- •Hematuria II: causes and investigation
- •Hematospermia
- •Lower urinary tract symptoms (LUTS)
- •Nocturia and nocturnal polyuria
- •Flank pain
- •Urinary incontinence in adults
- •Genital symptoms
- •Abdominal examination in urological disease
- •Digital rectal examination (DRE)
- •Lumps in the groin
- •Lumps in the scrotum
- •2 Urological investigations
- •Urine examination
- •Urine cytology
- •Radiological imaging of the urinary tract
- •Uses of plain abdominal radiography (KUB X-ray—kidneys, ureters, bladder)
- •Intravenous pyelography (IVP)
- •Other urological contrast studies
- •Computed tomography (CT) and magnetic resonance imaging (MRI)
- •Radioisotope imaging
- •Post-void residual urine volume measurement
- •3 Bladder outlet obstruction
- •Regulation of prostate growth and development of benign prostatic hyperplasia (BPH)
- •Pathophysiology and causes of bladder outlet obstruction (BOO) and BPH
- •Benign prostatic obstruction (BPO): symptoms and signs
- •Diagnostic tests in men with LUTS thought to be due to BPH
- •Why do men seek treatment for their symptoms?
- •Watchful waiting for uncomplicated BPH
- •Medical management of BPH: combination therapy
- •Medical management of BPH: alternative drug therapy
- •Minimally invasive management of BPH: surgical alternatives to TURP
- •Invasive surgical alternatives to TURP
- •TURP and open prostatectomy
- •Indications for and technique of urethral catheterization
- •Indications for and technique of suprapubic catheterization
- •Management of nocturia and nocturnal polyuria
- •High-pressure chronic retention (HPCR)
- •Bladder outlet obstruction and retention in women
- •Urethral stricture disease
- •4 Incontinence
- •Causes and pathophysiology
- •Evaluation
- •Treatment of sphincter weakness incontinence: injection therapy
- •Treatment of sphincter weakness incontinence: retropubic suspension
- •Treatment of sphincter weakness incontinence: pubovaginal slings
- •Overactive bladder: conventional treatment
- •Overactive bladder: options for failed conventional therapy
- •“Mixed” incontinence
- •Post-prostatectomy incontinence
- •Incontinence in the elderly patient
- •Urinary tract infection: microbiology
- •Lower urinary tract infection
- •Recurrent urinary tract infection
- •Urinary tract infection: treatment
- •Acute pyelonephritis
- •Pyonephrosis and perinephric abscess
- •Other forms of pyelonephritis
- •Chronic pyelonephritis
- •Septicemia and urosepsis
- •Fournier gangrene
- •Epididymitis and orchitis
- •Periurethral abscess
- •Prostatitis: presentation, evaluation, and treatment
- •Other prostate infections
- •Interstitial cystitis
- •Tuberculosis
- •Parasitic infections
- •HIV in urological surgery
- •6 Urological neoplasia
- •Pathology and molecular biology
- •Prostate cancer: epidemiology and etiology
- •Prostate cancer: incidence, prevalence, and mortality
- •Prostate cancer pathology: premalignant lesions
- •Counseling before prostate cancer screening
- •Prostate cancer: clinical presentation
- •PSA and prostate cancer
- •PSA derivatives: free-to-total ratio, density, and velocity
- •Prostate cancer: transrectal ultrasonography and biopsies
- •Prostate cancer staging
- •Prostate cancer grading
- •General principles of management of localized prostate cancer
- •Management of localized prostate cancer: watchful waiting and active surveillance
- •Management of localized prostate cancer: radical prostatectomy
- •Postoperative course after radical prostatectomy
- •Prostate cancer control with radical prostatectomy
- •Management of localized prostate cancer: radical external beam radiotherapy (EBRT)
- •Management of localized prostate cancer: brachytherapy (BT)
- •Management of localized and radiorecurrent prostate cancer: cryotherapy and HIFU
- •Management of locally advanced nonmetastatic prostate cancer (T3–4 N0M0)
- •Management of advanced prostate cancer: hormone therapy I
- •Management of advanced prostate cancer: hormone therapy II
