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

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.

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.

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.

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.