Introduction

Up to 5% of patients with colorectal cancer have Lynch syndrome (hereditary non-polyposis colorectal cancer (HNPCC) [1–3]. Unfortunately, only a small proportion of the expected number of patients undergo genetic testing. Identification of a hereditary predisposition can be life-saving. When more patients are traced with hereditary colorectal cancer, an increasing number of relatives can receive appropriate surveillance, which will prevent premature death from colorectal cancer [4]. To enhance the detection of Lynch syndrome, a special strategy has been developed for risk patients who cannot be recognized by family history. This new strategy called MIPA involves MSI-testing by pathologist in new patients with CRC below the age of 50 [5]. It is being introduced at an increasing number of hospitals. In this strategy, the pathologists select patients and tumour specimens for microsatellite instability (MSI) testing. In case of a positive MSI test, the patient is at risk for Lynch syndrome and thus referred for genetic counseling to a clinical genetic center.

For the patients, the difference between the new strategy and the existing procedure is that genetic counselling and testing is discussed very shortly after the diagnosis of colorectal cancer, instead of a long period after diagnosis and treatment. In this early stage after diagnosis, patients with colorectal cancer may be more emotionally vulnerable. Concurrently, these patients are confronted with three major tasks: (1) to cope with their cancer, (2) to cope with the consequences of a possible genetic risk and (3) to consider informing and discussing genetic counseling and DNA-testing with their blood relatives. Extended work already has been accomplished on familial cancer in general, including colorectal patients tested for Lynch syndrome. In a number of reviews on familial cancer, colorectal cancer was included as one of the familial cancers [6, 7]. Many studies describe the psychological impact of pre symptomatic testing for Lynch syndrome [8–22]. From these studies it can be concluded that in general genetic counselling and pre symptomatic testing for Lynch syndrome can lead to increased distress immediately after DNA-test disclosure but does not lead to long-term adverse effects. Other related studies assessed experiences of patients and family members with genetic counselling for hereditary cancer and [23], the impact of attendance of a familial colorectal clinic on cancer-related concerns [24], subjective perception regarding colorectal cancer [25, 26], compliance with screening after testing [26], genetic testing for Lynch syndrome in colorectal cancer survivors who were more than 1 year after diagnosis [27] and quality of life after various surgical procedures [28].

Obviously, this new Lynch detection strategy gave rise to systematically survey relevant data related to the issue of the impact of symptomatic genetic testing in patients with colorectal cancer in their first year after colorectal cancer diagnosis. A literature review was conducted to identify the psychological impact of colorectal cancer, focusing on the impact of the malignancy during the first year after primary treatment and of the additional impact of genetic testing for Lynch syndrome in affected patients.

Materials and methods

The electronic databases PubMed and PsychInfo were searched to identify all the reports published between January 1997 and October 2007 on the psychological impact of colorectal cancer and genetic testing for hereditary colorectal cancer (Lynch syndrome) in patients during their first year of colorectal cancer. Two searches were performed in each database.

Search 1 retrieved literature on the psychological impact of the diagnosis and treatment of colorectal cancer. A sensitive search strategy was adopted using the following keywords: colorectal cancer, colorectal tumour(s), colorectal carcinoma, colorectal neoplasms, psychological distress, psychological adaptation, coping, emotional adjustment, anxiety, depression and quality of life. Using these keywords, 470 abstracts were retrieved: 415 from PubMed and 55 from PsychInfo. After removing doubles, one of the reviewers (KL) checked all the titles and abstracts. Full text copies were obtained when the studies had possible relevance. Inclusion criteria were (1) studies on patients in their first year with colorectal cancer (2) psychological outcome measurements, (3) peer-reviewed articles in English, French or Dutch. From studies with a prospective design with long-term follow-up, only the results up to 1 year were retrieved. Exclusion criteria were (1) Patients with colorectal cancer aged >70 years. These patients are not generally referred for genetic testing due to their advanced age. (2) Colorectal cancer disease management studies and subjective experiences. (3) Qualitative design. (4) Research into non-standard medical treatment. (5) Publications of which no relevant data (mean scores) could be retrieved. Based on these criteria, 17 studies remained (see Fig. 1).

