Background
Randomized phase III SWOG-8710 trial of 317 patients with muscle-invasive bladder cancer (T2-T4a) randomized 1:1 to neoadjuvant chemotherapy followed by radical cystectomy versus cystectomy alone.
Interventions and follow up
Arm A: 3 cycles neoadjuvant M-VAC (methotrexate, vinblastine, doxorubicin, cisplatin) then radical cystectomy
Arm B: Radical cystectomy alone
Primary endpoint: Overall survival
Median follow up: 8.7 yr
Arm B: Radical cystectomy alone
Primary endpoint: Overall survival
Median follow up: 8.7 yr
Results
Median survival: 77 mo vs 46 mo (A vs B)
5-yr OS: 57% vs 43%; P=.06
pT0 at cystectomy: 38% vs 15% (A vs B)
Disease-specific survival: 54 vs 77 deaths from bladder cancer; favoring arm A (P=.002)
5-yr OS: 57% vs 43%; P=.06
pT0 at cystectomy: 38% vs 15% (A vs B)
Disease-specific survival: 54 vs 77 deaths from bladder cancer; favoring arm A (P=.002)
Adverse events
Hematologic (chemotherapy, n=126 treated): Grade 3-4 granulocytopenia in 33%; anemia and thrombocytopenia less common
Gastrointestinal: Grade 3+ nausea/vomiting and stomatitis with M-VAC; post-cystectomy GI grade 3+ events 8 vs 10 patients (A vs B)
Genitourinary: Post-cystectomy grade 3+ events 8 vs 8 patients (A vs B)
Gastrointestinal: Grade 3+ nausea/vomiting and stomatitis with M-VAC; post-cystectomy GI grade 3+ events 8 vs 10 patients (A vs B)
Genitourinary: Post-cystectomy grade 3+ events 8 vs 8 patients (A vs B)
Conclusions
Neoadjuvant M-VAC before cystectomy improved overall survival and increased the rate of pathologic complete response versus cystectomy alone in muscle-invasive bladder cancer, without compromising surgery.
Key Limitations
OS difference reached only borderline significance (P=.06); enrollment spanned many years with prolonged accrual. Classic M-VAC has largely been supplanted by dose-dense M-VAC and gemcitabine-cisplatin as neoadjuvant options.
Clinical Context
SWOG-8710 established cisplatin-based neoadjuvant chemotherapy as a standard before radical cystectomy for muscle-invasive bladder cancer, reinforced by meta-analyses and adopted in ASCO/ESMO guidance. Gemcitabine-cisplatin and dose-dense M-VAC are now preferred regimens.