Quality of life, distress, and posttraumatic growth 5 years after colorectal cancer diagnosis according to history of inpatient rehabilitation

Our analysis is based on CRC patients recruited in the DACHS (Darmkrebs: Chancen der Verhütung durch Screening) study, an ongoing population-based case–control study with long-term follow-up of CRC cases conducted in the Rhine-Neckar region of Germany. Details on the study design have been reported elsewhere (Brenner et al. 2011; Hoffmeister et al. 2015). German-speaking patients, at least 30 years of age, from the study region with first diagnosis of CRC (C18-C20, International Classification of Disease, revision 10), who are able to participate in a one-hour interview are eligible for the study. Patients are recruited in 22 cooperating hospitals by treating physicians, typically during the first hospitalization due to CRC. The study was approved by the ethic committees of the state medical board of Baden-Wuerttemberg and Rhineland-Palatinate as well as the Medical Faculty of Heidelberg.

Trained interviewers obtain sociodemographic data, lifestyle-related information, and the medical history of the participants during a standardized face-to-face interview at baseline close to initial diagnosis. For CRC patients, collected discharge letters and pathology reports provide tumor- and surgery-related information. Three years after diagnosis, therapy-related information including the utilization of ICR (yes/no) and name of rehabilitation clinic is given retrospectively by the attending general practitioners and/or oncologist. The physicians fill out questionnaires based on patient records and provide medical reports. Five years after diagnosis, participants receive a follow-up questionnaire by mail to assess HRQOL and further self-reported outcomes. If participants refuse to fill out the questionnaire but are willing to answer a short version of the questionnaire including only personal and medical information, the short version of the questionnaire is sent out. Throughout the study, patient’s vital status registered by the population registries is checked regularly. For this analysis, an additional retrospective collection of rehabilitation discharge letters via rehabilitation clinics and treating physicians was conducted for a subset of rehabilitants to approximate timing of ICR after CRC diagnosis.

For the current analysis, we included CRC patients diagnosed in 2005–2013 who were still alive 5 years after diagnosis and who participated in the 5-year follow-up (5YFU) in 2010–2018. We excluded CRC survivors with unavailable information on utilization of ICR or who underwent outpatient rehabilitation care only from the analysis. We furthermore excluded participants who provided a short version of the follow-up questionnaire only.

HRQOL was measured with the EORTC-QLQ-C30 questionnaire Version 3.0 (Aaronson et al. 1993) at 5YFU. The instrument was developed by the European Organization for Research and Treatment of Cancer and includes one global quality-of-life scale, five functioning scales (physical, cognitive, role, emotional, and social), and nine symptom scales (insomnia, fatigue, pain, dyspnea, constipation, diarrhea, appetite loss, nausea and vomiting, and financial impact). Participants were asked to rate each item on a Likert scale from 1 (“not at all”) to 4 (“very high”). Scores for every scale were calculated and linearly transformed to a 0–100 scale according to the scoring manual (Fayers et al. 2001). Higher scores on the global and functioning scales reflect better HRQOL, whereas higher scores on the symptom scales indicate higher symptom burden.

In addition to the core questionnaire, the CRC-specific submodule (EORTC-QLQ-CR29) was administered to assess 4 CRC-related functioning (future perspective, body image, weight, and sexual interest) and 18 symptom scales (Gujral et al. 2007; Whistance et al. 2009). Scoring and interpretation of scores were analogues to the core questionnaire (Fayers et al. 2001).

Cancer-related distress was measured with the Questionnaire on Stress in Cancer Patients (QSC-R10) (Book et al. 2011). Its ten items address the impact of cancer-related stressors including psychosomatic complaints, fears, information deficits, everyday life restrictions, and social strains. The instrument is regularly used as a screening tool in clinical practice to identify psychosocial supportive needs in cancer patients. Based on the total score, we classified a value above 14 points as a positive screening result (Book et al. 2011) reflecting an elevated level of distress.

Posttraumatic growth was measured with selected scales of the Posttraumatic Growth Inventory (Tedeschi and Calhoun 1996). The instrument assesses positive outcomes as consequences of a traumatic event. The 5YFU included all scale-specific items for the factors: new possibilities, spiritual change, and appreciation of life. Each factor scale ranges from 0 to 5. Higher scores imply stronger posttraumatic growth in the respective area (Tedeschi and Calhoun 1996).

