Study protocol of the CORRECT multicenter trial: the efficacy of blended cognitive behavioral therapy for reducing psychological distress in colorectal cancer survivors

Colorectal cancer (CRC) is one of the most frequently diagnosed cancers, with over 3.5 million survivors worldwide [1]. Although the majority of the colorectal cancer survivors (CRCS) are resilient and eventually adjust well, a significant proportion of CRCS experience on-going high levels of chronic distress [2]. The National Comprehensive Cancer Network (NCCN) defines distress as “a multi-factorial unpleasant emotional experience of a psychological (cognitive, behavioral, emotional), social and/or spiritual nature that may interfere with the ability to cope effectively with cancer, its physical symptoms and its treatment. Distress extends along a continuum ranging from common normal feelings of vulnerability, sadness and fears to problems that can become disabling such as depression, anxiety, panic, social isolation and existential and spiritual crisis” [3]. Distress occurs in approximately one third of CRCS [4, 5]. Distress is an unfavorable outcome in itself and a known risk factor for a poor outcome following a cancer diagnosis in the physical, mental and social domains of quality of live (QoL) [6, 7].

The problems related to CRC which underlie distress are very broad. Most previous research has investigated the role of physical, emotional or social problems during the phase of survivorship. A systematic review found that long-term CRCS have good overall QoL [8]. However, the majority of CRCS may still experience problems that can adversely impact upon their daily life. Frequently experienced adverse effects of CRC and its treatment are fatigue [9, 10], pain [11], neuropathy [12], poor body image [13] and gastrointestinal problems [13‐15]. A substantial amount of patients will have a permanent stoma after treatment for CRC and may experience ostomy-related problems including gas, constipation, change in clothing, travel difficulties, feeling tired, depressive feelings, and worry about odours and noises [16]. However, there is inconsistent evidence about whether or not there are differences in QoL amongst CRCS with and without a stoma [16, 17]. Sexual dysfunction after CRC treatment is a problem varying between 5 and 88% for men and approximately 50% of the women reported that problem [18].

In addition to distress caused by physical problems, anxiety and depressive symptoms are two major concerns of CRCS. The prevalence of anxiety and depressive symptoms amongst CRCS varies between studies. The reported prevalence of mild to moderate depressive symptoms among CRCS (0–6 years after diagnosis) ranges from 8 to 57% [9, 19‐21]. Prevalence rates of mild anxiety in CRCS (0–6 years after diagnosis) vary between 14 and 83% [9, 20, 21]. Moderate levels of anxiety have been reported in 6–68% of CRCS [20, 21]. A specific cancer related fear is the fear of cancer recurrence (FCR), defined as the “fear, worry, or concern relating to the possibility that cancer will come back or progress” [22]. Low to moderate levels of fear can be adaptive, and can motivate appropriate health behavior and surveillance, however moderate to high levels of FCR can have a negative impact on mood, daily functioning and QoL [22]. In a large sample of 10,969 CRCS, 50% of respondents reported fear of their cancer returning [23]. Custers and colleagues [24] found that 38% of the CRCS (N = 76) experienced high levels of FCR above a clinically validated cut-off. These high levels of FCR were associated with higher levels of distress, post-traumatic stress and lower QoL. A systematic review of interventions for distress in cancer patients has shown that psychological interventions have small to medium effects on distress levels in cancer patients whereas studies that included specifically participants with high distress showed larger effect sizes [25]. However, most research on distress and psychosocial interventions has been conducted with mixed cancer survivors or breast cancer patients [25]. Due to the prevalence of CRC-related distress, specific physical problems associated with CRC and growing numbers of CRCS, providing interventions for distress in CRCS is of increasing importance.

