Introduction
Each year, more than one million patients are diagnosed with colorectal cancer (CRC) worldwide and approximately 3% have Lynch syndrome [
1]. Identifying Lynch syndrome is highly relevant, because surveillance reduces morbidity and mortality in family members who carry a mutation in one of the mismatch repair genes [
2]. Patients at risk for Lynch syndrome can be detected effectively with a microsatellite instability (MSI) test, which is a molecular genetic test on CRC tumour DNA [
3‐
6]. In Lynch syndrome, almost all CRCs show high (positive) MSI.
In patients diagnosed with CRC at a relatively young age, a positive MSI test is strongly associated with genetic susceptibility [
7] and can therefore be used as an indicator for Lynch syndrome. Generally, patients with an MSI-positive tumour have good overall prognoses [
8,
9]. In the past, people underwent MSI testing after referral to a clinical genetic department, because of multiple CRCs in the family. However, only a minority of patients with Lynch syndrome were identified by their family history [
10‐
13]. A new cost-effective and efficient test (MSI-testing-indicated-by-a-Pathologist (MIPA) procedure) [
5,
14,
15] has enhanced the recognition of patients at risk for Lynch syndrome [
5,
14,
15]. Pathologists perform MSI testing on recently diagnosed patients if they meet one of the following MIPA criteria: (1) CRC diagnosed before the age of 50 years; (2) second CRC diagnosed before the age of 70 years [
5,
16,
17]. The MSI test result is reported to the surgeon. If the result is positive, the surgeon is advised to consider referring the patient for genetic counselling, which might include germline DNA analysis. One year before the introduction of the MIPA procedure, only 30% of patients at risk for Lynch syndrome were recognized as such by the traditional method based on family history [
18]. Other studies also reported that family history did not adequately identify patients at risk for Lynch syndrome [
10‐
13]. After the introduction of the MIPA procedure, performed by multidisciplinary teams that include surgeons and pathologists, the recognition of patients at risk for Lynch syndrome has increased substantially [
15].
The MIPA procedure implies that CRC patients are simultaneously confronted with (1) the diagnosis of cancer and its treatment; (2) a possibly hereditary predisposition for Lynch syndrome and (3) the need to inform children and relatives about their possible cancer risks. CRC itself is known to be responsible for considerable physical and psychosocial morbidity [
19]. The question therefore arises: To what extent will MSI testing add to this distress? Newly diagnosed CRC patients who were immediately offered genetic testing for hereditary CRC considered the test and the timing to be highly acceptable [
20]. However, little is known about the actual psychosocial consequences of discussing a high genetic risk for Lynch syndrome with CRC patients during the treatment phase. The aim of the present study was to investigate general distress and cancer-specific distress in these patients. Social support and cancer risk perception were also studied as possible predictors of distress levels [
21‐
24]. Furthermore, in the relatively young patients with CRC, the reactions of the partner were measured twice in the 6 months following MSI testing.
Discussion
To our knowledge, this is the first multicentre study on psychological distress in patients recently diagnosed with CRC following genetic pre-screening for Lynch syndrome by MSI testing. Our data indicated that disclosure of the MSI test result was not followed by high levels of distress in the majority of these patients. This is in agreement with a previous study in which a shorter time interval between the cancer diagnosis and genetic pre-screening for Lynch syndrome was not related to higher psychological distress [
40]. Data from our patients in the MIPAPS pilot study showed that the advantages of early screening, e.g. timely medico-prevention strategies for their children, outweighed any possible disadvantages [
41]. These two studies point in the same direction, namely that pre-screening for Lynch syndrome by MSI testing in patients recently diagnosed with CRC is justifiable from a psychological point of view.
Distress and cancer-specific distress levels were moderate in the MSI-positive group and MSI-negative group. However, it is important to note that a minority of our patients with CRC did report high levels of general psychological distress and cancer-specific distress after MSI testing. These high levels of distress decreased over time in the MSI-positive group and remained stable in the MSI-negative group. Six months after MSI test result disclosure, i.e. almost a year after CRC diagnosis, about 20% of the CRC patients were still highly distressed and about 40% were still experiencing high cancer-specific distress. Although the levels of general psychological distress and cancer-specific distress were independent of the MSI test result, they were found to be related to female gender. General psychological distress was also related to low social support and high cancer risk perception. In our study, the overall prevalence of high general psychological distress was lower than that in a previous study in which 32% of the newly diagnosed patients reported high distress [
27]. The literature has shown that two-thirds of patients with cancer will adapt to their diagnosis without any psychological intervention [
27]. Initial psychological adaptation to the diagnosis of cancer is strongly influenced by pre-existing psychosocial factors [
42]. These results highlight the necessity to identify patients with high levels of distress. In our opinion, psychological screening and if indicated, subsequent professional support, should take place soon after CRC diagnosis to avoid or reduce long-term distress.
