# Radiation Oncology/Bladder/Overview

* Front Page: Radiation Oncology | RTOG Trials | Randomized Trials
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