Relatively few studies have explored the effectiveness of psychological interventions designed to improve emotional outcomes for CRCS. A recent systematic review on psychosocial interventions for CRC patients of all disease stages identified 14 randomized controlled trials RCTs [26]. Only three of these RCTs proved to be effective for different mental health outcomes. These three interventions investigated emotional expression, a progressive muscle relaxation training, and an intervention to enhance self-efficacy. Besides the RCTs described in this systematic review, four other studies were found investigating an intervention specifically for CRCS. Lepore and colleagues [27] tested in a randomized trial whether a home-based expressive writing intervention improved QoL in patients with CRC. The intervention was however not effective. Jefford and colleagues [28] developed an intervention (SurvivorCare) which was nurse-led and consisted of educational materials, needs assessment, survivorship care plan, end-of-treatment session and three follow-up telephone calls. The addition of SurvivorCare to usual care showed no beneficial effect. White and colleagues [29] investigated the effect of a volunteer-delivered telephone-based intervention on reducing anxiety and depression among patients recently diagnosed with CRC. Results indicated no change in depressive symptoms, although there was a reduction in anxiety. Hawkes and colleagues [30] tested another telephone-based intervention which was provided by health coaches and aimed at health behavior change. This intervention improved psychosocial outcomes and QoL, but there was no effect on distress.

To summarize, previous studies on psychological interventions for CRCS are inconsistent with most studies failing to demonstrate a positive effect of the intervention. Most existing studies did not select patients based on distress level [26‐29] and therefore might have failed to identify those who might benefit the most from psychological interventions [25]. Furthermore, interventions were either nurse-led [26, 28, 29] or telephone-based [29, 30] which may be less sufficient to improve psychological outcomes compared to psychologist-led interventions. Finally, most intervention studies to date included either only short-term CRCS (< 1 year) or patients who were still during medical treatment [26, 28, 29]. Therefore, treatment efficacy for long-term CRCS is still unclear.

Due to the paucity of evidence-based interventions to reduce psychological distress in CRCS, and the limitations of existing intervention studies, there is an urgent need to develop and evaluate a cost-effective and easily accessible psychological intervention for CRCS. The CORRECT (COloRectal canceR distrEss reduCTion) intervention is a blended therapy to reduce psychological distress amongst CRCS which has been specifically developed to address this need. It is called blended therapy because it is a combination of face-to-face (F2F) cognitive behavioral therapy (CBT), interactive self-management activities at a secure website and telephone consultations. Blended therapy is an innovative and promising approach to psychological care delivery. It reduces therapist workload, and is known to lead to better outcomes and reduced patient dropout compared with internet-only interventions [31‐34]. By adding online activities to F2F psychological therapy, patients access treatment at home at their convenience. These online activities consist of homework assignments. Towards the end of the intervention period, self-management is increased through the use of the interactive website. In this way patients take charge of their own health and learn to cope more independently with future challenges. Furthermore, blended therapy provided in the CORRECT intervention is tailored to the needs of each individual. As we know, the CRC population is diverse and includes survivors with a variety of different characteristics and treatments therefore the physical and psychosocial consequences vary between individuals. Distress can be seen as a multi-factorial cluster concept. Despite individual variations in symptom profiles, based on previous research, we know that the most common symptoms in CRCS are distress related to physical consequences, anxiety and depressive symptoms. Therefore, in the present study the intervention is tailored according to individual needs in three optional modules: 1) distress due to physical consequences of CRC, 2) anxiety and FCR, and 3) depressive symptoms. The primary objective of the CORRECT study is to evaluate the efficacy and cost-effectiveness of the CORRECT intervention in decreasing psychological distress in CRCS. A secondary aim is to investigate the usage of online activities at the secure website and how online usage is associated with distress reduction.

The design, and evaluation of this intervention are in accordance with guidelines of conducting Internet intervention research [35], the CONSORT 2010 statement for parallel group randomized trials [36], and for eHealth interventions [37]. The Medical Ethics Committee of the Radboud university medical center (CMO Arnhem-Nijmegen) (NL55018.091.15) and relevant hospital and institutional human research ethics committees granted ethical approval. The current study is registered in the Netherlands National Trial Register (NTR6025).

