Burden of disease experienced by patients following a watch‐and‐wait policy for locally advanced rectal cancer: A qualitative study

Abstract Aim Patient‐reported outcome measures (PROMs) are increasingly being used in routine cancer care to evaluate treatment and monitor symptoms, function and other aspects of quality of life (QoL). There is no suitable PROM for rectal cancer patients following a watch‐and‐wait (W&W) programme. Insight into patient experiences with this programme is an essential step in the development of a PROM. The aim of this qualitative study was to provide insights into the most important functional outcomes and QoL features experienced by patients during our W&W programme. Method Patients with locally advanced rectal cancer who are enrolled in the W&W programme in the Netherlands were interviewed by telephone using a semistructured interview guide. All interviews were digitally audio‐recorded, transcribed verbatim and coded. A thematic approach was used to analyse the data and identify themes and subthemes of importance to patients. Results Eighteen patients were interviewed (78% male, mean age 68 years, range 52–83 years). Physical complaints after treatment were present, most notably gastrointestinal problems, neuropathy and fatigue. Furthermore, patients were anxious about a possible recurrence, had a fear of surgery or a stoma, or were experiencing a general feeling of apprehension in daily life. Many patients had different coping mechanisms, such as acceptance, and there were few limitations in daily life. Conclusion We identified important functional outcomes, such as gastrointestinal complaints, fatigue and neuropathy, in patients who were enrolled in this W&W programme. Furthermore, an emotional burden and unmet needs were reported by these patients. These findings can be used to improve clinical practice and inform the development of a PROM.


INTRODUC TI ON
In recent years, the organ-preserving treatment method of a watch-and-wait (W&W) policy after a clinically complete response following neoadjuvant chemoradiation therapy (nCRT) has being increasingly adopted in the treatment of locally advanced rectal cancer [1][2][3][4]. Its principle of having a clinically complete response to nCRT followed by a stringent follow-up scheme rather than surgical treatment has proven its value, with a 5-year overall survival of 85% and 5-year disease-specific survival of 94% [2]. Hupkens et al. state that patients enrolled in a W&W programme potentially have a better quality of life (QoL) and improved functional outcomes than patients who underwent nCRT and total mesorectal excision (TME) [5]. However, despite not undergoing surgery, approximately a third of the W&W patients experience symptoms of major low anterior resection syndrome (LARS) as a consequence of nCRT [5]. Nevertheless, the sample size in this and other studies is small, and the lack of validated instruments for the W&W population limits the generation of evidence [1,6,7]. During our W&W programme patients follow an intensive follow-up schedule, consisting of digital rectal examination, MRI, endoscopy (with biopsy) and carcinoembryonic antigen measurements every 3 months for the first 2 years and 6-monthly thereafter up to 5 years. Annual CT scans are used to detect distant metastases. During follow-up it is important not only to focus on oncological outcomes and physical symptoms but also to monitor the emotional, social and cognitive health of patients. However, patients do not always discuss these outcomes with clinicians, and clinicians often underestimate how much importance patients attach to functional outcomes and QoL compared with survival [8][9][10].
Patient-reported outcome measures (PROMs) reflect a patient's own evaluation of his or her symptoms, functional outcome and QoL. The routine use of PROMs is reported to have a positive impact on the level of care and patient outcomes [11][12][13]. They serve as a foundation for patients to discuss with their healthcare workers the issues that are important to them, improving communication and shared decision-making. PROMs may also encourage patients to reflect on their condition and to get a deeper understanding of how their condition affects them in their daily lives [11][12][13].
Questionnaires such as the EORTC-QLQ-C30 and EORTC QLQ-CR38 are examples of PROMs developed for cancer patients [14,15]. In addition, the Short Form 36 (SF-36) [16], the Vaizey score [17], the LARS score [18], the IIEF and FSFI questionnaires to indicate sexual problems [19,20] and the IPSS to assess problems of the urinary tract have been used in W&W patients [21]. None of these PROMs focus specifically on W&W patients. They were all developed and validated in patients who had surgery, except for the SF-36 and EORTC-QLQ-C30 which are suitable for the general population and a wide range of cancer patients, respectively. As a result, the relevance and usefulness of these PROMs may be limited in W&W patients. For use in clinical practice, a short PROM would support follow-up care as it would provide a clear overview of the problems experienced by W&W patients [22]. Currently, such a PROM is not available for patients enrolled in W&W programmes, and no data are available on patients' experiences or outcomes during the W&W follow-up period.
In this study, we aimed to identify the experiences and functional outcomes of W&W patients during their follow-up period and how the disease, its treatment and the W&W programme affect their daily lives. Findings from this study can aid in the development of a PROM for W&W patients to be used in clinical care.

