Urological Diseases: Diagnosis, Treatment & Clinical Interpretation

Quick Clinical Orientation

1. Benign Prostatic Hyperplasia (BPH)

Epidemiology

• Occurs in men over 50; by age 60, 50% have histological BPH
• Most common cause of bladder outflow obstruction (BOO) in men >70 years
• Affects the transitional zone of the prostate (submucous glands)

Anatomy of BPH

Clinical Features - LUTS

• Hesitancy (worsened when bladder is full)
• Poor urinary flow (not improved by straining)
• Intermittent stream (stops and starts)
• Terminal dribbling
• Sensation of incomplete bladder emptying
• Episodes of near retention

• Frequency
• Nocturia
• Urgency and urge incontinence

• Acute urinary retention (first symptom in some men)
• Chronic retention + hydronephrosis + renal impairment
• Bladder trabeculation and diverticula
• Urinary tract infections
• Bladder stones
• Recurrent hematuria (vascular prostate)

Diagnosis

• Urine dipstick (blood, leukocyte esterase, glucose, protein)
• Urine culture
• Serum creatinine (screen for renal impairment)
• Urinary flow rate + post-void residual (PVR) by ultrasound
  • Normal peak flow: >15 mL/s (voided volume >200 mL)
  • Equivocal: 10-15 mL/s
  • Low (suggestive of BOO): <10 mL/s
  • High voiding pressure: >80 cmH2O

• PSA (after counselling) - if free-to-total PSA <15% with PSA 4-10 ng/mL: suspicious for cancer; consider mpMRI
• Pressure-flow urodynamic studies (especially if: suspected neuropathy, dominant irritative symptoms, young/old men, post-surgical recurrence)
• TRUS-guided or transperineal biopsy if suspicious mpMRI lesion
• Upper tract imaging (IVU/CT urography/ultrasound) if hematuria or infection present
• Cystourethroscopy prior to prostatectomy to exclude stricture or bladder carcinoma

Treatment

• Fluid manipulation (avoid binge drinking, late-night fluids)
• Reduce caffeine and alcohol

• Alpha-blockers (e.g., tamsulosin, alfuzosin) - relax smooth muscle, rapid symptom relief
• 5-alpha reductase inhibitors (e.g., finasteride, dutasteride) - for large glands, shrink prostate over months
• Combination therapy (alpha-blocker + 5-ARI) gives better outcomes in glands >35 g

• Acute retention in fit men with no reversible cause (25% of prostatectomies)
• Chronic retention + renal impairment + PVR >250 mL + hydronephrosis (15% of prostatectomies)
• Complications: stone, infection, diverticulum
• Recurrent hematuria from a vascular prostate

• TURP (transurethral resection of the prostate) - gold standard
• HoLEP (holmium laser enucleation of the prostate) - for large glands
• Open/robotic simple prostatectomy - for very large glands
• Minimally invasive options: UroLift, Rezum, prostatic artery embolization

2. Prostate Cancer

Epidemiology

• Most common cancer diagnosed in men; second most common cause of cancer death in men (after lung cancer)
• Major risk factors: age >65, African American race, family history
• African Americans have 70% higher incidence than whites
• Most cases are indolent; symptoms arise late

Clinical Features

• Localized prostate cancer is asymptomatic - most often detected by PSA or DRE
• Clinically advanced disease: symptoms of urinary obstruction (mimics BPH)
• Firm, irregular nodule on Digital Rectal Examination (DRE) - but DRE sensitivity/specificity is low; predicts cancer in only 18-28% of cases
• Metastatic disease: bone pain (especially axial skeleton), weight loss, lymphadenopathy

Pathology

Diagnosis

• PSA (Prostate-Specific Antigen): Widely used but controversial for screening. Clear value in monitoring recurrence after treatment
  • PSA 4-10 ng/mL: indeterminate; free-to-total PSA <15% raises suspicion
  • Rising PSA after treatment indicates recurrence
• mpMRI (multiparametric MRI): Identifies suspicious index lesions
• Transrectal needle biopsy (TRUS-guided or transperineal): Required to confirm diagnosis

Treatment

• Localized, low-risk (Grade Group 1): Active surveillance (serial PSA + mpMRI + biopsy)
• Localized, high-risk: Radical prostatectomy OR radiation therapy (external beam or brachytherapy), with or without hormonal manipulation (androgen deprivation therapy, ADT)
• >90% of patients with localized high-risk disease who receive surgery or radiation can expect to live 15 years
• Metastatic disease: ADT (LHRH agonists/antagonists ± anti-androgens); enzalutamide, abiraterone for castration-resistant prostate cancer (CRPC); chemotherapy (docetaxel) for high-volume metastatic disease