Fig. 1
figure 1

Selection of studies on the psychological impact of colorectal cancer until 1 year after treatment (*1) and diagnostic genetic testing for hereditary colorectal cancer (*2)

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Search 2 retrieved literature on the psychological impact of genetic testing in patients with colorectal cancer. The keywords in search 1 were used in combination with the terms genetic testing, genetic predisposition to disease, genetic screening, genetic counseling and genetics. Using these keywords, 101 abstracts were retrieved. After removing doubles, one of the reviewers (KL) checked all the titles and abstracts. Full text copies were obtained of all the possibly relevant studies. Inclusion criteria were (1) patients diagnosed with colorectal cancer (2) psychological outcome measurement, (3) peer-reviewed articles in English, French or Dutch. Exclusion criteria were (1) Pre-symptomatic/predictive testing, because our focus was on the impact of genetic testing in patients diagnosed with colorectal cancer. (2) Qualitative design. (3) Genetic testing for Familial Adenomatous Polyposis (FAP). (4) Publications of which no relevant data (mean scores) could be retrieved. Based on these criteria, ten studies remained (see Fig. 1).

Additional free text searches were performed in PubMed, PsychInfo as well as in the Cochrane Library database and in Embase using all the above-mentioned keywords to select reviews on the psychological impact of colorectal cancer and genetic testing for hereditary colorectal cancer. However, none of these searches led to any relevant publications.

Methodological quality

The studies were assessed according to the guidelines for levels of evidence and grades of recommendation, supplied by the Oxford-Centre for Evidence-based Medicine. A level of evidence (LE) 1 refers to RCT studies, LE2 to cohort studies, LE3 to case-control studies, LE 4 to case-series and LE5 to expert opinions (http://www.cebm.net/levels of_evidence.asp).

Results

I Psychological impact of colorectal cancer

Table 1 gives a summary of each of the 17 papers [29–45] included in our review. The vast majority of the patients with colorectal cancer were older than 50 years. As a result of the heterogeneity of psychological variables and used measurement instruments of the retrieved studies, a limit was set in describing those studies that used the European Organization for Research and Treatment in Cancer (EORTC) QLQ-C30 scale. In ten out of the 17 studies, the European Organization for Research and Treatment in Cancer (EORTC) QLQ-C30 scale had been used to measure the quality of life of the patients [29–32, 35, 41, 43–46]. This scale has frequently been used to assess health-related quality of life in various groups of cancer patients [47].

Table 1 Characteristics of the studies on the psychological impact of diagnosis and treatment for colorectal cancer up to 1 year after primary treatment (n = 17)
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The mean scores on functional status were retrieved from the studies, because an important aim of this review was to evaluate functioning after treatment for colorectal cancer. The scores are presented in Table 2. Our comparison may not do justice to the special qualities of each individual study, as their designs were intended to provide answers to specific research questions, not to facilitate comparability. Nevertheless the comparison adds new dimensions to our knowledge in this area. To evaluate the significance of these function scores, they were compared to reference data from a random sample (n = 2081) of the general (non-cancer) adult population [47] and from breast cancer patients [48] (Table 2). According to the MIPA (MSI test by pathologist) procedure, MSI-positive patients are usually informed about the results and offered genetic testing within 3 months after surgery. Therefore, clear distinction is made between psychological functioning in the first 3 months after treatment and in the subsequent period up to 1 year after treatment. In the publications of Schmidt [42] and Tsunoda [44] the EORTC-QLQ-C30 data were presented in graph and mean data could not be obtained and used reliably. The study of Wilson et al. [45], only presented mean data on EORTC-QLQ-C30 Global Health Status. Therefore, these three studies are not reflected in Table 2.

Table 2 EORTC QLQ-C30 functioning scores concerning the psychological impact of colorectal cancer (scores from 0 to 100, higher score means better functioning)
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Regarding the psychosocial impact of CRC with other instruments than the EORTC-QLQ-C30, it appeared that often different questionnaires were used, concerning patients at different ages, with different types of colorectal cancer and often with different times of data collection. Still, an overall impression was obtained that demands of illness, especially psychosocial and existential concerns, were greater among the youngest age group below 45 years. Moreover, patients with a stoma showed higher levels of depression and poorer social function than non-stoma patients. Especially men with a stoma reported sexual problems as did patients after treatment for rectal cancer”.

Impact of colorectal cancer on functional status

Up to 3 months after treatment

Table 2 shows that compared to the reference data, colorectal cancer led to reduced social functioning (especially in the patients with a stoma) as well as to decreased role and physical functioning [29, 30, 32, 37, 41, 43]. Patients of younger than 65 years and those with a stoma reported reduced health-related quality of life 6 weeks after surgery [45]. In the group with rectal cancer the men suffered from more problems with their sexual functioning after abdominoperineal resection than the women [43]. It can be concluded that immediately after treatment for colorectal cancer, physical, social and role functioning were diminished especially in patients with a stoma, compared to levels of physical, social and role functioning of a selected sample of adults [47] and of patients with lung cancer (another common malignancy worldwide) [49, 50].

