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

• Published in: Radiotherapy and oncology Vol. 135; pp. 178 - 186
• Main Authors: Erlandsson, Johan, Lörinc, Ester, Ahlberg, Madelene, Pettersson, David, Holm, Torbjörn, Glimelius, Bengt, Martling, Anna
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.06.2019
• Subjects: Aged; Cancer; Colorectal cancer; Female; Humans; Male; Medicin och hälsovetenskap; Middle Aged; Neoadjuvant radiotherapy; Neoadjuvant treatment; Neoplasm Grading; Neoplasm Recurrence, Local; Neoplasm Staging; Radiotherapy; Rectal cancer; Rectal Neoplasms - mortality; Rectal Neoplasms - pathology; Rectal Neoplasms - radiotherapy; Neoadjuvant radiotherapy; Rectal cancer; Radiotherapy; Neoadjuvant treatment; Colorectal cancer; Cancer
• ISSN: 0167-8140; 1879-0887; 1879-0887
• DOI: 10.1016/j.radonc.2019.03.016

•After neoadjuvant radiotherapy in rectal cancer, patients with complete tumour regression or pathology graded complete response have a significantly better survival and fewer recurrences, compared to patients with less tumour response.•5 × 5 Gy with delayed surgery induces more tumour regression and pCR compared to 25 × 2 Gy.•Overall treatment time must exceed 4 weeks to achieve pCR after 5 × 5 Gy. 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 × 5 Gy surgery within one week (SRT), 5 × 5 Gy with surgery after 4–8 weeks, and 2 Gy × 25 with surgery after 4–8 weeks (LRT-delay). The aim of this substudy was to assess tumour regression and correlation to survival. 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). 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. SRT-delay induces pCR in about 10% of the patients and is in this aspect superior to 25 × 2 Gy. A complete tumour response, TRG 4 using the Dworak system, or a pCR, is associated with superior OS and TTR.