The main findings of our study
The use of FIT in symptomatic patients is associated with a better prognosis in CRC. Three-year survival was greater in the CRC group diagnosed after a positive FIT (72% vs 59%). The rate of early-stage disease was also higher in this group (51.3%) than in the group 2 (45.5%). Nonetheless, this test is still not widely used in primary care consultations in our region (having been requested for only a fifth of all symptomatic CRC patients).
There is already evidence that FIT is a useful tool for the diagnosis of CRC that helps to identify symptomatic patients requiring early colonoscopy [4,5,6,7, 17]. In fact, the diagnostic guidance (DG30) of the National Institute for Health and Care Excellence (NICE) and other clinical practice guidelines recommend its use for the assessment of patients with lower gastrointestinal symptoms [2, 15]. Despite this, according to our results, the FIT had been used as a diagnostic tool by general practitioners only in 20.7% (n = 317) of all the cases of CRC diagnosed in symptomatic patients, and only 18.3% (n = 279) of cases of CRC were diagnosed after a positive FIT. These figures demonstrate the low rate of adoption of this recommendation in our setting. In our health system, the FIT has been rolled out progressively in parallel with the screening programme initiated in 2009; however, its rate of adoption in primary care has been uneven and generally poor.
On the other hand, although the recommendation to use FIT is widely accepted, there are no data concerning whether this strategy improves patient survival. Our study indicates a better prognosis in CRC diagnosed after a positive FIT. In these cases, the disease was diagnosed at a localised stage in 51.3% of cases (vs 45.5% in the other group) and the 3-year survival was significantly greater (72% vs 59%), despite the fact that a higher percentage of those with a positive FIT were over 70 years of age.
One of the factors that may explain the better prognosis in CRC after a positive FIT is the shorter time to diagnosis. If patients who seek medical attention with unspecific symptoms undergo a FIT, rather than just having their condition monitored, it would be possible to reduce the time to diagnosis, on the one hand, because FIT has been carried out early, and on the other, because if the test is positive the patient is referred for urgent colonoscopy. In our study, we found that 75.1% of patients with CRC detected after a positive FIT were diagnosed within 3 months (from the FIT test results to histological diagnosis). It is already known that repeat primary care consultations lengthen the time to diagnosis [18, 19] and that diagnostic delay is one of the most important factors in terms of survival [20]. In this context, a FIT may be helpful in that it speeds up decisions on the clinical management of these patients. Another explanation would be that patients at more advanced stages have more severe symptoms and that, in these cases, general practitioners refer them directly to a gastroenterologist or even a hospital emergency department, while when symptoms are milder, and given the simplicity of the FIT, the test is requested to rule out the presence of CRC with certainty. Finally, it could be that some of these positive FIT are result of opportunistic screening because in 33,3% of performed FIT the reasons for requesting FIT were not registered.
Strengths and weaknesses of our study
The greatest strength of this research is that it is the first study that analyses the impact of the use of FIT on CRC survival in symptomatic patients, compared to other patients with CRC. To our knowledge, no previous studies have analysed whether the use of FIT in consultations, as a diagnostic test for symptomatic patients, has changed prognosis in CRC. Further, we should highlight that the study was carried out at population level. We identified all the patients with CRC from a registry of tumours at Donostia Hospital in the period 2009–2016, and we selected all the patients in the catchment area of the Donostialdea Integrated Healthcare Organisation. On the other hand, few studies have analysed, among all cases of CRC, the percentage detected by different routes and impact of route to diagnosis on prognosis in this disease.
Nonetheless, we recognise that our study has some limitations. Since it was a retrospective study, we were not able to assess patient comorbidities or other risk factors such as personal or family background. We do not know which factors related to patients or doctors could influence the decision of requesting the FIT or not. We were not able to determine accurately how group 2 patients were diagnosed (through the emergency department, inpatient wards or primary care consultations) or the time between symptom onset and diagnosis. Therefore,we have some limitations of making conclusions on causality because there may be biases in estimates due to residual confounding.
Our study compared with other research
Our data reflect that, as observed in other studies, the incidence of CRC is higher in men and at older ages, CRC being uncommon in under-55-year-olds (3.3%). The most common site is the distal colon and the most common histological type is adenocarcinoma.
According to our results, only 22.4% of all cases of CRC are detected in population screening. Most cases of CRC are detected in symptomatic patients. A study in Scotland found that 18% of cases of CRC were detected in population screening [21]. Unlike the Scottish programme, which used a guaiac-based test, in the Basque Country, the population screening programme is based on the FIT. Here, there is a high participation rate (69%), exceeding that recommended in European guidelines (65%), and 92% of those referred agree to colonoscopy, and despite this, 53% of cases of CRC detected in the screening-eligible age range (50–69 years) were diagnosed in symptomatic patients. This implies that we need to further increase the rate of participation in population screening. On the other hand, according to our data, 15.4% (304) of all the cases of CRC were diagnosed in individuals between 70 and 75 years old, and 55.1% of these had advanced-stage disease. According with others studies which show a high incidence of CRC in patients with more than 74 years [22], in order to improve the screening program, it is pivotal to consider the screening in the elderly. Therefore, we believe that if we extended the upper age limit for the screening programme, we would be able to increase the percentage of diagnoses made at earlier stages of the disease, and in turn, improve survival. It is already known that population screening programmes for CRC are associated with a reduction in mortality due to CRC [10, 11].
On the other hand, although FIT has a very high diagnostic accuracy for detecting CRC, [3, 8] in our study, we detected 49 cases of CRC in patients who had had negative FIT in the 24 months before the diagnosis. Therefore, these results indicate, in line with meta-analyses [12, 13, 23], that FIT is not a diagnostic test by itself but it is rather a diagnostic support tool that should be used together with clinical assessment of patients.
Various studies in the literature have described the clinical characteristics of interval cancers within screening programmes [24], but to our knowledge, none have analysed the clinical characteristics of cases of CRC in symptomatic patients who have had a negative FIT result. In our study, patients with CRC who had had a negative FIT were more likely to have disease in the proximal colon and at stage III, and to be a woman. Nonetheless, we did not observe statistically significant differences in survival, despite 57.1% of the patients being diagnosed at an advanced stage. These clinical characteristics are similar to those of interval cancers from population screening programmes [25]. Such tumours have often been found in patients with genetic abnormalities linked to Lynch syndrome, which is associated with a better prognosis. Nonetheless, our results are limited by the relatively small sample size. Further studies are required to confirm these results.
Implications for clinicians and managers
The FIT is useful as a simple, cheap diagnostic test that can be requested by primary care doctors and it is recommended by guidelines for the assessment of patients with digestive symptoms [2, 13]. It serves to select patients who should be referred for urgent colonoscopy [26] and together with a patient’s medical history and a physical examination allows significant colorectal disease to be ruled out, avoiding unnecessary colonoscopies [27, 28]. Moreover, some research has shown that if a FIT is used, along with other parameters such as age and gender (FAST score), rather than the criteria proposed by NICE, 42% more cases of CRC are detected [29]. Recent reports have shown that FIT is considered the most important parameter for the detection of CRC, among all the factors that are usually taken into account [30].
On the other hand, the better survival observed in our study in cases of CRC detected after a positive FIT suggests that it may be a useful diagnostic tool for the early detection of CRC. Given all these factors, it seems that this test should be more widely adopted in routine clinical practice, above all considering how little it is currently used by primary care doctors.
Nonetheless, there is a need for further research with larger samples sizes to confirm our results and, if they are confirmed, investigate the factors underlying the better prognosis.