Preoperative Cancer Antigen 125 Level as Predictor for Complete Cytoreduction in Ovarian Cancer: A Prospective Cohort Study and Systematic Review

Abstract

Background: The tumor marker ‘cancer antigen 125’ (CA-125) plays a role in the management of women with advanced stage ovarian cancer. This study aims to describe the predictive value of pre-treatment CA-125 level and the reduction after neoadjuvant chemotherapy (NACT) on surgical outcome. Methods: A systematic review and a prospective clinical study were performed. Multiple databases were searched from database inception to April 2022. The clinical study is part of a randomized controlled trial named “PlaComOv-study”. A regression analysis was performed to demonstrate correlations between preoperative CA-125 levels, CA-125 reduction after NACT, and surgical outcome. Results: Fourteen relevant articles were analyzed of which eleven reported that lower preoperative CA-125 levels were associated with a higher probability of complete cytoreduction. In the clinical study, 326 patients with FIGO stage IIIB-IV ovarian cancer who underwent CRS were enrolled from 2018 to 2020. Patients who underwent interval CRS with preoperative CA-125 levels ≤ 35 kU/L had higher odds of achieving complete CRS than patients with CA-125 level >35 kU/L (85% vs. 67%, OR 2.79, 95%CI 1.44–5.41, p = 0.002). In multivariable analysis with presence of ascites and peritoneal carcinomatosis, normalized preoperative CA-125 did not appear as a significant predictor for complete CRS. Conclusions: In literature, preoperative CA-125 levels ≤ 35 kU/L were associated with a significant higher percentage of complete CRS in univariable analysis. According to our cohort study, preoperative CA-125 level ≤ 35 kU/L cannot independently predict surgical outcome either for primary or interval CRS.

Unresectable Ovarian Cancer Requires a Structured Plan of Action: A Prospective Cohort Study

“…Although previous studies demonstrated a correlation between the percentage of decrease in CA-125 after NACT and surgical outcome, we neither found an association between the preoperative value of CA-125 nor the reduction rate of CA-125 level after NACT and unresectable disease. One study reported a significant relation between CA-125 level and complete CRS in multivariable analysis, while all other studies did not perform a multivariable analysis [15][16][17]. Although the study by Gupta et al found a significant correlation between a >95% decrease in preoperative CA-125 level and complete CRS, our study showed that this does not guarantee complete CRS.…”

Utility of CA-125 in interval surgery

“…This work coincides with the interval cytoreduction percentages according to our case series. 22 However, only the absence of ascites and peritoneal carcinomatosis during surgery, FIGO stage IIIB/IIIC and high-grade serous histology were significant independent predictors of CC in interval surgery, demonstrated in multivariate analysis. This analysis coincides with our review of cases where 100% of the histology was high-grade serous, which could explain the high response rate to NACT and CC.…”

“…6,12,13,[15][16][17][18][19][20][21] Results from a systematic review by Brons et al indicated a significant relationship between lower preoperative CA-125 values and CC in patients who underwent interval surgery. 22 However, the definitions of normal CA-125 value and optimal CA-125 reduction cut-off values varied between studies, denoting that the effect of CA-125 reduction rate after NACT could not be directly compared in the surgical outcome. The studies included in that systematic review did not report the effect of ascites or peritoneal carcinomatosis and lacked multivariable analysis.…”