Serum Alkaline Phosphatase Level as a Prognostic Tool in Colorectal Cancer: A Study of 105 patients

BACKGROUND: Serum alkaline phosphotase (ALP) levels are frequently elevated in patients with metastatic colorectal cancer (CRC). However, the significance of ALP in terms of detecting hepatic metastasis or prognosis is not well established. MATERIALS AND METHODS: Medical records of patients with CRC seen at University of Alabama at Birmingham (UAB) (1998-2002) were reviewed and statistical analysis was done to evaluate the significance of ALP as a prognostic tool. The normal range for ALP was quantified at 39 U/L to 117 U/L. Change in ALP levels over time (defined as time interval between two cycles; such as 4 weeks for Mayo regimen, 8 weeks for Roswell Park regimen and 6 weeks for IFL regimen) was categorized as large (120+ U/L), medium (20-119 U/L), and minimal (< 20 U/L). RESULTS: A total of 105 patients with eligible medical records were identified (Mean age: 59 yrs; 53% male; Staging: II: 43 patients, III: 31 patients, IV: 32 patients). Increasing ALP levels correlated with increasing stage (Mean: I = 116, II = 219, III = 302; P = 0.0003). ALP levels were elevated in 74% of patients with liver metastases (Mean, 290) and in 33% without liver metastases (Mean, 122) (P = 0.001). Patients with elevated ALP levels at the most recent time of progression were 5.7 (95% CI, 2.4-13.3) times more likely to have a liver metastases compared to patients with normal levels. Additionally, patients with elevated ALP levels at their most recent visit were 4.2 (95% CI, 1.7-10.7) times more likely to have a worse prognosis compared to patients with normal levels. However, after controlling for the effects of liver metastases, the association between elevated levels and prognosis was no longer significant. After controlling for the effects of age, sex, and liver metastases, large changes in AP levels were associated with a 4.4 (95% CI, 1.0-19.1) times greater odds of having a worse prognosis compared to patients with a minimal change. Patients with an ALP level greater than 160 were 12 (95% CI, 4.3-33.3) times more likely to have liver metastases than patients with an ALP level of less than 160. Mean CEA level was 78 for patients without liver metastases and 308 for patients with liver metastases. CEA levels were compared against ALP in a random sample of 18 patients, which revealed a correlation between increasing levels of CEA (.002) with increasing levels of ALP. CONCLUSION: Instead of the upper normal limit for ALP, our data shows that using an ALP cutoff of 160 U/L increases the sensitivity of liver metastases detection. Also, a change in ALP levels of greater than 120 U/L over four-to-six weeks may be indicative of disease progression. Monitoring ALP is a simple, low cost, and relatively sensitive screening tool. Prospective studies involving evaluation of ALP in addition to CEA in patients with CRC is indicated.