Anatomy and development
The kidney develops through three phases to form the metanephros, which migrates proximally as the tissue differentiates into the nephron and tubules, the calyces and the renal pelvis. At the same time, the urogenital sinus differentiates into the bladder and urethra and the ureteric bud, which communicates with the upper ureter arising from the metanephros. The prostate develops as an outgrowth of the urethral epithelium.
The kidneys lie retroperitoneally at the level of L1-2 and normally are supplied by single arteries, although up to 30% of people may have multiple arteries. The renal vein is again normally single on each side, draining into the inferior vena cava. Renal lymphatics drain to the para-aortic nodes.
The adult ureter is approximately 25 cm in length in adult life and runs retroperitoneally before swinging medially at the level of the ischial spine to pass through the bladder wall. The bladder lies within the pelvis but can expand upwards into the abdominal cavity. Arterial supply to the bladder and the lower ureters is via the internal iliac artery, and lymphatic drainage parallels venous drainage to the internal iliac nodes.
The male urethra passes through the prostate and is joined by the ejaculatory ducts. The prostate itself is a fibromuscular gland that drains into the urethra and, in terms of structure, is divided into peripheral, transitional and central zones (see Anatomy of the prostate.). The arterial supply to the urethra and prostate is through the inferior vesical artery, and venous drainage is through the periprostatic plexus to the internal iliac veins. Lymphatic drainage is to the obturator and internal iliac nodes.
Disorders of the male external genitalia will be considered in a separate chapter (External genitalia in the male). Specific disorders of the genitourinary tract will be considered under the headings of urinary tract calculi, urinary tract infection, prostatitis, urethral stricture, benign prostatic hyperplasia, prostatic cancer, renal cell carcinoma and urothelial cancer.
Urinary tract calculi
Urinary calculi are defined as insoluble substances formed from the constituents of urine. They consist of crystalloids deposited on an organic matrix. In developed countries most stones are in the upper tract and present in about 2% of the population.
Urinary tract calculi are divided into infective and metabolic stones. Infective stones are caused by bacteria, mostly Proteus species containing the enzyme urease, which splits urea to form an insoluble complex of magnesium-ammonium-calcium phosphate. Bacteria become embedded in these stones, which form cast or staghorn calculi in renal pelves to produce a combination of obstruction and infection with eventual destruction of the kidney.
Most metabolic stones contain calcium (in combination with oxalate and/or phosphate) and, unlike most gallstones, are radio-opaque on plain X-ray. There is often a familial susceptibility. Although the aetiology is multifactorial, defined predisposing conditions such as primary hyperparathyroidism, Paget's disease and other bone demineralisation conditions, hyperthyroidism, sarcoidosis, impaired ileal function, renal tubular acidosis and medullary sponge kidneys are identifiable in a minority of patients.
Uric acid stones are radiolucent. Patients with gout and clinical states characterised by rapid protein catabolism are at risk of urate stone formation. Urate stones form in patients whose urinary pH is invariably lower than 6.5. Pure cystine stones also form in acid urine. Cystine stones (about 3% of calculi) are faintly identifiable on plain radiographs. This disorder is inherited in autosomal recessive fashion.
The principles of stone formation in the majority of patients, who do not have defined clinically predisposing conditions, can be considered in terms of hypersecretion and hyperconcentration of solutes, anatomical factors including a foreign body serving as a nidus, the role of inhibitory substances, and the part played by macro-molecules and matrix in crystal precipitation and aggregation.
Infective stones will be discussed in the section on urinary tract infection (UTI). Metabolic stones usually present with pain called renal, or more correctly, ureteric colic. This is an extremely severe pain that, classically, occurs without warning. The patient cannot find a comfortable position and rolls around or paces about in agony. He (patients are more often male) may notice pain radiating to the groin and the genital region and, generally, the lower the pain, the lower the stone. Pain in the loin suggests arrest at the pelviureteric junction, pain in the flank or groin suggests arrest at the pelvic brim, and pain in the genitalia suggests arrest at the ureterovesical junction. Vomiting is not a dominating feature although it is not uncommon for the patient to have vomited once. Some tenderness in the loin and along the line of the ureter is often present.
The differential diagnosis is that of an acute abdomen so the patient should be assessed as for an acute abdomen. Microscopic blood is usually present in the urine (routinely detected by dip-stick). Macroscopic blood is uncommon with ureteric colic from stone disease. The absence of blood on ward-testing does not exclude a diagnosis of ureteric colic and, conversely, a positive result may occur with other conditions.
Stones in the lowermost ureter may cause frequency and burning attributed to inflammation of distal ureteric smooth muscle, which extends into superficial trigone and urethra. A UTI may need to be excluded.
The diagnosis is confirmed by intravenous urography (IVU; see Intravenous urogram showing a distended pelvicaliceal system with contrast tracking down to an obstructing stone in the upper ureter.) or, alternatively, especially if another cause for the pain is entertained, a spiral CT scan (which permits visualisation of the whole of both upper tracts). A plain radiograph by itself is insufficient, because phleboliths (calcified veins), calcified lymph nodes and, less commonly, radiolucent calculi may mislead. Unilateral partial obstruction is common at the time of acute presentation. Delay in excretion with dilatation of the collecting system above the obstruction is usually seen. Consequently delayed films may be required and, because excreted contrast medium is heavier than urine, patients should be in prone or erect positions for a little time before and during the taking of delayed radiographs so that contrast tracks to the level of obstruction.
