What are the potential sites of urothelial tumours?
Malignant tumours of the transitional cell epithelium lining (urothelium) can occur at any point from the renal calyces to the tip of the urethra
Most common site is the bladder
What percentage of urothelial tumours are of the bladder?
90%
What is the most common tumour type in bladder cancer?
Tumour type most often a transitional cell carcinoma
When is squamous cell carcinoma of the bladder common?
In areas where schistosomiasis is endemic
What are the risk factors for transitional cell carcinoma?
Smoking
Aromatic amines
Non-hereditary genetic abnormalities e.g. TSG, including p53 and Rb
What percentage of cases of transitional cell carcinoma does smoking account for?
40%
How does smoking affect the risk of recurrence of transitional cell carcinoma?
Tendency for TCC to recur, with higher recurrence risk in patients who continue to smoke
What are the risk factors for squamous cell carcinoma of the bladder?
Schistosomiasis - S. haematobium only
Chronic cystitis e.g. recurrent UTI, long-term catheter, bladder stone
Cyclophosphamide therapy
Pelvic radiotherapy
What is the presentation of bladder cancer?
Most frequent presenting symptom is painless visible haematuria
Occasionally, symptoms due to invasive or metastatic disease may be present
Haematuria may be frank or microscopic
Recurrent UTI
Storage bladder symptoms e.g. dysuria, nocturia, urgency +/- urge incontinence
What tumour type should be suspected if storage bladder symptoms are present?
Carcinoma in situ
What is the investigation of haematuria?
Urine culture (majority of painful haematuria will be UTI)
Cystourethroscopy
Upper tract imaging - intravenous urogram, US
Urine cytology
BP and U&Es
What is the risk of malignancy in > 50s with frank haematuria?
25-35%
What is the investigation of frank haematuria in over 50s?
Flexible cystourethroscopy within 2 weeks
IVU and USS (or CT-IVU)
Urine cytology - not very sensitive or specific so not routinely done
What is the risk of malignancy in > 50s with microscopic haematuria?
5-10%
What is the investigation of dipstix or microscopic haematuria in over 50s?
Flexible cystourethroscopy within 4-6 weeks
IVU and USS
What will IVU alone miss?
A proportion of renal cell tumours, especially those < 3cm
What will USS alone miss?
A proportion of urothelial tumours of the upper tract
How are urothelial tumours of the bladder assessed?
Grade and T stage
Cystoscopy and endoscopic resection
EUA to assess bladder mass thickening before and after TURBT
How are urothelial tumours of the bladder staged?
T, N and M stage
Cross sectional imaging - CT or MRI
Bone scan if symptomatic
IVU for upper tract TCC
What are the treatment options for urothelial tumours of the bladder?
Endoscopic or radical
How are bladder tumours classified?
Grade of tumour
Stage of tumour - TNM classification, T-stage; non-muscle invasive or muscle invasive
Combined to describe TCC e.g. G1pTa
What are the grades of TCC (WHO 1973)?
G1 - well differentiated, commonly non-invasive
G2 - moderately differentiated, often non-invasive
G3 - poorly differentiated, often invasive
Carcinoma in situ - non-muscle invasive but very aggressive
What does the treatment of bladder cancer depend on?
Site
Clinical stage
Histological grade of tumour
Patient age and co-morbidities
What is the treatment of low grade non-muscle invasive bladder cancer, e.g. Ta or T1?
Endoscopic resection followed by a single instillation of intravesical chemotherapy (mitomycin C) within 24 hours
What is the treatment for moderate grade bladder cancer?
Endoscopic resection followed by a single instillation of intravesical chemotherapy (mitomycin C) within 24 hours plus prolonged endoscopic follow-up
When should you consider a prolonged course of intravesical chemotherapy?
For repeated recurrences (6 weeks - 6 months)
What is the treatment of high grade non-muscle invasive cancer or CIS of the bladder?
Very aggressive treatment, endoscopic resection alone is not sufficient
Intravesical BCG therapy - maintenance course, weekly for 3 weeks, repeated 6 monthly over 3 weeks
Patients refractory to BCG need radical surgery
What is the risk of progression to muscle invasive stage of high grade non-muscle invasive cancer of the bladder?
50-80% risk of progression to muscle invasive stage
How does BCG work?
By inducing immunomodulatory tumour cell killing - mediated by natural killer cells and cytokines, especially IL-2
What is the risk of systemic BCG with BCG therapy?
1% risk - similar to TB, treated with anti-tuberculosis drugs
What is the treatment of muscle invasive bladder cancer e.g. T2-T3?
