Background
Oesophagectomy is an exemplar model of a complex operation, with a relatively high postoperative risk of major morbidity [
1], and defined nutritional and health-related quality of life (HR-QOL) implications [
2,
3]. Oesophageal cancer is the eighth most common cancer globally, with an estimated 456,000 new cases in 2012 (3.2% of all cancers) and the sixth most common cause of cancer mortality (4.9% of all cancer deaths) [
4]. Approximately 20% of patients diagnosed with oesophageal cancer undergo oesophagectomy with curative intent [
5]. This complex procedure involving upper laparotomy usually in combination with thoracotomy and one lung anaesthesia, and is associated with significant postoperative morbidity. Postoperative pulmonary complications (PPCs), which are among the most serious postoperative morbidity, occur in 15–30% of patients post-oesophagectomy and are the primary cause of postoperative mortality, contributing to 45.5–55% of post-oesophagectomy deaths [
6]. In the modern era, surgery is preceded by chemotherapy or combination chemoradiotherapy for the majority of patients who present with locally advanced disease [
2]; an approach which has contributed to 5-year survival rates of up to 47% [
7]. Accordingly, at a time when overall survival is improving, there is a growing emphasis on the nutritional, physical and emotional wellbeing of patients undergoing curative treatment for locally advanced disease [
8].
Oesophageal cancer and its treatment, particularly oesophagectomy, leads to significant anatomic and physiologic alterations of the gastrointestinal tract and thus the long-term nutritional implications of curative treatment for oesophageal cancer are well documented [
9]. Up to 80% of patients are cachexic at presentation [
10], with recent data demonstrating that weight loss, sarcopenia, malabsorption and altered gut hormone function persist into survivorship [
11‐
13]. Notwithstanding the considerable survival advantages of modern multimodal treatment regimens when compared with surgery alone [
2,
7], chemotherapy and chemoradiotherapy can adversely impact body composition and muscle strength [
14], with emerging evidence linking loss of skeletal muscle mass during neoadjuvant therapy with chemotherapy toxicity and major postoperative complications [
15].
It follows therefore that there is a significant risk of decline in physical functioning resulting from both curative treatment for oesophageal cancer and poor nutritional status. Declines in cardiopulmonary fitness, a key determinant of physical functioning [
16], ability to engage in activities of daily living [
17], and increased risk of postoperative complications [
18] are reported with neoadjuvant chemo(radio)therapy [
19‐
21], and associated with higher mortality risk at 1-year post oesophagectomy [
21]. Physical inactivity is associated with increased postoperative risk following oesophagectomy [
22] and is a defined problem among cancer survivors [
23,
24], associated with HR-QOL [
25] and, increasingly, survival outcomes [
26]. While an acute decline in physical fitness, muscle strength and HR-QOL is described from pre-oesophagectomy to post-operative discharge [
17], prospective evaluations characterising the impact of oesophagectomy on physical outcomes, particularly long-term evaluations of physical functioning, are lacking [
27]. Subjectively, patients report perceived deficits in physical functioning domains of HR-QOL which persist into survivorship [
28,
29]; however, the measured impact of oesophagectomy on physical functioning is inadequately quantified. We have previously described deficits in cardiorespiratory fitness and moderate-to-vigorous intensity physical activity participation in oesophageal cancer survivors at up to two years post-operatively, in comparison to age- and gender-matched controls [
30], suggesting that curative treatment exerts a profound and lasting impact on physical status.
With increasing emphasis on survivorship care in oesophageal cancer, there is a recognised need to better understand the physical consequences of oesophageal cancer and its treatment in order to develop tailored rehabilitation programmes involving exercise and diet prescription to attenuate the impact of treatment on physical functioning and optimise HR-QOL in recovery [
31]. Cancer survivorship models emphasise that exercise rehabilitation implemented early in the cancer continuum, particularly within the first 6-months postoperatively, is likely to have the greatest impact on HR-QOL [
32]. This study therefore seeks to characterise the impact of oesophagectomy on physical functioning and habitual physical activity participation in early postoperative recovery and up to 6-months post-oesophagectomy to inform targets and priorities for exercise rehabilitation during this period.
Discussion
This study provides a novel prospective evaluation of measured and perceived change in physical functioning following oesophagectomy. It demonstrates that habitual physical activity participation and perceived role functioning remain significantly impaired at 6-months post-surgery, despite exercise capacity recovering to preoperative levels. Consistent with previous reports, symptom scores worsened postoperatively [
41] and percentage weight loss was clinically significant at 6-months [
13]. This significant and clinically relevant pattern of deterioration highlights the challenges of transitioning from active treatment to survivorship post-oesophagectomy and adjusting to the
‘new normal’ after cancer.
The significant short-term and long-term impairments in global HR-QOL, and specifically in physical functioning and symptom burden, that arise following oesophagectomy are well-reported [
3,
29,
41‐
43]. Consistent with the pattern of deterioration in HR-QOL reported by others [
41,
42], we observed the largest postoperative impact in the physical functioning domain, specifically in the physical function and role function scales, of the EORTC QOQ-C30. While both scales had improved by 6-months post-surgery, role function remained a clinically relevant 33-points lower in comparison with pre-operative values. Clinically important deteriorations in physical functioning are reported with all curative interventions for oesophageal cancer, including neoadjuvant therapy, minimally invasive surgery and open surgical resection [
29]. Importantly however, despite improvements in the majority of HR-QOL domains over time, patient-perceived physical functioning remains impaired at 1-year [
41], 2-years [
44] and up to 3-years post oesophagectomy [
43]. Uniquely, we demonstrate that this profound patient-perceived deterioration in physical health is matched by clinically relevant changes in habitual activity participation.