- •Management of advanced prostate cancer: hormone therapy III
- •Management of advanced prostate cancer: androgen-independent/ castration-resistant disease
- •Palliative management of prostate cancer
- •Prostate cancer: prevention; complementary and alternative therapies
- •Bladder cancer: epidemiology and etiology
- •Bladder cancer: pathology and staging
- •Bladder cancer: presentation
- •Bladder cancer: diagnosis and staging
- •Muscle-invasive bladder cancer: surgical management of localized (pT2/3a) disease
- •Muscle-invasive bladder cancer: radical and palliative radiotherapy
- •Muscle-invasive bladder cancer: management of locally advanced and metastatic disease
- •Bladder cancer: urinary diversion after cystectomy
- •Transitional cell carcinoma (UC) of the renal pelvis and ureter
- •Radiological assessment of renal masses
- •Benign renal masses
- •Renal cell carcinoma: epidemiology and etiology
- •Renal cell carcinoma: pathology, staging, and prognosis
- •Renal cell carcinoma: presentation and investigations
- •Renal cell carcinoma: active surveillance
- •Renal cell carcinoma: surgical treatment I
- •Renal cell carcinoma: surgical treatment II
- •Renal cell carcinoma: management of metastatic disease
- •Testicular cancer: epidemiology and etiology
- •Testicular cancer: clinical presentation
- •Testicular cancer: serum markers
- •Testicular cancer: pathology and staging
- •Testicular cancer: prognostic staging system for metastatic germ cell cancer
- •Testicular cancer: management of non-seminomatous germ cell tumors (NSGCT)
- •Testicular cancer: management of seminoma, IGCN, and lymphoma
- •Penile neoplasia: benign, viral-related, and premalignant lesions
- •Penile cancer: epidemiology, risk factors, and pathology
- •Squamous cell carcinoma of the penis: clinical management
- •Carcinoma of the scrotum
- •Tumors of the testicular adnexa
- •Urethral cancer
- •Wilms tumor and neuroblastoma
- •7 Miscellaneous urological diseases of the kidney
- •Cystic renal disease: simple cysts
- •Cystic renal disease: calyceal diverticulum
- •Cystic renal disease: medullary sponge kidney (MSK)
- •Acquired renal cystic disease (ARCD)
- •Autosomal dominant (adult) polycystic kidney disease (ADPKD)
- •Ureteropelvic junction (UPJ) obstruction in adults
- •Anomalies of renal ascent and fusion: horseshoe kidney, pelvic kidney, malrotation
- •Renal duplications
- •8 Stone disease
- •Kidney stones: epidemiology
- •Kidney stones: types and predisposing factors
- •Kidney stones: mechanisms of formation
- •Evaluation of the stone former
- •Kidney stones: presentation and diagnosis
- •Kidney stone treatment options: watchful waiting
- •Stone fragmentation techniques: extracorporeal lithotripsy (ESWL)
- •Intracorporeal techniques of stone fragmentation (fragmentation within the body)
- •Kidney stone treatment: percutaneous nephrolithotomy (PCNL)
- •Kidney stones: open stone surgery
- •Kidney stones: medical therapy (dissolution therapy)
- •Ureteric stones: presentation
- •Ureteric stones: diagnostic radiological imaging
- •Ureteric stones: acute management
- •Ureteric stones: indications for intervention to relieve obstruction and/or remove the stone
- •Ureteric stone treatment
- •Treatment options for ureteric stones
- •Prevention of calcium oxalate stone formation
- •Bladder stones
- •Management of ureteric stones in pregnancy
- •Hydronephrosis
- •Management of ureteric strictures (other than UPJ obstruction)
- •Pathophysiology of urinary tract obstruction
- •Ureter innervation
- •10 Trauma to the urinary tract and other urological emergencies
- •Renal trauma: clinical and radiological assessment
- •Renal trauma: treatment
- •Ureteral injuries: mechanisms and diagnosis
- •Ureteral injuries: management
- •Bladder and urethral injuries associated with pelvic fractures
- •Bladder injuries
- •Posterior urethral injuries in males and urethral injuries in females
- •Anterior urethral injuries
