BLADDER CANCER Joseph H. Williams, MD Idaho Urologic Institute St. Alphonsus Regional Medical Center September 22, 2016 BLADDER CANCER = UROTHELIAL CANCER Antiquated term is Transitional Cell Carcinoma Urothelial lining is in between squamous epithelium (skin) and mucosa (bowel). transitional cell idea inaccurate Urothelium does not make mucous Unique in the body for its function Allow collection and storage of urine Evolutionary/functional origins 1
UROTHELIUM waterproof Inpenatrable to chemicals/fluids Non-absorptive Present throughout the urinary tract Calyceal fornices to the proximal urethra Once created, urine is therefore extra-physiologic UROTHELIAL CARCINOMA very transplantable with mechanical manipulation Saving grace is ease of endoscopic management Predisposed to by carcinogens eliminated via renal transport. Chemicals sit in the bladder. Leading carcinogen is metabolites of tobacco use 2
UROTHELIAL CARCINOMA Primary, secondary, tertiary tobacco use exposure are risk factors Family history not genetic Modern risk factors otherwise: Actos use, radiation therapy history, chemotherapy with cyclophosphamide Old risk factors: analine dyes, rubber industry, leather tanning chemicals, hair dye Diet rich in fruits and vegetables is protective Classic presentation: avocation with exposure + long voiding interval UROTHELIAL CARCINOMA New presentation usually painless gross hematuria Average patient is an elderly male with a smoking history Rare in young females Work-up is imaging and cystoscopy Imaging: CT:IVP vs U/S and RPG 3
UROTHELIAL CARCINOMA Primary surgical intent: biopsy and maintain function. Hopefully first TURBT is curative and definitive. Plan is to remove or destroy all abnormal appearing tissue. Random Bladder Biopsies for bladder mapping Urine cytology to assess for presence of cancer with negative biopsy Counseling discriminator: superficial vs. invasive BLADDER WALL ARCHITECTURE Urothelium Lamina Propria Muscle First half Second half Extravesical fat 4
UROTHELIAL CARCINOMA Path report leads to risk stratification: low, intermediate, high-risk Variant histology should trigger consideration for secondary resection and discussion for cystectomy STAGING Ta Tis T1 T2 pt2a pt2b pt3 pt3a pt3b Noninvasive papillary tumor Carcinoma in situ: flat tumor Invades subepithelial connective tissue Invades muscularis propria Inner half of muscle Outer half of muscle Invades perivesical tisue Microscopically Extravesical mass 5
STAGING pt4 pt4a pt4b Invading surrounding structures Prostatic stroma, uterus, vagina Pelvic wall, abdominal wall UROTHELIAL CARCINOMA High-risk, high grade Ta tumors and T1 disease should lead to repeat transurethral resection within 6 weeks. In suspected low or intermediate risk bladder cancer, consider intravesical chemotherapy (mitomycin C or epirubicin) except in cases of suspected perforation or extensive resection. This is intended to reduce risk of recurrence. In intermediate risk non-invasive cancer, consider 6 week induction of immunotherapy or chemotherapy 6
INTRAVESICAL IMMUNOTHERAPY Bacille Calmette-Guerin attenuated strain of Mycobacterium tubercolosis. This activates the immune system locally to induce replacement of tumor cells with healthy urothelium. Placed via atraumatic catheterization into the bladder. The patient holds this small amount of fluid in for 2 hours, then voids it out. 6 weekly treatments are given then a maintenance regimen for 1 year. 50% disease-free response for 4 years INTRAVESICAL CHEMOTHERAPY More frequently used in Europe Interferon Mitomycin C Epirubicin Thiotepa Side effects of chemotherapy are less common and less severe than BCG, but these agents are also less efficacious 7
INTRAVESICAL IMMUNOTHERAPY In high risk pathology, with CIS, High-grade T1 or High-risk Ta tumor, BCG is recommended. Continued treatment for 1 to 3 years should be a consideration SURVEILLANCE CYSTOSCOPY Every 3 to 6 months for 2 years then every 6 to 12 months for years 3 and 4, then annually. Urine Cytology gives added reassurrance that tumor isn t being missed. Upper tract imaging should be done at initial evaluation, then annually. 8
CYSTECTOMY Complete removal of the bladder With prostatectomy in men and with anterior vaginal wall resection in women Removal of urethra depends on pathology. Requires urinary diversion to remove urine from body CYSTECTOMY Should be offered in persistant high-grade T1 disease despite 2 courses of BCG or BCG maintenance within 1 year. Indicted in T2 to T4a, N0, M0 desease. Meticulous pelvic lymph node dissection ( not sampling) is a component of radical cystectomy. Carries risk of complication. 50% of cystectomy patients aren t cured and ultimately die of urothelial carcinoma. 9
NEOADJUVENT SYSTEMIC CHEMOTHERAPY NCCN guidelines favor this over adjuvant therapy In pt3-4 disease or node positive disease, it is considered as adjuvant therapy Doxorubicin-gemcitabine or paclitaxel-cisplatin regimens Bladder preservation regimens with chemotherapy and radiation therapy combinations in poor surgical candidates and in those who refuse cystectomy Partial cystectomy can be considered in isolated tumors of the dome URINARY DIVERSION Conduits: use of bowel to transmit urine out of the body in a non-continent fashion to a urostomy Stomach, all parts of the small bowel, large bowel can be used. Ileum has the least complicated impact on potential metabolic derangements Jejunum electrolyte abnormalities Stomach stomal problems from acid production Doudenum disrupt biliary tree Colon (transverse) a lot of work, but good stuff when necessary Ileum hyperchloremia, metabolic alkalosis 10
CUTANEOUS CONTINENT DIVERSION Ileum pouches Colon pouches Combinations Urostomy vs catherizable stomas NEOBLADDER Orthotopic urinary diversion Cobinations of bowel segments to create a new vessel to be anastomosed to urethra at the urogenital diaphragm Can provide acceptable continence. Patients void on a schedule as new vessel does not relay fullness status to the nervous system. Good patient selection critical. 11