To estimate HRQOL deficits among rehabilitants and non-rehabilitants in comparison to population controls, we included data from the LinDE study. The LinDE study was a cross-sectional survey conducted in 2013/2014 to obtain normative HRQOL data, among other self-reported health outcomes, in a randomly selected sample of the German population for comparisons with cancer patients and survivors. Age- and sex-based sampling was performed by the regional municipal offices. Potential participants, aged 18 and above, received study information and the questionnaire including the EORTC-QLQ-C30 instrument by mail. In contrast to most published aggregated normative HRQOL data (Nolte et al. 2019; Waldmann et al. 2013), the LinDE study was a nationwide study, oversampling the older age groups to guarantee a sufficient sample size for comparisons with cancer survivors in those age groups most affected by cancer. Moreover, data are available on an individual level. The response rate was 29%. Further study details are published elsewhere (Arndt et al. 2017). Based on the age- and sex-specific distribution of the CRC rehabilitants in the DACHS study, we performed a frequency distribution matching and drew a sample of comparable population controls after excluding controls outside of rehabilitants’ age range or with a prior history of CRC.

Among the 2125 CRC survivors who participated in the 5YFU (response rate 86.5%), 154 (7.2%) sent back a short form of the questionnaire only, for 63 participants (3.0%) prior ICR was unknown and two participants (< 0.1%) underwent outpatient rehabilitation only. In the final analyses, we included 1906 survivors (see Supplementary Fig. S1). Sociodemographic and clinical characteristics of survivors according to past utilization of ICR are presented in Table 1. About 11% of the survivors had experienced CRC recurrence until the 5YFU. The mean age of the participants was 66.3 at diagnosis and 71.3 at follow-up (± 10.4). Approximately half (49%) of the participants had undergone ICR. Rehabilitants were slightly younger and more likely to be employed at the time of diagnosis, to have no partner, to have statutory health insurance, and to have higher prediagnosis physical activity level, and were less likely to be diagnosed with cancer stage I compared to non-rehabilitants. Based on available rehabilitation discharge letters for a subset of rehabilitants (53%), time from diagnosis to start of ICR was calculated. The majority of rehabilitants underwent ICR within the first 2 months after CRC diagnosis (median = 1.7 months) and the mean time from diagnosis to start of ICR was 5.2 months (standard deviation = 7.4 months).

At first glance, lower levels of HRQOL and higher levels of distress among rehabilitants in comparison to non-rehabilitants may appear surprising, since a previous analysis from the DACHS study had suggested higher survival rates of patients who had undergone ICR (Scherer-Trame et al. 2021). Furthermore, previous, albeit much smaller studies had reported increases in HRQOL of CRC patients during ICR (Lamprecht et al. 2017; Riedl et al. 2017; Singer and Schulte 2009), even though positive changes in health-related outcomes generally seemed to wane over time (Allgayer et al. 2005, 2012; Biskup et al. 1994; Mehnert et al. 2013). However, respective studies also lacked a control group not undergoing ICR, and study results on treatment benefits on psychological distress are not conclusive (Klocker et al. 2018; Lamprecht et al. 2017; Riedl et al. 2017; Ross et al. 2015). Given the cross-sectional assessment of the patient-reported outcomes in our study, the analysis does not allow to draw any conclusions on potential causal relationships. In particular, despite comprehensive adjustment for a large number of potential confounders, there may still be relevant residual confounding by unmeasured covariates. More specifically, rehabilitants and non-rehabilitants likely differ by factors related to indication of ICR, which are hard if not impossible to completely adjust for. Indication-related health conditions possibly persist or recur after rehabilitation and may influence survivors’ quality of life several years after diagnosis. Finally, selective survival of rehabilitants and non-rehabilitants could also have led to apparent differences in patient-reported outcomes among 5-year survivors. Poorer health outcomes including general health problems, wellbeing, participation, and vitality among CRC survivors who had undergone ICR have been reported previously by Deck et al. (2019). Respective differences between rehabilitants and non-rehabilitants, however, were unadjusted and based on a small sample.

Although the aforementioned factors prohibit drawing firm conclusions, the patterns we observed may give rise to a number of hypotheses that might be worth to be followed up in future research. One such hypothesis would be that rehabilitants might be more health conscious and more alert with respect to detriments in HRQOL or symptoms, and such conscious perception might even be strengthened during ICR. Another hypothesis along similar lines of reasoning might be that ICR may support the development of posttraumatic growth, taking into account that a salutogenetic consciousness, the conveyance of which is a principle of rehabilitation care, and promotes self-care and constructive coping with the disease (Ochoa Arnedo et al. 2019). In addition, higher perceived burden of CRC diagnosis, which was shown to be related to posttraumatic growth (Jansen et al. 2011b), might have led to the decision of undergoing ICR. Nevertheless, for the time being, such hypotheses remain speculative. The final answer on potential effects of ICR on long-term patient-reported outcomes of CRC patients would have to come from randomized controlled trials (RCTs). Although a few mostly small controlled trials have evaluated short-term effects of different treatment modalities among rehabilitants (Allgayer et al. 2004, 2008), to our knowledge, no RCT to date on an intervention comparable to the multidimensional rehabilitation programs offered in Germany has compared long-term outcomes of rehabilitants and non-rehabilitants.