Study design
This study had a qualitative research design with semistructured interviews to explore patients' views regarding functional outcomes and QoL during our W&W programme. We chose semistructured interviews to ensure that certain topics were discussed while still allowing patients to discuss everything they wanted to share.
A purposive sampling technique based on age, gender and time in follow-up was used to include a variety of patients with a range of characteristics, representing the W&W population. The estimated sample size for the patient interviews was 15-20 patients, but saturation was used as a criterion for discontinuing the patient interviews [23].
All candidate patients were contacted by their treating colorectal surgeon (JM or SB) to assess their willingness to participate. If the patient was willing to participate, one researcher (AP) contacted the patient to explain the purpose of the study and procedures in depth, and to make an appointment for the interview.
At the start of each interview written consent was obtained. The

Study population
The study population consisted of patients with locally advanced rectal cancer who are enrolled now, or have been enrolled in the past,

What does this paper add to the literature?
This is the first study dedicated to the experience of patients in a watch-and-wait programme for rectal cancer.
The study provides new insights into the physical and emotional burden of patients in this programme; these insights can be used to develop a patient-reported outcome measure to improve individualized care for this population. in our W&W programme as described by Maas et al. [1]. Exclusion criteria were insufficient proficiency in the Dutch language or recurrence of disease during follow-up.

Data collection
Between August 2019 and January 2020 a telephone interview was conducted with each patient. All interviews were conducted by the same researcher (AP) who is a male medical doctor working as a clinical investigator and trained in conducting interviews.
The interviewer had no prior encounter or relationship with the patients. During the interviews, an interview guide was used that focused on three topics: (1) the initial treatment for rectal cancer, (2) experience during the W&W programme, (3) important functional outcomes according to the patient (see Appendix 1). The main focus of the interviews was on topics two and three, whereas topic one was used as an introduction to the interview. During each interview, patients were encouraged to describe the experiences and problems they had encountered during the W&W programme. The interview guide was designed to allow the patient to have the opportunity to elaborate on certain topics, so it contained follow-up questions such as: 'You mentioned [symptom/problem]. Can you tell me more about this?' All interviews were digitally audio-recorded and transcribed verbatim. Interview transcripts were fully anonymized.

Data analysis
Two researchers (AP and AG) analysed the data manually using a thematic approach as described by Ritchie et al. [25]. The researchers independently read and reread the first five transcripts and coded them descriptively using an inductive approach, then they compared codes and resolved discrepancies to create a coding tree for the remaining transcripts. Any new codes were discussed and, if appropriate, added to the coding tree. Finally, all codes were analysed and similar concepts were grouped into (sub)themes. Themes were discussed with MK (a senior health technology assessment researcher, with a focus on outcomes research) and SB (a consultant in colorectal surgery at the Maastricht University Medical Center involved in the W&W research).

RE SULTS
Eighteen patients participated in the study, of whom 14 (78%) were male and 4 (22%) female with a median age of 68 years (range 52-83 years). All patients received nCRT according to the Dutch national colorectal cancer guidelines [26]. The mean follow-up after inclusion into the W&W programme was 32 months (range 5-71 months).
Patients had different lengths of follow up (nine patients ≤2 years, seven patients between 3 and 5 years and two patients >5 years) ( Table 1).
Interviews lasted between 20 and 30 min. Analysis of the interviews showed that after the 15th interview no new codes emerged. However, the researchers conducted and analysed three additional interviews to ensure saturation, and still no new codes arose [23].
Four main themes were identified in the interviews: physical symptoms, emotional aspects, coping and impact on daily life.
Themes and associated subthemes are summarized in Figure 1.

Physical symptoms
Patients experienced a range of symptoms during initial treatment with nCRT and the W&W programme. Gastrointestinal symptoms, prolonged fatigue and persistent neuropathy caused by chemotherapy were the most frequently mentioned symptoms during the W&W period. One patient mentioned: 'As soon as I feel I have to go to the toilet I have to go, because I cannot defer defaecation for long.' Many patients reported complaints of diarrhoea and pain with bowel movement during and shortly after initial treatment, but these complaints mostly disappeared within the first 6 months after treatment. Fatigue also seemed to diminish in patients who experienced it during the treatment period. Others, who did not notice it as much at the beginning, mentioned needing to rest during the day to be able to function in the evening. One patient said: 'In the past (before treatment), I could sometimes take a nap in the afternoon, but now I have to do it every day otherwise I am exhausted at the start of the

Emotional aspects
The emotional impact of the W&W programme clearly emerged during the interviews. Anxiety was the most prominent emotion

Impact on daily life
When  By including patients at different time points in their follow-up, we were able to identify the range of issues that patients may face during their follow-up. We found that patients' perspectives may change over time. For example, we found that patients who were at least 2 years into the W&W programme reported fewer problems related to anxiety or insecurity compared with those who had just started within the programme.

