Researchers have found a set of genetic mutations that when present in tumor tissue predict benefit from neoadjuvant chemotherapy (NAC) in patients with muscle-invasive bladder cancer.
Genomic alterations in the DNA repair–associated genes ATM, RB1, and FANCC predicted response and clinical benefit after cisplatin-based NAC for muscle-invasive bladder cancer (MIBC) in discovery and validation sets of pretreatment tumor samples.
These results suggest that defective DNA repair renders tumors sensitive to cisplatin, according to an article printed online in European Urology.
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Cisplatin-based chemotherapy is the current standard of care for NAC before cystectomy in patients with muscle invasive bladder cancer, but only 25% to 50% of patients are expected to achieve a pathologic response.
Researchers investigated whether there were any prognostic biomarkers. Pretreatment MIBC samples were collected from patients who were enrolled in two separate trials of cisplatin-based NAC.
DNA from pretreatment tumor tissue was sequenced for all coding exons of 287 cancer-related genes and was analyzed for base substitutions, indels, copy number alterations, and selected rearrangements in a Clinical Laboratory Improvements Amendments–certified laboratory.
Results showed that patients with a pathologic complete response had more alterations than those with residual tumor in both the discovery and validation sets. In the discovery set, alteration in one or more of the three DNA repair genes ATM, RB1, and FANCC predicted pathologic response (P<0.001; 87% sensitivity, 100% specificity) and better overall survival (P=0.007). This test remained predictive for pathologic response in the validation set (P=0.033), with a trend towards better overall survival (P=0.055).
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Patients with a pathologic complete response had more alterations than those with residual tumor in both the discovery (P=0.024) and validation (P=0.018) sets. In the discovery set, alteration in one or more of the three DNA repair genes ATM, RB1, and FANCC predicted pathologic response (P<0.001; 87% sensitivity, 100% specificity) and better overall survival (P=0.007).
This test remained predictive for pathologic response in the validation set (P=0.033), with a trend towards better overall survival (P=0.055). These results require further validation in additional sample sets.
Reference
- Plimack ER, Dunbrack RL, Brenn TA, etc. Defects in DNA repair genes predict response to neoadjuvant cisplatin-based chemotherapy in invasive bladder cancer. Eur Urol. 2015. [epub ahead of print]. doi: 10.1016/j.eururo.2015.07.009.
