Renal,Bladder and prostate Cancer

1
A 50-year-old male painter who smokes 20 -30 cigarettes per day, presents with painless haematuria.

What is your clinical suspicion?

Introduction

Renal Cell Cancer/ Hypernephroma2:564/ Grawitz Tumour Bladder Cancer

• 2% of all cancers1:1416 • > 90% Transitional cell carcinoma (TCC)1:1446
• 80% Adenocarcinoma3:323
• Most common primary neoplasm of the kidneys • Non-muscle invasive bladder carcinoma
• Major subtypes o Usually papillary tumours that grow in an exophytic fashion into the
o Clear cell RCC bladder lumen
§ Most common o May be single or multiple
§ Accounts for majority of deaths o The tumours may be accompanied with concomitant CIS (worse
o Papillary RCC prognosis)
o Chromophobe RCC o Most common in the trigone and lateral walls of the bladder
• Muscle-invasive bladder carcinoma (MIBC)
o Nearly always solid
o Often large, broad-based, ulcerated
o Lymphatic and haematogenous spread is much more common
• Carcinoma in situ (CIS)
o Diagnosed only by histologic examination
o Can occur alone (primary CIS), with a new tumour (concomitant
CIS) or occur later in a patient who has previously had a tumour
(secondary CIS)
o Carries a risk of developing into a muscle-invasive cancer

Clinical Features
Patient Profile Patient Profile
• Male: Female = 2:11:1416, 2:564 • Male: Female = 3:14:376

• Arise from proximal convoluted tubules (PCT)1:1418 • Age: > 40 years

• 6th to 8th decades of life5 o Median age at diagnosis: 73 years1:1451
o Median age at presentation is 64 years

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2
Symptoms and Signs Symptoms and Signs
1:1417, 2:564
Features Due To The Primary Features Due to The Primary1:1448
• Asymptomatic • Painless gross haematuria: 95%2:567
• Classic triad o Intermittent or everytime bladder is emptied2:567
o Painless haematuria: 40%5 • Acute retention of urine
§ Intermittent2:564 o Fleshy mass obstructing the lumen at the bladder neck2:568
o Loin pain o Clot urinary retention
o Loin mass • Malignant cystitis (old name of CIS)
o TRIAD ONLY IN 10%: When present, it strongly suggests locally o Suprapubic pain
advanced disease5 o Frequency
• Clot colic o Dysuria
• LOA • Pelvic mass in advanced disease1:1449
• LOW • LOA, LOW, LUTS2:567
Features Due to Paraneoplastic Syndromes2:564
• PUO
• Anaemia
• Polycythaemia: The tumour cells produce erythropoietin
• Hypercalcaemia1:1418
o Overproduction of PTHrP
o Lytic bone metastases
Aetiology/Risk Factors1:1416-1417 Aetiology/Risk Factors1:1446
• Smoking • Chemical carcinogens
• Obesity o 2-naphthylamine, 4-aminobiphenyl, benzidine, chlornaphazine, 4-
• Hypertension chloro-o-toluidine, o-toluidine, 4,4′-methylene bis (2-choloroaniline),
• Tobacco chewing methylene dianiline, benzidine-derived azo dyes, auramine, aniline
• Asbestos3:323, Cadmium5 dyes, aromatic hydrocarbon4:376
• Chronic kidney disease • Occupations related to bladder cancer
• Long-term renal dialysis o Textile workers, dye workers, tyre rubber and cable workers, petrol
• Urban dwelling workers, leather workers, shoe manufacturers and cleaners, painters,
hairdressers, lorry drivers, drill press operators, chemical workers,
• Low socioeconomic status
rodent exterminators and sewage workers, metal workers5, paper
• Tuberous sclerosis
manufacturers2:567
• Renal transplant recipients
• Others
• Acquired renal cystic disease o Cigarette smoking: 40% of cancers
• Family history of renal cancer o Cyclophosphamide therapy5
• von Hippel-Lindau disease o Pelvic irradiation5
• Chronic hepatitis C infection o Genetics
• Long-term obstruction5/ trauma of catheter4:376
o For squamous carcinoma