Functional decline associated with cancer treatment is typically examined using validated, objective measures of physical functioning [
16]. Using this approach, we observed an acute deterioration in physical activity participation, as measured by accelerometry, at 1-month post-oesophagectomy, with physical activity levels and sedentary behaviour remaining impaired at 6-months. Consistent with this, we have previously reported that moderate-to-vigorous intensity activity participation is significantly lower at 2-years post-oesophagectomy in comparison with age- and gender-matched controls [
30]. Importantly, accelerometry captures habitual activity participation during waking hours and therefore, engagement in activities of daily living, a construct that is well-aligned with the role functioning domain of the EORTC QLQ-C30 [
45], which was were perceived by participants to remain considerably impaired in survivorship. Role functioning considers an individual’s ability to engage in activities that are typical for their age and social setting [
45]. In patients with cancer, physical activity levels are known to reduce at cancer diagnosis and rarely return to baseline levels following treatment completion [
24]. Compared to those who are inactive or sub-optimally active, cancer survivors who exercise to recommended levels consistently report higher HR-QOL scores, particularly in physical and role functioning domains [
25], hypothesised to be driven by the positive effects of physical fitness on mental wellbeing and social engagement [
46], making physical activity an important and influential target in survivorship care.
Cardiopulmonary fitness, the primary measure of physical functioning [
16], is impaired by the iterative attritional impact of multimodal treatment regimens in oesophageal cancer [
27]. We observed a large, clinically important reduction (− 39.10 (95%CI − 68.28 to − 9.92) m) in 6MWT distance at 1-month post-oesophagectomy, consistent with the decline previously reported in a Japanese cohort from pre-surgery (563.3 (73.2) m) to pre-hospital discharge (485.3 (85.6) m) [
17]. In colorectal resection, 6MWT distance at 4-weeks post-surgery is discriminative of older age, poorer physical status, open resection and occurrence of postoperative complications, and therefore is a valuable indicator of early physical recovery [
47]. While the 6MWT provides a valid measure of functional exercise status in patients with cancer [
48], reliability and reproducibility data is lacking [
16], and walking distances correlate poorly with cardiopulmonary fitness in comparison with incremental walking protocols [
49]. In contrast to our observation that 6MWT distance returned to preoperative values at 6-months postoperatively, suggesting an element of natural recovery in this cohort, a study in a Japanese cohort, utilising the highly sensitive cardiopulmonary exercise test, reported a reduction in exercise capacity from 1186.6 (300.30) ml/min pre-oesophagectomy to 916.1 (238.6) ml/min 3-months postoperatively (
p < 0.0001) following open resection [
50]. Furthermore, we previously reported significantly lower walking distance in disease-free patients up to 2-years post-oesophagectomy (558.33 (146.43)m) in comparison with age- and gender-matched controls (773.48 (114.00)m) using a progressive, incremental walking protocol [
30]. Therefore, it is likely that cardiopulmonary fitness remains impaired in oesophageal cancer survivorship; however further prospective evaluations using sensitive measures of fitness are required.
The nutritional challenge of recovery post-oesophagectomy is well-documented. Consistent with previous reports, in this cohort weight loss remained significant at 6-months [
13] and symptom burden was considerable in early post-operative recovery. While HGS, a reliable indicator of whole-body muscle strength and nutritional status [
51], remained stable over the study period, we have previously reported significant deficits in grip strength with loss of lean body mass during neo-adjuvant therapy [
14]. Furthermore, sarcopenia remains prevalent in survivorship with 35% of patients sarcopenic at 1-year post-oesophagectomy [
13]. This complex interplay between nutritional insufficiency and physical deterioration makes survivorship rehabilitation particularly challenging. We recently designed, implemented and evaluated the Rehabilitation Strategies Following Oesophagogastric Cancer (ReStOre) programme, a rehabilitation programme for oesophagogastric survivorship comprising exercise training, individualised dietary counselling and multidisciplinary education, with a strong focus on self-management [
52‐
54], leading to clinically important improvements in cardiopulmonary fitness [
52], inflammatory status [
53], and multiple domains of HR-QOL [
54]. The ReStOre programme, the first exemplar in oesophagogastric cancer rehabilitation, included participants up to 5-years post-surgery, however rehabilitative measures implemented earlier in survivorship, particularly within the first 6-months, are likely to have greatest effect [
32] and address the issues identified by this work. Consistent with established clinical rehabilitation models, cancer rehabilitation commencing from diagnosis and continuing through the treatment trajectory, may have a key role in attenuating the impact of multiple attritional oncologic treatments, optimising patient condition for surgical intervention and supporting patients through recovery and into survivorship [
8,
31].
This work has some limitations which are acknowledged. Firstly, participant retention was challenging with 69% of those initially recruited (
n = 52) available for evaluation at 6-months (
n = 36). This is an inevitable challenge of prospective data collection in a cohort undergoing complex surgical and medical interventions. Reasons for attrition are reported and were largely attributed to disease progression and protracted postoperative morbidity. Importantly, those included in the final analyses had comparable baseline characteristics to those lost to follow-up. Nonetheless, the final study cohort represent those who are recovering relatively well at 6 months post-surgery and therefore generalisability is limited. The sample size is comparable to other published work in this field [
17,
30,
50]. The use of objective measures of physical functioning is a considerable strength of this work. By employing these methods, multiple measurable and modifiable targets for physical rehabilitation were identified which were well-aligned with patient-reported survivorship issues.
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