Tumour regression after radiotherapy for rectal cancer - Results from the randomised Stockholm III trial

Background and purpose: Neoadjuvant radiotherapy (RT) in rectal cancer induces tumour regression with a possible complete response (pCR). The optimal fractionation and timing to surgery is not established. The Stockholm III trial randomly assigned 840 patients to 5 x 5 Gy surgery within one week (SRT), 5 x 5 Gy with surgery after 4-8 weeks, and 2 Gy x 25 with surgery after 4-8 weeks (LRT-delay). The aim of this substudy was to assess tumour regression and correlation to survival. Material and methods: All available microscopy slides were assessed by one pathologist, blinded to treatment, regarding tumour regression, graded according to the Dworak system (TRG), TNM-stage and other standard histopathology characteristics. Patients' data were collected from the Swedish ColoRectal Cancer Registry. Outcomes were TRG, pCR-rates, overall survival (OS) and time to recurrence (TTR). Results: 318, 285 and 94 patients were included in the SRT, SRT-delay and LRT-delay groups. Median follow up was 5.7 years. There were significantly lower tumour stages after SRT-delay. pCR was seen in 1 (0.3%), 29 (10.4%) and 2 (2.2%) patients in SRT, SRT-delay and LRT-delay, respectively. The pCR and Dworak grade 4 were associated with superior survival. pCR vs no-pCR Hazard Ratio (95% Confidence Interval) OS: 0.51 (0.26-0.99) p = 0.046, TTR: 0.27 (0.09-0.86) p = 0.027. Conclusion: SRT-delay induces pCR in about 10% of the patients and is in this aspect superior to 25 x 2 Gy. A complete tumour response, TRG 4 using the Dworak system, or a pCR, is associated with superior OS and TTR. (C) 2019 Elsevier B.V. All rights reserved.