Detecting hereditary nonpolyposis colorectal cancer syndrome (HNPCC) in patients with colorectal cancer (CRC): Optimal strategies at lower costs.

Abstract

396 Background: The optimal strategy to detect HNPCC in CRC pts remains controversial, and may include testing tumors for microsatellite (MSI) status and/or pts for mutations in DNA mismatch repair (MMR) genes. Costs of 6 testing strategies were compared against their risks of missing pt managed as HNPCC. Methods: 185 consecutive CRCs were prospectively tested by both immunohistochemistry (IHC, for protein expressions of MLH1, MSH2, MSH6, PMS2) and PCR-based MSI. Secondary tests included MLH1 promoter methylation, BRAF mutation, and germline mutation, as appropriate. A decision tree compared the strategy of performing both IHC and MSI in all (Strategy 1) to five alternatives (Strategies 2-6, Table ). Costs were obtained from commercial list prices, Medicare reimbursement, and literature; probabilities were calculated from pt data. Incremental cost-effectiveness ratios (ICERs) were reported for each additional pt managed as HNPCC Results: 20 (10.8%) pts were identified as being managed as HNPCC. Performing IHC and MSI in all (Strategy 1) or IHC first in all followed by MSI when IHC was normal (Strategy 4) detected all 20 cases. When compared to performing IHC only (Strategy 2), Strategy 4 demonstrated an ICER of $31,821 per additional case detected, while other strategies were more costly and/or less effective (Table). Between the two strategies that detected all cases of HNPCC, Strategy 4 was less costly ($1,049 vs $1,098 per patient, Table). Conclusions: When combined with appropriate secondary and confirmatory testing, performing IHC and MSI in all or IHC in all followed by MSI when IHC were normal, both showed a zero miss rate, while the latter was slightly more cost-effective. [Table: see text]