Factors that influence treatment delay in patients with colorectal cancer

A prospective study was performed of patients diagnosed with colorectal cancer (CRC), distinguishing between colonic and rectal location, to determine the factors that may provoke a delay in the first treatment (DFT) provided. 2749 patients diagnosed with CRC were studied. The study population was recruited between June 2010 and December 2012. DFT is defined as time elapsed between diagnosis and first treatment exceeding 30 days. Excessive treatment delay was recorded in 65.5% of the cases, and was more prevalent among rectal cancer patients. Independent predictor variables of DFT in colon cancer patients were a low level of education, small tumour, ex-smoker, asymptomatic at diagnosis and following the application of screening. Among rectal cancer patients, the corresponding factors were primary school education and being asymptomatic. We conclude that treatment delay in CRC patients is affected not only by clinicopathological factors, but also by sociocultural ones. Greater attention should be paid by the healthcare provider to social groups with less formal education, in order to optimise treatment attention.


INTRODUCTION
Colorectal cancer (CRC) is a major public health problem, with major impact on morbidity and mortality. It is the second most prevalent malignancy worldwide, and is also second in incidence and mortality in most developed Clinical Research Paper www.impactjournals.com/oncotarget together with diagnostic and therapeutic advances, the this situation is placing great pressure on the cancer care diseases as a public health problem.
Early diagnosis of cancer and hence early treatment is a fundamental objective in cancer care procedures. Although delays attributable to the health system constitute a small proportion of the biological life of a to diagnosis or from diagnosis to treatment) may provoke stress and decrease the patient's quality of life. In fact, delays in initiating treatment are the leading cause of While some studies indicate that treatment delay negatively affects the prognosis of patients with cancer, particularly CRC, others have found no such association attributable to tumour factors such as clinical stage and location, and not only to the health system, such as hospital admission procedures. The impact of treatment own behaviour, the clinical course, the functioning of the Taking into account the dearth of prospective studies designed to analyse treatment delay, with large cohorts of patients and distinguishing between colonic and rectal tumours, in this study we evaluate the degree to which conditions of patients and by the clinical and pathological characteristics of the tumour.

Descriptive analysis
from the study because it was not possible to determine clinicopathological characteristics of the study population

Treatment delays and types of treatment
For all tumours, the most common initial treatment chemotherapy were also the most common treatment A histogram showing the distribution of treatment treatment administered and by tumour location, there was a higher frequency of delay for surgical treatment for the other treatment strategies.

Relation between treatment delay and the patients' sociodemographic and clinicopathological characteristics
In our analysis of the relation between the presence of DFT and each of the sociodemographic variables, DFT in patients with cancer of the colon were male sex, most relevant tumour characteristics were small local extension and the absence of nodes, of metastasis and of perineural invasion. Treatment delays in patients with tumours presenting normal values for carcinoembryonic among patients presenting abnormal values for these parameters. Finally, the treatment delay in patients who had received prior screening was greater than among a higher level of DFT were primary studies or no formal education, being asymptomatic and having had prior After adjusting for variables found to be statistically revealed the following to be independent protective factors against increased DFT: having university studies, for colon However, DFT was greater in the patients with colon cancer

DISCUSSION
Our study highlights the existence of delayed www.impactjournals.com/oncotarget Unlike other studies on diagnostic and treatment delays in patients with CRC, our study population is distributed according to the location of the tumour (colon greater for rectal tumours, as was also reported in the treatment was surgery, but not when it was chemotherapy or radiotherapy. This association is consistent with the in surgical treatment for advanced stage (according to the Dukes system) rectal tumours, but not for tumours of advanced rectal tumours, and unlike for colon cancer, other diagnostic tests are required prior to treatment, such as pelvic magnetic resonance imaging and rectal endoscopic the two types of cancer was the relationship between DFT only observed in patients with rectal cancer and moderate to severe symptoms, compared with mildly symptomatic and alarming symptoms resulting from rectal tumours, subacute ones provoked by colon tumours, lead patients with rectal cancer to seek a medical consultation at an circuit. The physician prescribing the treatment will probably give preference to symptomatic patients, who are at increased risk of presenting complications from the tumour and therefore have a worse prognosis. It should also be taken into account that some patients with advanced tumours do not state the actual date of onset of their symptoms, or minimise it, due to a feeling of guilt at not having consulted the doctor sooner, and this too can Studies of CRC have evaluated the relationship between tumour stage and diagnostic and therapeutic delays, and have found no association between these that the DFT is shorter for patients presenting advanced www.impactjournals.com/oncotarget

<0.001
Delay before surgery

0.235
Delay before radiotherapy

1.000
With or without radiotherapy

Currently in work
Yes

Smoking habit
Current smoker studies have shown that advanced rectal tumours present an increased risk of DFT, in comparison with the initial stages, while no such differences were found for cancers advanced stages, but only in tumours of the colon. This difference might arise from the lower priority assigned are usually less apparent and hence delay the start of the therapeutic process. In a study of breast cancer, our group evaluated the different periods of delay, noting that higher tumour stages were associated with a shorter DFT, time. This outcome is probably produced by the priority granted by doctors to patients whose symptoms are more greater delay is associated with decreased survival time. This inverse correlation between treatment delay and survival has been described previously in studies of the In our analysis of clinicopathological characteristics with known prognostic value and associated with increased tumour aggressiveness, the degree of histological differentiation and of lymphovascular invasion presented no relation to DFT. However, they were found to be related to distant metastases, lymph node involvement, perineural invasion and elevated tumour markers, all of which decrease the risk of severe DFT. However, when a multivariate analysis was performed, and other variables were taken into account, these differences did not persist, probably because the variables in question are more dependent on the biological behaviour of the tumour