Neoadjuvant chemotherapy for local tumour - down-staging and systemic control
Followed by
Radical radiotherapy and/or radical cystoprostatectomy for men or anterior pelvic exenteration with urethrectomy in women, with extended lymphadenectomy
What is radical surgery for muscle invasive bladder cancer combined with?
Radical surgery is combined with incontinent urinary diversion i.e. ileal conduit, continent diversion e.g. bowel pouch with catheterisable stoma or othrotopic bladder substitution
What does the prognosis of bladder cancer depend on?
Stage Grade Size Multi-focality Presence of concurrent CIS Recurrence at 3 months
What is the 5-year survival of non-invasive low grade bladder TCC?
90%
What is the 5-year survival of invasive high grade bladder TCC?
50%
What is the presentation of upper urinary tract transitional cell carcinoma?
Frank haematuria
Unilateral ureteric obstruction
Flank or loin pain
Symptoms of nodal or metastatic disease e.g. bone pain, hyperclacaemia, lung/brain symptoms
What are the diagnostic investigations for upper urinary tract transitional cell carcinoma?
CT-ICU or IVU - shows filling defect in renal pelvis
Urine cytology
Ureteroscopy and biopsy and histology
What are the commonest sites of upper tract TCC?
Renal pelvis or collecting system commonest
Ureter less commonly
What are the typical characteristic of upper tract TCC?
Tumours are often high grade and multi-focal on one side
When is there a high risk of local recurrence of upper tract TCC?
If treated endoscopically or by segmental resection
Is the risk of contralateral disease low or high with upper tract TCC?
Low risk
When is upper tract TCC difficult to follow up?
If treated endoscopically
How are most upper tract TCCs treated?
Nephro-ureterectomy
What is the treatment of upper tract TCCs in patients unfit for nephro-ureterectomy or with bilateral disease?
Absolute indication for nephron-sparing endoscopic treatment e.g. ureteroscopic laser ablation
Need regular surveillance ureteroscopy
When is there a relative indication for endoscopic treatment of upper tract TCCs?
If unifocal and low-grade disease
What is there a high risk of in all cases of upper tract TCCs?
Synchronous and metachronous bladder TCC
Surveillance cystoscopy is needed
What is the risk of synchronous and metachronous bladder TCC in upper tract TCC?
40% over 10 years
What are the benign tumours in renal cancer?
Oncocytoma
Angiomyolipoma
What are the malignant tumours in renal cancer?
Renal adenocarcinoma - most common adult renal malignancy
What are the histological subtypes of renal cancer?
Clear cell 85%
Papillary 10%
Chromophobe 4%
Bellini type ductal carcinoma 1%
What are the risk factors for renal adenocarcinoma?
Family history - autosomal dominant e.g. familial clear cell RCC, hereditary papillary RCC Smoking Anti-hypertensive medication Obesity End-stage renal failure Acquired renal cystic disease
What is the presentation of renal adenocarcinoma?
Asymptomatic in 50%
Classic triad of flank pain, mass and haematuria in 10%
Paraneoplastic syndrome in 30%
- anorexia, cachexia and pyrexia
- hypertension, hypercalcaemia and abnormal LFTs
- anaemia, polycythaemia and raised ESR
Metastatic disease in 30% - bone, brain, lungs, liver
What are the modes of spread of renal adenocarcinoma?
Direct - through renal capsule
Venous - to renal vein and vena cava
Lymphatic - to nodes
Haematogenous - to bone and lungs
What are the T stages of the TNM classification of renal cancer?
T1 - tumour < 7cm confined within renal capsule
T2 - tumour > 7cm confined within renal 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
What is the investigation of renal adenocarcinoma?
CT scan (triple phase) of abdomen and chest - mandatory, provides radiological diagnosis and complete TNM staging, and assesses contralateral kidney Bloods - U&Es and FBC
Optional tests:
IVU - shows calyces distortion and soft tissue mass
Ultrasound - differentiated tumour from cyst
DMSA or MAG-3 renogram to assess split renal function if doubts about contralateral kidney
What is the treatment of renal adenocarcinoma?
Surgical - radical nephrectomy
Laparoscopic radical nephrectomy is standard for T1 tumours or T2 tumours in laparoscopic centres
Worthwhile even with major venous invasion i.e. T3b or higher
Curative if T2 or lower
What is the treatment of renal adenocarcinoma in patients with metastatic disease who have symptoms from the primary tumour?
Palliative cytoreductive nephrectomy is beneficial, prolongs median survival by 6 months
What is the treatment of metastases in renal adenocarcinoma?
