Study design and data sources

The data presented in this study derives from a large national study on late effects in long-term colorectal cancer survivors in Denmark (≥ 5 years since cancer diagnosis with no recurrence and no residual disease), including a randomized controlled trial (RCT) of a therapist-guided internet-delivered intervention for FCR (see protocol: Lyhne et al. [29]). The present paper reports secondary exploratory analyses of questionnaire data and clinical assessments of FCR and HA from the RCT of the internet-delivered treatment of FCR [30].

Study sample

All colorectal cancer survivors in Denmark, located through the Danish Colorectal Cancer Database (DCCG) [31], were invited to participate if they fulfilled the following inclusion criteria: (a) above 18 years, (b) diagnosed with colorectal cancer between 2014 and 2018, and (c) treated with curative intent. The questionnaire was distributed electronically from REDCap [32, 33] between May 2023 and April 2024 to a digital citizen mailbox used for communication between citizens and public authorities in Denmark.

Participants were divided into two groups as part of the recruitment for the RCT:

(1)

Individuals with FCRI-SF scores ≥ 22 (i.e., above the established cutoff for clinically significant FCR [8, 34] and the inclusion criteria for the RCT) were offered a diagnostic assessment as part of the RCT inclusion process. These assessments were conducted within 2 weeks of survey completion to facilitate timely enrolment.

(2)

A random subset of individuals with FCRI-SF scores < 22 was invited to undergo a diagnostic assessment to evaluate the robustness of the cutoff [35] and to identify clinically relevant cases not captured by the threshold. These participants were not eligible for inclusion in the RCT; instead, they were randomly selected by clinicians from the pool of consenting respondents who had agreed to be contacted for a diagnostic assessment interview, irrespective of the time elapsed since questionnaire completion.

In both groups, assessors had access to participants’ questionnaire scores in advance as part of their preparation for the diagnostic assessment.

Inclusion criteria for the assessment were as follows: (a) filled in the FCRI-SF questionnaire, (b) had not had an incidence of cancer recurrence or new cancer, and (c) gave consent to a diagnostic assessment. At the assessment, participants were excluded if they did not speak Danish, had a severe psychiatric diagnosis other than HA, or were not interested in the RCT (for relevant participants).

Intervention and RCT

Participants in the RCT were randomized to either internet-delivered treatment of FCR or augmented treatment as usual. The latter included the assessment and referral to a website with a non-guided, publicly available E-learning program in cancer rehabilitation. The intervention was a therapist-guided (TG) version of iConquerFear, which was originally a self-guided digital intervention derived from the face-to-face therapist-delivered ConquerFear [29, 36, 37]. The TG-iConquerFear was designed to reduce FCR and comprised of six modules delivered over 10 weeks containing educational text, interactive exercises, and short videos focusing on attention training, increasing metacognitive awareness, acceptance strategies, detached mindfulness, promotion of appropriate screening behavior, and values-based goal setting. The participants received weekly written feedback from an experienced therapist delivered asynchronously via an embedded text-messaging system.

Investigated psychological clinical characteristics

In this study, the characteristics investigated from the assessment were onset of illness worries, subject of illness worries, number of late effects, and psychiatric comorbidity. The characteristics investigated from the questionnaires were subscales on the FCRI, symptoms of emotional distress, anxiety, and depression measured using the Symptom Checklist and illness worries measured using the Whiteley-6-R (see below).

MeasuresDemographics

Demographic information regarding age, sex, cancer type, and treatment were extracted from the DCCG registry. Participants self-reported additional demographic (education, marital status, occupational status, children) and clinical information (treatment course).

Clinical assessment

Clinical assessments were conducted over the phone by one of three psychologists with previous (5–20 years) clinical experience with assessment and treatment of HA. The psychologists supervised each other, and the first six interviews were conducted together in pairs of two.

The psychologists were trained in and used the Research Interview for Functional somatic Disorders (RIFD) [38]—a modified version of Schedules for Clinical Assessment in Neuropsychiatry (SCAN) [39]—to assess HA, depression, panic disorder, social anxiety, generalized anxiety, and obsessive-compulsive disorder and to screen for psychotic experiences. The RIFD was supplemented with questions related to cancer course and late effects after cancer. Psychologists assessed if illness worries started before or after cancer diagnosis, if the worries were exacerbated by cancer diagnosis, and if the illness worries were limited to colorectal cancer or extended to other illnesses.

