Prognostic and Predictive Value of P53, Bcl2, Rb and Egfr for Bladder Preservation in Invasive Bladder Carcinoma Treated by Trimodality Approach

Abstract

Purpose: To update long-term results with selective organ preservation in invasive bladder cancer using aggressive transurethral resection of bladder tumor (TURBT) and radiochemotherapy (RCT) and to identify prognostic and predictive value of the biomarkers ;p53, pRB, BCL2 and EGFR. Patients and Methods: Between 2000 and 2006, a total of 55 patients with T2-T3 bladder cancer were enrolled in 2 sequential bladder-sparing protocols including aggressive TURB and RCT. From September 2000 to May 2003, 25 patients (in protocol no. 1) were treated by TURBT followed by radiotherapy 46 Gy with concurrent cisplatin 20 mg/m² day1-5, followed for complete and partial responders by radiotherapy 20 Gy with concurrent cisplatin (same dose) on the last five days. From December 2004 to April 2006, thirty patients were entered in protocol no. 2 that consisted of radiotherapy 60 Gy with concurrent Cisplatin 75 mg/ m2 q. 3 ws and Gemcitabine 300 mg / m2 D 1, 8 and 15 q. 3 ws for 2 cycles. In case of invasive residual tumor or recurrence, salvage cystectomy was recommended. All specimens were examined for expression of the biomarkers (p53, bcl2, Rb and EGFR) using immunohistochemical staining. results: The median follow-up for all patients is 30 months (range 4-84), 38 months (range 9-84) for patients in P1 and 22 months (4-54) for patients in P2. The actuarial 5-year OS were 58 % (SE 5), 52% (SE 7) and 61% (SE 6),for the whole series, P1 and P2 protocols respectively, (P =0.270). The corresponding figures for cancer specific survival (CSS) were 60%, 55% (SE 7) and 63% (SE 4), (P = 0.452). The 5-year actuarial OSB for all series, P1 and P2 protocols were 51% (SE 6), 46% (SE 7) and 55% (SE 9), respectively, (P = 0.323). For all patients, altered expression of p53, bcl2, pRb and EGFR were detected in (47.3%, 56.4%, 52.7% and 40% respectively The results of UVA showed that tumor stage and altered expression of pRB, BCL2 and EGFR were significantly associated with CSS and OS (P<0.05). There were no grade 4 toxicity and no treatmentrelated deaths. conclusion: Trimodality therapy to preserve the bladder is a therapeutic option that results in a high rate of long-term survivors retaining functional bladders in carefully selected patients. Patients with higher tumour stage and altered biomarkers; pRB, BCL2 and EGFR might not be candidate for bladder preserving approach.

Trimodality bladder-sparing approach versus radical cystectomy for invasive bladder cancer

“…2 In addition, this operation has been associated, sometimes, with poor quality of life results, as there is still no substitute for the patient's own fully functional bladder. 3 For all patients, overall survival (OS), cancer-specific survival and OS with bladder preservation (OSBP) rates at 5 years reached 58, 60 and 51%, respectively. 5,6 We had updated our experience in Assiut university hospitals with trimodality bladdersparing approach.…”

“…In the female patient an anterior exenteration is performed, which includes the bladder and urethra, the ventral vaginal wall and the uterus. 3 Therefore, recent strategies have combined the three modalities: transurethral resection of the bladder tumour (TURBT), chemotherapy and radiation therapy in an attempt to improve longterm survival and bladder preservation rates, 4 with salvage cystectomy being reserved for patients with incomplete response or local relapse. 2 In addition, this operation has been associated, sometimes, with poor quality of life results, as there is still no substitute for the patient's own fully functional bladder.…”

“…Unfortunately, after this radical cystectomy (RC) for locally advanced bladder cancer, there is a significant rate of recurrence (56% among patients with pathological stage T3), most commonly as distant metastases 2 . In addition, this operation has been associated, sometimes, with poor quality of life results, as there is still no substitute for the patient's own fully functional bladder 3 …”

“…We had updated our experience in Assiut university hospitals with trimodality bladder-sparing approach 3 . For all patients, overall survival (OS), cancer-specific survival and OS with bladder preservation (OSBP) rates at 5 years reached 58, 60 and 51%, respectively.…”

“…2 In addition, this operation has been associated, sometimes, with poor quality of life results, as there is still no substitute for the patient's own fully functional bladder. 3 Therefore, recent strategies have combined the three modalities: transurethral resection of the bladder tumour (TURBT), chemotherapy and radiation therapy in an attempt to improve longterm survival and bladder preservation rates, 4 with salvage cystectomy being reserved for patients with incomplete response or local relapse. 5,6 We had updated our experience in Assiut university hospitals with trimodality bladdersparing approach.…”