Hematuria and Related Urologic Oncology Jamison S. Jaffe, D.O. Director of Minimally Invasive Urologic Surgery Director of Robotic Surgery Drexel University College of Medicine Hahnemann University Hospital

Urologic Oncology Renal cancer Bladder cancer Ureter / Renal pelvis cancer

Renal Cell Carcinoma 3% of all adult malignancies Male-to-female ratio is 2:1 Projections for 2007 51,190 estimated cases of RCC 12,890 deaths from RCC American Cancer Society 2007 Increased incidence of 100% since 1970 Chow et al. JAMA 1999

Renal Cell Carcinoma Typically presents in the 6th to 7th decade Most lethal of all GU malignancies 40% mortality rate vs. 20% bladder/prostate Landis et al. J Clin Cancer 1999

Renal Cell Carcinoma Etiology Tobacco High fat / protein diet (obesity) Coffee Occupational exposures Metal / coke oven / asbestos / cadmium Iatrogenic Radiation Familial Von Hippel-Lindau Disease Hereditary Papillary Renal Cell Carcinoma

Renal Cell Carcinoma Presentation Classic triad (10%) Hematuria (40%) Flank pain (40%) Palpable mass in the flank or abdomen (25%) Asymptomatic – 25% Most common presentations Other signs and symptoms Weight loss (33%) Fever (20%) Hypertension (20%) Hypercalcemia (5%) Night sweats Malaise Varicocele, (2% of males)

Renal Cell Carcinoma Paraneoplastic syndromes – due to cytokine release Hypercalcemia Erythrocytosis Nonmetastatic hepatic dysfunction (ie, Stauffer syndrome) Anemia Fever Cachexia Weight loss Increased erythrocyte sedimentation rate Hypertension

Renal Cell Carcinoma Diagnosis Radiographic diagnosis (CT/MRI) Do not biopsy the mass (not exactly) Spread Needle track seeding Bleeding Surgical removal

Renal Cell Carcinoma Pathology Conventional (Clear Cell) 70-80% Papillary 10-15% Chromophobic 4-5% Collecting Duct <1% Medullary Cell <1% * Sarcomatoid lesions represent poorly differentiated elements of above cell types Storkel et al. Cancer, 1997

Renal Cell Carcinoma Treatment Surgery remains the mainstay of curative treatment Radical nephrectomy Nephron-sparing surgery Partial nephrectomy Ablative techniques Cryosurgery RFA *Open vs. laparoscopic Chemotherapy and radiation not useful Lap is associated with diminished pain, shorter hospital stay, and quicker recovery. Good option for small volume tumors < 8cm

Bladder Cancer Bladder cancer is the second most common GU tumor 2004 statistics 60,200 new patients diagnosed 12,700 of those patients died from the disease Bladder cancer is more common in whites than in blacks; however, blacks have a worse prognosis than whites. Male-to-female ratio is 3:1 Women generally have a worse prognosis than men. The median age at diagnosis is 68 years, and the incidence increases with age. Mostly from SEER data.

Bladder Cancer Etiology Smoking – most common Industrial exposures Aromatic amines in dyes, paints, solvents, metals, leather dust, inks, combustion products, rubber, and textiles Prior exposure to radiation treatment of the pelvis Chemotherapy with cyclophosphamide increases the risk of bladder cancer Acrolein Long-term indwelling catheters Coffee – not true Artificial sweeteners – not true

Bladder Cancer Presentation Painless gross hematuria (80-90%) Consider all patients with gross hematuria to have bladder cancer until proven otherwise Suspect bladder cancer if any patient presents with unexplained microscopic hematuria Irritative bladder symptoms (20-30%) Dysuria Urgency Frequency of urination Pelvic or bony pain Lower-extremity edema Flank pain from ureteral obstruction

Definitions Microscopic Hematuria Gross Hematuria Presence of 3 or more RBC per hpf 3 % of normal individuals will excrete up to 3 RBC Gross Hematuria Presence of blood in the urine that is visible to the naked eye

Hematuria Evaluation UA Urine culture ± Cytology Upper tract imaging CT/MRI ± contrast Cystoscopy

Hematuria DDx S – Stones H – Hematologic I – Infection T – Tumors T – Trauma T – TB S - Strictures

Diagnosis and Staging Cystoscopy Important to note that the exam was performed AFTER the TUR. If you remove the bulk of intravesicle tumor, anything left palpable can be assumed extravesicle. 80% of patients with bladder CA present with gross hematuria.

Diagnosis and Staging Transurethral Resection Important to note that the exam was performed AFTER the TUR. If you remove the bulk of intravesicle tumor, anything left palpable can be assumed extravesicle. 80% of patients with bladder CA present with gross hematuria.

Bladder Cancer Pathology Transitional cell carcinomas (TCC) (90%) Squamous cell carcinoma (SCC) (5%) Adenocarcinomas (2%) Nonurothelial primary bladder tumors (<3%) Small cell carcinoma Carcinosarcoma Primary lymphoma Sarcoma

Bladder Cancer Pathology tidbits SCC is the most common form worldwide (75%) US associated with persistent inflammation from long-term indwelling Foley catheters and bladder stones Underdeveloped nations, SCC is associated with bladder infection by Schistosoma haematobium Adenocarcinomas Observed most commonly in bladders extrophy or in the urachus

Bladder Cancer Staging

Bladder Cancer Superficial bladder cancer 75% recurrence 25% progress to muscle invasive

Bladder Cancer Treatment Superficial cancer Muscle invasive cancer ± Intravesical treatment (BCG/Mitomycin C) Surveillance cystoscopy Repeat TURBT if it recurs Muscle invasive cancer Radical cystectomy Male – bladder and prostate Females – bladder, urethra, uterus, ovaries, and anterior vaginal wall Diversion vs. neobladder Bladder preservation Chemotherapy and radiation (gemcitabine and cisplatin)

Urothelial Tumors of the Renal Pelvis and Ureter Background Rare Renal pelvis – 10% of all renal tumors Ureter – ¼ the incidence of renal pelvis tumors Mean age – 65 years Male to female ratio 3:1 Balkan nephropathy 100-200x increase risk of upper tract TCC

Urothelial Tumors of the Renal Pelvis and Ureter Etiology Tobacco (3x ↑) Most strongly associated with upper tract TCC Coffee (> 7 cups/day) Analgesic abuse Occupational exposure Petrochemical, plastic, and tar industries Chronic infections Chronic irritation Cyclophosphamide

Urothelial Tumors of the Renal Pelvis and Ureter Pathology Transitional cell carcinoma – 90% Squamous cell carcinoma - 1-7% Adenocarcinoma - <1% Location Renal pelvis - 58% Ureter - 35% Both renal pelvis and ureter - 7% Bilateral - 2-5%

Urothelial Tumors of the Renal Pelvis and Ureter Symptoms Gross or microscopic hematuria (75%) Flank pain (18%) Dysuria (6%) Advanced disease Weight loss, anorexia, flank mass, or bone pain

Urothelial Tumors of the Renal Pelvis and Ureter Diagnosis CT scan / MRI (hematuria evaluation) Cystoscopy ± retrograde pyelogram “Goblet sign” Ureteroscopy with biopsy

“Goblet Sign”

Urothelial Tumors of the Renal Pelvis and Ureter Treatment Nephroureterectomy with excision of the bladder cuff (gold standard) Nephron sparring surgery Segmental ureterectomy coupled with ureteral reimplantation Tumors located in the distal ureter Ipsilateral recurrence rate is 25% Ureteroscopic treatment Small, low-grade superficial lesions are the best candidates for this approach