The currently published paper “Reduced fitness and physical functioning are long-term sequelae after curative treatment for esophageal cancer: a matched control study” by Gannon et al. (1) focuses on a highly relevant topic of esophageal surgery, which has been greatly under-addressed in the past. Objective data on physical performance outcomes and health-related quality of life (HRQOL) of disease-free survivors after esophagectomy for cancer compared with a noncancer control group are rare (1). Data by Gannon et al. clearly show that disease-free survivors of curative esophageal cancer treatment display a significant compromise in physical functioning as compared to the control group, highlighting the multiple, complex rehabilitative needs of this cohort (1).
In the recent years, new surgical techniques with reduced operative trauma, such as hybrid, minimally-invasive or robotic esophagectomy (2) and advanced possibilities of postoperative intensive care treatment, as well as measures with positive impact on enhanced recovery-rehabilitation (3) as optimized clinical pathways (4,5) have been introduced. In principal, these measures should prevent cardiorespiratory complications and restore patients’ physical functioning and fitness more quickly and, thus, quality of life. Regardless of these improvements, persisting long-term dysfunctions and their respective consequences following esophagectomy for cancer still seem a largely underestimated feature in clinical practice. In this context, the enormous delay of recovery after surgery does not only influence patients’ private life, life quality and physical, psychological and social re-integrity, but also health-economic and socio-medical aspects, considering additional costs associated with prolonged stationary or ambulatory medical treatments, as well as loss of working hours due to sick leave. Thus, the study of Gannon et al. (1) hints to two relevant approaches, which consequently have to be drawn from their data: the urgent need for (I) prevention, preconditioning and prehabilitation before surgery, and for (II) more comprehensive, complex and holistic rehabilitation measures after esophagectomy. Analysis of the current literature clearly concludes a paradigm shift emphasizing the high value of preconditioning and promoting a culture of prehabilitation for the surgical cancer patient (6). Multimodal prehabilitation has impressively been shown to improve patients’ functional capacities in the long run (7). Preliminary findings indicate that a group of interventions, such as physical exercise, nutrition and anxiety reduction/coping in the preoperative period can improve functional restoration and complement the enhanced recovery program as facilitating the return to baseline activities of daily living (6). However, it is not clear at this stage, whether the preoperative increase in functional capacity mitigates the burden of postoperative morbidities and subsequent cancer therapies (6).
Oncologic esophagectomy for cancer is a demanding and sophisticated two-hole (abdomino-thoracic) procedure accompanied by significant surgical trauma, thus relevantly interfering with patients’ physiologic state and physical integrity. Initially reduced physical well-being, due to malnutrition caused by dysphagia (8), or even due to sarcopenia (9) at first presentation may further compromise clinical outcome. Additionally, neoadjuvant therapy alone or in combination with (radio-) chemotherapy at the time of surgery may each for itself decrease the cardiorespiratory and muscular reserves (10) and deteriorate the postoperative course, with the possibility that in some patients the harms of neoadjuvant therapy may outweigh its benefits (11).
Esophagectomy entails the risk of relevant morbidity and mortality (12). Perioperative complications influence short- and long-term outcomes after esophagectomy. Patients undergoing surgery for esophageal cancer have a high risk for postoperative deterioration of lung function and consequently for pulmonary complications. This is partly due to one-lung ventilation during thoracotomy/thoracoscopy. It often accounts for prolonged stay on the intensive care unit, delayed postoperative reconvalescence, and reduced quality of life. Potential surgical complications in the postoperative phase contain—on top of medical and general events, such as the above mentioned pulmonary, as well as cardiovascular, thromboembolic and infectious events—the risk of anastomotic leak, tracheobronchial fistula, arrosion bleeding, conduit necrosis, chyle leak, vocal cord injury/palsy, which can be life-threatening (12,13). If severe post-esophagectomy complications occur and patients survive, they might exert a persisting negative effect on HRQOL in the long run (14). Specific restrictions and aspects of quality of life do even deteriorate throughout the follow-up in patients with major postoperative complications, as compared to patients without major complications (14). With regard to surgical factors associated with HRQOL outcomes after esophagectomy for cancer, Rutegård et al. in a population-based study clearly showed, that there is no evidence to suggest that less extensive surgery for esophageal cancer should be recommended from the perspective of HRQOL (15). Thus, extensive surgery, as indicated by a transthoracic approach, more extensive lymphadenectomy, wider resection margins and a longer duration of surgery, was not associated with worse HRQOL measures than less extensive operations, and dysphagia was similar in patients who had handsewn and stapled anastomoses (15). However, technical surgical complications had significant deleterious effects on several aspects of HRQOL (15). In analogy to the study of Gannon et al. (1), HRQOL items were assessed 6 months after esophagectomy (15). Interestingly, the same study group reported, that HRQOL in long-term survivors after esophagectomy does not improve between 6 months and 3 years after surgery, and is worse than in a comparable age- and sex-adjusted reference population (16). Much longer intervals after esophagectomy for cancer, in turn, seem to improve and restore quality of life and functioning scores significantly, as shown by own data, assessing quality of life, as well as secondary cancers/diseases and esophagectomy-related, or unrelated interventions in the long-term course of surgery (17). Patients defined as long-term survivors (
