Bcl-2 expression identifies patients with advanced bladder cancer treated by radiotherapy who benefit from neoadjuvant chemotherapy

Objective To assess the prognostic significance of Bcl-2 expression on the clinical outcome after radiotherapy for muscle-invasive bladder cancer, and to determine if it is possible to identify a subgroup of patients to whom neoadjuvant chemotherapy can be targeted to improve survival. Patients and methods Immunohistochemical staining for Bcl-2 and p53 was per formed on the tumours of 51 patients with stage T2-T4a NXM0 transitional ce ll carcinoma of the bladder who had been included in a randomized clinical trial of radiotherapy with or without neoadjuvant cisplatin. The associatio n between positive staining and salvage cystectomy rate and overall surviva l was examined, with a median follow-up of 12 years. Results Bcl-2 and p53 expression was positive in 31 (61%) and 39 (76%) of t he tumours, with no association between either, or with tumour stage or gra de. There was no difference according to Bcl-2 positivity in the salvage cy stectomy rate (P = 0.83) or survival (P = 0.68) for the 51 patients as a wh ole, but Bcl-2-negative patients receiving neoadjuvant cisplatin had a sign ificantly better prognosis, with a median survival of 72 months compared to 17 months in Bcl-2-positive patients, and a 5-year survival rate of 55% (P = 0.03). Conclusions Quantifying Bcl-2 in patients undergoing radiotherapy for advan ced bladder cancer identifies those who may benefit from neoadjuvant chemot herapy. Further studies of other members of the Bcl-2 family and other prot eins controlling both cell proliferation and apoptosis are warranted, to de fine the roles and the interactions between them that may contribute to onc ogenesis and resistance to standard treatments. This may allow the targetin g of specific treatments to patients known to be sensitive to them, and aid the future development of novel therapies for bladder cancer.