Background: Current guidelines for BC surveillance in asymptomatic pts recommend annual mammography and periodical physical examination. These recommendations arise from two trials conducted in the 1980's: since then no other randomized controlled trials (RCTs) have been conducted on BC follow-up. However our knowledge on BC biology, diagnosis of metastases and treatment has improved. The aim of this prospective RCT is to verify if the serial measurement of CEA and CA15.3 (followed by 18-FDG PET) can anticipate the diagnosis of breast cancer recurrence compared to control arm. If this intermediate end-point will be met a subsequent extension trial will investigate the impact of the earlier diagnosis of distant metastases on survival. Methods: Pts diagnosed with stage I-III BC, who underwent adequate surgery are eligible. Special histologies and low-risk cases according to St. Gallen criteria are excluded. We will include pts at the beginning of the follow-up after the conclusion of primary treatment (cohort 1), and pts that have concluded without relapse the first 5 years of follow-up (cohort 2). Eligible pts will be randomized in a 1:1 ratio to follow-up according to local practice (control arm) or to three-monthly serial dosing of CEA and CA15.3 and subsequent imaging studies (18-FDG PET) only in case of an increase of CEA and/or CA 15.3 greater than a critical difference (CEA +100% and/or CA15.3 +75%) compared to baseline (experimental arm). The following stratification factors will be used: node negative vs positive, HER2 negative vs positive, ER positive vs negative. Eight-hundred pts will be enrolled over 3 years. For such a calculation, we made the assumption of a 20% 5-year incidence of relapse. The target reduction of 3 months in restricted mean survival time (RMST) between the two arms implies a median time of diagnostic anticipation, conditional on having breast cancer recurrence, of 10 months. The follow-up will continue until 10 years from surgery. The first patient was enrolled on 23rd October 2014, up to now 434 pts have been enrolled. The present trial was approved by the Ethical Commitee of S. Orsola-Malpighi Hospital and is registered on (NCT02261389).

Citation Format: Zamagni C, Gion M, Mariani L, Stieber P, Quercia S, Rubino D, Bernardi A, Cacciari N, Fini A, Lenzi M, Minichillo S, Pizzirani C, Pagliaro M, Tomasini S, Barbieri E. Three-monthly dynamic evaluation of CEA and CA15-3 (followed by 18-FDG PET) vs usual practice in the follow-up of early breast cancer (BC) patients (pts): A prospective randomized trial (KRONOS-patient-oriented new surveillance study, Italy) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT3-05-01.