Tumours of the Urinary System 2: Urothelial and Renal Cancers

Question 1

what are sites of urothelial tumours?

Answer 1

Malignant tumours of the lining transitional cell epithelium (urothelium) can occur at any point
from renal calyces
to the tip of the urethra.

Most common site - bladder - 90%
“Bladder Cancer”

Question 2

what is the most common tumour type for bladder cancer?

Answer 2

transitional cell carcinoma (i.e. 90% in UK)

Question 3

what are the risk factors for bladder cancer?

Answer 3

smoking (accounts for 40% of cases)
aromatic amines
non-hereditary genetic abnormalities (e.g. TSG incl. p53 and Rb)

Question 4

what are risk factors for squamous cell carcinoma bladder cancer?

Answer 4

Schistosomiasis (S. haematobium only)
chronic cystitis (e.g. recurrent UTI, long term catheter, bladder stone)
cyclophosphamide therapy
pelvic radiotherapy
Adenocarcinoma
-Urachal

Question 5

what is the most frequent presenting symptom of bladder cancer?

Answer 5

painless visible haematuria

Question 6

what are occasional symptoms of bladder cancer?

Answer 6

Occasionally
symptoms due to invasive or metastatic disease

recurrent UTI
storage bladder symptoms
dysuria, frequency, nocturia, urgency +/- urge incontinence
bladder pain
if present, suspect CIS

Question 7

how may haematuria present?

Answer 7

Frank - reported by patient
Microscopic - detected by doctor

Question 8

what should be done urgently in investigation of haematuria?

Answer 8

Upper tract imaging
CT Urogram (IVU)
ultrasound scan
Urine Cytology
Limited use in Dipstick haematuria

BP and U&E’s

Question 9

what should be done in investigation of haematuria?

Answer 9

Urine culture
majority of painful haematuria = UTI

Cystourethroscopy
commonest neoplastic cause is TCC bladder

Question 10

what investigations should be done for frank haematuria?

Answer 10

> 50 yrs - Risk of malignancy - 25-35%
Flexible cystourethroscopy within 2 weeks
IVU & USS
CT Urogram & USS
Urine Cytology may also be useful (but not very sensitive nor specific)

Question 11

what investigation should be done for microscopic haematuria?

Answer 11

> 50 yrs - Risk of malignancy - 5-10%
Flexible cystourethroscopy within 4-6 weeks
USS

Question 12

how are urothelial tumours diagnosed?

Answer 12

IVU alone will miss a proportion of renal cell tumours (especially if <3cm)

USS alone will miss a proportion of urothelial tumours of the upper tracts

cystoscopy and endoscopic resection (TURBT)
EUA to assess bladder mass/thickening before and after TURBT

Question 13

how are urothelial tumours in the bladder staged?

Answer 13

cross-sectional imaging (CT, MRI)
Bone scan if symptomatic
CTU for upper tract TCC (2-7% risk over 10 years; higher risk if high grade, stage or multifocal bladder tumours)

Question 14

what is treatment available for urothellial tumours of the bladder?

Answer 14

endoscopic or radical

Question 15

how are bladder tumours classified?

Answer 15

Grade of tumour

Stage of tumour
- TNM classification
- T-stage :
- non-muscle invasive (or ‘superficial’)
- muscle invasive

Combined to describe TCC e.g. G1pTa

Question 16

what does appropriate treatment of bladder cancer depend?

Answer 16

Site
Clinical stage
Histological grade of tumour
Patient age and co-morbidities

Question 17

what is treatment for Low grade non-muscle invasive (i.e. Ta or T1)?

Answer 17

endoscopic resection followed by single instillation of intravesical chemotherapy (mitomycin C) within 24 hours
prolonged endoscopic follow up for moderate grade tumours
consider prolonged course of intravesical chemotherapy (6 weeks months) for repeated recurrences

Question 18

what is treatment for High grade non-muscle invasive or CIS?

Answer 18

very aggressive – 50-80% risk of progression to muscle invasive stage
endoscopic resection alone not sufficient
CIS consider intravesical BCG therapy (maintenance course, weekly for 3 weeks repeated 6 monthly over 3 years)
patients refractory to BCG – need radical surgery

Question 19

what is treatment for muscle invasive bladder (T2 - T3)?

Answer 19

neoadjuvant chemotherapy for local (i.e. downstaging) and systemic control; followed by either :
radical radiotherapy and/or;
radical cystoprostatectomy (men) or anterior pelvic exenteration with urethrectomy (women); with extended lymphadenectomy
radical surgery combined with incontinent urinary diversion (i.e. ileal conduit), continent diversion (e.g. bowel pouch with catheterisable stoma) or orthotopic bladder substitution

Question 20

what is prognosis of bladder cancer dependent on?

Answer 20

stage
grade
size
multifocality
presence of concurrent CIS
recurrence at 3 months

Question 21

what is the five year survival of non-invasive, low grade bladder TCC?