- •Testicular injuries
- •Penile injuries
- •Torsion of the testis and testicular appendages
- •Paraphimosis
- •Malignant ureteral obstruction
- •Spinal cord and cauda equina compression
- •11 Infertility
- •Male reproductive physiology
- •Etiology and evaluation of male infertility
- •Lab investigation of male infertility
- •Oligospermia and azoospermia
- •Varicocele
- •Treatment options for male factor infertility
- •12 Disorders of erectile function, ejaculation, and seminal vesicles
- •Physiology of erection and ejaculation
- •Impotence: evaluation
- •Impotence: treatment
- •Retrograde ejaculation
- •Peyronie’s disease
- •Priapism
- •13 Neuropathic bladder
- •Innervation of the lower urinary tract (LUT)
- •Physiology of urine storage and micturition
- •Bladder and sphincter behavior in the patient with neurological disease
- •The neuropathic lower urinary tract: clinical consequences of storage and emptying problems
- •Bladder management techniques for the neuropathic patient
- •Catheters and sheaths and the neuropathic patient
- •Management of incontinence in the neuropathic patient
- •Management of recurrent urinary tract infections (UTIs) in the neuropathic patient
- •Management of hydronephrosis in the neuropathic patient
- •Bladder dysfunction in multiple sclerosis, in Parkinson disease, after stroke, and in other neurological disease
- •Neuromodulation in lower urinary tract dysfunction
- •14 Urological problems in pregnancy
- •Physiological and anatomical changes in the urinary tract
- •Urinary tract infection (UTI)
- •Hydronephrosis
- •15 Pediatric urology
- •Embryology: urinary tract
- •Undescended testes
- •Urinary tract infection (UTI)
- •Ectopic ureter
- •Ureterocele
- •Ureteropelvic junction (UPJ) obstruction
- •Hypospadias
- •Normal sexual differentiation
- •Abnormal sexual differentiation
- •Cystic kidney disease
- •Exstrophy
- •Epispadias
- •Posterior urethral valves
- •Non-neurogenic voiding dysfunction
- •Nocturnal enuresis
- •16 Urological surgery and equipment
- •Preparation of the patient for urological surgery
- •Antibiotic prophylaxis in urological surgery
- •Complications of surgery in general: DVT and PE
- •Fluid balance and management of shock in the surgical patient
- •Patient safety in the operating room
- •Transurethral resection (TUR) syndrome
- •Catheters and drains in urological surgery
- •Guide wires
- •JJ stents
- •Lasers in urological surgery
- •Diathermy
- •Sterilization of urological equipment
- •Telescopes and light sources in urological endoscopy
- •Consent: general principles
- •Cystoscopy
- •Transurethral resection of the prostate (TURP)
- •Transurethral resection of bladder tumor (TURBT)
- •Optical urethrotomy
- •Circumcision
- •Hydrocele and epididymal cyst removal
- •Nesbit procedure
- •Vasectomy and vasovasostomy
- •Orchiectomy
- •Urological incisions
- •JJ stent insertion
- •Nephrectomy and nephroureterectomy
- •Radical prostatectomy
- •Radical cystectomy
- •Ileal conduit
- •Percutaneous nephrolithotomy (PCNL)
- •Ureteroscopes and ureteroscopy
- •Pyeloplasty
- •Laparoscopic surgery
- •Endoscopic cystolitholapaxy and (open) cystolithotomy
- •Scrotal exploration for torsion and orchiopexy
- •17 Basic science of relevance to urological practice
- •Physiology of bladder and urethra
- •Renal anatomy: renal blood flow and renal function
- •Renal physiology: regulation of water balance
- •Renal physiology: regulation of sodium and potassium excretion
- •Renal physiology: acid–base balance
- •18 Urological eponyms
- •Index
230 CHAPTER 6 Urological neoplasia
Management of localized and radiorecurrent prostate cancer: cryotherapy and HIFU
These two minimally invasive treatments for localized prostate cancer are in use in many locations. Proponents claim that they are viable alternatives to radical surgery or radiotherapy and that they are options for salvage treatment of organ-confined recurrent disease following radical radiotherapy.
