Outcome of BC2001 patients (CRUK/01/004) who received neoadjuvant chemotherapy prior to randomization to chemo-radiotherapy (cRT) versus radiotherapy (RT).

Abstract

298 Background: Neoadjuvant chemotherapy is considered standard of care for patients with muscle invasive bladder cancer (MIBC). Gemcitabine plus cisplatin or carboplatin (GC) has been adopted as a standard neoadjuvant regimen for MIBC. BC2001 showed that adding chemotherapy (5FU+MMC) to radiotherapy (55Gy/20f or 64Gy/32f) significantly improved rates of muscle invasive bladder cancer (MIBC) locoregional control (LRC) [James 2012]. We report outcome of patients (pts) receiving neoadjuvant chemotherapy prior to starting BC2001 trial treatment (cRT or RT alone). Methods: Between August 2001 and April 2008, 360 pts were randomised to RT (178) or cRT (182); 117 (32.5%) received neoadjuvant chemotherapy (61 RT, 56 cRT). Primary endpoint was LRC, secondary endpoints included toxicity, overall survival (OS) and metastasis free survival (MFS). Cox models adjusted by known prognostic factors were used to estimate randomised treatment effect in this subgroup of pts. Toxicities were compared by Chi squared tests. Results: Median age of the 117 pts was 66 (interquartile range: 60-73) years, 86% were male, 73% had baseline 0 WHO performance status. 81% had T2 and 87% G3 tumours. Neoadjuvant treatment received was GC (73.5%), MVAC (13.6%), CMV (11.1%) or other (<2%). 92.3% cRT and 91.8% RT pts completed radiotherapy as planned. Grade 3 or above adverse events during treatment occurred in 27.4% pts (32.2% cRT vs 22.9 RT, p-value(p)=0.27), and in 9.5% during follow-up (13.4% cRT vs 5.3% RT, p=0.21). There was a trend for improved LRC in the cRT group (hazard ratio HR=0.64, 95CI% 0.33-1.23, p=0.18), while no differences in OS (HR=0.95, 95CI% 0.57-1.57, p=0.83) or MFS (HR=0.93, 95CI% 0.52-1.65, p=0.80) were observed. Median OS was 46.7 months ,cRT: 50.4 months vs RT: 46.7 months. MFS: Median: 68.5 months, cRT: 118.5 months vs RT: 54.2 months. Conclusions: The benefit in improved LRC of synchronous chemotherapy with 5FU/MMC was also found in the subgroup of BC2001 pts receiving neoadjuvant chemotherapy, with no significant increase in late toxicity. Neoadjuvant chemotherapy did not compromise the delivery of radical curative treatment with RT or cRT. Clinical trial information: ISRCTN68324339.