Based on the ability to distinguish between areas of residual cancer and treatment induced fibrosis after neoadjuvant treatment, a 5-tier MRI-based (mr)TRG system that follows the principles of the pathological (p)TRG system previously proposed by Dworak has been developed for RC. However, limited data exist regarding the correlation between mrTRG and pTRG, and the prognostic value of mrTRG in patients who are assessable for pTRG is unclear.
mrTRG, as assessed by a radiologist according to Patel et al (J Clin Oncol 2011), and pTRG, as assessed by a pathologist according to Dworak et al (Int J Colorect Dis 1997), were compared in MRI-defined, high-risk, locally-advanced RC patients from two phase II trials (EXPERT and EXPERT-C). All patients had received an intensified neoadjuvant treatment with induction chemotherapy followed by chemo-radiotherapy. The agreement between radiologist and pathologist was assessed with the weighted κ test while the Kaplan-Meier method was used to estimate survival outcomes.
191 patients who had undergone neoadjuvant treatment and surgery with a curative intent were included. Median time from completion of neoadjuvant treatment to pre-operative MRI and surgery was 4.1 weeks (interquartile range [IQR]: 3.7-4.7) and 6.6 weeks (IQR: 5.9-7.6), respectively. Fair agreement was found between mrTRG and pTRG when regression was classified according to standard 5-tier systems (κ = 0.24) or modified 3-tier systems (κ = 0.25). After a median follow-up of 65.5 months (95% CI: 65.1-66.2), survival outcomes of patients with intermediate pathological regression (pTRG 2) were numerically better if good/complete regression was also observed on imaging (mrTRG 1-2) compared to poor regression (mrTRG 3-5) (5-year recurrence-free survival 76.9% versus 65.9%, p = 0.18; 5-year overall survival 80.6% versus 68.8%, p = 0.22).
Only fair agreement was found between mrTRG and pTRG which suggests that these parameters may represent biologically distinct phenomena. Assessing tumour regression on pre-operative MRI may provide complementary prognostic information to pTRG and help to refine stratification of RC patients after surgery.
Clinical trial identification
Legal entity responsible for the study
The Royal Marsden NHS Foundation Trust
National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research. The EXPERT study was supported by a fellowship grant from the Pelican Cancer Foundation and by an education grant from Sanofi-Aventis which also provided the study drug. The EXPERT-C trial was endorsed by Cancer Research UK and was supported by a research grant from Merck & Co. Sanofi-Aventis and Merck & Co. provided the study drugs.
D. Cunningham: Research funding from Roche, Amgen, Celgene, Sanofi, Merck Serono, Novartis, AstraZeneca, Bayer, Merrimack and MedImmune. C. Peckitt: Advisory roles with Sanofi. I. Chau: Advisory roles with Merck Serono, Roche, Sanofi Oncology, Bristol Myers Squibb, Eli-Lilly, Novartis, Gilead Science; research funding from Merck-Serono, Novartis, Roche and Sanofi Oncology; honoraria from Roche, Sanofi-Oncology, Eli-Lilly, Taiho. All other authors have declared no conflicts of interest.