The SURVIVE study: Liquid biopsy guided surveillance after intermediate- to high-risk early breast cancer.

TPS620 Background: Current guidelines limit routine breast cancer (BC) follow-up to clinical examinations and breast imaging. This is based on the results of two large cohort studies conducted in the 1980s that showed no improvement in overall survival (OS) by an intensified screening for distant metastases. Thus, imaging for distant metastases should currently only be performed in patients with specific symptoms. To detect distant relapse in a pre-symptomatic stage, we suggest the evaluation of a liquid biopsy-guided intensified surveillance, analyzing tumor markers (CA 27.29, CA 125 and CEA), circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA). Methods: Funded by the German Federal Ministry of Education and Research, the SURVIVE study is the first large, randomized BC surveillance trial to investigate the potential survival benefit of a liquid biopsy guided follow-up care in intermediate- to high-risk early breast cancer patients. The trial is a German multicenter, controlled phase 3 superiority study, in which 3500 patients are randomized in a 1:1 ratio to standard vs. liquid biopsy guided intensified follow-up care. Eligible patients are adults with confirmed primary invasive intermediate to high-risk early BC, defined as an indication for (neo-)adjuvant chemotherapy, and/or large tumor size (> 50 mm), and/or positive lymph nodes (≥ pN1mi), and/or high grade (≥ G3). Primary anti-tumor therapy (surgery, adjuvant chemo- or radiotherapy) must have been completed previously. Patient enrollment during adjuvant endocrine, antibody- or targeted therapy is allowed. The total study duration is 144 months. Stratification factors are study site as well as HR-, HER2- and nodal status at surgery.Both study arms receive standard follow-up according to national guidelines, and the intensified surveillance arm will be tested for standard tumor markers, CTCs and ctDNA via tumor-informed approach (RaDaR assay). Pre-specified abnormal findings of any of the liquid biopsy markers indicative of minimal residual disease trigger complete staging. In the event of confirmed disease recurrence, guideline-based treatment follows, otherwise, liquid biopsy testing continues. If applicable, study participants may enter interventional trials. Statistics:The two primary objectives are to determine whether intensified, liquid biopsy-guided surveillance leads to better OS or an overall lead-time effect, compared to standard surveillance. OS will be analyzed in the ITT population using Kaplan Meier methods and cox regression models, the overall lead time effect is a purely descriptive composite measure. Secondary objectives include IDFS, DDFS, DRFS, BCSS and quality of life (QoL). Aims: We propose a liquid biopsy guided follow-up method, with high sensitivity and specificity for the earlier detection of distant (oligo-)metastases, to enable earlier initiation of therapy. Clinical trial information: NCT05658172 .