BRCA1 mRNA expression in patients (p) with bladder cancer treated with neoadjuvant cisplatin-based chemotherapy

Abstract

5021 Background: In p with locally-advanced bladder cancer, neoadjuvant chemotherapy followed by cystectomy improves survival compared to surgery alone, especially in p attaining a pathological response (pT0–1N0M0). However, at present no clinical markers are available to predict response to chemotherapy in bladder cancer. BRCA1 mRNA expression has been associated with chemosensitivity and survival in lung and ovarian cancer p (Taron et al. 2004; Quinn et al. 2007) and could be a useful predictive marker in bladder cancer as well. Methods: We analyzed BRCA1 mRNA expression by quantitative PCR in tumor biopsies obtained by transurethral resection from 51 p with locally-advanced bladder cancer. 44 p were clinically staged as cT3–4N0M0, 5 p had regional lymph nodes (cTxN+), and 2 p had distant lymph nodes. 35 p received cisplatin, methotrexate plus vinblastine; 16 p were treated with gemcitabine plus cisplatin. Results: After a median of 3 cycles of chemotherapy, cystectomy was performed in 49 p (96%). A significant pathological response (pT0 or T1) was attained in 25 p (50%). A close correlation was found between BRCA1 levels and pathological response. 21 p (65%) with low/intermediate BRCA1 levels but only 4 p (26%) with high BRCA levels obtained a pathological response (P=0.01). Median disease-free survival (DFS) was 120 months (m) in 17 p with low BRCA1 levels, 184 m in 17 p with intermediate BRCA1 levels, and only 14 m in 17 p with high BRCA1 levels (P=0.02). In the multivariate analysis of DFS, only BRCA1 levels and lymphatic invasion emerged as independent prognostic markers (table). Conclusions: Low levels of BRCA1 can predict response to neoadjuvant cisplatin-based chemotherapy and longer DFS in p with bladder cancer. Clinical trials of customized chemotherapy based on BRCA1 levels are warranted. The prognostic role of BRCA1 in p with bladder cancer merits further investigation. Hazard Ratio 95% CI p BRCA1 mRNA levels Low 1 (ref.) Intermediate 1.16 0.4–3.36 0.77 High 3.1 1.15–8.40 0.02 Lymphatic invasion Yes 7.8 2.54–23.90 <0.0001 No 1 (ref.) No significant financial relationships to disclose.