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Features Due To Spread/Metastasis Features Due To Spread/Metastasis
• Direct 2:564
• Direct
o Acute-onset left-sided varicocoele: Due to occlusion of left renal o Pneumaturia: Spread to the rectum
and testicular veins o Nerves: Refered pain to the suprapubic region, groins, perineum,
o Oedema of both legs and abdominal wall: IVC obstruction anus and thighs1:1448
• Lymphatic • Lymphatic
o Hilar lymph nodes o Iliac nodes
o Para-aortic lymph nodes3:323 o Para-aortic nodes3:323
• Hematogenous • Hematogenous1:1448
o Liver: Jaundice, hepatomegaly3:323 o Liver: Jaundice, hepatomegaly
o Lung: Persistent cough, haemoptysis4:374, ipsilateral pleural o Lung: Persistent cough, haemoptysis
effusion2:564 o Bone: Bone pain, pathological fracture
o Bone: Bone pain, pathological fracture, rarely warm and o Brain: Early morning headache, vomiting
pulsatile2:564
o Brain: Early morning headache, vomiting3:323

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4
At the end of a detailed history and examination, you’re convinced that this patient has a malignancy.

But, which one is it?

And, how do you confirm the diagnosis?

Investigations
• Confirm the diagnosis
• Assess spread
• Assess fitness for treatment

Confirm The Diagnosis Assess Spread Assess Fitness For Treatment

• UFR3:323 • Liver • FBC
o Confirm haematuria o CECT abdomen1:1419 • FBS
o Malignant cells1:1449 • Lung • Heart1:1449
o Infection o Chest X-ray1:1451 o ECG & 2D Echo
• USS abdomen o CECT thorax1:1419 • Lungs
o Renal mass5 • Bone4:374 o Chest X-ray
• Cystourethroscopy + / - TURBT (Transurethral Resection of the Bladder o Serum calcium • Kidneys1:1449
Tumour) o ALP o Blood urea & serum
o All haematuria needs cystoscopy even if an alternative cause o Bone scan: In staging of RCC5 and creatinine
found1:1449 MIBC1:1451 o Serum electrolytes
o Visualize urethra and the bladder1:1449 • Brain • Nutrition
o Full thickness biopsy involving the muscle to detect muscle invasive o CECT scan o Serum proteins
tumours1:1447-1448
§ Non-muscle invasive • MRI
§ Muscle invasive: ASSESS SPREAD o To determine whether RCC extends
§ Carcinoma in situ (CIS) into the vasculature1:1419
o Flexible: Lignocaine gel1:1449
o Rigid: GA1:1449 • CECT abdomen also determines whether
• CT IVU/ CECT1:1419 the RCC is organ-confined or extends to
o Renal Ca perinephric fat of the renal hilum1:1419
• CT or MR intravenous urography (IVU)1:1449
o Should be performed in all patients with painless haematuria
• Full blood count (FBC)
o Iron-deficiency anaemia: Haematuria4:374
o Polycythaemia: PNS2:564

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Preparation for CT IVU/ CECT
• Date for the investigation • Investigations
• Informed written consent o FBC
• Exclude allergy and bronchial asthma 5 o RFT: Serum creatinine, Serum electrolytes, eGFR5
o If BA or other allergy is present, start oral prednisolone (steroids) o PT/INR
10mg/tds/3days • Overnight fasting: 6 hours
o If the patient presented only on the day before the procedure, • Good hydration: 1 L saline for 6 hours before and 12 hours after the
methylprednisolone can be given 12 hours and 2 hours before the procedure
procedure, 32 mg each time o 100 ml/hour, beginning 6-12 hours before and continuing 4-12
o If the patient has had a significant reaction to contrast in the past hours after the procedure5
and the investigation is essential this time, an anaesthetist and all • Omit metformin
necessary equipment for resuscitation should be available in the • Prepare bowel
Radiology department • IV access
• Send to the Radiology department

Treatment
Renal Cell Carcinoma Bladder Cancer
• Multi-Disciplinary Team (MDT) approach Non-Muscle Invasive: 70%1:1447-1448
• Curative1:1420: Localized disease • Intravesical chemotherapy
o Radical nephrectomy • Intravesical immunotherapy
o Partial nephrectomy o Regular instillations of BCG
§ Peripheral tumour < 7 cm1:1420 • Regular check cystoscopies at 3-monthly intervals over the first year1:1450
§ In patients who only have 1 kidney • Avoid open surgical excision1:1450
§ Bilateral synchronous RCC1:1420 • Can offer cystectomy for patients with high-grade disease or when the disease
• Palliative: Metastatic disease4:374 persists after BCG therapy1:1448
o Interferons and interleukins Muscle Invasive: 25%1:1447, 1451
o Tyrosine kinase inhibitors, anti-VEGF antibodies1:1420-1421 • Surgery: If not spread
o Radical cystectomy + Ileal conduit diversion
What is the place of chemo-radiation?4:375 • External beam radiotherapy
• Chemotherapy
o Systemic
o Neoadjuvant
o No good evidence for the use of adjuvant chemotherapy5
Carcinoma In Situ (CIS): 5%1:1447-1448
• Intravesical immunotherapy
o BCG
• If no response to BCG, radical cystectomy
• Regular check cystoscopies
• NO external beam radiotherapy
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Prognosis