Approximately one third of the CRCS experience high levels of psychological distress. Due to the rising numbers of CRCS, widely accessible and evidence-based supportive care is needed to deal with this growing need. This protocol paper describes the CORRECT multicenter trial which evaluates a blended CBT intervention (CORRECT) for reducing high psychological distress in CRCS. The primary objective is to evaluate the efficacy and cost-effectiveness of the CORRECT intervention in decreasing psychological distress in CRCS. To our knowledge, this is the first blended psychological intervention with self-management elements which is specifically aimed at reducing psychological distress amongst CRCS.

CRCS are an under-served population with respect to psychosocial supportive care research. Few studies investigate psychological interventions specifically designed for CRCS. The CORRECT study addresses this gap in current research. Most studies on distress and psychosocial interventions over-represent women with breast cancer [25]. Interventions that might be proven to be effective for women with breast cancer may not be as effective for males or for survivors of other tumor types. Within CRCS samples gender may be an important mediator of the efficacy of psychological interventions. In the current study we both include male and female CRCS, which makes it possible to explore possible differences in our mixed group.

Reviews indicate that psychological interventions are most effective for patients who are pre-selected for high distress [25, 41]. In order to identify highly distressed patients, every CRCS at participating sites who scores above cut-off on the nationally mandated DT (≥ 5) will be offered inclusion in the CORRECT study. The CORRECT intervention is therefore highly-specialized and tailored care to help CRCS deal with their unique problems of survivorship. This may be a strength, however it may also be a barrier. A study by Van Scheppingen and colleagues [85] found implementing screening to be inefficient for recruiting distressed cancer survivors to a RCT. They found need for psychological services to be much lower than they anticipated before the start of the trial. In another study it was concluded that, “depending on the clinical context, screening might be more efficient if unmet needs for services are assessed rather than psychological distress” [86]. We try to obviate this issue by using a telephone protocol in which the researcher will go through the completed DT with the patient and verbally confirm there is a need for a psychological intervention. Further, we expect our retrospective recruitment method to overcome this issue by first asking if a patient is willing to participate in the trial and then screening the patient for high distress level. An additional strength of this trial is that it is conducted using a rigorous methodology and in accordance with CONSORT guidelines. Patient recruitment is conducted in different hospitals (both regional and academic hospital settings) in two regions of the Netherlands, which may enhance its generalizability. Furthermore, it is delivered by experienced therapists who are working in clinical practice and not therapists specially recruited and trained for therapy delivery in academic centers. This will facilitate implementation should the therapy be proven effective.

The CORRECT intervention is developed in close collaboration with patients from the participating hospitals and patient representatives from patient organizations. CRCS have been involved in different phases of the research and intervention development. A pilot study has demonstrated that the screening procedure is feasible and acceptable to CRCS. Patient participation in the CORRECT study helps to ensure that the intervention is provided in a manner consistent with patient needs and preferences. Further, we aimed to use the person-based approach to ground our intervention design as intended: “in a rigorous, in-depth understanding of the psychosocial context of the people who will use the intervention” [87]. Taking the needs and experiential knowledge of patients into account is considered to result in the improvement of individual health care [88]. Patient participation in the intervention development will help ensure the intervention is provided in a manner consistent with patient needs and preferences. If proven effective, this will increase the likelihood of high uptake when implemented in routine care.

A secondary objective of the CORRECT study is to investigate the use of online activities and how website usage is associated with distress reduction, in accordance with usage evaluation in a previous study of online self-management intervention for breast cancer survivors [84]. Usage evaluations are relatively new and growing area of interest in online intervention research. Analysis of usage data provides information on which patient subgroups experience the greatest benefits. This facilitates knowledge about personalizing psychosocial interventions for CRCS and further a growing body of research on the relationship between e-health interventions and psychological and behavioral change.

In conclusion, the CORRECT intervention is a promising method of reducing psychological distress, improving QoL and enhancing personalized supportive care for CRCS. Should this trial prove its efficacy, the ultimate goal will be to implement and disseminate the CORRECT intervention nationally and internationally.