De-ESCAlating RadioTherapy in breast cancer patients with pathologic complete response to neoadjuvant systemic therapy: DESCARTES study

Purpose Neoadjuvant systemic therapy (NST) is increasingly used in breast cancer patients and depending on subtype, 10–89% of patients will attain pathologic complete response (pCR). In patients with pCR, risk of local recurrence (LR) after breast conserving therapy is low. Although adjuvant radiotherapy after breast conserving surgery (BCS) reduces LR further in these patients, it may not contribute to overall survival. However, radiotherapy may cause early and late toxicity. The aim of this study is to show that omission of adjuvant radiotherapy in patients with a pCR after NST will result in acceptable low LR rates and good quality of life. Methods The DESCARTES study is a prospective, multicenter, single arm study. Radiotherapy will be omitted in cT1-2N0 patients (all subtypes) who achieve a pCR of the breast and lymph nodes after NST followed by BCS plus sentinel node procedure. A pCR is defined as ypT0N0 (i.e. no residual tumor cells detected). Primary endpoint is the 5-year LR rate, which is expected to be 4% and deemed acceptable if less than 6%. In total, 595 patients are needed to achieve a power of 80% (one-side alpha of 0.05). Secondary outcomes include quality of life, Cancer Worry Scale, disease specific and overall survival. Projected accrual is five years. Conclusion This study bridges the knowledge gap regarding LR rates when adjuvant radiotherapy is omitted in cT1-2N0 patients achieving pCR after NST. If the results are positive, radiotherapy may be safely omitted in selected breast cancer patients with a pCR after NST. Trial registration: This study is registered at ClinicalTrials.gov on June 13th 2022 (NCT05416164). Protocol version 5.1 (15-03-2022).