Significance of CA125 Monitoring during Maintenance Treatment with Poly(ADP-Ribose) Polymerase Inhibitor in Ovarian Cancer after First-Line Chemotherapy: Multicenter, Observational Study

TL;DR

This study finds that monitoring CA125 levels with a new threshold improves detection of ovarian cancer recurrence during maintenance treatment with PARP inhibitors.

Contribution

Proposes a new CA125 threshold (≥3× nadir) for detecting ovarian cancer recurrence during PARP inhibitor treatment, improving sensitivity and diagnostic accuracy.

Findings

GCIG criteria missed 46.3% of progressing patients during PARP inhibitor treatment.

The ≥3× nadir criterion achieved 79.63% sensitivity and 98.86% specificity for detecting progression.

The new criterion offers higher diagnostic accuracy (91.55%) compared to GCIG (82.39%).

Abstract

Monitoring of Cancer Antigen 125 (CA125) during ovarian cancer (OC) maintenance treatment with poly(ADP-ribose) polymerase inhibitors (PARPis) may be insufficient when using Gynecologic Cancer Intergroup (GCIG) biochemical progression criteria. This study aimed to evaluate the usefulness of CA125 monitoring in detecting OC recurrence during PARPis maintenance treatment.

This multicenter retrospective cohort study included patients with primary OC who achieved complete or partial response after first-line platinum-based chemotherapy followed by PARPis maintenance treatment. Progression was defined using Response Evaluation Criteria in Solid Tumors (RECIST) and GCIG biochemical criteria. New biochemical progression definitions, based on CA125 nadir determined using receiver operating characteristic (ROC) curve analysis, were proposed. Concordance between radiological and biochemical progression was assessed.

Of 142 patients, progression was detected in 54 (38.03%) and 29 (20.42%) using RECIST and GCIG criteria, respectively. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the GCIG criteria were 53.70% [95% confidence interval (CI): 39.61%–67.38%], 100.00% [95% CI:95.91%–100.00%], 100.00% [95%CI: 88.10%–100.00%] and 77.88% [95% CI: 72.54%–82.43%], respectively. A cut-off of 1.59× nadir achieved 88.90% sensitivity and 87.20% specificity [Area Under Curve (AUC): 91.10%, 95% CI: 84.70%–97.40%] with a false positive rate (FPR) of 12.67%. Defining biochemical progression as an increase in CA125 of ≥3× nadir achieved sensitivity, specificity, PPV, NPV, and FPR of 79.63% [95% CI: 66.47%–89.37%], 98.86% [95% CI: 93.83%–99.97%], 97.73% [95% CI: 85.91%–99.67%], 88.78% [95% CI: 82.35%–93.06%], and 1.14%, respectively. Diagnostic accuracy was higher using the ≥3× nadir criterion compared with GCIG definition (91.55% vs. 82.39%).

GCIG biochemical progression criteria during PARPis maintenance treatment after first-line chemotherapy missed 46.3% of progressing patients. A new criterion—CA125 ≥3× nadir—improves sensitivity and NPV, while maintaining high specificity, offering a simple and practical approach for clinical implementation.

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