Radiolucent stones cause filling defects. Ultrasound has little, if any, place diagnostically, because definition below the uppermost ureter is usually not provided. Furthermore, dilatation does not equal obstruction. Uncommonly, obstruction does occur without dilatation so that a functional study such as an IVU is much more informative.
A definitive diagnosis by IVU or spiral CT scan is essential soon after presentation. Narcotic analgesia is recommended initially. Subsequent analgesia may be provided by indomethacin suppositories (± paracetamol) rather than repeated doses of narcotic analgesia. Intravenous fluids should only be given to replenish fluids if the patient is too nauseated to drink normally or is dehydrated. A diuresis is to be avoided at this stage, because this may exacerbate obstruction and worsen pain. It is not the hydrostatic pressure from a distended ureter that causes advancement of the stone, but rather coaptation of the ureteric walls above the stone advancing it distally.
Approximately 80% of upper tract stones pass spontaneously. Calculi of 4 mm diameter almost always pass without intervention, but most stones greater than 6 mm will not. Indications for surgical intervention include a stone too large to pass, complete obstruction (a rare occurrence), obstruction and infection, as well as the very relative indication of persisting pain without any progress in stone movement.
Chemolysis is often effective in causing dissolution of urate stones. A dilute urine with a pH higher than 7 is advised (usually induced by sodium bicarbonate). Allopurinol is also prescribed to minimise further uric acid formation.
Large renal stones are usually treated primarily by percutaneous nephrolithotomy with stone disintegration by extracorporeal shock wave lithotripsy (ESWL) used for calculi that are less than 2 cm in diameter; ESWL involves focusing a shock wave, generated outside the body, onto a stone localised by X-rays or ultrasound. Open renal surgery is now practised infrequently, its main role being stone removal en passant at the time of corrective surgery for predisposing anatomical abnormalities such as pelviureteric junction obstruction.
Stone basketry has been used for many years. With distal ureteric calculi, basketry may be performed through a cystoscope without ureteroscopy. However, basketry without ureteroscopic guidance is not recommended for stones above the distal few centimetres of ureter because of the risk of ureteric intussusception. Disintegration of ureteric stones may be effected by intracorporeal targeting with a ureteroscope (using laser, ultrasound, shock wave and physical energy sources) as well as ESWL (most effective in the upper ureter). An internal ureteric stent may facilitate passage of a stone by relieving obstruction (urine flowing mainly around the stent) and serving as a ‘slide’ for the calculus. The stent needs to be removed soon after it has served its purpose, as it may serve as a nidus for stone formation. Apart from a chest X-ray and routine biochemical profile to exclude predisposing and correctable underlying medical conditions, together with chemical analysis of the calculus, other investigations are reserved for recurrent stone formers. All patients should be induced to drink sufficient fluid so that their urine is visibly dilute at all times.
Urinary tract infection
Urinary tract infections (UTIs) are extremely common in females, with most women experiencing at least one in a lifetime.
Causative organisms are Escherichia coli (approximately 80% of UTI in the community and about 50% in hospitals), Proteus species (the presence of which should always alert to the possibility of an infective stone), Pseudomonas, Klebsiella and Enterobacter, as well as the Gram-positive cocci Streptococcus faecalis and, occasionally, Staphylococcus aureus.
Both bacterial and host factors are relevant. Bacteria from the bowel or external genitalia colonise the urethral meatus then migrate in a retrograde fashion into the bladder. Other forms of access to the urinary tract (such as haematogenous, lymphatic and innocula introduced with instrumentation) are less common. Variation in bacterial virulence factors (such as adhesin expression and phase variation) and host-cell receptivity to bacteria (due to intrinsic and extrinsic factors) dynamically affect the host-bacteria relationship.
The most common site of bacterial infection in the male is the prostate. A diagnosis of UTI is based on a combination of symptoms and bacteriological findings. Patients complain of burning and frequency, with a feeling of wanting to void continually. Lower abdominal discomfort is common. If haematuria is present this requires thorough investigation subsequently.
A significant proportion of female patients with these symptoms do not have a UTI. The differential diagnosis includes detrusor instability, vaginitis, abacterial cystourethritis and, rarely, carcinoma in situ. Consequently, urinary bacteriology is essential to make an accurate diagnosis. Normal urine is abacteriuric. By convention, more than 105 organisms per millilitre from a freshly voided midstream specimen is regarded as infection, as this figure indicates a higher than 90% probability of UTI rather than contamination.
Increased numbers of leucocytes are to be expected in a UTI. Increased numbers of epithelial cells strongly suggest contamination.
Acute pyelonephritis is diagnosed on the basis of loin pain and tenderness in association with fevers in a constitutionally unwell patient. Persisting pyuria may be due to resolving UTI, stone, foreign body, sloughed papilla and, uncommonly in Australasia, tuberculosis (TB). Schistosomiasis due to Schistosoma haematobium contracted in Africa or the Middle East may also cause pyuria although non-specific UTIs do occur as with genito-urinary TB.
