Long-term effects of a program of bladder preservation using chemotherapy plus radiotherapy in muscle invasive bladder cancer (BC). Analysis of biologic predictive factors and health-related quality of life (QOL)

Abstract

e16014 Background: Long-term effects of a combined approach of transurethral resection (TUR) plus chemotherapy (CT) and pelvic radiotherapy (RT) in terms of bladder preservation, survival, QOL are largely unknown. Moreover we investigated whether p53, Ki67, bcl-2, c-erbB-2 protein expression predict the achievement of a complete response (CR). Methods: From March 1994 to June 2000, 75 pts with muscle invasive BC were treated with a bladder sparing approach including an initial TUR, 3 cycles of CT (cisplatin + 5- FU) alternating with pelvic RT (40 Gy). At the response evaluation, pts with biopsy proven residual disease were considered incomplete responders (IR) and underwent immediate cystectomy. Pts with CR were treated with two additional CT cycles plus a bladder RT boost (20- 24 Gy). Paraffin embedded blocks of the primary tumors were collected and Ki67, p53, bcl-2 and c-erbB-2 protein expression were evaluated in a blind fashion. The Expanded Prostate Cancer Index Composite (EPIC) scores for urinary function, (especially storage, voiding symptoms and bowel function) was used to explore QOL in bladder preserved and compared with a group of matched patients treated by radical cystectomy only. Results: Median age was 67 yrs (range 42–80); T2a-T2b: 42%; T3a-T3b: 47%; T4a: 11%; G3: 88%; hydronephrosis: 32%. Overall, 56 (74.7%) pts achieved a CR and the achievement of a CR was significantly related to lower T stage (p= 0.002), high Ki67 (p=0.001), absence of hydronephrosis (p= 0.007) and high p53 overexpression (p=0.007). Multivariate analysis showed that only a low T stage (p=0.002) and high p53 expression (p=0.043) predict the obtaining of a CR. At 5 years of follow-up, 44 (59%) were alive and in 33 of them (75%) bladder was preserved; after 10-years 28 (37.3%) were alive and in 23 of them (82%) bladder was preserved. Analysis of QOL scores is ongoing. Conclusions: This approach induces a long term survival similar to radical cystectomy with a high rate of bladder preservation and represents a valid treatment for muscle invasive BC. Overexpression of p53 is a predictive marker for the obtaining of CR and for bladder preservation. No significant financial relationships to disclose.