Although the DoH Guidelines aimed to identify 90 per cent of CRC patients as they presented to their GP, the literature identified by this paper indicated that only 10.3 per cent were eventually diagnosed with CRC. This figure is based on the assumption that all TWR referrals were appropriate. Less than a quarter of all CRC patients had been referred using the TWR, the same proportion had been referred as emergency cases and just over half of all CRC patients diagnosed during the time of the studies had been referred using alternative routes. There was no evidence to indicate any significant improvement in detecting CRC at an earlier stage in CRC patients referred using the TWR compared to those referred by alternative routes.
This paper reviewed all relevant peer-reviewed evidence from studies performed after 2000 reporting on the impact of the TWR. There was a limited amount of peer-reviewed literature in this field, with only 12 publications meeting our inclusion criteria, and only eight of these reporting comparable datasets. A single researcher assessed the literature, but the tight focus on the inclusion and exclusion criteria should have reduced any bias in the selection of eligible studies. As far as we are aware, no other evaluation of the literature in this field has been performed to date.
Our assessment of the guidelines was based on calculating the percentage of TWR-referred patients eventually diagnosed with CRC from all the studies and determining a weighted average. We also compared the proportion of CRC patients referred by the TWR compared with alternative routes into secondary care using weighted averages calculated from the original papers.
The low number of CRC patients identified following a TWR referral suggests that the Guidelines were not as effective in identifying CRC patients as they presented to their GP as was hoped. This may be explained by GPs referring patients who did not conform to the Guidelines, possibly due to the incorrect interpretation of the Guidelines or to intentionally speed up diagnoses in low-risk patients where the routine waiting list was too long.
The studies identified reported that the proportion of CRC patients diagnosed by alternative routes (excluding emergencies) was more than double those referred using the TWR. These patients may not have exhibited any of the high-risk symptoms specified by the Guidelines, or they may have been internally referred following radiological or pathological investigations from within secondary care, where the TWR cannot be applied. Alternatively, it may be the result of the referral practices of GPs . These high numbers of non-TWR referrals are cause for concern and the TWR referral methodology may need to be changed to capture these CRC patients.
Almost a quarter of all CRC patients were diagnosed following an emergency referral, although we were unable to determine whether the source of their referral was primary or secondary care. The majority of CRC patients diagnosed following this route could not have been diverted onto the TWR route if they presented with "emergency" symptoms in need of immediate treatment, especially if they presented to A&E instead of their GP.
The TWR did not result in CRC patients being diagnosed at an earlier, more treatable stage of their disease. This could be because patients correctly referred using the TWR Guidelines need to exhibit high-risk symptoms indicative of later stage CRC, whilst early stage CRC patients may not have any alarm symptoms and may have been referred using alternative routes.
Although CRC lacks any highly specific symptoms , Selvachandran et al have successfully used a patient questionnaire to prioritise CRC referrals . The studies identified in this review have shown that compiling highly specific Guidelines for symptomatic CRC patients using TWR referrals without compromising on their ability to detect early CRC can be problematic [8, 10, 13, 14]. A literature search performed by Hamilton and Sharp concluded that the DoH Guidelines were based on a reasonable evidence base  but the studies identified for this paper indicate otherwise, although it is worth noting that TWR referrals were assumed to be appropriate in accordance with the Guidelines. Research into the positive predictive value of CRC symptoms in the UK population is ongoing  to improve the sensitivity and specificity of the Guidelines, although the revised TWR referral Guidelines by NICE , published in 2005, are almost identical to the original DoH Guidelines and so, are not likely to increase the proportion of CRC patients diagnosed using the TWR.
The TWR was rapidly implemented throughout NHS cancer diagnostic services with no pilot studies done to indicate potential problems. Both primary and secondary care services had to cope with the new referral protocols and their subsequent impact on services. We would question whether the TWR has had any positive effect on the identification of CRC patients at an earlier stage of their disease. To address this, we recommend that the TWR and the revised NICE Guidelines should be officially evaluated by an independent group to determine whether there is any subsequent increase in the identification of CRC patients, accompanied by an improvement in the cancer stage at diagnosis to make the TWR worthwhile. A small scale evaluation has already been successfully established  and could be used as a basis for a nationwide study. We also recommend that the new NICE Guidelines be made compulsory for all GPs and that TWR referral documentation is standardised so that comparisons can be made during any evaluations.