• Poor prognositic factors4:375 • 5-year survival in muscle invasive cancer is 40-50%1:1451

o Extracapsular spread • Metastatic TCC has poor prognosis: Median survival is 13/124:377
o Invasion of the renal vein
o LN involvement
• 5-year survival is at 73%5

Important Points

• Other bladder cancers

o Squamous cell carcinoma: 5%1:1446
§ Bilharzia: Schistosomiasis1:1445
§ Bladder calculi1:1448
§ Recurrent infection2:567
o Adenocarcinoma: 1-2%1:1446
§ Arise in the urachal remnant
§ Can be treated with partial cystectomy1:1448

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A 60-year-old male, presents with lower uninary tract symptoms (LUTS). You A 70-year-old male, presents with lower uninary tract symptoms (LUTS). He
also notice B/L inguinal herniae. also complains of lower back pain.

What is the most likely diagnosis? What is the most likely diagnosis?

Lower Urinary Tract Symptoms: LUTS1:1459

Voiding/ Obstructive Symptoms Storage/ Filling /Irritative Symptoms

• Hesitancy • Frequency
• Poor stream • Urgency
• Intermittent stream • Urge incontinence
• Straining at micturition • Nocturia
• Terminal dribbling • Nocturnal enuresis
• Sense of incomplete emptying
• Episodes of near retention

Severity Of Symptoms5
IPSS: International Prostate Symptom Score
AUA-SI: American Urological Association Symptom Index

• 7 questions on LUTS (Score 0 – 5)

o Incomplete emptying
o Frequency
o Intermittency
o Urgency
o Weak stream
o Straining
o Nocturia
• Severity
o 0 – 7 = Mild
o 8 – 19 = Moderate
o 20 – 35 = Severe

1 question on quality of life (0 = delighted, 6 = terrible)

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Clinical Features

Benign Prostatic Hyperplasia Prostate Cancer

Patient Profile Patient Profile
• In males • In males
• Age • Age: 70% of men are over 80 years1:1469
o 25% between 40 – 60 years
o 40% in age > 60 years
Symptoms and Signs Symptoms and Signs
• LUTS • Only advanced disease gives rise to symptoms
• LUTS
Aetiology/ Risk Factors4:362 Aetiology/ Risk Factors
• Unknown • Age: 70% of men are over 80 years1:1469
• Possible factors • Family history1:1468
o Androgens: No BPH in those who have had early castration • Race
o Oestrogens: Increased oestrogen : testosterone ratio with age o Highest among the North American blacks5
o Growth factors: High concentrations of TGF-alpha (Tramsforming o Low in the Far East1:1469
Growth Factor) • Life style5
o Dietary fat, smoking, alcohol
Complications Spread/ Metastasis
• Acute retention of urine (ARU) • Local/direct spread
o Severe pain2:568 o Symptoms: Haematospermia5, haematuria1:1470, perineal pain,
o Bladder2:568: Visible, palpable, tender, dull to percussion lump impotence
o Median volume of retained urine: < 700ml o Locations: Seminal vesicle, bladder neck, ureters, urethra, nerves1:1469
o Commonest cause is BPH5 (70%) • Lymphatic spread1:1469
• Chronic retention of urine (CRU) o Internal iliac nodes, external iliac nodes, retroperitoneal nodes,
o No pain2:569 mediastinal nodes, supraclavicular nodes
o Bladder2:569: Visible, palpable, dull to percussion • Haematogenous spread
o Median volume of retained urine: 1500ml o Bones1:1469
o Loin mass: Hydronephrosis1:1463 § Most common primary for bone metastasis
• Overflow incontinence § (Others: Breast, kidney’s, bronchus, thyroid)
• Haematuria4:362 § Lower lumbar and pelvis (axial skeleton)
• Obstructive uropathy: Symptoms and signs of CRF1:1461 § Femoral head, rib cage, skull
• UTI § Osteosclerotic lesions1:1472, back pain, pathological fractures4:378
• Stone formation o Liver: Jaundice, hepatomegaly3:328
• Hernias: Due to straining o Lung: Persistent cough, haemoptysis
o Brain: Early morning headache and vomiting
• May also present with ARU, CRU and CRF like BPH1:1470, 4:386
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Complications of BPH