Between 3 and 12 months after treatment

Reduced role, emotional and social functioning continued up to 1 year after treatment. The women reported poor physical functioning [43] compared to the reference data [47] and the scores from a severely fatigued breast cancer group [48]. Global health status scores of the patients with colorectal cancer were also poorer than the reference data [47]. Severe limitations were found in emotional and social functioning up to 1 year after treatment. These problems were especially likely to affect patients of younger than 60 years [30]. In the men, strain due to sexual impairment appeared to persist [29, 43, 46]; the men with a stoma had more sexual problems than those without [41]. Rectal cancer patients reported poor role and social functioning compared to the reference data [47] up to 1 year after treatment [32]. In the patients who had pre-operative radiotherapy, emotional functioning was impaired compared to the norm data [47]. At 12–16 months after radiotherapy, these scores had returned to normal levels [29]. Thus, severe problems with emotional and social functioning persisted up to 1 year after treatment, especially in the patients of younger than 60 years and in those with a stoma.

Impact of colorectal cancer on demands of illness and spiritual well-being

In two studies, patients younger than 45 years reported greater demands of illness (hardships or stressors that require coping or adjustment to illness) than the older patients [33, 36]. Fernsler et al. [33] also showed that such demands of illness were greater in men and in men and women who had received treatment in the previous 2 months; in contrast, the women reported significantly higher spiritual well-being than the men. This leads to the conclusion that colorectal cancer caused more hardships and stressors in men and in patients diagnosed before the age of 45 years.

II Psychological impact of genetic testing for Lynch syndrome

Summaries of the ten relevant studies are shown in Table 3. Nearly all the studies had gathered data on the patients before disclosure of the genetic test result. Two studies had made assessments pre-test and post-test [16, 51], whereas one study had only made assessments post-test [52]. Very few studies gave specific details about the time interval since the diagnosis of colorectal cancer and inclusion in the study [53, 54]. Table 3 also shows the diversity in outcome measures and (self-administered) questionnaires to gather data [16, 51, 55–58]. The aim of this review was to determine how patients with colorectal cancer reacted to (the offer of) genetic testing. Therefore, the psychological reactions were documented according to stage of genetic testing the patients had reached at the time of the studies. The process of genetic counselling was divided into three distinct stages: (1) Period of genetic counselling and if desired, having a blood sample taken. (2) Period of waiting for the result of the DNA analysis. (3) Period after disclosure of the genetic test result.

Table 3 Characteristics of studies on the psychological impact of diagnostic genetic testing for Lynch syndrome on patients with colorectal cancer (n = 10)
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Psychological reactions before genetic counselling

The three relevant studies showed that patients with colorectal cancer tended to have positive attitude towards genetic testing [56, 57, 59]. Their most common motivation to undergo genetic testing was concern about the risk of colorectal cancer in close relatives. Motivation was the highest in the younger patients, in those with early stage disease and in those who had more frequent thoughts about hereditary colorectal cancer [57]. In a group of patients with colorectal cancer who attended an information session about Lynch syndrome, 28% developed a clinically significant level of cancer-worry-related distress [56]. In conclusion, motivation to undergo genetic testing was primarily the need to know if close relatives were at increased risk for colorectal cancer and was strongly present in younger patients.

Psychological reactions before and after genetic counseling

Other studies obtained data on the patients after patients had consented to have a blood sample taken for DNA analysis. Keller [55] and Murakami found clinically relevant depression scores before and after genetic counseling in 19 and 5% of the patients, respectively [51]. Another study reported clinically relevant anxiety levels in 32% of the patients before genetic counseling, whereas the scores dropped to 16% after genetic counseling [55]. In a group of patients who had given a blood sample for genetic testing, the prevalence of depressive symptoms was 24%, although all the scores remained within the clinically normal range [54]. Patients in the age group of younger than 50 years had higher levels of anxiety and depression but the scores were within the normal range; their data also showed significant associations between pre-test distress, a history of familial mortality from colorectal cancer and anticipation of becoming depressed post-test [53]. Characteristics associated with depression were female sex, less formal education, fewer sources of social contact; associations with anxiety were younger age, less formal education, Non-Caucasian race, more severe disease and fewer sources of social contact [54]. Intrusion scores reached clinically relevant levels in 14% of the patients [55]. Higher intrusion and avoidance scores were found in women and in the patients who had been diagnosed with colorectal cancer less than 1 year previously, although all the scores remained within the normal clinical range [53]. Clinically relevant cancer-worry-related distress was detected in 25% of the patients before genetic counseling, but after genetic counseling, this dropped to 13% [55]. In conclusion, most psychological distress scores remained within the normal range before the result of the genetic test was disclosed, although a minority of the patients developed clinically relevant anxiety and depression levels. Vulnerable subgroups were female patients and male patients diagnosed before the age of 50 years.