Patients presenting acutely with symptoms of UTIs need to be treated as having a UTI until an alternative diagnosis is proven. After providing a specimen for urine microscopy and bacteriology, patients are advised to take a single dose (200 mg nitrofurantoin or 600 mg trimethoprim) or a 3–5-day course of combination amoxycillin/clavulinic acid, trimethoprim or nitrofurantoin.
A further micro-urine examination is required following treatment of an uncomplicated UTI to confirm eradication of the offending organism. If there is a recurrence of symptoms, further microscopy and bacteriology are required to determine whether this is another UTI and, if so, whether this is due to a different organism (recurrent infection) or a recrudescence of a prior, partially treated UTI (relapse). Approximately 90% of subsequent UTI episodes are due to different organisms (i.e. recurrent infections).
For relapsing UTI a reason for failure of eradication needs to be sought. This may be due to not taking the medication, a large residual urine in the bladder, a stone or foreign body or renal scarring as a consequence of childhood vesico-ureteric reflux.
Patients with acute pyelonephritis require intravenous fluids together with gentamicin and amoxycillin during the acute phase followed by maintenance trimethoprim, or oroquinolones for 2–4 weeks. An IVU during the period of hospitalisation will identify those patients who have a complicating stone.
As a principle, before prescribing any medications for women or adolescent females, enquire regarding the patient's current pregnancy status and, if in doubt, prescribe a medication approved for use in pregnancy.
All men with UTIs and women with complicated UTIs (which include relapsing and upper tract infections) require investigation. An IVU may provide information regarding renal scarring and stone formation with suspected incomplete bladder emptying confirmed by catheter or trans-abdominal ultrasound estimation of residual urine. Occasionally a technetium-99m dimercapto-succinic acid (99mTc DMSA) renal scan will be required to demonstrate scarring.
A Proteus UTI should always raise the possibility of an infective stone. Cast or staghorn calculi form with bacteria entrapped so that a combination of obstruction and infection ensues, with destruction of renal parenchyma as the end result. Antibacterial therapy alone is ineffective. Stone clearance is required.
If untreated, a pyonephrosis may develop from an infective stone to extend to form a perinephric abscess. This may become large, inducing chronic ill health and anaemia. Perinephric abscesses can also develop from renal carbuncles that are metastatic infections to the renal cortex, the bacteria in these cases most often being staphylococci. Perinephric abscesses require drainage followed by treatment of underlying predisposing causes. Abdominal ultrasound is valuable in diagnosis and in instituting drainage.
Asymptomatic bacteriuria in healthy women seldom needs treatment because it is self-limiting and usually transitory. Similarly, asymptomatic patients with indwelling catheters and bacteriuria should not be prescribed antibacterial drugs because, apart from the untoward risks and costs associated with drug therapy, resistant organisms are likely to emerge. However, treatment of asymptomatic bacteriuria is advised in girls and pregnant women because of the considerable likelihood of symptomatic UTI developing.
Genitourinary TB, always secondary to TB elsewhere (usually in the lung), may present as a non-specific UTI. If suspected a chest X-ray and three early morning urine specimens for culture for acid-fast bacilli are indicated. Microscopy alone is not sufficient, because acid-fast contaminants may cause a misdiagnosis. Long-term monitoring is imperative. Treatment is undertaken with standard anti-tuberculous drugs.
Urinary tract infections in children
Children need to be regarded differently because of the higher likelihood of underlying congenital abnormalities. In the neonatal period girls and boys are afflicted in comparable numbers, but girls predominate subsequently. Urinary tract infections are diagnosed in approximately 5% of schoolgirls, highlighting the frequency of such infections.
Haematogenous spread of infection to the kidney is common in neonates, while the ascending route via the urethra predominates in older children. Escherichia coli is the offending organism in 80% of cases.
Before the age of 2 years children often present looking ill with fevers and non-specific symptoms of vomiting and diarrhoea with dehydration. In older children, burning, frequency and back pain may be present, although some have symptoms not referable to the urinary tract.
Abdominal ultrasound examination is routine. If the child is less than 2 years old or an abnormality is detected, a micturating cystourethrogram is ordered. The underlying conditions of particular importance that are sought are vesico-ureteric reflux, and urethral valves in boys. Vesico-ureteric reflux in the presence of a UTI and intrarenal reflux (of the compound calices at the upper and lower poles) result in scarring. Long-term sequelae are chronic pyelonephritis and hypertension.
Ideally, management of vesico-ureteric reflux is orchestrated by liaison between a paediatric urologist or a paediatric surgeon and a paediatric nephrologist. Most children require long-term maintenance antibacterial prophylaxis, with only the most severe cases needing surgical intervention. The presence of urethral valves is an indication for prompt intervention.
The conditions previously constituting the prostatitides were reclassified in 1997. New National Institute of Health categories of chronic pelvic pain syndromes (CPPS) are acute and chronic bacterial prostatitis (CPPS I & III), chronic abacterial prostatitis (CPPS IIIa) and prostatodynia (CPPS IIIb). Category CPPS IV consists of asymptomatic inflammatory prostatitis, with the diagnosis made incidentally by prostatic biopsy or by white cells in expressed prostatic secretions or semen, identified during evaluation of other disorders.
