The use of higher nadir CA-125 levels below the upper normal limit to indicate poorer prognosis in CCR EOC patients and the consequent need for further consolidation or maintenance therapy has been a long-standing issue . The primary therapy of EOC patients commonly ends after standard treatment, most including cytoreduction surgery and adjuvant chemotherapy. Several studies have suggested that the CA-125 level may be used to stratify high-risk recurrent patients . As heterogeneous groups, different EOC pathological types present distinct clinical characteristics that indicate patient prognosis, including the CA-125 level. The use of a uniform reference value or interval may not be appropriate for estimating the prognosis of all types of EOCs. The inconsistent results from different studies may be also partially attributed to the unspecific use of CA-125 for all EOC types.
In the present study, we found that the nadir CA-125 level is an independent prognosis indicator of HG-SOC. The OS and PFS varied between the subgroups with median nadir serum CA-125 levels (10 U/mL). Although the CA-125 level has been associated with EOC prognosis, no consensus has been reached regarding a fixed cut-off value for the nadir CA-125 level when predicting prognosis. Several studies have suggested a CA-125 level based on the observed median value . Others used an arbitrary cut-off value, such as 10 U/mL and 12 U/mL, or an interval for the stratification of cohorts, such as 5 U/mL, 21 U/mL, and 18 U/mL [12, 16, 22–24]. However, the median and arbitrary cut-off values vary among the different EOC subtypes. The median nadir CA-125 level of HG-SOC was 10 U/mL in both MDACC and JICR populations. Furthermore, the OS and PFS were longer for the pCR subgroup than for patients with residual tumors confirmed by second-look surgery; however, this issue remains controversial [25–30]. Although the serum CA-125 level is known to reflect the tumor burden, our results did not confirm its role in determining the minimal degree of residual disease [31–33]. Given that only 80 of 616 patients (13.0%) were included in the analysis, the validity of our findings for the population with HG-SOC is unclear.
Based on the consideration that CA-125 can predict prognosis, the conventional concept of the CCR as the end of primary treatment needs further evaluation . Identifying the best therapy and defining the patient groups that might best benefit from a consolidation or maintenance strategy are equally challenging, given that the present strategy assumes that all HG-SOC cases will recur. Thus, clinicians will be able to advise patients who achieve CCR after primary chemotherapy by determining the therapeutic ratio of possible harm versus potential benefit for an individual patient. The same recruitment standards and analysis methods were used to study HG-SOC from two different cancer centers. Thus, the bias in this study was reduced to a certain extent. The nadir CA-125 level associated with prognosis does not reflect the presence of residual tumors. CA-125 is ineffective for minor tumor burdens.
The baseline CA-125 is found a significant but not independent variables. Actually, higher decline rate of CA-125 means higher baseline level in CCR ovarian cancer with negative CA-125 level (<35 U/mL). CA-125 level >10 U/mL meanwhile decreasing more than 97.6% decreasing kinetics <1/32) indicates poorer OS and PFS, in another words, baseline CA-125 level more than or equal to 424-1484 U/ml indicate more relapse and death. Our results suggest that for patients even achieved CCR, we need pay more attention to those with high initial CA-125 level.
This retrospective analysis has several limitations. First, given the long survival durations of our study population from the two institutions, the heterogeneity of treatment strategies used throughout the 28-year study period, the emergence of new treatment regimes, such as paclitaxel-based chemotherapy and molecular target therapy [34, 35], the influence of the therapy and evaluate strategy is difficult to exclude. Second, we focused on the nadir CA-125 level in HG-SOCs. However, 8.4% negative tissue expression and 11.2% normal serum level were observed for CA-125.
Our study supports the emerging evidence showing that the nadir CA-125 level in HG-SOCs may be an independent prognostic factor for both OS and PFS. The application of CA-125 strata for future prospective trials of HG-SOC consolidation or maintenance should be considered.