Little effective treatment since RCC is radio-resistant and chemo-resistant
Immunotherapy - interferon alpha, interleukin 2
Multi-targeted receptor tyrosine kinase inhibitors
Rare spontaneous regression of metastases may occur following nephrectomy
What is the response rate to immunotherapy in treatment of metastases in renal cancer?
20% at most with either interferon alpha or interleukin 2
Give an example of a multi-targeted receptor tyrosine kinase inhibitor?
Sunitinib
Sorafenib
Temsirolimus
Superior response rates than to immunotherapy but no improvement in survival
What is the 5 year survival of stage T1 renal adenocarcinoma?
95%
What is the 5 year survival of stage T2 renal adenocarcinoma?
90%
What is the 5 year survival of stage T3 renal adenocarcinoma?
60%
What is the 5 year survival of stage T4 renal adenocarcinoma?
20%
What is the 5 year survival of stage N1 or N2 renal adenocarcinoma?
20%
What is the survival of stage M1 renal adenocarcinoma?
12-18 months median survival
How many new cases of prostate cancer are there per year in the UK?
41,000
How many cases of prostate cancer are there per 100,000 men per year?
134 cases per 100,000 men/year
What percentage of new cases of prostate cancer are in men aged > 65?
75%
What percentage of new cases of prostate cancer are in men aged < 50?
1%
What percentage of new cases of prostate cancer are in men aged < 70?
45%
What are the risk factors for prostate cancer?
Age Race/ethnicity Geography Family history - HPC1, BRCA1 and 2 Diet Drugs
What is the increase in risk of prostate cancer in men with a first-degree relative with prostate cancer?
Relative 2x risk
What foods/dietary components have an effect on prostate cancer risk?
Selenium
Lycopene
Vitamin E
Omega 3 fatty acid
What effect does finasteride/dutasteride have on the risk of prostate cancer?
Relative risk reduction of 25-30% but higher risk of developing higher grade prostate cancer
How is prostate cancer diagnosed?
Diagnostic triad of PSA, digital rectal examination and TRUS-guided prostate biopsies
(remember PSA is prostate-specific but not necessarily cancer-specific)
What is the presentation of local disease prostate cancer?
Weak stream Hesitancy Sensation of incomplete emptying Frequency Urgency Urge incontinence UTI
What percentage of newly diagnosed prostate cancers are localised?
80%
What is the presentation of locally invasive prostate cancer?
Haematuria Perineal and suprapubic pain Impotence Incontinence Loin pain or anuria resulting from obstruction of the ureters Symptoms of renal failure Haemospermia Rectal symptoms, including tenesmus
What is the presentation of metastatic prostate cancer, with distant metastases?
Bone pain or sciatica
Paraplegia secondary to spinal cord compression
Lymph node enlargement
Lymphoedema, particularly in the lower limbs
Loin pain or anuria due to obstruction of the ureters by lymph nodes
What is the presentation of metastatic prostate cancer with widespread metastases?
Lethargy
Weight loss
Cachexia
How is prostate cancer diagnosed in a symptomatic male?
PSA - prostate specific antigen
DRE
Transrectal ultrasound and needle biopsy
Incidental finding at TURP
What produces PSA?
Glands of prostate
What is the normal serum range of PSA?
0-4.0 ug/mL
What is the serum range of PSA in < 50s?
2.5x upper limit
What is the serum range of PSA in 50-60 years?
3.5x upper limit
What is the serum range of PSA in 60-70 years?
4.5x upper limit
What is the serum range of PSA in > 70s?
6.5x upper limit
What are the causes of elevated PSA?
UTI Chronic prostatitis Instrumentation Physiological Recent urological procedure BPH Prostate cancer
What is the half-life of PSA?
2.2 days
When should you re-check PSA if a repeat test is needed?
In 3 weeks
What is the probability of cancer based on PSA levels; 0-1.0 1.0-2.5 2.5-4.0 4.0-10 > 10?
0-1.0 - 5% 1.0-2.5 - 15% 2.5-4.0 - 25% 4.0-10 - 40% > 10 - 70%
What is the risk of death from prostate cancer within 15 years according to the Gleason Score?
Score 2-4 - risk 4-7% Score 5 - risk 6-11% Score 6 - risk 18-30% Score 7 - risk 42-70% Score 8-10 - risk 60-87%
For the purposes of treatment and prognosis, what 4 categories is prostate cancer divided into?
Localised stage
Locally advanced stage
Metastatic stage
Hormone refractory stage
How is localised prostate cancer staged?