CPPS I, II and IIIa are those in which white cells are detected in prostatic secretions, post-prostatic massage urine or semen from symptomatic men, with accompanying bacteria for both CPPS I and II, but not CPPS IIIa. With the exception of acute prostatitis (CPPS I), which is a distinct clinical entity, CPPS II (chronic bacterial prostatitis) and both CPPS III sub-category patients have clinically indistinguishable chronic pelvic pain.
Acute bacterial prostatitis
This is a potentially life-threatening affliction characterised by high fever, chills, rigors, lower urinary tract symptoms and the presence of a tender, often hot, swollen prostate on digital rectal examination (DRE). To minimise any risk of septic emboli, DRE should be performed gently. Gram-negative bacteria are present in urine samples.
Treatment, after obtaining urine and blood samples for bacteriology, consists of parenteral gentamicin and amoxycillin with intravenous fluids initially. A minimum of 8 weeks of trimethoprim or one of the new oroquinolones, after the patient is no longer toxic, is recommended. If urinary retention develops, a stab suprapubic catheter is advocated in preference to a urethral catheter.
Chronic prostatitides (CPPS II, IIIa and IIIb)
Patients are young adult to middle-aged, complaining of urethral burning, perineal pain, suprapubic discomfort and frequency. The prostate is not abnormal on DRE. Differentiation between the three clinical conditions is provided by microscopy and bacteriological culture of an initial voided (urethral) specimen, followed by a midstream urine (bladder) analysis, prostatic fluid expressed by prostatic massage and a urethral massage (post-void urine).
Chronic bacterial prostatitis (CPPSII)
Patients have episodes of urinary infection with intermittent asymptomatic periods of days to months. Prostatic fluid contains increased numbers of white cells and Gram-negative bacilli (most often E. coli). Absolute bacterial counts and white cell numbers are less important than their presence.
Treatment options are limited by the small number of antibacterial drugs able to concentrate in adequate levels in the prostate. Trimethoprim and the new oroquinolones, in particular ciprofloxacin, are effective, with protracted treatment required for resistant cases.
Abacterial prostatitis (CPPS IIIa)
The aetiology remains unknown. A 4–8-week course of tetracycline or erythromycin may benefit some, although these men often return with further symptoms. Non-traditional dietary supplements are sometimes beneficial, with quercin recently shown to demonstrate clinically significant relief in a double-blind, placebo trial.
Non-inflammatory chronic pelvic pain syndrome (CPPSIIIb)
Non-inflammatory pelvic pain syndrome patients may have a non-prostatic cause for their symptoms and the differential diagnosis includes interstitial cystitis (IC), drug effects, such as the non-steroidal antiinflammatory drugs tiaprofenic acid and diflunisal and DO. After voided urinary cytology, cystoscopy and urodynamic studies may reveal a cause.
Strictures represent a pathological narrowing of the urethral lumen, causing both anatomical and functional obstruction.
Aetiology and classification
Strictures may be congenital or acquired, or due to inflammation or trauma (from both internal and severe external trauma), although often the cause remains unknown (idiopathic). Submeatal and bulbomembranous regions are the most common sites.
Presentation and diagnosis
The classical presentation is with a narrowed or weak flow. By the time the stream is noticeably thin, the luminal diameter is reduced considerably.
An ascending urethrogram is the most useful diagnostic investigation. For a urethrogram to be considered normal, dye should outline an anterior urethra of regular calibre and needs to be seen entering the bladder without having extravasated.
Dilatation by either rigid or flexible dilators remains the most common form of management. Flexible dilators may be introduced under direct urethroscopic vision or blindly. Patients may keep their urethral lumina patent by self-catheterisation once or twice a week. Catheters are passed completely into the bladder to ensure that the whole of the urethra is traversed.
Urethrotomy under vision is unlikely to be successful if there is full-thickness bulbo-spongio-fibrosis but may be of value in partial-thickness strictures. Excision and re-anastomosis is suitable for some short strictures, with substitution (buccal mucosa or skin) urethroplasty employed in others.
Restricturing is common after dilatation or urethrotomy. Bacteraemia may occur during treatment (particularly dilatation). Prophylactic pre-procedural gentamicin and amoxycillin are administered routinely to these patients in order to avoid this problem.
Benign prostatic hyperplasia
If they live long enough nearly all men will develop microscopic benign prostatic hyperplasia (BPH). About half of these men will develop macroscopic enlargement of the gland, with only one half again developing symptomatic BPH.
Pathogenesis and pathology
BPH is a result of hyperplasia of both epithelial and stromal elements of the transition zone (see Anatomy of the prostate.) with stromal elements (mostly smooth muscle and connective tissue) predominating.
BPH may cause bladder outflow obstruction (BOO), which is a functional obstruction with catheters and instruments able to be passed in an antegrade fashion, usually without difficulty. Prostatic size bears no relationship to whether or not BOO is present.
Symptoms attributed to BPH are predominantly those of bladder dysfunction, with only hesitancy and slow stream reported to correlate with BOO. What is perceived as poor flow may be due to small volumes voided. The irritable symptoms of urgency, urgency incontinence and frequency are non-specific.
Frequency, excluding polyuria, is due to a functionally small (rarely an anatomically small) bladder. The functionally reduced bladder capacity may be due to sensory or motor causes (or both).
DO due to inappropriate bladder muscle contractions with generation of raised intravesical pressures, occurs in most patients with significant BOO. Once BOO is relieved, DO usually disappears, but may persist if the cause is neuropathic or idiopathic. (An idiopathic aetiology is increasingly common with ageing, for both genders).