Furthermore, there is growing interest in “focal therapy,” whereby only a portion of the prostate is treated, sparing side effects that may be associated with more aggressive treatments.
Proponents note that of all local therapies, these are the only two that can be repeated if there is a recurrence. Cryotherapy is widely available, whereas HIFU is not yet FDA approved in the United States.
Cryotherapy
A transperineal ultrasound-guided cryoprobe delivers argon or liquid nitrogen at a temperature of –20*C to –40*C. When applied in two cycles of freeze–thaw, cellular necrosis occurs. The diameter of the ice ball is monitored using ultrasound; precautions must be taken to protect the urethra, external sphincter, and rectal wall, such as using warming devices.
An anesthetic is required; this is a day-case procedure that can be repeated.
Results
PSA nadir is usually achieved within 3 months; 25–48% of men with localized disease achieve a PSA nadir of <0.1 ng/mL in 3 months, and 96% of men achieve PSA <0.2 ng/mL within 6 months. Positive biopsies are observed in 8–25% of patients after cryotherapy.
Long-term results are promising but appear inferior to other standard therapies and are not endorsed by the AUA in their 2007 treatment guidelines for localized disease.1
Complications
These include ED (40–80%); incontinence (4–27%); LUTS due to urethral sloughing; pelvic pain; transient penile numbness; and rectourethral fistula (rare).
In the salvage setting, good short-term PSA responses are reported in 66% of men, at the expense of significant morbidity, including incontinence and urinary retention (70% each).
High-intensity focused ultrasound (HIFU)
HIFU has the potential of selective destruction of tissues at depth without damaging intervening structures. Tissue is heated to the point of
1 Gleave M, Klotz L, Taneja SS. (2009). The continued debate: intermittent vs. Continuous hormonal ablation for metastatic prostate cancer. Urol Oncol. 27(1):81–86.
MANAGEMENT OF RADIORECURRENT PROSTATE CANCER 231
coagulative necrosis by high-energy ultrasound transmitted to the prostate using a transrectal device. The tissue temperature is raised locally at this point (over 85°C).
With each firing of the probe, a cigar-shaped volume of damage is produced (a lesion). After one lesion is created, the focus is repositioned by computer guidance to create the next lesion with the same heating process. Lesions are placed side by side to create a continuous volume in which the tissue is necrosed. The rectal wall and the surrounding tissues are undamaged.
An anesthetic is required; this is a day-case procedure that can be repeated. The likelihood of morbidity is increased in the salvage treatment setting. Long-term results are awaited.
Complications
These include ED, urinary retention, stress incontinence, and recto-ure- thral fistula (rare).
232 CHAPTER 6 Urological neoplasia
Management of locally advanced nonmetastatic prostate cancer (T3–4 N0M0)
EBRT
EBRT in combination with hormone therapy has consistently demonstrated better outcomes than those with EBRT alone, which is associated with a 15–30% 10-year survival. In a European randomized study1 the hormone therapy group received LHRH analogues for 3 years starting at the time of EBRT. Their 5-year overall survival was 79% compared to 62% in the group treated with EBRT alone; the 5-year disease-free survival was 85% compared to 48%.