Answer 21

90% 5-year survival

Question 22

what is the five year survival of invasive, high grade bladder TCC?

Answer 22

50%

Question 23

Upper tract TCC (or upper tract urothelial cancer – UTUC) main symptoms?

Answer 23

Frank haematuria
Unilateral ureteric obstruction
Flank or loin pain
Symptoms of nodal or metastatic disease
Bone pain
Hypercalcaemia
Lung
Brain

Question 24

what diagnostic investigations are done for UTUC?

Answer 24

CT-IVU or IVU

Urine cytology

Ureteroscopy and biopsy

Question 25

what will IVU/CT-IVU show in UTUC?

Answer 25

shows
filling defect
in renal pelvis

Question 26

upper tract TCC?

Answer 26

renal pelvis or collecting system commonest
ureter less commonly
tumours are often high-grade and multifocal on one side
high risk of local recurrence if treated endoscopically or by segmental resection
low risk of having contralateral disease
difficult to follow up if treated endoscopically
hence, most upper tract TCCs are treated by nephro-ureterectomy

Question 27

indications for treatment in UTUC?

Answer 27

If unfit for nephro-ureterectomy or has bilateral disease - absolute indication for nephron-sparing endoscopic treatment (i.e. ureteroscopic laser ablation); needs regular surveillance ureteroscopy

If unifocal and low-grade disease - relative indication for endoscopic treatment

In ALL cases, high risk of synchronous and metachronous bladder TCC (40% over 10 years); hence need surveillance cystoscopy

Question 28

what are examples of benign renal tumours?

Answer 28

oncocytoma, angiomyolipoma

Question 29

what are examples of malignant renal tumours?

Answer 29

renal adenocarcinoma
commonest adult renal malignancy
synonyms : hypernephroma or Grawitz tumour
most arise from proximal tubules

histological subtypes :
clear cell (85%)
papillary (10%)
chromophobe (4%)
Bellini type ductal carcinoma (1%)

Question 30

what are risk factors for renal adenocarcinoma?

Answer 30

Family history (autosomal dominant e.g. vHL, familial clear cell RCC, hereditary papillary RCC; can be bilateral and/or multifocal)
Smoking
Anti-hypertensive medication
Obesity
End-stage renal failure
Acquired renal cystic disease

Question 31

what is the presentation of renal adenocarcinoma?

Answer 31

Asymptomatic (i.e. incidentally noted on imaging for unrelated symptoms) : 50%
‘Classic triad’ of flank pain, mass and haematuria : 10%
Paraneoplastic syndrome : 30%
anorexia, cachexia and pyrexia
hypertension, hypercalcaemia and abnormal LFTs
anaemia, polycythaemia and raised ESR
Metastatic disease : 30%
bone, brain, lungs, liver

Question 32

how is renal cancer staged?

Answer 32

T1 - Tumour < 7cm confined within renal capsule
T2 - Tumour >7cm & confined within capsule
T3 - Local extension outside capsule
T3a - Into adrenal or peri-renal fat
T3b - Into renal vein or IVC below diaphragm
T3c - Tumour thrombus in IVC extends above diaphragm
T4 - Tumour invades beyond Gerota’s fascia

Question 33

what are the different mechanisms of spread for renal adenocarcinoma?

Answer 33

Direct spread
(invasion) through
the renal capsule

Venous invasion
to renal vein
and vena cava

Haematogenous
spread to lungs
and bone

Lymphatic spread
to paracaval nodes

Question 34

what investigations are done for renal adenocarcinoma?

Answer 34

CT scan (triple phase) of abdomen and chest is mandatory
provides radiological diagnosis and complete TNM staging
assesses contralateral kidney
Bloods : U&E, FBC
Optional tests :
Ultrasound differentiates tumour from cyst
DMSA or MAG-3 renogram to assess split renal function if doubts about contralateral kidney

Question 35

what is the treatment for renal adenocarcinoma?

Answer 35

Treatment is surgical – i.e. radical nephrectomy
laparoscopic radical nephrectomy is standard of care for T1 tumours (T2 tumours in laparoscopic centres)
worthwhile even with major venous invasion (≥T3b)
curative if ≤T2

Even in patients with metastatic disease who have symptoms from primary tumour, palliative cytoreductive nephrectomy is beneficial (prolongs median survival by 6 months)

Question 36

how are metastases of renal adenocarcinoma treated?

Answer 36

Metastases - little effective treatment since RCC is radioresistant and chemoresistant
multitargeted receptor tyrosine kinase inhibitors
relatively new
sunitinib, sorafenib, panzopanib,temsirolimus
superior response rates to immunotherapy
trials ongoing
immunotherapy
Interferon alpha
Interleukin-1

Question 37

what is the prognosis for different stages of renal carcinoma?

Answer 37

T1 – 95% 5-year survival
T2 – 90% 5-year survival
T3 – 60% 5-year survival
T4 – 20% 5-year survival
N1 or N2 – 20% 5-year survival
M1 – Median survival 12-18 months