Adjuvant chemotherapy improves survival outcomes in patients with stage III rectal cancer.1–5 Nodal disease, which distinguishes stage II from stage III disease, is known to be associated with worse survival outcomes, disease recurrence and is an independent marker of poor prognosis.6–10 Nevertheless, the survival benefit following adjuvant chemotherapy for patients with stage II disease is not so clear, and much of the current advice given to patients is based on a combination of historical trial evidence and personal opinion of the treating clinician.
Extramural venous invasion (EMVI) is a known independent tumour factor associated with disease recurrence and metastases.11–13
Despite this, it has not been considered as a risk factor for routine adjuvant chemotherapy. This may be explained partly by the inconsistent definitions of the past, and the variability in pathological detection and techniques.14
However, more recently, magnetic resonance imaging (MRI) has been shown to accurately identify EMVI (mrEMVI), which correlates highly with EMVI detected by pathology.15
It is now recognised as part of the minimum data reporting set for (colo)rectal cancer.16
The current use of adjuvant chemotherapy in stage II rectal cancer varies widely.5
There is no robust randomised trial evidence with regard to novel prognostic factors such as EMVI and outcomes in stage II rectal cancer. It is therefore not surprising that there is such variability in practice. The aim of this study was to explore the variability between clinicians in treating patients with EMVI positive, stage II rectal cancer.
The results of the survey show that EMVI is recognised by both surgeons and oncologists as a prognostic factor, and discussed in almost all MDT meetings. Furthermore, whether it was detected on pathology and/or radiology, it is a consideration in treatment decisions. Nevertheless, oncologists seemed to be more selective in their approach to EMVI. Although this survey did not explore the relative importance of EMVI compared with other prognostic factors, it is notable that it is considered in overall management strategy. A further point highlighted is that most clinicians are now prepared to treat patients on the basis of MRI findings preoperatively. This signals a significant shift in attitude towards risk stratification in the last decade as MRI can now be used confidently to be more selective in terms of which patients should be offered preoperative treatment.
MRI plays a central role in the local staging and risk stratification of patients with rectal cancer in the UK and Europe. Important prognostic factors such as circumferential resection margin involvement and extent of tumour spread into the mesorectum (T3 substaging), which influence treatment decisions, are readily identifiable on MRI.17,18
The standard of care for locally advanced high risk rectal cancer without metastatic disease is preoperative chemoradiation.19
Along with refinement of surgical technique, this has led to significant improvements in local recurrence rates and overall survival.20
Although there has been some debate surrounding the benefit of adjuvant chemotherapy in patients who have already undergone neoadjuvant chemoradiation,21,22
it still forms the mainstay of treatment for systemic disease and the risk of metastases.
The QUASAR trial is the most frequently quoted with regard to adjuvant chemotherapy decisions for stage II tumours and the perceived survival benefit for patients is approximately 3.6%.23
However, the National Surgical Adjuvant Breast and Bowel Project R-01 trial showed a survival benefit in terms of overall survival and disease free survival for patients randomised to chemotherapy over observation or radiation.1
Histopathological staging remains the basis for decision making and it is important that stage II tumours, which may benefit from adjuvant therapy, are identified through high quality pathology reporting.22
The emphasis is very much on the pathologist examining the specimen diligently with appropriate sections to reveal as much information as possible. Quirke et al
have reported extensively on the importance of this.24–26
EMVI is arguably the most debated of these additional risk factors in deciding on oncological treatment. There is little doubt that venous invasion has a prognostic influence but lack of consistent reporting in both pathology and radiology has made it difficult for clinicians to understand its exact clinical relevance. This lack of confidence in accurate detection of EMVI may be one of the reasons why it is not considered as a mandatory treatment factor. Nevertheless, a study by Chand et al
from 2013 has demonstrated the importance of mrEMVI as a potential prognostic (and predictive) imaging biomarker in rectal cancer,27
giving further support to MRI detected tumour characteristics being used for treatment decisions. Furthermore, the importance of EMVI in stage II disease has now been shown on multivariate analysis as a prognostic marker of disease recurrence.28
In the present study, surgeons were more likely to rely on MRI than oncologists for decision making (85% vs 77%) and, specific to EMVI, oncologists were less likely to base treatment on mrEMVI. Despite this, the responses to the clinical scenarios of offering adjuvant chemotherapy to a patient with stage II rectal cancer with evidence of EMVI but no other adverse features and to a patient with no adverse features whatsoever were similar (71% surgeons vs 69% oncologists).
However, while the surgeons were divided equally as to whether the perceived survival benefit was >5% or <5%, 55% of the oncologists thought the benefit was <5% and 33% thought it was >5%. The interesting point is that the QUASAR trial shows that the benefit for patients in receiving adjuvant chemotherapy is 3.6%23
but more than a third of surgeons and oncologists believe the benefit to be >5%. In the second scenario, where there were no adverse features in stage II disease, the surgeons were less likely to offer adjuvant chemotherapy (11%) (a proportion that is consistent with the current literature) than the oncologists (22%), who would offer adjuvant treatment with no obvious evidence base.
One of the limitations of this survey is that there were no detailed explanations from the respondents regarding reasons for decision making. As the results include a degree of subjectivity and are not based entirely on trial evidence, it would have been interesting to understand the rationale behind some of the decisions. It should also be noted that this questionnaire was sent predominantly to UK-based clinicians. The importance and understanding of EMVI as a prognostic factor is more apparent in the UK than in other countries such as the US. Furthermore, the central role of MRI and using it to guide treatment through risk stratification is also more common in the UK, where a more selective approach is taken in the use of preoperative therapy.