Digital Rectal Examination (DRE)

• Feel for prostate: BPH Vs. Prostate Ca
BPH Vs. Prostate Ca
BPH1:1461 Prostate Ca2:571
• Enlarged prostate • Enlarged prostate
• Symmerrical convex shape • Asymmetry
• Smooth surface • Irregular/nodular surface
• Firm consistency • Hard
• Median groove palpable2:570 • Obliteration of median sulcus
• Mobile rectal mucosa over the gland • Fixed overlying mucosa

• Neurological examination: Back and lower limbs2:570

o Prostate carcinoma can present with vertebral metastasis and spinal
cord compression

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Investigations
BPH Prostate Ca
Biochemical1:1462 Confirm the Diagnosis
• Urine: Exclude infection • PSA1:1457
o Urine full report (UFR) o Glycoprotein produced by prostatic epithelium
o Urine for culture and ABST o Facilitates liquefaction of semen
• Renal Function Tests: Blood urea, serum creatinine, serum electrolytes o Level correlates to the stage and grade of the tumour
• PSA (Prostate specific antigen) § < 10 – 15ng/ml: Locally confined prostate cancer
o There is no real normal upper limit: 15-20% of men with a PSA value § > 30ng/ml: Metastatic cancer
of 1-4 ng/ml have prostate cancer1:1457 • Trans rectal ultrasound (TRUS) and Tru-cut biopsy
o 3 – 15ng/ml: BPH or early prostate cancer1:1457 o 12 biopsies taken from 6 areas1:1462
o > 3ng/ml: Need prostatic biopsy in men aged 50-69 years1:1457-1458 o Histology report will give grading as Gleason’s score1:1469
o Other causes of increased PSA5 § Minimum score: 2 Vs. Maximum score: 10
§ Prostatitis, urethral or prostatic instrumentation, vigorous § Has excellent correlation with prognosis
DRE, ejaculation, exercise, TURP, acute retention of urine

Uroflowmetry1:1431, 1462 Assess Spread1:1471,1472

• Average flow rate • Bone
• Maximum flow rate o X-ray lumbo-sacaral spine and pelvis
o > 15 ml/s: Normal o Bone scan
o 10 – 15 ml/s: Equivocal o ALP
o < 10 ml/s: Low • Liver
• Voiding pressure o USS abdomen / CECT abdomen
• Voiding time, volume and pattern o ALP
• The patient is asked to void into a flowmeter • Lung
o Chest X-ray/ CECT thorax
• Local spread
o MRI: Most accurate
o TRUS
Radiological1:1462 Assess Fitness For Treatment
• USS KUBP • FBC 1:1472
, FBS
o Residual volume of urine • Heart
o Prostate volume/size o ECG and 2D Echo
o Upper tract dilatation4:359-360 • Lungs
o Bladder wall thickness o Chest X-ray
• Transrectal USS • Kidneys
o Prostate size: May be more accurate than USS KUBP o Blood urea & serum creatinine3:329
o Serum electrolytes

