So much effort, so little progress?

In colorectal cancer (CRC), the treatment guidelines differ for Union International Contrè Cancer (UICC) stage II and III colon cancer patients. In patients with stage II colon cancer without risk factors such as T4 tumor, tumor perforation, emergency surgical procedure, or less than 12 removed lymph nodes, the low risk of recurrence is justifying no role of adjuvant chemotherapy. It would be critical to identify patients with stage II colon cancer who have higher risk of recurrence based on molecular testing and would benefit from adjuvant chemotherapy. On the other hand, for UICC stage III patients, 5-fluorouracil (5-FU)–based adjuvant chemo-therapy has increased the absolute five-year survival rate by 10% to 15%, and the addition of oxaliplatin in the adjuvant setting further increased the absolute five-year disease free survival rate by 5% to 6% to 71% to 73% (1,2). The combination of a fluoropyrimidin in combination with oxaliplatin for a period of six months is recommended for those patients (1,2). Without the identification of high risk factors of recurrence and markers of efficacy of FOLFOX, a large proportion of patients will receive chemotherapy without any benefit. The future challenge is to define the patient population that benefits from adjuvant chemotherapy in stage II and III based on a biomarker test that helps to guide this critical decision. During the last decade, several molecular signatures/tests have been introduced, however, the predictive value, despite huge efforts, is only marginally better than the assessment of clinical risk factors such as obstruction, T4 tumor, perforation, the presence of lymphovascular or perineural invasion, and a high carcinoembry-onic antigen. Di Narzo and colleagues (3) tested the predictive value of four (Genomic Health, Veridex, ALMAC, and an MD Anderson score) previously published and in part validated colon cancer recurrence risk scores using microarray gene expression data from FFPE (formalin-fixed paraffin-embedded [tissue]) material from patients enrolled in PETACC3 (4). With the exception of the ALMAC score, which also used microarray data from FFPE samples, all other scores either used different material (fresh frozen), a different expression assay (Q-RT-PCR), or both to calculate the risk of recurrence-free survival (RFS), survival after relapse (SAR), or overall survival (OS). Therefore, the data coming from PETACC3 microarrays had to be adjusted to the respective score. Using multivariate analysis, RFS was predicted by two tests (Genomic Health and Veridex), SAR by one score (MD Anderson), and OS by two (Genomic Health and MD Anderson) …