT
- MRI
61
What is the treatment of wilms tumour
- nephrectomy
- radiotherapy
- chemotherapy
62
What type of cancer is bladder cancer
- Transitional cell carcinoma
63
What is the second most common urological malignancy in the UK
- bladder cancer
64
where do transitional cell carcinoma arise
- affect urothelium and may occur anywhere between renal pelvis and urethra
65
any episode of haematuria should be...
Any episode of haematuria should be investigated to exclude bladder cancer
66
where do transitional cell carcinoma eventually infect
- tumours begin in the urothelium and become deeper eventually penetrating the muscle and getting fixed to other pelvic structures such s there ectum
67
What are the two main risk factors for transitional cell carcinoma
- aniline dyes
| - smoking
68
Name other risk factors for transitional cell carcinoma
- Men>women (x2.5)
- smoking
- age
- occupational - aniline dyes, rubber/paint
- cyclophosphamide
- chronic inflammation of bladder mucosa
69
What are the risk factors for squamous cell carcinoma of the bladder
- schistomiasis
- BCG Treatment
- smoking
70
What is the presentation of bladder cancer
- painless macroscopic haematuria = age >50: 34% have TCC bladder, age <50: 10% have TCC bladder
- microscopic haematuria = age> 50: 7-13% have TCC, age<50: 5% have TCC
- lower urinary tract symptoms
- recurrent UTIs
- pain
- leg oedema
71
What investigations should you carry out if you suspect bladder cancer
Persistent microscopic haematuria (2/3 dipstick tests) or macroscopic haematuria must be investigated:
- Bloods – U&Es
- Urine – MC&S, cytology
Imaging –
- Renal USS
- Intravenous urogram (IVU)
- Flexible cystoscopy + biopsy – diagnostic
- CT urogram – diagnostic + staging
- CT/MRI – pelvic lymph node involvement
72
What is the pathology of bladder cancer
- Papillary – 70%
- Mixed papillary and solid – 10%
- Solid – 10%
- Carcinoma in situ – 10%
Grade 1 – differentiated
Grade 2 – intermediate
Grade 3 – poorly differentiated
73
Where does bladder cancer spread to
- local = pelvic structures
- Lymphatic = para-aortic nodes
- Haematogenous - liver + lungs + bone
74
what is the management if bladder cancer is Tis/Ta/T1
Surgical
- Diathermy via transurethral cystoscopy or
- TURBT
- consider intravesical chemotherapy for multiple small tumours or high grade tumours
- mitomycin C, doxorubicin, cisplatin as maintenance
75
What is the management of bladder cancer if it is T2-3
T2-3
Radical cystectomy – gold standard
- Radiotherapy preserves the bladder but gives worse survival rate
- “Salvage” cystectomy can be performed if radiotherapy fails (less effective than first-line surgery)
- Post-op chemotherapy is effective but toxic – M-VAC (Methotrexate, Vinblastine, Adriamycin & Cisplatin)
- Neoadjuvant chemotherapy of CMV (Cisplatin, Methotrexate, Vinblastine) ↑survival vs. stand-alone cystectomy or radiotherapy
- If the bladder neck isn’t involved, reconstruction can de attempted, not at the cost of full tumour resection (vs. urostoma) – both use ~40cm of ileum (review with oncologist and urologist)
76
What is the management of T4 bladder cancer
- Palliative chemotherapy and/or radiotherapy
| - chronic catheterisation and urinary diversions may ease pain
77
what is the follow up for bladder cancer
- Hx, examination and regular cystoscopy ± CT
- High-risk tumour 🡪 every 3months for 2yrs; every 6months afterwards
- Low-risk tumour 🡪 1st cystoscopy at 9 months; annually afterwards
78
What is the complications of bladder cancer
- sexual and urinary dysfunction
| - bladder haemorrhage
79
What is the prognosis of bladder cancer
- median survival = 12-15 months
| - 8% of those with metastatic disease will be cured
80
what chemosensitive combinations are proposed for bladder cancer
o gemcitabine and cisplatin
| o cisplatin and methotrexate
81
What are the two types of germ cell tumours
- seminomas
| - non-seminomas
82
What tumour markers do germ cell tumours produce
- Alpha-fetoprotein (AFP)
- Beta-human chorionic gonadotrophin (β-HCG)
- Lactate dehydrogenase (LDH)
83
Where do germ cell tumours arise
- retroperitoneum
| - mediastinum
84
What are the risk factors for germ cell tumours
- race (Caucasian x 3 compared to afro-caribbean)
- undescended testicles
- HIV
- Infertility
- first degree relative
85
How does germ cell tumours present
Most commonly presents as stage 1
- confined to testes
- painless scrotal lump
delay seeking of help - metastasis (lymph nodes, lungs, liver and brain)
- weight loss
- bone pain
- secondary hydrocele
- SOB
- abdominal masses
86
What are the investigations of germ cell tumours
- Blood – tumour markers (AFP, β-HCG, LDH), LFTs, bone profile, FBC
Imaging –
- Testicular USS – hypoechoic region distorting normal architecture
- CT abdo and chest (staging)
- CXR
- Excision biopsy
87
Name the types of germ cell tumours
Germ cell tumours (90%)
- Seminoma (SGCT)
- Non-seminoma (NSGCT)
Non-germ cell tumours
Sex cord stromal tumours (3%)
- Leydig cell
- Sertoli cell
88
What is the management of germ cells
- non metastatic disease
- metastatic disease
- seminoma
- non-seminoma
- Non-metastatic disease: orchidectomy (+radiotherapy = ~95% cure)
- Metastatic disease: orchidectomy + chemotherapy (3-4 cycles) of cisplatin+ etoposide +bleomycin (85-90% cure)
- Seminoma – single-dose chemotherapy + resection of mets if needed
- Non-seminoma – single-dose multidrug treatment
89
What is the main risk factor for penile cancer
Human papilloma virus is the main risk factor
90
if you are circumcised you do not get..
penile cancer
91
What is the management of penile cancer
- Surgical removal - including nodal block dissection
- Radiotherapy - to draining inguinal nodes
- Chemotherapy - cisplatin, fluorouracil, docetaxel