3. Bladder Cancer

Epidemiology

• Incidence increases with age; 4x more common in men than women; white men have 2x higher incidence than African Americans
• Cigarette smoking is the most prominent risk factor (4-7x increased risk)
• Other risk factors: aromatic amines (dye/rubber industry), benzidine, cyclophosphamide, pelvic radiation, chronic catheterization, aristolochic acid

Clinical Features

• Painless hematuria (gross or microscopic) = most common presenting sign
• Irritative LUTS (frequency, urgency) - especially with carcinoma in situ (CIS)
• Advanced disease: flank pain (ureteric obstruction), pelvic pain

Pathology

• 75-85% are superficial (non-muscle-invasive) at diagnosis: stages pTa, pT1, carcinoma in situ
• Remainder are muscle-invasive (pT2+) or metastatic at presentation
• Histology: predominantly transitional cell (urothelial) carcinoma; squamous cell and adenocarcinoma are less common

Diagnosis

• Cystoscopy + biopsy - gold standard for diagnosis and staging
• Urine cytology - high specificity; false negatives limit sensitivity
• No imaging test reliably detects all bladder cancers, but CT urography evaluates upper tracts and extent of disease

Treatment

• Transurethral resection of bladder tumor (TURBT)
• Intravesical BCG (Bacillus Calmette-Guerin) therapy - reduces recurrence and progression for high-risk NMIBC
• Intravesical chemotherapy (mitomycin C) - for low-to-intermediate risk

• Radical cystectomy (gold standard) + urinary diversion; robotic-assisted cystectomy increasingly used
• Neoadjuvant cisplatin-based chemotherapy before cystectomy improves survival
• Bladder-preserving trimodality therapy (TURBT + chemotherapy + radiation) for selected patients

• Cisplatin-based chemotherapy (gemcitabine + cisplatin)
• Immune checkpoint inhibitors (atezolizumab, pembrolizumab) for platinum-ineligible patients or second-line

4. Urinary Tract Infection (UTI) and Pyelonephritis

Classification

• Lower UTI: Cystitis (bladder), urethritis
• Upper UTI: Pyelonephritis (kidney parenchyma), urosepsis

Clinical Features

Diagnosis

• Urinalysis (dipstick): leukocyte esterase, nitrites, blood
• Urine microscopy: pyuria (>5 WBC/hpf), bacteriuria
• Urine culture + sensitivity (gold standard)
• Blood cultures if sepsis suspected
• Imaging (ultrasound or CT) if: obstruction suspected, treatment failure, recurrent infection

Treatment

• Uncomplicated lower UTI (women): Trimethoprim-sulfamethoxazole 3 days, or nitrofurantoin 5-7 days, or fosfomycin single dose
• Complicated UTI / pyelonephritis: Fluoroquinolones (ciprofloxacin) 7-14 days; IV antibiotics if septic (piperacillin-tazobactam, ceftriaxone)
• Pre-surgical UTI: Treat to sterile urine before manipulation; if preoperative sterilization impossible, culture-guided perioperative antibiotics
• Key principle: Antibiotics for sepsis should be administered as soon as possible; culture first if feasible

5. Urinary Calculi (Urolithiasis / Nephrolithiasis)

Epidemiology & Risk Factors

• Calcium oxalate stones: most common (80%)
• Struvite (infection) stones: associated with urea-splitting organisms (Proteus, Klebsiella)
• Uric acid stones: associated with gout, low urine pH
• Cystine stones: rare, genetic (cystinuria)
• Major risk factors: dehydration, obesity, hypercalciuria, hyperoxaluria, hypocitraturia, anatomical anomalies, metabolic disorders (renal tubular acidosis, hyperparathyroidism), Medullary sponge kidney

Clinical Features

• Renal colic: Sudden, severe, colicky flank pain radiating to the groin/ipsilateral testicle/labia - classic presentation
• Hematuria (gross or microscopic) in ~90%
• Nausea and vomiting
• Fever = medical emergency (obstruction + sepsis requires urgent decompression)
• CVA tenderness
• Large stones may be palpable as a mass (hydronephrotic kidney)

• Renal transplant patients: no typical renal colic (denervated kidney); may mimic graft rejection
• Pregnancy: most common non-obstetric cause of acute abdominal pain; incidence ~1:1500 pregnancies
• Obesity: limits diagnostic imaging options and treatment delivery (weight limits for CT/fluoroscopy, SWL focal length challenges)