DISCUSS ION AND CON CLUS IONS
We found that physical complaints were consistent with a recent study by Han et al. on symptoms after treatment for colorectal cancer [27]. Gastrointestinal complaints were the most common, most likely related to the effects of radiotherapy on anorectal function in this population [28]. Other studies confirm this unfavourable short-and long-term effect of radiotherapy on anorectal function [29,30]. Besides gastrointestinal symptoms, fatigue and neuropathy were common complaints that are frequently seen in colorectal cancer patients after chemo(radio)therapy [27].
Remarkably, no patients reported any urinary dysfunction, even though this problem is commonly reported after rectal cancer treatment, especially TME [31][32][33]. The fact that our patient population did not undergo surgery, thereby preserving pelvic innervation, could be an explanation for this finding. Furthermore, only a few male patients mentioned sexual dysfunction. This too could be related to the fact that our population did not undergo surgical resection. The absence of sexual dysfunction in the female patients was notable. Yet we cannot conclude that sexual dysfunction is absent or less important in female patients based on our study findings. Sexual dysfunction in women is multifactorial and complex, involving physical and psychological aspects such as libido, sexual arousal and body image [34]. It is possible that participants felt uncomfortable or the questions did not probe the participants to open up about such a sensitive and complex topic in our study setting (e.g. telephone interview, male interviewer). Furthermore, the small number of female participants may have resulted in underreporting of these problems. A recent study by Angenete et al. [35] showed that female rectal cancer patients indeed experience considerable sexual dysfunction in the form of dyspareunia and a reduced ability to achieve an orgasm after abdominoperineal resection. Nevertheless, women were less affected by these problems than men in their daily life.
Only a few patients reported cognitive impairment in daily life, mostly experienced during work-related activities. However, a study by Vardy et al. [36] showed that colorectal cancer patients had significant cognitive impairment compared with healthy controls after neuropsychological testing. However, these results were only mildly associated with self-reported cognitive impairment [36]. This could explain the low reports of cognitive impairment in this study.
The most prominent emotional impact after treatment and while in the W&W programme was anxiety in the form of fear of recurrence. This fear is common among cancer patients [37,38].
Participants said that levels of anxiety increased around checkups. This may suggest that patients enrolled in the W&W programme experience more anxiety or anxiety-related complaints than other CRC patients because of the strict follow-up schedule.
Compared with regular follow-up in colorectal cancer, patients in the W&W programme undergo sigmoidoscopies and MRI scans every 3 months during the first 2 years. Hupkens et al. [5] conducted a study comparing W&W patients with patients who underwent nCRT and surgery (TME) and found that W&W patients scored lower on general health according to the SF-36 questionnaire. The authors hypothesized that this might be because the rectum is not resected and the possibility of regrowth still exists [5]. However, participants in this study stated that a good result during follow-up visits reassured them that no tumour was present and immediately decreased their fear. Patients are informed at the start of the W&W programme, however, that the probability of recurrence is highest during the first 2 years after treatment [39].
While there is no difference in overall survival between the W&W population and patients who underwent nCRT with resection, the chance of local regrowth is higher in the W&W population [40].
Although not explicitly mentioned by patients in this study, this may induce anxiety during the programme, especially in the first 2 years.
The interviews provided insight into the different ways of coping by colorectal cancer patients (e.g. acceptance, support by clinicians, social support, positive reappraisal and optimism). It is known that such an active coping strategy is associated with posttraumatic growth [41]. Posttraumatic growth or benefit is defined as experiencing positive psychological changes following trauma or life crises (e.g. cancer diagnosis) [42]. The different ways of coping can explain why patients feel so little hindrance in daily life. This is a common finding in cancer patients at all different stages of disease [43] The findings of this study will be used to inform the development of a novel PROM for W&W patients. Together with outcomes identified in the literature, the outcomes expressed by patients in this qualitative study will inform a longlist of potential outcomes to be incorporated in a PROM. With patient representatives and a team of experts from the International Watch-and-Wait Database collaboration we have set up an international Delphi study involving a range of stakeholders to reach consensus on the issues and outcomes to be addressed in the PROM [47]. With the possibility of underrepresentation of female participants in this study, we will strive for equal participation of female and male patients in the Delphi study to ensure both perspectives are included in the final PROM.
In conclusion, through direct engagement with patients in the form of individual interviews, this study provides a deeper insight into important outcomes, potential unmet needs and coping strategies in patients enrolled in our W&W programme.

Participants
Participants will be purposively drawn from a prospectively maintained database of rectal cancer patients followed in a wait-and-see approach at MUMC+ and the Antoni van Leeuwenhoek Hospital. A purposive approach to sampling has been selected with the aim of maximizing diversity within the study participants. Criteria have been selected to ensure that subsets within the study population that may express contrasting views and experiences are present. These criteria for difference will be used to populate a sampling matrix.

Sampling matrix
Key criteria for identifying difference will include: