Is Bcl-2 a predictive marker of neoadjuvant chemotherapy response in patients with urothelial bladder cancer undergoing radical cystectomy?

Abstract

Background: Response to neoadjuvant cisplatin treatment in bladder cancer has been linked to expression of Bcl-2 protein by cancer cells. The objective of this study was to test Bcl-2 as a predictive marker of neoadjuvant cisplatin chemotherapy response in a patient cohort from randomized cystectomy trials. Methods: Tumor samples were taken from 247 patients with T2-T4 bladder cancer enrolled in two randomized trials comparing cystectomy with or without neoadjuvant chemotherapy. Tissue microarrays from pre-intervention transurethral resection specimens were assessed for Bcl-2 protein status by immunohistochemistry. Extension of staining above 10% was regarded as positive. Downstaging and survival ratios in relation to Bcl-2 immunoreactivity and neoadjuvant chemotherapy utilization were calculated using the log rank test and multivariate Cox proportional hazards regression analyses. Results: Bcl-2 expression was positive in 38% and negative in 62% of the 236 evaluable patients. Bcl-2 negative patients receiving neoadjuvant chemotherapy had a significant increase in survival (p ¼ 0.009), while Bcl-2 positive patients showed no difference (p ¼ 0.4). However, the interaction variable between neoadjuvant chemotherapy and biomarker status was not significant (p ¼ 0.38). When the prognostic value was assessed in the no-chemotherapy group, 5-year overall survival times were significantly better among Bcl-2 positive patients than among Bcl-2 negative patients (42 months vs 33 months, p ¼ 0.04), but again Bcl-2 status did not remain independent when other factors were adjusted. Also, in a multivariate analysis with all patients, Bcl-2 was not significant. Conclusions: Bcl-2 status is not an independent predictor of neoadjuvant cisplatin chemotherapy response and is not prognostic in muscle-invasive bladder cancer.

CD34 and Bcl-2 as predictors for the efficacy of neoadjuvant chemotherapy in cervical cancer

“…Our study showed that no significant difference was found in pre-NACT Bcl-2 expression among different NACT efficacy. The earlier clinical study conducted among 247 bladder cancer patients with NACT reported similar findings to ours [ 8 ]. With regard to cervical cancer, Harima et al [ 34 ] also presented that the Bcl-2 expression prior to radiotherapy did not correlate with treatment response.…”

“…Bcl-2 plays an important role in the intrinsic apoptotic pathway of malignant cancer and has been shown to interfere with chemotherapy [ 7 ]. Preferentially, the expression of CD34 and Bcl-2 were proved to be the predictors of neoadjuvant chemotherapy in urothelial bladder cancer [ 8 ] and breast cancer [ 9 , 10 ]. However, up until now, less study has been dedicated to clarify the association between CD34 or Bcl-2 expression and the response to NACT in cervical cancer.…”