Discussion

The risks of underdiagnosis of Lynch syndrome in colorectal cancer patients are significant, but universal testing may not be cost effective. Selective screening strategies include the use of risk prediction models to identify high-risk patients, the Jerusalem guidelines5 (advocating the screening of colorectal cancer patients under 70 years by immunohistochemistry or microsatellite instability analysis) and the revised Bethesda guidelines. The revised Bethesda guidelines are a consensus-based set of criteria requiring clinical and histological data available in most clinical settings. They have largely been adopted in Europe as the screening tool of choice to select colorectal patients at high risk of Lynch syndrome for further assessment.

To our knowledge, this is the first study to analyse the routine use of the revised Bethesda criteria in UK practice. We found no evidence that these guidelines were formally applied to any colorectal cancer patient in either of the two centres assessed during the study period. Although lack of documentation does not equate to lack of consideration, 77% of patients eligible for Lynch syndrome screening did not receive an appropriate follow-up investigation. Family histories were poorly recorded; had they been more accurately detailed, it is likely that even more of the patients would have met the criteria for screening. This may not have guaranteed an appropriate referral for germline testing, however, as the study centres failed to refer all of the patients with a positive screen result.

Of the factors expected to influence patient selection for Lynch syndrome screening, only a record of a family history of cancer appeared to prompt investigation. However, a statistically significant correlation was identified in only one of the two methods used in this study. In any case, the family histories documented were brief and clinically inadequate. Moreover, the patients’ reports may themselves have been inaccurate.6

With positive screen results in the majority of eligible patients who did undergo testing, and no real systematic bias distinguishing those selected for investigation from those who were not, it is likely that many cases of Lynch syndrome were missed. The possibility of a hereditary colorectal cancer was simply not routinely addressed, and, as a result, the medical care of patients and their families was lacking.

This is not purely a matter of surgical teams failing to think beyond the patient in front of them. Each patient assessed in this study would have had their management discussed in a formal multidisciplinary team meeting, a regular forum with representatives from surgical and medical teams as well as their colleagues from radiology, pathology and oncology.7 The management decision—active treatment or palliation, referral to a speciality, or further investigation—is a joint one, with collective responsibility for the outcome. Failure to consider a Lynch syndrome diagnosis is a collective failure, and clearly a common one.

This finding of an ad hoc approach is, sadly, far from unique. Previous work has shown inconsistent uptake of the revised Bethesda criteria in mainland Europe.8 The reasons for this are multifactorial, and include time constraints, a lack of awareness of hereditary cancers, inadequate family history assessment, and patients themselves being unaware of their family histories.9 With this in mind, the deficiencies in practice identified in our two centres are likely to be entirely representative of the clinical reality in other locations around the country. UK clinicians involved in colorectal cancer treatment decisions routinely feel that some other, unspecified clinician should manage their patients with inherited cancer syndromes, and cannot agree which group should take on this professional responsibility (K.J. Monahan, 2013, unpublished data). Again, this supports our assertion that our results are emblematic of a more widespread, chaotic approach to Lynch syndrome management throughout the country.

One may still argue that the revised Bethesda tool is imperfect, failing to identify patients for Lynch syndrome screening who can be diagnosed by other means,10 and that its use is therefore of little consequence. It may rely too heavily on an accurate family history, which can be deceptively difficult to elicit.6 However, these criticisms apply equally to the alternative selective screening strategies, against which it performs well.11 It is also cost effective.12 ,13 Nonetheless, a recent publication advocates a broader screening strategy.14

Risk prediction models, such as MMRpredict,15 PREMM,16 MMRPro17 and MsPath,18 calculate an individual's risk of Lynch syndrome, predominantly using a combination of family history, the patient's age at diagnosis, and the site of the colorectal tumour. There is no agreement, however, on the risk threshold meriting formal screening for Lynch syndrome. Armed with a percentage risk, the clinician is still required to make an arbitrary judgement as to the need for further investigation. As with the revised Bethesda guidelines, reliance on an accurate and comprehensive family history has limited the utility of these algorithms, and the required information is not collected in the current NBOCAP dataset.

Universal screening of all colorectal cancer patients for Lynch syndrome, the real alternative to any selective screening strategy, was initially thought to be unfeasible. Recent work, however, has identified the incremental gains of a universal testing strategy compared to a selective screening tool such as the revised Bethesda criteria,19 at least in a research setting. It is certainly widely recognised that that some mismatch repair gene mutation carriers do not fulfil the Bethesda criteria. However, universal testing is more expensive, and provides—at best—only a modest increase in diagnostic yield.

In practice, however, the main fallibility of the revised Bethesda guidelines comes from the fact that they are simply not used routinely, in the UK or in Europe, despite being upheld as the current standard of best practice. Unless they are systematically incorporated into routine colorectal cancer assessment, a universal screening strategy may be the only one that busy clinicians remember to employ.

Ultimately, the fundamental issue for UK clinicians is not which tool to use for assessment of possible hereditary cancer. It is of paramount importance that a tool is chosen, and then applied consistently and reliably to all patients with newly diagnosed bowel cancer. It is unlikely that universal screening for Lynch syndrome will be adopted in the UK in the near future. We therefore recommend that colorectal cancer multidisciplinary meetings incorporate a revised Bethesda assessment into their routine discussion of each new patient, and that these data be collected as part of the NBOCAP colorectal audit. Making this routine assessment a required quality standard in the evaluation of a colorectal team's performance may be appropriate.