Psychological reactions after disclosure of the genetic test result

Disclosure of the genetic test result led to significant depression scores in 7% of the patients and post-traumatic stress symptoms in 5% [51]. Lynch syndrome mutation carriers showed higher test-specific distress than non-carriers but these scores returned to baseline between 2 and 12 weeks after receiving the test result [16]. The only predictor of psychological distress after disclosure of the test result was a history of depression [51]. It can be concluded that disclosure of the genetic test result did not lead to any relevant levels of psychological distress in most patients. Vulnerable subgroups seemed to be patients with pre-test distress, high familial mortality from colorectal cancer and a history of depression. Therefore, a subgroup of vulnerable patients whose genetic test discloses Lynch syndrome mutation carrier ship may benefit from extra psychological counselling.

Discussion

This literature review shows that little is known about the additional psychological impact of obtaining a genetic test disclosure in newly diagnosed patients with colorectal cancer. Only ten studies were identified on diagnostic genetic testing in colorectal patients. Most of these studies measured distress prior to genetic test disclosure, but did not obtain data after disclosure of the test result. Prior to disclosure of the genetic test result, female patients and men who were diagnosed with colorectal cancer before the age of 50 years appeared to be more vulnerable to genetic-test-related distress. A history of depression and high levels of pre-test distress were strongly associated with genetic-test-related distress and cancer related worries. It is generally known that a young age at diagnosis and multiple family members with cancer are hallmarks of heredity. Therefore, significant levels of anticipated psychological distress prior to disclosure of the genetic test result in patients with a history of familial mortality from cancer [53] can also be regarded as relevant to patients with colorectal cancer who are suspected of Lynch syndrome carriership.

The few studies available on distress after disclosure of the genetic test result revealed ambiguous results. For patients with different types of cancer, the impact of genetic testing many years after the initial cancer diagnosis and treatment was strongly influenced by their former experience of cancer [7]. Dorval hypothesized that after disclosure of the genetic test result, cancer patients may be more aware of their own risk developing a second primary tumour and be more conscious of the contribution of genetics to an increased risk of cancer in their offspring [60]. When genetic testing was offered to recently diagnosed colorectal cancer patients, the majority did not object to an active approach [61]. Individuals at high-risk for Lynch syndrome proved to know very little about microsatellite instability (MSI) testing, a hallmark for patients at risk for Lynch syndrome, but held positive attitudes towards MSI test utility [62].

This literature review also shows that most patients with colorectal cancer experience diminished physical, social and role functioning during the first 3 months after primary treatment. Decreased emotional and social functioning could persist for up to 1 year after treatment, especially in patients of younger than 60 years and in those with a stoma. Specific subgroups of patients with colorectal cancer appeared to be more vulnerable to genetic-testing-related distress, but their actual levels of distress did not generally reach clinical significance. Reduced emotional and social functioning may be related to the many taboos that still surround bowel dysfunction [63]. Especially the younger patients reported severe distress due to maladjustment to their colorectal cancer. Having a stoma can lead to feelings of stigmatisation and lead to withdrawal from social activities [64, 65]. Recurring themes in patients with colorectal cancer are loneliness and isolation [63]. It might be expected that disabilities after colorectal cancer treatment prevent the younger patients from going to work and contribute to their impaired social and role functioning, but it was found that most patients with colorectal cancer returned to work after treatment [64, 66]. An additional source of distress especially in younger male patients was the possible impact on sexual functioning [64, 67]. Studies have shown that after treatment for rectal cancer, sexual problems were common, inadequately discussed and/or treated by physicians [67]. Furthermore, the potential for impotence due to treatment for colorectal cancer was a serious concern especially in patients of younger than 60 years [64].

Conclusion

This review identifies the psychological impact of colorectal cancer during the first year after treatment and indicates specific subgroups of patients with colorectal cancer who could be vulnerable for genetic-testing-related distress. Most of the retrieved studies on diagnostic genetic testing for Lynch syndrome exclusively measured distress prior to genetic test disclosure and focused on patients who were diagnosed with colorectal cancer several years ago. Therefore, we are still unable to identify the psychological impact of genetic testing for Lynch syndrome in recently diagnosed patients with colorectal cancer.