DRE PSA Transrectal US guided biopsy CT MRI
What is the treatment for localised prostate cancer?
Watchful waiting
Radiotherapy - external beam, brachytherapy
Radical prostatectomy - open, laparoscopic, robotic
Cryotherapy and thermotherapy treatments under investigation
What is the treatment of locally advanced prostate cancer?
Watchful waiting
Hormone therapy alone
Hormone therapy followed by surgery or radiation
Intermittent hormone therapy
What are the types of hormone therapy for prostate cancer?
Surgical castration - bilateral orchidectomy
Chemical castration - LHRH analogue
Anti-androgens
Oestrogens
What are the potential complications of metastatic and hormone refractory prostate cancer?
Bone - pain, pathological fractures, anaemia, spinal cord compression
Rectal - constipation, bowel obstruction
Ureteric - obstruction resulting in renal failure
Pelvic lymphatic obstruction - lymphoedema, DVT
Lower urinary tract dysfunction - haematuria, acute retention
What is the mainstay of treatment for metastatic and hormone refractory prostate cancer?
Immediate hormone therapy
Supportive treatment e.g. palliative radiotherapy to bony metastases, palliative care support may also be given
When will the hormone refractory stage of prostate cancer be reached?
In 18-24 months of treatment
What are the complications of diethylboestrol?
High risk of thromboembolic and cardiovascular complications
What is the survival benefit of docetaxel?
3 months
What is the presentation of testicular cancer?
Usually a painless lump
Tender inflamed swelling
History of trauma
Symptoms/signs from nodal or distant metastases
When is the peak incidence of testicular cancer?
3rd decade
When is there a higher risk of testicular cancer?
Testicular maldescent
Infertility
Atrophic testis
Previous cancer in contralateral testis
What is a precursor lesion for testicular cancer?
Testicular germ cell neoplasia in situ
What tumour markers might be present in testicular cancer?
Alpha fetoprotein - teratoma
Beta-HCG - seminoma
Lactase dehydrogenase - non-specific marker of tumour burden
How is testicular cancer diagnosed?
Lump in testis is a testicular tumour until proven otherwise
MSSU
Testicular ultrasound and CXR
Tumour markers
What are the differential diagnoses for a lump in the testis?
Infection
Epididymal cyst
Missed testicular torsion
What is the treatment of testicular cancer?
Radical orchidectomy is essential
Occasionally may need biopsy of normal contralateral testis, if there is a high risk for another tumour
Further treatment depends on tumour type, stage and grade
What percentage of testicular tumours are germ cell tumours?
95% germ cell
5% non-germ cell
What are the types of germ cell tumours?
Seminomatous GCT - classical, spermatocytic or anapaestic
Non-seminomatous GCT - teratoma, yolk sac, choriocarcinoma, mixed GT
What are the types of non-germ cell tumour?
Leydig
Sertoli
Lymphoma (rare)
What age group does seminomatous mainly affect?
30-40 year olds
What age group does non-seminomatous GCT mainly affect?
20-30 year olds
How are testicular tumours graded?
Based on histological assessment of differentiation
Assessment of aggressiveness
Low grade - well differentiated
High grade - poorly differentiated
How are testicular tumours staged?
Assessment of spread
Staged using TNM system
Local staging via pathological assessment of orchidectomy specimen
Nodal staging via CT
Distant staging via CT of chest, abdomen and pelvis
Tumour markers can also provide staging and prognostic information
What are the ways in which testicular cancer can spread?
Local - to adjacent structures
Regional - lymphatic invasion
Distant - to bone, lungs, liver etc.
What are the stages of testicular cancer?
Stage I - confined to the testis
Stage II - infra-diaphragmatic nodes involved
Stage III - supra-diaphragmatic nodes involved
Stage IV - extra-lymphatic disease
What does further treatment for testicular cancer following orchidectomy depend on?
Tumour type, stage and grade
What is the treatment for testicular cancer with low grade and negative markers?
Orchidectomy followed by one of;
- surveillance
- adjuvant radiotherapy (SGCT only)
- prophylactic chemotherapy
What is the treatment for testicular cancer with nodal disease, persistent markers or relapse on surveillance?
Orchidectomy
Combination chemotherapy or lymph node dissection (NSGCT only)
What is the treatment for testicular cancer with metastases?
First and second line chemotherapy
What is the 5 year survival of stage 1 testicular cancer?
99%
What is the 5 year survival of stage 2/3 testicular cancer?
96^
What is the 5 year survival of stage 4 testicular cancer?
73%