Using the magnetic resonance tumour regression grade (mrTRG) as a novel biomarker to stratify between good and poor responders following chemoradiotherapy in rectal cancer: a multicentre randomised control trial.
Almost half of all patients diagnosed with rectal cancer are offered chemotherapy and radiotherapy (CRT) before surgery. There is great variability in how each tumour responds to this treatment. We know this by looking at the cancer specimen after the surgery. Some tumours completely respond to chemoradiotherapy and no cancer cells can be found in the cancer specimen. Other tumours do not respond at all or occasionally continue to grow during treatment. Unfortunately despite digital rectal examination, endoscopic assessment (telescopic examination of the inside of the bowel), MRI and other imaging, there is currently no reliable way of knowing this before surgery.
In many hospitals patients receive an MRI scan before and after treatment (CRT). Unfortunately at the moment there is little evidence that the MRI scan performed after treatment is useful or reliable. The current recommendations are not to use the post-treatment MRI for decision-making but to plan treatment using the baseline (pre-treatment) MRI alone. We don’t know whether the post-treatment MRI scan is valuable to patient management. On the one hand we may be putting patients through the stress, noise and expense of an MRI scan but on the other it may be possible to gain valuable information about how the tumour has responded to treatment.
Emerging evidence suggests that by viewing the MRI scans in a smarter way it may be possible to assess how the tumour has responded to treatment. This ‘smarter’ non-invasive technique is called the ‘mrTRG’ (MRI Tumour Regression Grade).
The TRIGGER trial aims to evaluate whether the post-treatment MRI is worthwhile and if it can be used to evaluate response to treatment. In the ‘control’ arm patients will receive the best current practice, which means treatment based on the baseline MRI, along with optimal clinical assessment. In the ‘intervention’ arm patient care will be based on the ‘mrTRG’. Broadly patients in the intervention arm will receive treatment according to a good or poor response to treatment.
If the mrTRG shows a good response (mrTRG 1&2):
In a ‘good response’ the tumour may shrink to the extent that no cancer cells are detectable and surgery may not be needed. This can lead to deferral of surgery. Rectal cancer surgery is a major undertaking and may lead to a life-long stoma, deferral of surgery is appealing because it avoids the need for such things. However the long-term management, safety and the frequency of follow-up remains uncertain. Therefore deferral of surgery should only be offered in the context of a trial or study.
In the trial, the clinician will discuss the options between surgery and deferral of surgery with the patient and the patient may consent to their preferred option.
If the mrTRG shows a poor response (mrTRG 3-5):
Patients with a tumour that has shown little or no response have a high risk of recurrence and a worse overall prognosis. By detecting these poor responders before surgery, we plan to offer additional therapy in the hope that a response can be achieved which in turn should improve the patients prognosis.
Led by Professor Gina Brown (Radiologist) and Mr Nick Battersby, this study will assess the feasibility of using the ‘mrTRG’ test to guide pre-surgical treatment. The primary aim of the study is to improve overall survival in rectal cancer.
The trial is currently open and recruiting patients, with several more centres due to join the study in the very near future. For further information on TRIGGER, please contact Xian van Gelder on email@example.com.