Incomplete bladder emptying does not equal obstruction and there is a group of patients with poorly contracting detrusors who do not have BOO and for whom prostatic resistance lowering strategies are unlikely to be helpful. Chronic urinary retention is considered when residual urine is less than 300 mL. Patients with high-pressure chronic retention classically present with nocturnal enuresis and few, if any, urinary symptoms. These men may also have bilateral hydronephrosis and impaired renal function due to back-pressure.
Acute urinary retention (painful bladder distension) is more common. It may be precipitated by a diuresis (with or without alcohol), alpha-stimulant drugs or anticholinergic medication, a rectum loaded with faeces, acute prostatitis or prostatic infarction. The possibility of a neuropathic cause should always be considered.
The severity of symptoms should be assessed. The significance to the patient may be semi-quantified by symptom scores (e.g. the International Prostate Symptom Score [IPSS]) completed independently by the patient.
Nocturia, the most disruptive symptom, should be considered in context with length of slumber and whether or not the patient's bladder wakens him. Fluid and drug (including alcohol) taking patterns and a voiding time-volume chart (recording every volume voided with the time of micturition over several representative 24 hour periods) are pertinent. Nocturnal polyuria may result from nocturnal diuresis after evening alcohol ingestion, fluid redistribution in cardiac failure or abnormal anti-diuretic hormone (ADH) production from sleep apnoea or tumours. Following abdominal and limited neurological examination, DRE is essential.
A micro-urine examination and urine culture are essential to exclude infection. Transabdominal ultrasound examination of the upper tracts with a plain X-ray of the abdomen and pelvis (rather than IVU) is recommended. Ultrasound of the lower tracts also permits estimation of residual urine.
As an accurate diagnosis of BOO from BPH cannot be made on symptoms alone, a voided urinary flow rate and urodynamic studies, with bladder pressure/voided urine flow recordings, may be used to provide objective evidence of BOO. However, sustained symptomatic relief following effective lowering of bladder outflow resistance does not correlate accurately with the presence or absence of demonstrable obstruction prior to treatment.
Apart from acute urinary retention in the presence of preceding symptoms supportive of BOO and chronic retention with upper tract dilatation and bladder calculi, indications for treatment are relative. In the short term, symptoms due to BOO fluctuate, although with time they gradually worsen. Treatment strategies available for BOO include pharmacological and procedural approaches.
There is evidence that the “natural product” saw palmetto (Serenoa repens) can be effective in reducing lower urinary tract symptoms.
5α-reductase inhibitor drugs competitively inhibit conversion of testosterone to dihydrotestosterone, causing a reduction in prostatic size due to an effect on epithelial cells with an associated decrease in prostate-specific antigen (PSA) levels by approximately 50%. Patients with larger prostates are more likely to experience symptomatic relief, after 3 to 6 months, and a reduced likelihood of acute urinary retention. Several placebo-controlled trials confirm the durability of 5α-reductase inhibitor drugs in the management of BOO which, unlike α-1 blocking agents, are better tolerated in the longer term. α-1 blocking agents reduce urethral and prostatic smooth muscle tone, producing a symptomatic effect within weeks. There is comparable efficacy for all members of this family of drugs, with postural hypotension the main untoward effect. Although a selective α-1A subtype antagonist is available, dizziness remains problematical as an unwanted effect.
The operative procedure of transurethral resection of prostate (TURP) is the standard operation for relieving BOO due to BPH. Open enucleative prostatectomy is now reserved for large, vascular glands and selected patients with narrowed or strictured urethras.
There is an erroneous view that TURP is a simple ‘rebore’ of the prostate able to be performed almost mechanically on any patient. It requires regional or general anaesthesia and is associated with peri-operative and post-operative morbidity and mortality (albeit low). Retrograde emission is to be expected following TURP because the bladder neck is resected. Potency difficulties are not commonly a problem. Dribbling and urgency incontinence may occur post-operatively, with strictures and chronic urinary infections as the possible long-term sequelae.
A less invasive procedure, better suited to small prostates, is bladder neck incision (BNI), which involves making one or two incisions completely through the region of the bladder neck extending to just above the distal sphincter. This enables the prostatic urethra to open and funnel during voiding, thus relieving BOO. Retrograde emission is less likely, because the bladder neck is incised rather than resected. Consequently, the bladder neck should continue to remain closed during ejaculation (when the distal sphincter relaxes), only opening with detrusor contractions.
Of a number of other procedures introduced over the recent past, those which have established a niche as being less invasive than TURP yet effective and durable include transurethral microwave thermotherapy and radio-frequency-needle ablation thermotherapy. Laser techniques have evolved over the past few years such that laser prostatectomy is now comparably effective with TURP as well as providing the advantages of minimal peri-operative blood loss and shorter inpatient times.
This is the most common cancer diagnosed clinically in men and the second most common cause of male cancer deaths in Australasia. The lowest rates are in Asia and the highest rates in Scandinavia and the United States, particularly in African Americans.
The significance of prostate cancer as a major health issue is underestimated. The oft-quoted line that ‘more men die with prostate cancer than from it’ misleads, falsely implying an innocuous nature. Importantly, age has no significant prognostic effect in contemporary series. The morbidity that prostate cancer exacts from middle-aged and elderly men, both from the disease itself and its various treatments is considerable, the magnitude of unwanted effects (and costs) escalating with advancing stage of disease.