The results of our study on young patients recently diagnosed with CRC are in line with those from studies on patients recently diagnosed with breast cancer who were actively approached for genetic counselling and testing. Overall, no additional short-term or long-term psychological distress was found in this group of patients [
43,
44]. One of the explanations given previously was that the possibly hereditary nature of cancer is not nearly as distressing as the diagnosis of cancer itself [
45]. According to our clinical observations, a genetic diagnosis may help patients to understand at least a part of the origin of CRC and reduce psychological distress. However, these observations need to be confirmed by further research.
Another explanation might be that in general, MSI-positive CRC patients have good overall prognoses and there is often less need for adjuvant therapy, as was the case in our study. Therefore, patients who have a high risk of Lynch syndrome may have psychologically compensated for any potentially negative effects based on these factors. The reason why levels of distress and cancer-specific distress remained stable over time in the MSI-negative CRC patients might lie in their poorer prognoses and more general need for adjuvant therapy. However, we could not detect any correlation between adjuvant therapy and psychological distress.
The partners of the patients in the MSI-positive group and MSI-negative group showed moderate to high levels of self-esteem. These levels were comparable with those described in the literature on partners of patients with CRC [
35] or other types of cancer [
39]. In the two groups, levels of perceived distress decreased over time. This was in concordance with the previous literature in which the treatment phase was experienced as the most stressful period, as it involved the greatest need for emotional and informational support [
46].
One limitation of our study was the low response rate in the eligible patients. This may have biased our results, especially if the surgeons had consciously avoided recruiting patients with a (very) poor prognosis or emotional problems. Such bias would have resulted in underestimation of psychological distress. At present, we cannot assess whether bias was present. However, we note that in our sample, the levels of psychological distress were lower than those described in the literature. Another reason for the low response rate may have been the complex logistic inclusion procedure [
15], if communication of the test result to the patient exceeded the inclusion criterion of 6 months. In some cases, it took several months before the MSI-test report, written by the pathologist, was sent to the surgeon and a number of weeks more before the patient was contacted. Another limitation of our study was that no firm conclusions could be drawn, because the large number of tests increased the possibility of a type I error, which we have not corrected for.
Despite some methodological concerns, we can conclude that moderate levels of distress were present following MSI testing in patients recently diagnosed with CRC. These levels were similar to those in other patients diagnosed with CRC [
27,
47,
48]. High cancer-specific distress was observed in 40% of the MSI-positive patients and was significantly correlated with female gender.
Acknowledgments
We would like to thank all patients who participated in the study. We also thank Ria ter Winkel for her help with data collection and Dr. Rogier Donders for his valuable contribution to statistical analysis. We are very grateful to the surgeons and gastroenterologists of the following Dutch hospitals for their cooperation: Albert Schweitzer Hospital Dordrecht; Alysis Zorggroep Arnhem/Velp/Zevenaar, Antonius Hospital Sneek; Bernhoven Hospital Oss/Veghel; Canisius Wilhelmina Hospital Nijmegen; Catharina Hospital Eindhoven; The Tjongerschans Hospital Heerenveen; Elkerliek Hospital Helmond; Gelderse Vallei Ede; Jeroen Bosch Hospital ‘s-Hertogenbosch GZG/Carolus; Maas Hospital Boxmeer; Maxima Medical Centre Eindhoven; Maxima Medical Centre Veldhoven; Meander Medical Centre Amersfoort; Medical Centre Leeuwarden; Medical Spectrum Twente Enschede; Nij Smellinghe Hospital Drachten; Regional Hospital Koningin Beatrix Winterswijk; Regional Hospital Midden Twente Hengelo; Rivas Zorggroep Gorinchem; Slingeland Hospital Doetinchem; St. Anna Hospital Geldrop; St Elisabeth Hospital Tilburg; St Jansdal Hospital Harderwijk; Talma Sionsberg Dokkum; Twee Steden Hospital Tilburg; Twenteborg Hospital Almelo; University Medical Centre Groningen and University Medical Centre Nijmegen. The following laboratories of pathology are also kindly thanked for providing relevant MIPA data: Department of Pathology Erasmus Medical Centre in Rotterdam (Monique Hoogmans, Erwin Beerens and Winand Dinjens); Foundation of Public Health Laboratory Friesland (Joris Grond), Medical Laboratory PAMM Eindhoven (Ineke Lijnschoten), Department of Pathology UMCG (Yvonne Vos) and Department of Pathology UMCN (Riki Willems, Monique Goossens). This work was supported by a grant of the Netherlands Digestive Diseases Foundation [grant number SWO 05-07].