The HRQOL deficits we observed in this cohort of CRC were consistent with previous findings from other studies (Arndt et al. 2017; Caravati-Jouvenceaux et al. 2011; Jansen et al. 2011a; Thong et al. 2019). CRC survivors of both treatment and age groups reported higher levels of bowel dysfunctions and younger survivors generally experienced detriments in social participation and higher financial strain. Contrary, the lower pain levels we observed among this cohort of survivors are in line with findings by Thong et al. (2019) and might be explained by a response shift that reflects a general higher threshold of pain perception and tolerance following cancer treatment (Visser et al. 2013). However, in addition to the confirmation of previous results, we were able to identify a group of CRC survivors—younger rehabilitants—who seem to experience deficits in almost every dimension, whereas non-rehabilitants and older rehabilitants showed HRQOL scores comparable to population controls apart from the aforementioned scales. Since employed patients were more likely to receive ICR than retired patients (Scherer-Trame et al. 2021), poorer cognitive, role functioning, and larger financial strain in younger rehabilitants could derive from an unsuccessful return to work as described in breast cancer patients (Schmidt et al. 2019). Larger deficits in social participation might be linked to higher level of digestive dysfunctions as we have found a significant moderate negative correlation between the scales social functioning and diarrhea for both treatment groups (r = − 0.30/− 0.33). Gas and stool leakages and the need for a restroom within reach can affect mobility and social participation severely (Rothbarth et al. 2001). Deficits with respect to emotional and cognitive functioning as well as higher levels of fatigue and insomnia suggest a symptom cluster that indicates higher psychological strain among younger CRC survivors that had undergone ICR.

Younger CRC patients who had undergone ICR may benefit from follow-up concepts after ICR. Follow-up programs aim to maintain treatment success, promote the return to work, and support the rehabilitants applying recommendations into daily life (German Pension Insurance 2019; Koch and Bergelt 2019). However, uptake of these programs is rather low in cancer rehabilitants compared to other indication groups. In recent years, the implementation of telephone- or web-based follow-up concepts has been discussed and tested as pilot projects, since this approach could potentially facilitate nationwide access as well as cost-effective and indication-specific care (Sewöster et al. 2014; Zwerenz et al. 2017).

We were able to assess differences with respect to past ICR in a large representative cohort of survivors 5 years after CRC diagnosis. Major strengths of the study include comprehensive confounder adjustment, satisfying completeness of data and the high response rate among the DACHS follow-up participants. Non-responders did not differ regarding sex or cancer stage, but were found to be older, lower educated and to have a higher comorbidity score. However, differences seemed to be minor, and ICR utilization was similar among non-responders (44%) and responders (49%). Valid information on possible repeated ICR stays and on ICR that was administered 3 years after diagnosis was not available. Thus, findings refer to any ICR within the postulated period. Standardized cancer-specific instruments were administered to measure HRQOL and distress, but the cross-sectional assessment did not allow us to draw any conclusions on effectiveness of treatment. Longitudinal assessment of the outcomes and relevant information on medical indication for ICR would be prerequisites to evaluate effectiveness.

We identified HRQOL deficits in rehabilitants and non-rehabilitants in comparison to the general population. In addition to the confirmation of previous findings concerning deficits in CRC survivors, we were able to point out the disease-related health burden in younger survivors who had undergone ICR. The response rate within the LinDE study was low which is common for population-based surveys. Therefore, the possibility has to be kept in mind that healthier individuals were more likely to participate. Since this also might be true for the recruitment of the DACHS study or the participation in the follow-up, observed deficits may still not be overestimated. Education levels were higher among the population controls, but this difference could be adjusted for in the analysis. Despite some limitations, the LinDE study served as a very useful population-based reference due to application of the same questionnaire instruments and conduction during the same calendar years.

The utilization of ICR predicted worse HRQOL scores in several dimensions and distress but also higher posttraumatic growth among CRC survivors. Differences by treatment groups were pronounced in survivors, who were younger than 70 years at follow-up. We found younger rehabilitants to experience strongest deficits of functioning and highest symptom burden when compared to age-matched pairs from the general population. Observed long-term deficits possibly reflect the initial indication for past ICR. Future studies of controlled design and longer observation period are essential to investigate long-term effectiveness of rehabilitation treatment. To optimize treatment allocation and content, further research on determinants of therapy success including potential follow-up concepts after ICR is needed.