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