Nearly 1.4 million new patients are diagnosed with colorectal cancer (CRC) each year. Of these, ~24% are diagnosed with stage II disease (i.e., ~336,000pa), where there is no histological evidence of tumour spread to lymph nodes locally or distally to liver. Despite stage II tumour resection, the risk of disease recurrence remains at ~20% for these patients (i.e., ~67,200pa). This high-risk is likely due to micrometastasis or minimal residual disease present despite resection causing clinically-silent metastasis. Most seriously, subsequent recurrence is detected when CRC is at a more advanced stage (e.g., III or IV), where survival rates are reduced. Currently, there are no FDA-approved biomarkers that can discriminate high-risk stage II CRC patients who require further adjuvant treatment after surgery.
In our immunohistochemical study, we have discovered a high-risk stage II rectal cancer (RC) prognostic biomarker. In a large study of RC stage II patients (n=168) who did not receive chemotherapy/radiotherapy, we demonstrated that strong tumour expression of urokinase plasminogen activator receptor (uPAR) resulted in a significantly lower overall survival (p=0.017; HR=1.6; 12yr follow-up). After resection, survival for patients with strong uPAR expression was poorer, correlating with the proportion of patients who recurred within 5 years of surgery. Equally, patients with no/low uPAR had near normal life expectancies, indicating resection was likely curative. For the first time, the data identified uPAR as a “actionable” tissue biomarker that does discriminate high-risk stage II rectal cancer patients.
To determine if tumour uPAR expression is a reliable, inexpensive, prognostic biomarker discriminating all high-risk stage II CRC patients, we are currently expanding our RC-only study to a larger cohort of both colon and rectal cancers (n=760) with long clinical follow-up. Furthermore, using this CRC cohort, we will co-evaluate other potential high-risk stage II protein biomarkers (e.g., CDX2, CXCR3 and SATB1) to determine whether these proteins add additional discriminatory power to IHC tumour uPAR determinations.