Expression of ribonucleoside reductase subunit M1, but not excision repair cross-complementation group 1, is predictive in muscle-invasive bladder cancer treated with chemotherapy and radiation.
The aim of this study was to determine the prognostic and predictive values of ribonucleoside reductase subunit M1 (RRM1) and excision repair cross-complementation group 1 (ERCC1) expression in patients with muscle-invasive bladder cancer treated with chemoradiotherapy. The expression of RRM1 and ERCC1 in pretreatment tumor samples of retrospectively identified patients was determined by immunohistochemical analysis. A total of 39 patients were included in this study; 49% were treated with neoadjuvant chemotherapy and 67% with concomitant chemoradiotherapy; 56% were treated with gemcitabine-based and 51% with platinum-based chemoradiotherapy. The median follow-up was 19 months (interquartile range, 11-50 months). Based on the immunohistochemical analysis, 44 and 32% of the tumors exhibited increased expression of RRM1 and ERCC1, respectively. The complete response (CR) and local recurrence rates following chemoradiotherapy were 79 and 21%, respectively. A low expression of RRM1 was associated with a higher rate of CR to chemoradiotherapy (95 vs. 57%, P=0.012); however, there was no such association with low ERCC1 expression (67 vs. 84%, P=0.39). RRM1 expression predicted an improved CR in patients treated with gemcitabine-based chemoradiotherapy (57 vs. 100%, P=0.036), but not in those treated with other agents (56 vs. 88%, P=0.29). ERCC1 expression was not found to be correlated with CR (67 vs. 84%, P=0.39), even when restricted to patients treated with platinum agents (71 vs. 75%, P=1.0). In the univariate analysis, RRM1 expression, but not ERCC1 expression, was identified as a prognostic marker for worse cancer-specific survival in all the patients and in those treated with gemcitabine-based regimens. No independent prognostic factor was identified in the multivariate model, which included tumor stage, vascular invasion, hydronephrosis and RRM1 status. Although these findings require further validation, they suggest that RRM1 may be a beneficial stratification variable for the selection of chemotherapy regimens for chemoradiotherapy, with patients with low RRM1 expression being considered suitable for gemcitabine treatment.
Department of Oncology, Rambam Health Care Campus, Haifa 31096, Israel ;
Mark
M
Shilkrut
Departments of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Angela
A
Wu
Departments of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Dafydd G
DG
Thomas
Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, USA.
Daniel A
DA
Hamstra
bladder cancer; chemotherapy; excision repair cross-complementation group 1; prognostic marker; radiotherapy; ribonucleoside reductase subunit M1