Karam JA et al. (2007) Use of combined apoptosis biomarkers for prediction of bladder cancer recurrence and mortality after radical cystectomy. Lancet Oncol 8: 128–136

Karam et al. investigated whether expression of four apoptosis-related biomarkers (Bcl-2, p53, caspase 3 and survivin), alone or in combination, could aid prediction of outcome after radical cystectomy for bladder cancer. Conventional prognostic features (tumor stage, grade, and lymph-node metastasis) are not accurate enough to predict outcomes after radical cystectomy, because patients with similar disease features experience varied outcomes.

In this retrospective study, the authors analyzed apoptosis-related biomarker expression in bladder tumors from 226 patients who had undergone radical cystectomy and bilateral lymphadenectomy for urothelial-cell carcinoma. During follow-up (median 36.9 months), 101 of these patients had experienced bladder cancer recurrence and 82 died of metastatic bladder cancer. Immunohistochemical staining of serial tissue microarrays was used to categorize expression of each marker as either normal or altered. Increasing numbers of altered apoptosis-related markers correlated with a progressively worse prognosis. Alteration of all four markers conferred the highest risks of disease recurrence and death from bladder cancer (hazard ratios 4.03 [P = 0.021] and 6.84 [P = 0.016], respectively), independently of conventional prognostic features.

The authors call for prospective clinical trials to elucidate whether these four apoptosis-related markers could be used to direct treatment strategies for patients after radical cystectomy: individuals with altered expression of all four markers might benefit from early initiation of aggressive adjuvant chemotherapy, whereas those with normal marker expression could avoid unnecessary treatments.