Clinical evaluation of CEA, CA19-9, CA72-4 and CA125 in gastric cancer patients with neoadjuvant chemotherapy

Abstract

Background: In the clinical practice of neoadjuvant chemotherapy, response markers are very important. We aimed o investigate whether tumor markers CEA(carcino-embryonic antigen), CA19-9(carbohydrate antigen 19-9), CA72-4(carbohydrate antigen 72-4), and CA125(carbohydrate antigen 125) can be used to evaluate the response to neoadjuvant chemotherapy, and to evaluate the diagnosis and prognosis value of four tumor markers in the patients of gastric cancer.

Methods: A retrospective review was performed of 184 gastric cancer patients who underwent a 5-Fu, leucovorin, and oxaliplatin (FOLFOX) neoadjuvant chemotherapy regimen, followed by surgical treatment. Blood samples for CEA, CA19-9, CA72-4, and CA125 levels were taken from patients upon admission to the hospital and after neoadjuvant chemotherapy. Statistical analysis was performed to identify the clinical value of these tumor markers in predicting the survival and the response to neoadjuvant chemotherapy.

Results: Median overall survival times of pretreatment CA19-9-positive and CA72-4-positive patients (14.0 +/-2.8 months and 14.8 +/-4.0 months, respectively) were significantly less than negative patients (32.5 +/-8.9 months and 34.0 +/-10.1 months, respectively) (P = 0.000 and P = 0.002, respectively). Pretreatment status of CA19-9 and CA72-4 were independent prognostic factors in gastric cancer patients (P = 0.029 and P = 0.008, respectively). Pretreatment CEA >50 ng/ml had a positive prediction value for clinical disease progression after neoadjuvant chemotherapy according to the ROC curve (AUC: 0.694, 95% CI: 0.517 to 0.871, P = 0.017). The decrease of tumor markers CEA, CA72-4, and CA125 was significant after neoadjuvant chemotherapy (P = 0.030, P = 0.010, and P = 0.009, respectively), especially in patients with disease control (including complete, partial clinical response, and stable disease) (P = 0.012, P = 0.020, and P = 0.025, respectively). A decrease in CA72-4 by more than 70% had a positive prediction value for pathologic response to neoadjuvant chemotherapy according to the ROC curve (AUC: 0.764, 95% CI: 0.584 to 0.945, P = 0.020).

Conclusions: Our results suggest that high preoperative serum levels of CA72-4 and CA19-9 are associated with higher risk of death, high pretreatment CEA levels (>50 ng/ml) may predict clinical disease progression after neoadjuvant chemotherapy, and a decrease (>70%) of CA72-4 may predict pathologic response to neoadjuvant chemotherapy.

Figure 1

Survival curves of patients according to CEA, CA199, CA724, and CA242 pretreatment serum positivity. A. The difference between CEA-negative patients and CEA-positive patients was not statistically significant (P = 0.085). B. The difference between CA19-9-negative patients and CA19-9-positive patients was statistically significant (P = 0.000). C. The difference between CA72-4-negative patients and CA72-4-positive patients was statistically significant (P = 0.002). D. The difference between CA242-negative patients and CA242-positive patients wasnot statistically significant (P = 0.409).

Figure 2

Mean levels of four tumor markers before and after neoadjuvant chemotherapy. A. Mean level of CEA was decreased significantly after neoadjuvant chemotherapy (P = 0.030). B. Mean level of CA19-9 was decreased after neoadjuvant chemotherapy, the difference was not statistically significant (P = 0.251). C. Mean level of CA72-4 was decreased significantly after neoadjuvant chemotherapy (P = 0.010). D. Mean level of CA242 was decreased significantly after neoadjuvant chemotherapy (P = 0.009).

Figure 3

Mean levels of four tumor markers before and after neoadjuvant chemotherapy in disease control (CR + PR + SD) and PD (disease progression) group respectively. A. C. D shows CEA, CA724, and CA125 decreased more significantly in the disease control (CR + PR + SD) group than the disease progression (PD) group (P = 0.012, P = 0.020, and P = 0.025, respectively). B. show the decreased levels of CA199 was not statistically significant (P values was 0.849).

Figure 4

ROC curves for the decrease of the four tumor markers to predict the disease control after neoadjuvant chemotherapy. A, B. shows the decrease of CEA, CA199 was not statistically significant (P values were 0.785, and 0.540, respectively). C. The area under the ROC curve of CA72-4 change values was 0.764 (95% CI: 0.584 to 0.945, P = 0.020); the optimal cutoff which simultaneously maximized both the sensitivity (77.8%) and specificity (80%) of the test was decreased by 71.1%. D. The area under the ROC curve of CA125 change values was 0.800 (95% CI: 0.537 to 1.063, P = 0.128); the optimal cutoff which simultaneously maximized both the sensitivity (100%) and specificity (60%) of the test was decreased by 40.0%.

Figure 5

ROC curves for pretreatment levels of tumor markers to predict the disease progression after neoadjuvant chemotherapy. A. The area under the ROC curve of CEA pretreatment levels was 0.694 (95% CI: 0.517 to 0.871, P = 0.017); the cutoff that maximized both sensitivity (57.1%) and specificity (85.4%) of this test was 50 ng/ml. The correlation coefficient between CEA pretreatment levels and pathologic response was 0.199, and the P value was 0.017. B.C.D show the pretreatment levels of CA72-4, CA199, and CA125 were not statistically significant (P values were 0.381, 0.719, and 0.967 respectively).