The significance of the change pattern of serum CA125 level post-treatment for judging recurrences of EOC
The clinical data statistical analysis shows that there was a relationship between patient outcomes and serum CA125 levels before treatment and the extent and speed of serum CA125 decrease after treatment. The outcomes of patients with pre-treatment serum CA125 ≤ 35 U/ml were better than those with serum CA125 > 35 U/ml. The outcomes of patients with serum CA125 logarithmic decrease or decrease to normal within a month after treatment were also better than those with a non-logarithmic decrease, or taking more than a month to decrease to normal.
Comparing patients with a serum CA125 logarithmic decrease and those with a non-logarithmic decrease, the median PFS was 45 and 34 months, respectively, P = 0.043, a statistically significant difference. Results of multivariate Cox regression analysis showed that CA125 levels before treatment and a decreased speed in decline of serum CA125 after treatment were independent prognostic factors.
The serum CA125 level pre-treatment is closely related to tumor size. The higher the serum CA125 levels, the larger the tumor lesions are, and the deeper and wider the tumor infiltrates, making cytoreductive surgery (CRS) harder. Whether CRS is successful or not has a great influence on continued treatment, so it affects prognosis. Eltabbakh et al. [
2] explored influence factors of optimal CRS and found that 72 patients with advanced ovarian cancer could have an optimal CRS if serum CA125 was ≤ 500 U/ml. Vorgias et al. [
3] analysed the relationship between the preoperative CA125 levels of 426 patients with Stage III/IV ovarian carcinoma and the surgical outcome. The data indicated preoperative CA125 is a good predictor for optimal CRS. The area under curve of the ROC curve was 0.89, 98 % C.I. = [0.828–0.952], indicating very good discriminating capability. The level of 500 IU/ml was found to have the most predictive power. The sensitivity of CA125 at that level was 78.5 %, the specificity 89.6 %, the positive predictive value 84.2 %, the negative predictive value 85.4 % and its accuracy 85 %. Furthermore, the likelihood ratio for correct discrimination between optimal and sub-optimal CRS, dropped sharply from 6.33, 95 % C.I. [5.19–10.91] at the level of 500 IU/ml to 0.58, 95 % C.I. [0.21–1.63] at the level of 600 IU/ml. The data indicate that the best threshold for this prediction proved to be 500 IU/ml. These patients may be candidates for neo-adjuvant chemotherapy treatment.
There is a close relationship between post-treatment serum CA125 levels and the size of residual lesions after CRS. The larger the residual size, the slower the serum CA125 level decreases. If the serum CA125 level does not decrease rapidly after CRS it always means that the residual lesions are large, the prognosis is worse, and the patients can relapse easily. The speed of serum CA125 decrease to normal after treatment has significance for diagnosing relapse to some degree. Patients with a high pre-treatment level of serum CA125 have a better prognosis if their serum CA125 decreases to normal rapidly after surgery, while patients with a low pre-treatment level of serum CA125 have a worse prognosis if their serum CA125 does not decrease to normal rapidly after surgery.
Systemic, regular, and full doses of chemotherapy are necessary, and after chemotherapy the serum CA125 levels decrease. The half-life of serum CA125 can show the changing rate of serum CA125 in early treatment by chemotherapy and we can judge the prognosis according to the half-life of serum CA125. Na et al. [
4] showed that patients with a serum CA125 half-life of more than 20 days (group 1) have a 3.2 times greater risk of recurrence than those with a serum CA125 half-life of less than 20 days (group 2). The average relapse-free time of group 1 was 11 months and that of group 2 was 43 months. Digant et al. [
5] Reported that reduction in CA125 after 3 months of therapy is associated with better overall survival in ovarian cancer. Patients without a significant decline in CA125 after 3 months of therapy have a particularly poor prognosis.
The significance of the change pattern of serum CA125 levels post-treatment for diagnosing recurrence of EOC
Our data show that the serum CA125 level of most relapsed patients would rises. The average increased level is 116.28 U/ml; the average time between an increase in serum CA125 and detection of the recurrent lesion by physical examination or imaging examination is 122 days, and there is a relationship between the pattern of serum CA125 level increases and finding the recurrent lesion by physical or imaging examination. The increased level of serum CA125 has a negative correlation with the time before finding the recurrent lesion. The higher and faster serum CA125 increases, the shorter the time to find the recurrent lesion by physical or imaging examination. These results are similar to the results of Levy [
6]. Levy’s team observed the change pattern of serum CA125 in relapsed patients with EOC and found that PFS or OS of relapsed patients with serum CA125 that increased slowly are longer than for those whose serum CA125 increased rapidly. In this study, the area under the ROC curve was 0.879, and the sensitivity and specificity for diagnosing recurrence were 67.39 and 86.79 %, respectively. The sensitivity of diagnosing recurrence was low, may be because of the following reasons: (1) The recurrent tumors are small and the levels of antigen may be too low to activate an antibody response. (2) There is a fibrous envelope around the cancer tissue which might block the release of the antigen into the blood circulation. (3) Chemotherapy drugs may have changed the biological behavior of the cancer cells. Some studies found that in patients with negative serum CA125, the negative rate of second surgical exploration was as high as 43.8 %. A previous study confirmed that serum CA125 is positive if the patients suffer from pelvic inflammation, endometriosis, pleura and peritoneum pathological changes, or liver cancer.
Solutions for EOC patient with simple serum CA125 increases post-treatment
There is still a controversy about whether patients should receive treatment when their serum CA125 increases alone post-treatment [
7,
8]. A prospective multicenter clinical trial showed that patient outcomes were not improved if chemotherapy was given when serum CA125 increased, and it reduced quality of life [
9]. This may be because the tumor cells were not in the proliferation period and were not sensitive to chemotherapy drugs.