Aetiology and pathology
Prostate cancer is rare before 40 years, with prevalence increasing with age. Family susceptibility is regarded as comparable with that of breast cancer, with the risk of developing prostate cancer increasing with the number of genetic relatives diagnosed with this disease.
The large majority of tumours are adenocarcinomas. Because of their heterogeneous nature histologically, the Gleason scoring system has become accepted as most useful clinically. Most prostate cancers progress slowly so that, with contemporary earlier diagnosis, the overall 10-year survival expectancy is comparable with men without prostate cancer but at 15 years, there is a considerable difference. However, for patients with higher Gleason scores the average life expectancy is approximately 5-10 years.
Clinically, prostatic cancer presents late either with BOO or with symptoms from metastases. There are no early symptoms of this disease. Approximately 10–15% of patients who have TURP for what is clinically BPH have carcinoma diagnosed in the resected fragments: 25% of prostatic cancers arise in the same (transition) zone as BPH, with 70% in the peripheral zone and 5% in the central zone. About 50% of solitary nodules felt by DRE will be malignant. A histological diagnosis of prostatic cancer is required before any form of treatment is contemplated.
Prostatic cancers also present as sciatica, anaemia, weight loss or with bony pain.
Prostate specific antigen
Raised serum PSA levels occur with BPH, bacterial prostatitis (CPPS I & II), prostate cancer and following instrumentation. A normal DRE is unlikely to cause elevation. PSA is a labile enzyme, fluctuating diurnally. Raised PSA levels are found in 90% or more of patients diagnosed with prostatic cancer. However PSA is not a test for cancer because it is neither sensitive nor specific enough, and should be employed together with DRE.
Adaptations to improve the discriminatory ability of PSA include PSA velocity (rate of increase in PSA with time) and age-related PSA changes. Assays vary so PSA velocity assessments need to be made using the same assay. The ratio of free to total PSA is also useful with a lower free component present in patients with prostate cancer. However, ejaculation may result in a temporary surge of free PSA in the serum.
Although serum PSA is definitely not a specific screening or diagnostic test for prostatic cancer, once a tumour has been diagnosed, it usually serves as a very sensitive indicator of progress of disease and response to treatment.
Transrectal ultrasound (TRUS) permits definition of prostatic anatomy, but not prostatic cancer. Its main value is for spatial positioning of spring-loaded needles for transrectal prostatic biopsies. These biopsies are uncomfortable procedures with a small but definite risk of septicaemia despite routine pre-procedural enema and antibacterial prophylaxis. Haematospermia, blood on faeces and haematuria with difficulty voiding are not unexpected short-term sequelae.
Prostate cancer spreads by local extension to periprostatic tissues, lymphatic spread to obturator, internal iliac and presacral nodes, and venous spread to involve the axial skeleton, predominantly with osteosclerotic metastases.
Prostate cancer is only curable when localized to the prostate. Lymph node involvement indicates systemic disease. Currently, radionuclide bone scanning is the standard method for detecting bony metastases. However, even when the cancer is thought to be localised clinically, up to 25% of patients have occult metastases.
Management options include a role for ‘watchful waiting’, with radiotherapy and total (radical) prostatectomy remaining the only potential curative therapies for tumours confined to the prostate. Androgen suppression affords palliation for most patients with metastatic disease. There is no established place for chemotherapy in routine treatment.
Localised prostatic cancers usually progress slowly with an estimated doubling time of 2 years. As all interventional strategies are associated with unwanted effects and co-morbidity is common in the elderly, a place for a watch and wait (close surveillance) policy remains appropriate, especially if life expectancy is less than 10 years. Most men die with, rather than from, their prostate cancers. However, because of its proclivity to metastasise to the axial skeleton, men dying of prostate cancer have the potential to die badly.
Total (radical) prostatectomy
Radical prostatectomy is generally regarded as the reference treatment, with a 90% 10-year disease-specific survival for organ-confined tumours. The incontinence rate is approximately 7% at 12 months and the impotence rate is at least 30%. Other significant complications are urethral stricture, lymphocele, and deep venous thrombosis. Morbidity is greater in elderly patients and there is a definite, albeit low, peri-operative mortality of less than 0.5%.
The other potentially curative form of treatment is radiotherapy. Supervoltage radiotherapy is probably comparably effective as radical prostatectomy with lower mortality and incontinence rates. Impotence following supervoltage radiotherapy for prostate cancer is not uncommon, with varying degrees of proctitis; rectal bleeding and faecal soiling remain incapacitating for a minority well beyond the end of therapy — sometimes requiring definitive surgical treatment subsequently. The routine use of many months of periprocedural androgen suppression therapy adjunctively, shown to improve survival in the intermediate term, adds a further dimension to the unwanted effect profile with contemporary supervoltage treatment.
Over the past few years, a resurgence of interest has developed regarding local radiotherapy (brachytherapy) alone or in combination with supervoltage radiotherapy. Improved imaging and isotope placement techniques have resulted in excellent cancer control in the medium to long term in selected patients. Brachytherapy is attractive because of its minimal invasiveness and perceived lack of side effects. While irritative voiding and minor proctitis problems are common in the short term, long-term unwanted effects are less of a problem. Patients with severe preceding urinary symptoms and those who have previously had a TURP are most at risk to have continence problems subsequently: potency difficulties are not uncommon following brachytherapy.
