Radiation Oncology/Bladder/Overview

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Bladder Cancer Overview


Epidemiology[edit]

  • 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[edit]

  • Genetic abnormalities
  • 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[edit]

  • 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[edit]

  • Painless gross hematuria
  • Unexplained irritative voiding and frequency
  • Advanced cases pelvic pain, ureteral obstruction, hydronephrosis

Work Up[edit]

  • 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[edit]

  • 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[edit]

  • 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[edit]

  • 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