There are potential advantages in starting hormone therapy prior to EBRT as has been performed in other positive studies. The optimal timing and duration of hormone therapy in this setting remain unclear, but most agree that 6 months is inadequate, and 24–36 months should be considered a standard of care in high-risk disease.1
Hormone therapy
Hormone therapy alone is another option in elderly patients or those unwilling to consider radiotherapy, but its risk and benefit ratio are not clear. Outside the United States, a nonsteroidal antiandrogen (e.g., bicalutamide 150 mg) regimen is often used.
In the U.S., standard androgen ablation involves orchiectomy or LHRH analogue or antagonist. However, discussion should include the point at which hormone therapy is not a treatment offered with curative intent.
A randomized trial of hormone therapy alone vs. EBRT plus hormone therapy demonstrated that the hormone-only regimen was inferior to the combination treatment.2
Watchful waiting or active surveillance
This is also an option for nonmetastatic T3 disease in an elderly asymptomatic man who may wish to avoid side effects of treatment.
Palliative treatment of locally advanced disease
Palliative TURP or medical therapy for LUTS or retention may be necessary. Incontinence can be due to sphincter involvement, though bladder outflow obstruction and instability should be considered: a urinary convene sheath or catheter may be required.
Percutaneous nephrostomies or ureteral stents are occasionally necessary for ureteral obstruction.
1 Bolla M, de Reijke TM, Van Tienhoven G, et al. (2009). Duration of androgen suppression in the treatment of prostate cancer. N Engl J Med 360(24):2516–2527.
2 Widmark A, Klepp O, Solberg A, et al. (2009). Endocrine treatment, with or without radiotherapy, in locally advanced prostate cancer (SPCG-7/SFUO-3): an open randomised phase III trial. Lancet 373(9660):301–308.
MANAGEMENT OF ADVANCED PROSTATE CANCER 233
Management of advanced prostate cancer: hormone therapy I
Metastatic disease is the cause of nearly all prostate cancer–related deaths. Currently incurable, 5-year survival is 25%; 10% survive <6 months, while <10% survive >10 years. The mainstay of treatment is hormone therapy, with cytotoxic chemotherapy used in cases of castration-resistant prostate cancer.
The concept of hormone therapy was realized in 1941 when Huggins and Hodges reported favorable acid and alkaline phosphatase responses in prostate cancer patients who were castrated or given estrogens.
Hormone dependence of prostate cancer
Of circulating androgen, 95%, mainly testosterone, is produced by the Leydig cells of the testes under the influence of luteinizing hormone (LH). The anterior pituitary synthesizes LH, stimulated by LH-releasing hormone (LHRH) produced by the hypothalamus. The remaining 5% of circulating androgen is synthesized by adrenal cortex from cholesterol.
Testosterone is metabolized to the more potent dihydrotestosterone (DHT), by types 1 and 2 5A-reductase (5AR) enzymes. DHT binds to the androgen receptor, travels to the cell nucleus, and exerts its positive effect on cell growth and division in the androgen-sensitive cell.
All prostate epithelial cells are dependent on androgens and fail to grow or undergo programmed cell death in their absence. Similarly, most previously untreated prostate cancer cells are dependent on androgens.
Androgen deprivation results in a reduction in PSA and clinical improvement in the majority of patients. However, most will still die within 5 years because of the development of androgen-independent growth, a state now commonly referred to as “castration resistant disease.” This is considered due to growth of androgen-independent cell clones rather than to a dedifferentiation of previously androgen-dependent cells.
Traditionally, the mean time to disease progression after androgen deprivation is 14 months in men with metastatic disease, although more recent series suggest that this time is actually longer.
Prognostic factors
Predictors of poor hormone therapy response include the following:
•t5 metastatic lesions at presentation
•Elevated alkaline phosphatase at presentation
•Anemia at presentation
•Poor performance status at presentation
•Low serum testosterone at presentation
•Failure of bone pain to improve within 3 months of treatment
•Failure of PSA to normalize within 6 months of treatment (a PSA nadir (= lowest value) of <0.1 ng/mL predicts a long-term response)