Systemic chemotheRapy and the liVEr-fiRSt approach compared to index colorectal resection for colorectal cancer presenting with synchronous liver metastases (the RVERS trial)

Is there disease-free survival 12 months after enrolment into protocol with the new "reverse" approach to the management of patients with colorectal cancer with synchronous liver metastases compared with classical management

1. Disease progression in patients who are not disease-free at the end of protocol:
The most sensitive measure of change is likely to involve a metric incorporating tumour size. There is evidence that CT-based volumetric assessment of metastases (seeded region growing method, slice-based segmentation or threshold-based segmentation) is more accurate for assessment of disease progression than the RECIST 1.1 method of largest axial diameter. It is acknowledged that although RECIST criteria provide an objective means of assessment of solid tumour response to treatment, there is a risk of inter-observer bias. Further, RECIST criteria may be insufficient to assess response to treatment in patients with colorectal liver metastases treated by biologic agents such as bevacizumab. Thus, disease progression at end of protocol will be assessed by RECIST 1.1 criteria and compared to volumetric assessment.
2. Timelines for completion of treatment protocol:
This is defined as the amount of time in days from enrolment to completion of full protocol. In the reverse protocol, patients may complete the protocol without rectal cancer resection if there is a complete oncological response and a watch and wait policy is adopted.
3. Failure to complete treatment protocol:
This is defined as drop-out prior to completion of allocated arm. It will be further categorised as due to disease progression, patient choice or un-related to colorectal cancer (for example myocardial infarction) and will be recorded as the timepoint in days from enrolment.
4. Resection margin status:
R0 bowel resection and R0 liver resection (no residual cancer status after colorectal resection and after liver resection).
5. Complication and treatment-related morbidity profiles:
Complications will be recorded prospectively according to the criteria defined above (see treatments) and assessed at the end of the study. Complication profiles in patients in the reverse arm will be compared to those in the classic arm. The morbidity associated with each intervention step will be recorded separately. Morbidity will include unplanned re-admission and re-operation rates. Requirement for non-elective surgery for colonic complications (obstruction, perforation, bleeding) will be recorded. Resection margin status for both colorectal and liver resection will be recorded.
6. Avoidance of stoma after colorectal surgery:
Use of stoma (either temporary or permanent) will be recorded.
7. Mortality:
Overall and cancer-related mortality in either arm after enrolment will be recorded. All-cause mortality will be determined using the Demographics Batch Service (DBS) to access the national electronic database of the UK NHS (National Health Service).
8. Cost of care:
Health service costs in either arm will be assessed.
9. In-patient and critical care occupancy:
A record will be made of in-patient and critical care occupancy associated with intervention.
10. Quality of life:
Quality of life will be assessed using the European Organization for Research and Treatment of Cancer QLQ-LMC21 questionnaire which has been validated for assessment of patient-reported outcomes during treatment of colorectal liver metastases. The questionnaire will be completed by patients at time of enrolment and after completion of protocol.