2 Research recommendations
- 2.1 Treatment of patients with moderate-risk locally advanced rectal cancer
- 2.2 The value of prognostic factors in guiding optimal management in patients with locally excised, pathologically confirmed stage I cancer
- 2.3 The most effective sequence to perform magnetic resonance imaging (MRI and PET-CT) in patients with colorectal cancer metastasised to the liver to determine whether the metastasis is resectable
- 2.4 Follow-up after completion of oncological treatment
- 2.5 Patient-reported outcome measures in colorectal cancer
In 2011, the Guideline Development Group made the following recommendations for research, based on its review of evidence, to improve NICE guidance and patient care in the future. The Guideline Development Group's full set of research recommendations is detailed in the full guideline.
As part of the 2014 update, the Standing Committee made an additional research recommendation on treatment options for stage I rectal cancer. This can be found in the addendum.
The effectiveness of preoperative chemotherapy should be compared with SCPRT, chemoradiotherapy or surgery alone in patients with moderate‑risk locally advanced rectal cancer. Outcomes of interest are local control, toxicity, overall survival, quality of life and cost effectiveness.
Variation exists as to whether or not patients with moderate‑risk locally advanced rectal cancer are offered a preoperative treatment or not. If they are offered treatment, variation also exists as to whether it is with SCPRT or chemoradiotherapy. At present, preoperative chemotherapy, without radiotherapy, is limited to use in clinical trials. Patients with moderate‑risk locally advanced rectal cancer are at risk of both local recurrence and systemic relapse, but the use of either form of radiotherapy carries the risk of significant morbidity, which may affect quality of life. It is therefore important to establish whether better outcomes can be achieved with preoperative chemotherapy or surgery alone, and whether there are groups of patients whose benefit from either SCPRT or chemoradiotherapy is greater than the risk of late effects.
2.2 The value of prognostic factors in guiding optimal management in patients with locally excised, pathologically confirmed stage I cancer
An observational study should be conducted, incorporating standardised assessment of pathological prognostic factors, to assess the value of the proposed prognostic factors in guiding optimal management in patients with locally excised, pathologically confirmed stage I cancer. Outcomes of interest are disease‑free survival, overall survival, local and regional control, toxicity, cost effectiveness and quality of life.
The NHS bowel cancer screening programme is detecting increasing numbers of stage I cancers, but the optimum management for these very early tumours is far from clear. The available studies looking at pathological risk factors have not used standardised features, either in terms of the factors included or the methods of assessment. Furthermore, although some consensus can be reached on the pathological risk factors that lead to poorer outcomes, there is no evidence about how these risk factors might be used to guide subsequent clinical management, particularly when the resection margins are considered to be clear. The therapeutic options are varied and there is no realistic prospect for a successful randomised control trial. Therefore, careful follow‑up of patients whose tumours have been analysed in a standardised way to define specified pathological risk factors, and who have been treated with one of the possible options, could form the basis of an observational study.
2.3 The most effective sequence to perform magnetic resonance imaging (MRI and PET-CT) in patients with colorectal cancer metastasised to the liver to determine whether the metastasis is resectable
A prospective trial should be conducted to investigate the most clinically‑effective and cost‑effective sequence in which to perform MRI and PET‑CT, after an initial CT scan, in patients with colorectal cancer that has metastasised to the liver, to determine whether the metastasis is resectable. The outcomes of interest are reduction in inappropriate laparotomies and improvement in overall survival.
Nearly 7% of all patients with liver metastases from colorectal cancer are now being considered for liver resection with curative intent. These operations are costly and have their own inherent risks, including futile laparotomy, which can be psychologically devastating for patients and carers. After the initial diagnosis of suspected liver metastases on diagnostic or follow‑up CT scan, it is clear that PET‑CT (which is patient‑specific to detect incurable extra‑hepatic disease) and MRI (which is liver‑specific to accurately characterise detected liver lesions) both play roles in the decision algorithm when considering surgery. Both of these investigations are expensive and can lead to delays in starting appropriate treatment. Research is needed to determine the correct sequence of these investigations to reduce the rate of futile laparotomy, improve cost effectiveness of treatment, and ultimately improve overall survival.
Strategies to integrate oncological surveillance with optimising quality of life, reducing late effects, and detecting second cancers in survivors of colorectal cancer should be developed and explored.
Traditionally, oncological surveillance has focused on the early detection of either local recurrence or distant metastases. Although there is increasing evidence that the early detection of such recurrences is worthwhile in terms of subsequent oncological outcomes there are other issues, which are particularly important to patients, that can be detected and managed by appropriate follow‑up. The detection of late effects and impact on quality of life are particularly important and research into reducing the likelihood and managing the consequences of such effects makes this all the more relevant to patients. There are numerous different models of surveillance and research should aim to establish strategies that address patient concerns.
Colorectal cancer‑specific patient‑reported outcome measures (PROMs) should be developed for use in disease management and to inform outcome measures in future clinical trials.
Quality of life and PROMs are now frequently being used as secondary endpoints in clinical trials of cancer management. However, some investigators continue to use non‑disease‑specific generic methodology for this purpose. The treatment of colorectal cancer leads to very specific side effects relating to bowel function and activities of daily living. The Guideline Development Group therefore believes that colorectal cancer‑specific patient‑reported outcome measures should be developed to standardise the interpretation of quality‑of‑life reporting as a secondary endpoint in future clinical trials in colorectal cancer.
You can also see this guideline in the NICE Pathway on colorectal cancer.
To find out what NICE has said on topics related to this guideline, see our web page on colorectal cancer.