Androgen suppression is the mainstay of treatment for non-localised disease. Approximately 80% of patients demonstrate a durable response, with a median duration response of 24–36 months. The faster the PSA returns to the normal range, the better the response and prognosis. Methods currently used for androgen suppression include bilateral orchidectomy (the reference treatment), depot injections of long-acting luteinising hormone-releasing hormone (LHRH) analogues and anti-androgens.
There is no clear evidence that commencing androgen suppression early improves survival. An initial testosterone surge (“flare effect”), loss of muscle mass, osteoporosis, anaemia, hot flushes and adverse cognitive changes accompany LHRH analogue administration; liver dysfunction, depression, drowsiness and gynaecomastia result from anti-androgen therapy. Loss of sexual desire and impotence have been identified as the most important factors adversely affecting the quality of life of these men. Unfortunately, not all unwanted effects are reversible, negating the benefit of intermittent androgen blockade (IAB) compared with a delay in commencing androgen suppression initially. The use of maximal androgen blockade (MAB) to also address adrenal androgens affords little if any benefit in terms of tumour control but certainly increases the likelihood and magnitude of unwanted effects.
Renal cell carcinoma
Renal cell cancer (RCC) constitutes approximately 2–3% of malignancies. Approximately 60% of RCCs are diagnosed in men, with the incidence increasing from the mid-fifties.
Aetiology and pathology
The aetiology remains unknown, but RCC arise more commonly in patients afflicted by Von Hippel-Lindau (VHL) disease. A VHL gene mutation rate of 33–70% has been reported in sporadic RCCs. RCCs usually develop de novo as solid, parenchymal lesions but may arise in the wall of complex, septated cysts.
Clear cell (75–85%), chromophilic (papillary) (15%), chromophobic (5%), oncocytic (uncommon) and collecting duct (rare) tumours constitute the 5 subtypes of RCC. The best prognostic projection from histology is afforded by the nuclear grading system of Fuhrman. Descriptions of other mass lesions are given in Other mass lesions of the kidney. Direct spread, with a predilection for venous propagation and metastases and lymphatic spread to hilar and retroperitoneal lymph nodes are features of this neoplasm.
In the past RCC presented late, being clinically quiescent until quite large with haematuria, the most common presenting symptom. Increasingly, RCC is being diagnosed as an incidental finding on abdominal imaging studies.
Pathological kidneys are prone to injury with even trivial trauma. Pain occurs from local extension and clot colic. A varicocele that develops after early adulthood raises the possibility of a left testicular vein obstruction from a propagated renal tumour thrombus (see External genitalia in the male).
A pyrexia of unknown origin as a mode of presentation occurs in only a small percentage of patients, although fever is said to occur in approximately 20% of patients during their clinical course. Anaemia may result from bone marrow metastases, but also from toxic effects, as can a hepatopathy with abnormal lactate dehydrogenase and serum alkaline phosphatase levels as well as impaired prothrombin production. These effects are reversible with removal of the tumour.
Renal cell carcinomas are able to produce many hormones. Erythrocytosis is the most common manifestation. Ectopic renin and other tumour products causing hypertension may contribute to the development of heart failure, and high-output cardiac failure may develop as a result of shunting through large pathological vascular channels.
A CT scan with radiocontrast (see Computed tomography scan through both kidneys following intravenous contrast injection. There is a slightly enhancing space-occupying lesion in the right kidney protruding beyond the kidney.) is the next investigation following ultrasound of a spaceoccupying lesion (SOL) not demonstrating the classical features of a simple cyst (viz. anechoic with posterior wall accentuation). Classically, RCCs protrude from and replace renal parenchyma and/or distort the pelvicaliceal arrangement. They ‘contrast enhance’ in the post-injection phase in most instances by virtue of their vascularity. If an upper pole tumour is suspected, the adrenal gland must be identified, as adrenal tumours (especially phaeochromocytomas) may be difficult to distinguish. The possibility of tumour thrombus should be sought, with ultrasound often useful in this regard. Identifiable hilar, paracaval and para-aortic lymph nodes may be due to follicular hyperplasia or secondary deposits. The contralateral kidney, liver, lung fields and vertebrae should be examined thoroughly in the search for possible metastases.
Radioisotope bone scanning using a labelled phosphate compound that concentrates in sites of increased phosphate metabolism in bone remains the standard for detecting metastatic osseous deposits. Reference plain X-rays may be required to exclude false-positive ‘hot spots’ from non-metastatic lesions such as Paget's disease, and healing fractures.
Radical nephrectomy with a surrounding envelope of fat and fascia, which remains the only effective form of treatment, has little place for patients with secondary tumours unless performed to relieve local symptoms. With few exceptions, if lymphatic metastases are present, the patient has systemic disease, with less than 35% chance of surviving 5 years. Where the tumour is confined to the kidney or within Gerota's fascia, 5-year survival rates of around 60% can be expected.