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Treatment
BPH Prostate Cancer
Conservative1:1464 Localized Disease
• Indications: For mild symptoms Life Expectancy < 10 Years (Age > 70 years) 4:378, 1:1474
• Restricting fluid intake in the evenings: Prevent nocturia • Watchful waiting1:1472
• Avoid caffeine and alcohol: Diuretic effect5 o Low volume, low grade cancers
• Bladder re-training o Regular follow up: 3-6 monthly DRE. PSA, TRUS
o Pass urine with onset of the urge: Avoid over distension of the bladder
o Double voiding5 Life Expectancy > 10 Years (Age < 70 years) 1:1473-1474
o No over straining when passing urine • Surgery: Radical prostatectomy with sampling of pelvic lymph nodes
• Avoid anti-histamines and decongestants used for common colds (can cause • Radiotherapy
acute retention of urine) 1:1428 o External
• Reassess in 3-6 months o Brachytherapy
Pharmacological Locally Advanced Disease/ Life Expectancy 5 Years
• Indications 1:1464
: For moderate symptoms, waiting for surgery, not willing to • Hormonal treatment4:379
undergo surgery or if surgery is contraindicated • Radiotherapy5
• Relaxers: Selective alpha-adrenergic blockers o External
o Relaxes the smooth muscle of prostate and proximal urethra5 o Brachytherapy
o Does not reduce the size of the gland • Channel TURP
o Prazocin: Causes postural hypotension4:363 o Symptomatic patients
o Tamsulosin: More postate specific – Less postural hypotension5
• Shrinker: 5-alpha reductase inhibitor – Finasteride1:1464 What is the main principal in the treatment of metastatic disease?
o Inhibits convertion of testosterone to 5 dihydrotestosterone (5DHT)
o Reduce the size of the gland and PSA levels5
o For at least 6 months
• Side effects4:363, 5
o Impotence, decreased Libido, ejaculatory disorders, gynaecomastia
o Use condom: Drug excreted in semen
Surgery Metastatic Disease/ Life Expectancy 2 Years
• Indications 1:1463
: Increased severity of symptoms, failed drug treatment, • Orchidectomy: Surgical castration1:1474
complications of BPH • LHRH agonist: Medical castration1:1474
• TURP (Trans Urethral Resection of the Prostate)4:363 • Anti-androgens5, 1:1474
• TUIP (Trans Urethral Incision of the Prostate)4:363 o Steroidal anti-androgens
• Open prostatectomy4:363 § Cyproterone acetate: Blocks androgen receptors
• Minimally invasive treatment o Non steroidal anti-androgens
o Laser1:1467 § Flutamide: Blocks androgen receptors
o TUNA (Trans-Urethral Needle Ablation): Now known as, Transurethral • Oestrogens: Diethyl stilboesterol5
radiofrequency ablation of the prostate5 o Younger people with no CVS complications: Due to Na and water
o HIFU (High Intensity Focused Ultrasound) retention3:329
o TURis (Trans-Urethral Resection in saline) • Radiotherapy for bone metastasis1:1474
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Complications of TURP

Immediate1:1466 Early1:1466 Late1:1466

• Primary bleeding • Reactionary or secondary bleeding • Incontinence
• TURP Syndrome5 • Clot retension • Urethral stricture
• Perforation of the bladder or prostatic capsule o 3-way catheter and continuous irrigation • Retrograde ejaculation (65%)1:1464
• Intraoperative priapism for 24 hours or so post-op to prevent this • Impotence
• Infection • Recurrence
• Epididymoorchitis • Bladder neck contracture

TURP Syndrome5
Symptoms related to hyponatraemia as a result of systemic absorption of hypotonic irrigating fluid used in some transurethral prostate resection procedures

Clinical Features Treatment Prevention

• Cerebral oedema (confusion) • Stop the surgery • Avoid TURP in large prostates > 80g
• Pulmonary oedema (SOB) • Hypertonic saline • Use sterile isotonic glycine as irrigation fluid
• Hyponatraemia • IV frusemide intra-operatively1:1467
• Haemolysis1:1467 • Use isotonic saline post operatively for
irrigation

Important Facts
Benign Prostatic Hyperplasia Prostate Cancer

• Increase in both connective tissue stroma and glandular epthelium1:1458 • Most common malignant tumour in men over the age of 65 years1:1469
o Usually affects the submucous group of glands in the transitional • Majority in the peripheral zone1:1469: 70%
zone1:1458 o Therefore, may not produce symptoms at an early stage2:570
• A common cause of lower urinary tract symptoms (LUTS) in middle-aged • Transition zone: 25-30%
and elderly men1:1458 • Central zone: 5%
o Commonest cause of BOO in men > 70 years1:1458 • PSA and DRE are used for screening5
• With age the serum testosterone level decreases significantly, but the level o Men > 50 years: Annually
of oestrogenic steroids does not reduce equally. Therefore, the prostate o High risk patients > 45 years
enlarges due to increased oestrogenic effects1:1458 • Patients with prostate cancer can have normal PSA1:1469
• Differential diagnosis5 • Adenocarcinoma: 98%
o Prostate cancer, urethral stricture and meatal stenosis, UTI, bladder
stones, bladder carcinoma, neurogenic bladder disorders, poor
detrusor contractility
o Drugs
§ Eg: Diuretics, anti-cholinergics

Clinical Surgery