Presentation Authors: Toshiki Kijima*, Ryu Teramatsu, Shohei Fukuda, Hiroshi Fukushima, Shingo Moriyama, Sho Uehara, Yosuke Yasuda, Soichiro Yoshida, Minato Yokoyama, Junichiro Ishioka, Yoh Matsuoka, Kazutaka Saito, Yasuhisa Fujii, Tokyo, Japan
Introduction: Heat-shock factor 1 (HSF1) is the master transcriptional regulator of the cellular response to various proteotoxic stressors. HSF1 has the pro-oncogenic potential and recent reports revealed that the transcriptional programs regulated by HSF1 are commonly activated in a range of human malignancies. Although high levels of HSF1 has been shown to predict poor survival in several cancers, predictive and prognostic role of HSF1 in bladder cancer is unexplored. The aim of this study was to evaluate associations of HSF1 expression with oncological outcomes in muscle-invasive bladder cancer (MIBC) patients treated with chemoradiotherapy (CRT)-based bladder sparing protocol.
Methods: We performed immunohistochemical analysis of HSF1 expressions in bladder cancer tissues obtained from 52 MIBC patients who were treated with CRT-based bladder sparing protocol. According to the protocol, the patients underwent maximal transurethral resection and induction CRT (40 Gy with concurrent cisplatin), followed by consolidative partial cystectomy for bladder preservation or radical cystectomy. Associations of HSF1 expression status with response to CRT and cancer-specific survival (CSS) were evaluated by logistic and Cox regression analysis.
Results: After induction CRT, 28 (54%) achieved clinical CR. Seven (13%) and 27 (52%) patients underwent partial and radical cystectomy, respectively, while the remaining 18 (35%) had no surgery (the overall 5-year CSS rate: 51%). High expression of HSF1 was observed in 29 (56%) of the 52 patients and was associated with poor response to CRT (clinical CR rate; 8/29 [28%] in HSF1 high vs 15/23 [65%] in HSF1 low, p < 0.01). The patients with high expression of HSF1 had worse CSS compared to those with low HSF1 expression (5-year CSS rate; 34% for HSF1 high vs 75% for HSF1 low, p=0.01). Among the clinical variables, high HSF1 expression, cT3-4 tumor, and non-curative resection at initial transurethral resection were independently associated with an increased risk of cancer death.
Conclusions: High expression of HSF1 is associated with poor response to CRT and decreased survival in MIBC patients receiving CRT-based bladder sparing protocol. Our findings indicate that HSF1 is a potential biomarker and could be a therapeutic target to overcome chemo- and radioresistance in MIBC.