Propagation of tumour thrombus into the venous system, seemingly in preference to direct and lymphatic spread in some patients, involves the IVC in 5–10% of cases and may extend into the right atrium. Tumour thrombus in the IVC does not cause the tumour to be inoperable, because prognosis relates to the presence or absence of lymphatic and other metastases. However, in general terms, the higher the tumour thrombus the worse the prognosis because of the increasing likelihood of coexisting metastases.
The urothelium is the epithelial lining of the urinary tract extending from the collecting tubules to the urethral meatus.
Although urothelial cancers can involve any part of the urothelium, most arise in the bladder. In the upper tract, renal pelvis and lower ureter are the most common sites. Upper tract to lower tract rate is approximately 1 : 30. The incidence of bladder cancer has increased by 50% in the past 35 years and this tumour now forms approximately 3% of all new cancers. The male to female ratio is 7 : 3.
Cigarette smoking is considered responsible for approximately 40% of bladder cancers, with 25% attributed to occupational exposure. Occupations considered to be ‘at risk’ include those associated with handling of chemicals, especially naphthylamine, magenta, auramine and benzidine.
Phenacetin has been incriminated as the carcinogenic agent in compound headache powders containing aspirin, phenacetin and caffeine (APC) that were ingested habitually in Australia in the past. These patients also developed papillary necrosis and renal failure, although these manifestations are now less common with legislation that bans the sale of such compound powders. Bilharziasis from Schistosoma haematobium, a common condition in Egypt and East Africa, predisposes to bladder cancer, particularly squamous cell carcinoma.
These are largely transitional cell carcinomas (90– 95%), with squamous cell carcinoma and occasional adenocarcinomas constituting the remainder. Adenocarcinoma of the bladder is a rarity and is a secondary tumour (mostly from bowel) until proven otherwise.
Superficial tumours are limited to the mucosa and lamina propria (70–75%), invasive tumours involve the muscularis propria and beyond (20–25%), with the remainder being widespread flat carcinoma in situ (CIS). In the bladder, CIS is a malignancy rather than a premalignant condition.
The presenting symptom in the vast majority of patients is haematuria, with day- and night-time frequency (often without haematuria) the dominant symptom for CIS. A history of haematuria, even if fleeting, must never be ignored, with prompt exclusion of a urothelial cancer of paramount importance.
Voided urine cytology is the most useful adjunctive, non-invasive test but, by itself, is insufficiently sensitive to replace the definitive investigations below. Cytology is particularly valuable for detecting the presence of CIS.
Upper tract urothelial tumours produce filling defects or obstruction on IVU or helical CT scan with radiocontrast. The status of the upper tracts should be determined before cysto-urethroscopy to permit the option of retrograde studies, mostly retrograde pyelograms and saline lavaging to disaggregate tumour cells for cytology, at the time of endoscopic examination. Alternatively ureteroscopy (± biopsy) may also be performed.
The non-contrast phase of CT scans distinguishes radiolucent calculi from other causes of a filling defect on IVU. Tumours, blood clots and sloughed papillae are of tissue density. In addition, a CT scan of the pelvic region may aid in determining extravesical extension, although early tumour extension into the bladder wall is not reliably demonstrable radiographically.
Cysto-urethroscopy forms the basis for the diagnosis of bladder and urethral cancers, initial inspections being performed increasingly by flexible instruments. Tumours are biopsied through the working element of the cystoscope and adequate biopsy will allow the depth of invasion of the bladder wall (stage) to be determined and the degree of anaplasia (grade) to be assessed.
Tumours of the upper and lower tracts require different forms of treatment.
Ureteric and renal pelvic urothelial cancers
Treatment for ureteric and renal pelvic urothelial cancers is by nephro-ureterectomy, together with excision of a cuff of bladder. Periodic check cystoscopies are performed because further tumours are likely to develop subsequently.
Superficial bladder cancer
Superficial and submucosally invasive tumours of the bladder are treated by endoscopic transurethral resection of the bladder (TURB), using a resectoscope with cutting and coagulating diathermy. The tumour base is resected separately to facilitate histopathological staging. There is a high risk of recurrence after treatment of the initial lesion, with at least 50% of tumours recurring, with up to 25% of those recurrences progressing to invasive cancer, with a worsening of prognosis. In order to reduce this tendency to recur, it is now common practice to instill mitomycin C into the bladder in the immediate post-operative period.
Cystoscopy, in conjunction with voided urinary cytology, remains routine for monitoring and diagnosing tumour recurrences. In general, with the exception of a small group of patients whose superficial tumours are recognisably aggressive so that treatment as for invasive disease is indicated, current practice is to commence with an examination every 3 months, extending these progressively to 12-month intervals if findings remain negative. These patients are prone to further tumour formation indefinitely and must be followed for life.
Fulguration is used extensively for recurrent small tumours without obvious invasion, although biopsy of at least some lesions is essential to record stage and grade.
Intravesical chemotherapy with epirubicin and mitomycin C, and immunotherapy with Bacillus Calmette-Guérin (BCG) are effective in reducing the likelihood of recurrences. Although BCG is the most effective agent, it is also potentially more toxic. Viability of the bacilli may be jeopardised by antibacterial drugs which, in addition to anticoagulant and anti-inflammatory agents which impair fibronectin attachment, should be avoided during the periods of intravesical therapy. If haematuria is present or traumatic catheterisation occurs, BCG should not be introduced into the bladder as there is an increased risk of systemic infection from this organism.