Validation of the CTS5 in four prospective, multicenter, randomized ABCSG trials

Abstract

Background: The Clinical Treatment Score post-5 years (CTS5) is a clinicopathological tool designed to estimate late distant recurrence (LDR) in hormone receptor-positive (HR+) breast cancer patients after 5 years of adjuvant endocrine therapy (ET). While intended as a prognostic algorithm, its predictive value for ET extension remains uncertain. Methods: The score was calculated in 4931 patients from four prospective randomized ABCSG trials (ABCSG-6, -6a, -8, and -16) with 250 LDR events. We assessed its prognostic power, calibration accuracy, and predictive value. Time to LDR was analyzed using Cox regression models. Results: In our cohorts, the CTS5 provided prognostic information whether used as a continuous or categorical score. In the ABCSG-8 cohort (n = 2054) and the combined ABCSG-6+8 cohort (n = 3308), a higher continuous score was significantly associated with increased LDR risk. The categorical CTS5 showed that high-risk patients had significantly higher LDR rates compared to low- or intermediate-risk patients. The score slightly overestimated LDR risk, regardless of predicted risk. Although no significant predictive value was found on the relative scale, an absolute LDR risk reduction of 23.4 % was found in patients with a high CTS5 of 5 when extended ET was administered additional five than two years. In patients with a CTS5 of 2, no benefit was found when ET was extended to 10 instead of 7 years. Conclusion: The CTS5 is a valid tool for LDR risk stratification in HR + breast cancer, but should be used cautiously for determining benefits from ET extension, as no significant predictive value was found.

Keywords

• CTS5
• Adjuvant setting
• Endocrine therapy
• Predictive value
• Late distant recurrence