Radiation Oncology/Bladder/Overview

Bladder Cancer Overview Epidemiology 5th most common cancer in U.S., incidence ~71 thousand cases (2009), with ~14 thousand deaths Increasing incidence, +20% over 20 years Male:female = 3:1 Peak in 50's - 70's ~4% incidence of synchronous upper urothelial lesion (ureters or renal pelvis) 70% are superficial, 25% muscle invasive, 5% metastatic at presentation. Two separate behaviors driven by separate molecular alterations Superficial (Ta, Tis, T1): commonly recur, but progression to muscle invasion is rare (10-20%) and prognosis is good Muscle-invasive (T2-T4): poor prognosis, 80% mortality within 2 years if untreated Risk factors Genetic abnormalities Please see below in Pathology Chemical exposure Tobacco - increases risk 2-3x Aromatic amines, aniline dyes, and nitrites and nitrates (e.g. leather industry workers) Cyclophosphamide Chronic irritation - increases risk for squamous cell tumors Indwelling catheters Schistosoma haematobium Pelvic RT Screening No good screening test Screening for microhematuria In normal population, microhematuria present in 4%-20% In patients with microhematuria, bladder cancer in 1%-5% Yield low (0.005%-0.2%), and patients typically have superficial disease Cytology 40-60% sensitivity, but ~90% specificity Clinical Presentation Painless gross hematuria Unexplained irritative voiding and frequency Advanced cases pelvic pain, ureteral obstruction, hydronephrosis Work Up Cytology Cystoscopy Renal/ureter CT scan TURBT - determines clinical staging Urethral biopsies should be considered for patients at high risk for involvement (recurrent cancer, bladder neck involvement, vaginal extension in women) Bimanual examination to evaluate extravesical extension If muscle-invasive disease on TURBT, need systemic staging Anatomy Hollow, muscular organ Located in deep pelvis, but it is a true intra-abdominal organ that can project above the umbilicus Several segments Apex: ends as fibrous cord (derivative of urachus) connecting the bladder to the umbilicus Superior surface/Dome: only part of bladder covered by peritoneum Base: Posterior, separated from rectum by vas deferens/seminal vesicles in men and uterus/vagina in women Inferior and lateral surfaces: separated from pubic bone by retropubic space Bladder neck: inferior-most portion, above prostate in men and urethra in women. Fixed in place during distention Ureters: enter bladder superior and lateral to seminal vesicles Bladder mucosas is lined with transitional epithelium Lymphatic drainage Anterior and posterior: internal illiac and common illiac Trigone: external illiac Pathology Transitional cell carcinoma (TCC) in 93%, squamous cell in 5% in US (higher in countries with Schistosoma), adenoCA, small cell Tumors of mixed histology (with squamous or adeno components) are frequent, and are classified (and behave) as TCC Molecular alterations: Superficial: deletions of chromosome 9, mutation of FGF receptor (FGFR3), mutation of PIK3CA kinase, mutation of Ras Muscle-invasive: multiple genetic abnormalities, including EGFR (overexpressed 10-50%; 19% on RTOG trials), p53 and Rb inactivation, and CDKN2A To demonstrate muscle invasion (T2+), muscularis propria must be present in the slide, though fragmentary nature of TURBT makes estimate of true depth of invasion difficult Spread Lymph nodes Overall LN+ ~20% pT1 ~5% pT2-T3a ~30% pT3b-T4 50%-60% Distant spread ~8% It has been estimated that as many as 50% of muscle-invasive patients may already have occult metastatic disease, accounting for the high rate of metastatic failure after local treatment