Abstract
BackgroundThe role of adjuvant chemotherapy and the value of molecular biomarkers in bladder cancer have not been determined. We aimed to assess the predictive and prognostic values of excision repair cross-complementation 1 (ERCC1) in identifying appropriate patients who may potentially benefit from adjuvant chemotherapy for bladder cancer.MethodsA retrospective analysis was performed on 93 patients with completely resected transitional cell carcinoma of the bladder. ERCC1 expression was assessed by immunohistochemistry. ERCC1 expression was analyzed in 57 patients treated with adjuvant gemcitabine plus cisplatin chemotherapy and 36 who were not treated.ResultsAmong 93 patients, ERCC1 expression was positive in 54 (58.1%) and negative in 39 (41.9%). ERCC1 positivity was significantly associated with longer survival (adjusted hazard ratio for death, 0.12, 95% confidence interval [CI] 0.014-0.99; P = 0.049) in the group without adjuvant chemotherapy while ERCC1 positivity was associated with shorter survival among patients who have received adjuvant chemotherapy (adjusted hazard ratio for death, 2.64; 95% CI 1.01-6.85; P = 0.047). Therefore, clinical benefit from adjuvant chemotherapy was associated with ERCC1 negativity as measured by overall survival (test for interaction, P = 0.034) and by disease-free survival (test for interaction, P = 0.20).ConclusionsAmong patients with completely resected transitional cell carcinoma of the bladder, those with ERCC1-negative tumors seemed to benefit more from adjuvant gemcitabine plus cisplatin chemotherapy than those with ERCC1-positive tumors. Future prospective, randomized studies are warranted to confirm our findings.
Highlights
The role of adjuvant chemotherapy and the value of molecular biomarkers in bladder cancer have not been determined
Perioperative chemotherapy has been investigated for patients who undergo cystectomy for locally advanced transitional cell carcinoma of the bladder, and clinical benefit from neoadjuvant cisplatin-based chemotherapy has been demonstrated in several randomized trials [1,2,3]
No significant differences were found in the clinicopathologic parameters between patients with excision repair crosscomplementation 1 (ERCC1)-positive and those with ERCC1negative tumors in groups with or without adjuvant chemotherapy or in the total population (Table 2)
Summary
The role of adjuvant chemotherapy and the value of molecular biomarkers in bladder cancer have not been determined. We aimed to assess the predictive and prognostic values of excision repair crosscomplementation 1 (ERCC1) in identifying appropriate patients who may potentially benefit from adjuvant chemotherapy for bladder cancer. Perioperative chemotherapy has been investigated for patients who undergo cystectomy for locally advanced transitional cell carcinoma of the bladder, and clinical benefit from neoadjuvant cisplatin-based chemotherapy has been demonstrated in several randomized trials [1,2,3]. Further research investigating the effect of adjuvant chemotherapy on bladder cancer survival is of high importance considering its current practice. Cisplatin is the most important adjuvant chemotherapy agent for bladder cancer and is usually administered with gemcitabine. Its increased expression is associated with resistance to cisplatin-based chemotherapy in various tumor types [12,13,14,15,16,17]
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