Randomized clinical trials of neo-adjuvant cisplatin-based combination chemotherapy for locally advanced muscle invasive bladder cancer has shown a survival benefit over cystectomy alone. Pathologic complete response (pT0) after neo-adjuvant chemotherapy is emerging as a potentially important surrogate clinical end point.
The advantages of neo-adjuvant chemotherapy over an adjuvant design include: (1) better tolerance of chemotherapy prior to cystectomy than post-operatively; (2) avoidance of delay in administering chemotherapy due to post-operative morbidity and recuperation often encountered in the adjuvant approach; (3) urinary diversion after radical cystectomy may be associated with some decrement in renal function, thus limiting the use of adjuvant cisplatin, one of the most active agents in bladder cancer. Furthermore, neo-adjuvant chemotherapy allows individual assessment of in vivo tumor response, which can be a guide to future chemotherapy agent selection. Also, downstaging allows for better resectability, and in some selected patients, bladder conservation . The main disadvantage of neo-adjuvant chemotherapy is that definitive local therapy (cystectomy or radiotherapy) is delayed during the treatment period. Furthermore, significant toxicity associated with neo-adjuvant chemotherapy may preclude potentially curative definitive local therapy. In addition, given that neo-adjuvant therapy relies on clinical (rather than pathologic) staging, some low-stage, low-risk patients may unnecessarily receive chemotherapy.
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