Editing Muscle-Invasive Bladder Cancer (section)

===== Evidence =====
* '''<span style="color:#ff0000">2 large phase III clinical trials have demonstrated an OS benefit with the use of NAC prior to RC</span>'''
** '''<span style="color:#ff00ff">SWOG 8710</span>'''
*** '''Population: 317 patients with cT2-T4aN0M0 MIBC'''
*** '''Randomized to 3 cycles of neoadjuvant MVAC (methotrexate, vinblastine, adriamycin [doxorubicin], cisplatin) + RC vs. RC alone'''
*** '''Results:'''
**** '''Absolute risk difference for pT0 status at the time of cystectomy: 23% with NAC''' (38% chemotherapy vs. 15% controls)
***** Patients who were downstaged to pT0 achieved excellent outcomes with 80% alive at 5 years compared to 40% of patients with residual disease
**** Absolute benefit median OS: 31 months (77 months MVAC vs. 46 months in RC-only group)
**** '''Absolute benefit 5-year OS: 14% (57% MVAC vs. 43% in RC-only arm). However, the survival results failed to reach statistical significance (P = .06)'''
*** [https://pubmed.ncbi.nlm.nih.gov/12944571/ Grossman, H. Barton, et al.] "Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer." New England Journal of Medicine 349.9 (2003): 859-866.
** '''<span style="color:#ff00ff">BA06 30894</span>'''
*** Population: 976 patients with MIBC
*** Randomized to neoadjuvant CMV vs. cystectomy alone
*** [https://pubmed.ncbi.nlm.nih.gov/21502557/ International Collaboration of Trialists.] "International phase III trial assessing neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: long-term results of the BA06 30894 trial." Journal of Clinical Oncology 29.16 (2011): 2171.
* '''2005 meta-analysis''' combining individual patient data from 9 trials (these 2 trials with 9 phase II trials) involving 3005 patients comparing neoadjuvant chemotherapy plus local treatment with the same local treatment alone found that '''<span style="color:#ff0000">neoadjuvant chemotherapy was associated with improved:</span>'''
** '''<span style="color:#ff0000">5-year OS: absolute benefit 5%</span>'''
** '''<span style="color:#ff0000">5-year DFS: absolute benefit 9%</span>'''
** '''Pathologic complete response (pT0) rate of 30-40% compared to 15% (SWOG trial results) without NAC'''
** Advanced Bladder Cancer (ABC) Meta-analysis Collaboration. “Neoadjuvant chemotherapy in invasive bladder cancer: update of a systematic review and meta-analysis of individual patient data advanced bladder cancer (ABC) meta-analysis collaboration.” Eur Urol. 2005 Aug;48(2):202-5; discussion 205-6. Epub 2005 Apr 21.
* '''Gemcitabine-cisplatin (GC) is a combination frequently used for NAC in MIBC due to relatively lower risk of toxicity, despite level 1 evidence for MVAC and CMV only'''
** No completed prospective randomized trials have compared GC to other regimens as NAC for MIBC. Several retrospective cohort studies suggest that there may not be a significant difference in outcome between GC and MVAC
* '''The best regimen and duration for cisplatin-based NAC remains undefined; most studies have evaluated 3-4 cycles of preoperative chemotherapy over about 3 months'''