Diagnosis

• Non-contrast CT KUB (CT urogram) - gold standard; detects all stone types, measures size and location
• Ultrasound - preferred in pregnancy; detects hydronephrosis
• Plain KUB X-ray - detects radio-opaque stones (calcium, struvite); uric acid stones are radiolucent
• Urinalysis + urine culture
• Serum creatinine, calcium, uric acid
• 24-hour urine metabolic evaluation (for recurrent stone formers)

Treatment

• Adequate hydration + analgesics (NSAIDs, opioids)
• Alpha-blockers (tamsulosin) to facilitate medical expulsive therapy
• Most stones <5 mm pass spontaneously

• ESWL (Extracorporeal Shock Wave Lithotripsy): Stones ≤2 cm; non-invasive
• Ureteroscopy + laser lithotripsy (URS): Ureteral stones; preferred in pregnancy (avoid fluoroscopy)
• Percutaneous Nephrolithotomy (PCNL): Large stones >2 cm, staghorn calculi; requires prone positioning
• Ureteral stent / nephrostomy tube: Emergency decompression for obstructed infected kidney

6. Renal Cell Carcinoma (RCC)

Epidemiology & Risk Factors

• Clear cell RCC (ccRCC): most common subtype; associated with VHL gene mutations (von Hippel-Lindau)
• Risk factors: smoking, obesity, hypertension, hereditary syndromes (VHL, hereditary papillary RCC)

Clinical Features - "Classic Triad" (seen in <10% of cases)

• Hematuria
• Flank pain
• Palpable flank mass

Diagnosis

• CT scan (abdomen/pelvis) with contrast - key modality; enhancing renal mass
• MRI if iodine allergy or inferior vena cava thrombus assessment
• Biopsy if small/indeterminate mass or prior to systemic therapy

Treatment

• Surgical: Radical or partial nephrectomy (robotic-assisted increasingly used) for localized disease
• Targeted therapy: VEGF inhibitors (sunitinib, pazopanib) or mTOR inhibitors for metastatic disease
• Immunotherapy: Nivolumab + ipilimumab combination - first-line for intermediate/poor-risk metastatic RCC; pembrolizumab + axitinib for favorable-risk

7. Testicular Cancer

Epidemiology

• Most common solid tumor in men aged 15-35
• Risk factors: cryptorchidism, prior contralateral testicular cancer, Klinefelter syndrome
• Isochromosome 12p is a hallmark chromosomal finding

Classification

• Germ cell tumors (GCTs): 95% of cases
  • Seminoma (35%): more common; radiosensitive; elevated hCG in ~15%
  • Non-seminomatous GCT (NSGCT): teratoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma; elevated AFP and/or hCG

Clinical Features

• Painless testicular mass - classic presentation
• Testicular heaviness or dragging sensation
• ~10% present with acute pain (mimicking epididymo-orchitis)
• Metastatic: back/flank pain (retroperitoneal lymphadenopathy), gynecomastia (hCG-secreting tumors)

Diagnosis

• Testicular ultrasound - first-line imaging; highly sensitive
• Serum tumor markers: AFP, beta-hCG, LDH - essential for staging and monitoring
• CT chest/abdomen/pelvis for staging
• Radical orchiectomy (inguinal approach) - definitive diagnosis + treatment of primary; never do a scrotal biopsy (risk of lymphatic spread to inguinal nodes)

Treatment

• Stage I seminoma: Radical orchiectomy + surveillance, or adjuvant carboplatin x1 cycle, or radiotherapy to para-aortic nodes
• Stage I NSGCT: Orchiectomy + surveillance, or RPLND (retroperitoneal lymph node dissection)
• Advanced (Stage II/III): BEP chemotherapy (bleomycin, etoposide, cisplatin) - highly curative even in metastatic disease
• Prognosis is excellent: overall cure rate >95% for seminoma, ~80% for NSGCT

Clinical Decision Summary

PAINLESS HEMATURIA → Bladder cancer (cystoscopy)
                   → Also consider: RCC, upper tract urothelial cancer

PAINFUL HEMATURIA + COLICKY FLANK PAIN → Urolithiasis (CT KUB)

LUTS IN OLDER MAN (hesitancy, weak stream)
  → BPH (most likely)
  → Rule out: prostate cancer (PSA + DRE), urethral stricture

PSA ELEVATED + ABNORMAL DRE
  → Prostate cancer (mpMRI + biopsy)

FEVER + DYSURIA + CVA TENDERNESS → Pyelonephritis (urine culture + imaging)

FEVER + FLANK PAIN + STONE ON CT → Emergency decompression (septic obstruction)

YOUNG MAN + PAINLESS TESTICULAR SWELLING
  → Testicular cancer (ultrasound + tumor markers + inguinal orchiectomy)
  → Differential: epididymo-orchitis (painful, tender, fever)