Surgery
Chemotherapy Radiotherapy and on its intrinsic aggressiveness than on the period of treatment delay, as suggested by Symonds in a study of between the presence of more aggressive features and a include the non expression of hormone receptors, or non response to hormonal treatments in tumours that do treatment may be expedited when the physician is aware Among the sociocultural factors analysed, the lack of formal education or only having had primary rectal and colon tumours. Interestingly, this association, which has not received much previous research attention, explanation for this might be that these patients do not therapy process, and may also fail to keep the medical to be undertaken. This population group, with a low cultural level, might also delay the start of treatment for from them. This possibility was raised in a recent study in which DFT was associated with a lack of knowledge of symptoms suggestive of cancer, and with the patient's unwillingness to visit the doctor, among other factors population groups, with unhealthy living habits and a low this respect, a retrospective study was conducted to obtain an ecological estimation of the socioeconomic status of such relationship with DFT or with diagnostic delay was found, although it should be noted that this study included Retrospective studies have evaluated social factors and/or elderly patients with rectal cancer were subject to unmarried patients were found to be most subject to this delay. Other studies evaluating prehospital delay have also found that lower socioeconomic level and lower education Another feature of our population which the univariate analysis showed to be associated with increased colon cancer. This relation would be explained, in part, by the complication of abdominal examination in the presence of a large pannus. One of the main causes of obesity in the West is an unhealthy living habit in terms independent predictor of treatment delay. The remaining have more limitations of the respiratory function and require a larger number of tests before surgery. On the other hand, a patient who gives up smoking will probably believe him/herself at less risk of serious disease than a communication with the doctor after diagnosis. In this Our results show that a prior positive screening, in which faecal occult blood is detected, is associated not been reported in previous studies. A priori, it seems illogical that a patient who has received CRC screening before any treatment is undertaken should suffer a delay for this reason. However, probably due to the person's asymptomatic state at the time of the consultation, no preference is expressed (unlike the case of a patient with manifest symptoms and at increased risk of complications from the tumour, requiring prompt treatment).
confounding and of interaction with the other variables, and always obtained the same relationship between prior model (data not shown).
Although it has been shown that delayed diagnosis and treatment does not appear to increase the risk of death in patients with symptomatic CRC, among the asymptomatic population early diagnosis and treatment The results presented should be considered with caution, and are subject to further analysis to determine whether, in the screened population, the greater delay observed impacts on survival.
The delay before cancer treatment is started is an important factor to be evaluated. This delay, which is a criterion of health care quality, should be prevented and reduced as far as possible in order to avoid the psychologically negative impact it may cause to patients. associated with certain clinical factors in CRC, but the not only on clinicopathological characteristics of the also on sociocultural characteristics of the population. We conclude, therefore, that more attention should be paid to health education regarding the initial symptoms related to this disease, especially among less educated social groups. The physician responsible for the patient's treatment, too, must be aware that these patients require special attention. www.impactjournals.com/oncotarget Finally, more multicentre studies should be conducted, in other countries and where different healthcare plans are used, in order to generalise the research would be to determine whether treatment delay also impacts on survival, as this association has not been

Study design
This prospective, multicentre observational study was six regions of Spain (Andalusia, Canary Islands, Catalonia, The patients were recruited prospectively and consecutively at each of the participating hospitals population included patients diagnosed with new colon or urgently or scheduled. All patients were included, whether or not they had previously received treatment, and a follow directly from patients and also from their medical history. treatment, in accordance with national guidelines and be surgery, chemotherapy, radiotherapy, biological therapy or best supportive care. Date of diagnosis was the date when this coincided with the date of the intervention. In this case, The anatomical location of the tumour and the The following inclusion criteria were applied: The exclusion criteria were: rectum in situ. patient from answering the questionnaires.

The project was evaluated by the corresponding Research Committees and Clinical Research Ethics
Committees at the hospitals. Informed consent was requested of the patients before surgery. Current legislative requirements regarding personal data (any information were followed at all times. All personal data were processed in such a way that the information obtained

Study variables
Data were compiled regarding the patients' medical history: Sex, age, body mass index, prior screening, date (surgery, chemotherapy, radiotherapy, biological therapy or best supportive care). The date of diagnosis was taken as the presence of cancer, was issued, except patients treated at date of diagnosis the suspected diagnosis date. The following laboratory and pathological factors were also recorded: tumour location (rectum or colon), degree of histological perineural invasion, presence of metastasis, status of tumour markers such as carbohydrate antigen (CA) 19-9 and serial patient: family history of colorectal cancer and other tumors, marital status, occupation at the time of the study, surgery, date of onset of symptoms.

Statistical design
A descriptive analysis was performed, with measures of central tendency and dispersion for the quantitative variables and frequency distributions for the qualitative ones. Differences were determined by bivariate analysis, segmenting by type of tumour and qualitative ones. Finally, the treatment delay variable was used to perform a multivariate logistic regression analysis,

ACKNOWLEDGMENTS
This research was partially supported by grants from Regional (FEDER).