BLADDER CANCER

When to think of bladder cancer?: Recurrent or complicated UTIs, macroscopic

hematuria, persistent microscopic hematuria, ongoing irritable symptoms, and
abnormal anatomy like spinal cord compression leads to urinary stasis and predispose to
bladder cancer.

Risk factors for bladder cancer: Old age, W>AA, M>F, neurogenic bladder, external beam
XRT, recurrent UTIs, stones, chronic indwelling catheters, shistosoma haematobium
(Egypt), a herb called Aristolochia (used for weight loss in Taiwan), and chemicals like
hair colors, aniline, organic solvents and exposure to arsenic.

TNM staging: Tis: CIS, Ta urothelial, T1 subepithelia, T2a superficial muscle, T2b deep
muscle, T3a perivesicle fat (micro), T3b: perivesicle fat (macro), T4.

Metastatic bladder cancer stage IV

o Cisplatin based regimen MVAC, Cisplatin+Gem (GC), or HDi-MVAC are all level 1.
o GC versus MVAC q28 days: GC less toxic and as effective as MVAC (5 year PFS is
10%).
o MVAC: neutropenia and neutropenic fever.
o Should not forget that some people are curable with metastatic disease. Those
cured are most likely to have no evidence of visceral metastasis (only LN
involvement).
o Independent prognostic factors in stage IV disease: 1. performance status; 2.
visceral metastasis. The survival is less than 1 year if two risk factors are present.
o Patients with good response to chemotherapy and had one organ site of residual
disease may benefit from post chemotherapy consolidation surgery (resection of
the metastatic site), in one study 33% of patients (10/30) had a 5 year survival
(treated with MVAC followed by surgical resection).
o Classic MVAC: MTX days 1, 15, 22; Vinblastin 2, 15, 22, Adriamycin day 2, and
Cisplatin day 2 q28 days. In high dose intensity MVAC (HDi-MVAC) you eliminate
days 15 and 22 from classic MVAC and you give the regimen q14 days. In HDi
MVAC you add G-CSF. Less side effects and better tolerance, and even showed
better OS.
o Vinflunin approved in Europe for second line therapy in metastatic bladder
cancer but not in USA.

o Unfit patients: Hearing loss, neuropathy, chronic renal failure, or poor PS then
give carboplatin plus gemcitabin not cisplatin.
o Conclusions for stage IV disease: GC, MVAC+G-CSF, or HDi-MVAC+G-CSF are all
level 1 evidence. Carboplatin is inferior to Cisplatin especially if the goal is cure.
Cure is possible especially in patients with good PS and no visceral involvement.
Cisplatin based therapy is the priority for 0, 1 risk disease due to curability.
Consider post chemotherapy surgery in responding patients with one site of
residual disease.
Muscle invasive bladder cancer (T2-T4a)
o Cystectomy: 5 year OS 60% pT2, 30% pT3, and 25% pT4.
o Proper surgery; for males: cystoprostatectomy and bilateral pelvic lymph node
dissection (PLND). For females: cystectomy+ TAH&BSOP+ superior vaginal vault +
bilateral PLND. The more PLN resected the better the outcome.
o Neoadjuvant chemotherapy: Neoadjuvant MVAC (3 cycles) is level 1 evidence
(Grossman et.al NEJM 2003). Three cycles of CMV (cisplatin, vinblastine, and
MTX) is as good as MVAC and used especially if you dont want to give
Adriamycin.
o A study looked at Gemcitabine plus Cisplatin (GC) versus GC with taxol (two
versus three drugs): No difference in OS, but ORR was better with three drugs so
if we need a better control of loco-regional disease we might use three drugs
before surgery; however three drugs are more toxic. We commonly use GC
extrapolation from the metastatic setting.
o Small cell bladder cancer: always treat neoadjuvant first with platinum plus
Etoposide then resect.
o Cystectomy + bilateral PLND after neoadjuvant chemotherapy are an absolute
requirement if maximal survival is the goal.
o We do not know yet if adjuvant chemotherapy improves OS (level 2)
o Bladder preservation by trimodality therapy is a viable option.
Superficial bladder cancer
o Poor prognostic signs: Presence of CIS with any tumor, tumor size >3 cm is bad,
vascular invasion is bad.
o Favorable: Ta, low grade, no dysplasia, long term tumor free interval.
o Unfavorable: T1, high grade, CIS, short term tumor free interval.
o TURBT for T1 lesions, despite that 35% progress to muscle invasion so
intravesicle BCG (6 successive weeks) is given after surgery and this reduces the
progression rate to 16%.

o CIS is bad entity especially when associated with papillary or nodular tumors.
Muscle invasion develops in 40-80%. It is a sign of an aggressive phenotype.
Intravesicle BCG for 6 successive weeks is superior to intravesicle chemotherapy.
o Recurrent treatment for superficial disease example: treated twice then
recurrence is back; move to definitive therapy either chemoradiation used a lot
in Europe or cystectomy upfront common in USA.
o Bladder preservation by trimodality therapy is a viable option: Debulk by TURB,
then chemoradiation (cisplatin + XRT or 5FU+mitomycin+XRT) repeat cystoscopy
with biopsy (half the way after starting chemoradiation): if there is a response,
continue chemoradiation, if not do radical cystectomy.