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

• Published in: BJU international Vol. 85; no. 7; pp. 829 - 835
• Main Authors: Cooke, P.W., James, N.D., Ganesan, R., Burton, A., Young, L.S., Wallace, D.M.A.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.05.2000; Blackwell
• Subjects: Adult; Antineoplastic Agents - therapeutic use; Bcl‐2; Biological and medical sciences; bladder cancer; Chemotherapy, Adjuvant; chemo‐therapy; Cisplatin - therapeutic use; Female; Follow-Up Studies; Humans; Immunohistochemistry; Male; Medical sciences; Middle Aged; neoadjuvant; Neoplasm Invasiveness; Nephrology. Urinary tract diseases; Proto-Oncogene Proteins c-bcl-2 - metabolism; radiotherapy; survival; Survival Analysis; Treatment Outcome; Tumor Suppressor Protein p53 - metabolism; Tumors of the urinary system; Urinary Bladder Neoplasms - drug therapy; Urinary Bladder Neoplasms - metabolism; Urinary Bladder Neoplasms - radiotherapy; Urinary tract. Prostate gland; Antineoplastic agent; Human; Urinary system disease; Carcinoma; Malignant tumor; Urinary tract disease; Radiotherapy; Survival; TNM-System; Neoadjuvant treatment; Chemotherapy; Treatment; Urinary bladder; Follow up study; Bladder disease
• ISSN: 1464-4096; 1464-410X
• DOI: 10.1046/j.1464-410x.2000.00612.x

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 performed on the tumours of 51 patients with stage T2‐T4a NXM0 transitional cell carcinoma of the bladder who had been included in a randomized clinical trial of radiotherapy with or without neoadjuvant cisplatin. The association between positive staining and salvage cystectomy rate and overall survival 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 the tumours, with no association between either, or with tumour stage or grade. There was no difference according to Bcl‐2 positivity in the salvage cystectomy rate (P = 0.83) or survival (P = 0.68) for the 51 patients as a whole, but Bcl‐2‐negative patients receiving neoadjuvant cisplatin had a significantly 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 advanced bladder cancer identifies those who may benefit from neoadjuvant chemotherapy. Further studies of other members of the Bcl‐2 family and other proteins controlling both cell proliferation and apoptosis are warranted, to define the roles and the interactions between them that may contribute to oncogenesis and resistance to standard treatments. This may allow the targeting of specific treatments to patients known to be sensitive to them, and aid the future development of novel therapies for bladder cancer.