Assessment of HA

HA was assessed using the diagnostic research criteria established by Fink et al. [15]. The core symptom for HA is illness rumination [15] which needs to be present together with at least one associated symptom to fulfill diagnostic criteria (see supplementary material for diagnostic criteria, Textbox S1). To identify ruminations, the psychologists specifically assessed whether the worries were obsessive and interfered with daily life including emotional and overall functional impact (work, family, leisure).

Assessment of FCR

The assessment of FCR did not adhere to specific criteria for clinical FCR as the original RCT study did not rely on this. Psychologists rated the level of FCR based on the assessment of illness-related worries, persistence of worries, and preoccupation with and hypervigilance to bodily symptoms which reflect the consensus-based criteria for clinical FCR [10]. In addition, control or avoidance behavior and the participants’ answer to the following question, “How much have the mentioned concerns about fear of recurrence overall disrupted your usual daily activities?”, informed the rating. The psychologists rated either no impact, little impact or discomfort, moderate impact or discomfort, or severe and invalidating impact or discomfort. The psychologist assessed the overall functional impact (emotional, work, family, leisure) during the last 6 months. No or little impact corresponded to non-clinical FCR while moderate to severe impact corresponded to clinical FCR.

Late effects other than FCR

A psychologist registered the presence of known late effects after colorectal cancer by asking participants if they experienced any of the following symptoms: abdominal pain, diarrhea/frequent loose stool, difficulty emptying bowels, involuntary passage of gas/loose stool, defecation urgency, involuntary urination, bleeding from the bladder, frequent urination, difficulty emptying the bladder, bladder pain, sexual dysfunction, peripheral neuropathy, fatigue, memory issues, or difficulty concentrating.

Questionnaire data Fear of cancer recurrence inventory

The FCRI is a validated 42-item self-report measure used to assess FCR [8] and was the primary outcome measure in the RCT study [30]. It contains seven subscales (triggers, severity, psychological distress, functioning impairment, insight, reassurance, and coping strategies) which are all answered on a 5-point rating scale with higher scores indicating more severe symptoms (total score range 0–168) [40]. The FCRI has shown good test–retest reliability and convergent validity with other measures of FCR [8]. Internal consistency/reliability of the FCRI in the present study was good as measured using Cronbach’s alpha (r = 0.95).

The nine-item severity subscale is also used as the short form of the FCRI (FCRI_SF) which is answered on a 5-point scale (range 0–36, with higher scores indicating more fear). The FCRI-SF has also shown good test–retest reliability and convergent validity with other measures of FCR [8] and has been validated in Danish [35]. In the present study, the internal reliability of the FCRI-SF was good as measured using Cronbach’s alpha (r = 0.93).

Illness worries

The Whiteley Index 6-item revised version (Whiteley-6-R) was used to measure illness worries and preoccupation with fear of suffering from a serious illness [41, 42]. Questions are rated from 0, “not at all,” to 4, “a lot,” and a sum score is calculated from the six items (range 0–24). The Whiteley-6-R has shown to have good external validity and high reliability [41]. In the present study, the internal reliability was good measured using Cronbach’s alpha (r = 0.93).

Symptom checklist

The SCL-8 [43], SCL-ANX4, and SCL-DEP6 [44] are subscales from the Symptom Checklist-90-Revised [45] and measure emotional distress, anxiety, and depression. It has shown satisfactory sensitivity and specificity in detecting depression and anxiety and emotional distress in relation to emotional psychiatric disorders [43, 44]. It is scored from 0, “Not at all,” to 4 “Extremely.” Internal validity in the present study was good for all three subscales: SCL-ANX4 = 0.89, SCL-8 = 0.93, and SCL-DEP6 = 0.87.

Statistics

Analyses were conducted using Stata 18 [46]. Descriptive statistics were calculated for participants’ demographic and clinical information. Continuous variables were summarized as means and standard deviations (SD) for normally distributed data and as medians and ranges for non-normally distributed data. Categorical variables were presented as frequencies and percentages and compared using chi2. Comparisons of continuous variables were performed using independent t-tests for parametric data and Mann–Whitney U tests for non-parametric data. Significance levels were adjusted using Bonferroni correction. Results from assessments and treatment outcomes were reported using descriptive statistics only due to the small sample sizes.

Ethics

All participants provided electronic and verbal consent to participate in the study. The study was approved by The Regional Committee on Health Research Ethics for Southern Denmark (Project-ID S-20190061) and was in agreement with the Declaration of Helsinki.