The challenge in esophageal surgery, thus, consists of preoperatively elevating functional reserves and capacities to levels above baseline, as they are known to decline below baseline immediately after the operation. Using this measure of prehabilitation, functional recovery in the postoperative course is then much faster and on a higher level as compared to standard care (6). Physical preconditioning has become a crucial leverage to optimize fitness and lung function in patients scheduled for esophagectomy, in particular during the time period of neoadjuvant therapy, which should be utilized meaningfully for each patient, dependent on initial and developing individual capacities. Data derived from thoracic surgery strongly indicate, that preoperative exercise training (PET) in moderate to intense modalities exerts positive effects on aerobic capacity, physical fitness and quality of life (18). A reduction of postoperative complications and length of hospital stay was evident, whereas specific programs and intensities of training, especially the respiratory exercises, as well as outcome parameters were heterogeneous in the systematic review by Pouwels et al. (18). However, it was not stated, if smoking cessation was obligatory and successful in all studies (18). The feasibility and effectiveness even of a home-based exercise training program (HBETP) before lung resection surgery (LRS) has been demonstrated by Coats et al. in patients with lung cancer awaiting LRS (19). HBETP improved both exercise tolerance and muscle strength. The authors pointed out the clinical relevance, as poor exercise capacity and muscle weakness are known predictors of postoperative complications (19). Even patients with only low experience of physical activity and poor baseline walking capacity are most likely to improve their functional status preoperatively within a multimodal prehabilitation concept (20). Benefits have even been demonstrated for “medium-risk” surgery, as colorectal resections, where even short-term programs (e.g., preoperative exercise for 4 weeks) with minimum effort [e.g., 6-minute walk distance (6MWD)] significantly increased the amount of moderate- and vigorous-intensity physical activities performed and where patients with prehabilitation also demonstrated a greater improvement in 6-minute walk test (6MWT) compared to controls (21). As patients undergoing 6MWD before colorectal surgery—in spite of greater improvement in walking capacity throughout the whole perioperative period, when compared to rehabilitation started after surgery—displayed no significant differences with respect to complications and the duration of hospital stay (7), such programs may be more clinically meaningful and cost-effective, if targeted to specific subgroups with high perioperative risks, such as patients undergoing esophagectomy.
However, structured supervision, monitoring and follow-up, ideally by a professional sport’s therapist, patients’ security, adherence and compliance are the main pillars of sustained and long-term success performing prehabilitation. Indisputable in the context of preconditioning prior to esophagectomy is the positive effect of inspiratory muscle training to prevent postoperative pulmonary complications (PPC), especially with the use of high-intensity inspiratory exercise, being significantly more effective than endurance training (22), and to improve respiratory function (23).
The ongoing PREPARE study (preoperative inspiratory muscle training to prevent postoperative pulmonary complications in patients undergoing esophageal resection) by Valkenet et al. (trial registration: NCT01893008) is the first multicenter randomized controlled trial to evaluate the hypothesis that preoperative inspiratory muscle training leads to decreased pulmonary complications in patients undergoing esophageal resection (24). Patients have to complete 30 dynamic inspiratory efforts twice daily for 7 days a week until surgery with a minimum of 2 weeks. Main study endpoint is the incidence of postoperative pneumonia. Secondary objectives are to evaluate the effect of preoperative inspiratory muscle training on length of hospital stay, duration of mechanical ventilation, incidence of other postoperative (pulmonary) complications, quality of life, and on postoperative respiratory muscle function and lung function (24). However, intervention in this study does not start before the recovery period after (radio-) chemotherapy, potentially losing a valuable time interval, and it focuses on inspiratory exercise only. Follow-up measurements, e.g., of lung function, will end before hospital discharge and long-term data are not intended in the current study protocol (24).
Thus, we initiated the iPEP-study (internet-based Perioperative Exercise Program) (trial registration: NCT02478996), a prospective multicenter randomized-controlled trial. The objective is to evaluate the impact of an internet-based exercise program on postoperative respiratory parameters and pneumonia rates in patients with Barrett’s carcinoma scheduled for esophagectomy (25). Training consists of a combination of endurance, strength and intensive respiratory exercise. During the whole neoadjuvant therapy and recovery, patients in the intervention group receive an individually designed intensive exercise program based on functional measurements at baseline. Personal feedback of the supervisor with customized training programs is provided in weekly intervals. Primary endpoint is the change in peak oxygen uptake (VO2peak), secondary endpoints are the changes in forced expiratory volume in 1 second (FEV1) and in forced vital capacity (FVC) directly prior to surgery and at 12 weeks after surgery. Tertiary endpoints are pneumonia, surgical complications, length of postoperative stay, quality of life, and social support of disease coping (25). This study will evaluate, if an intensive individually adapted training program via online supervision during neoadjuvant therapy will improve cardiorespiratory fitness and reduce pulmonary complications following esophagectomy for cancer.
The above discussed programs and current studies will contribute to optimizing outcomes following esophagectomy for cancer and to counteracting postoperative reduced fitness, physical functioning and quality of life. Further research including large patient cohorts are warranted, in order to more comprehensively understand the ideal timing, intensity, duration, modalities and respective dynamics of perioperative prehabilitation and rehabilitation. In addition, detailed analyses of the simultaneous application of neoadjuvant (radio-) chemotherapy and physical exercise programs with regard to patients’ immune function and tumor behavior will provide more insights into the wide range from possibilities of improvement to potential threats of tumor spread. Physical, psychological and social integrity after esophagectomy correlate with quality of live dimensions and, thus, sustainable good functional outcomes should be the highest goal of esophageal cancer treatment in addition to high-quality oncologic results with favorable long-term prognosis.
Conflicts of Interest: The authors have no conflicts of interest to declare.
- Gannon JA, Guinan EM, Doyle SL, et al. Reduced fitness and physical functioning are long-term sequelae after curative treatment for esophageal cancer: a matched control study. Dis Esophagus 2017;30:1-7. [Crossref] [PubMed]
- Gockel I, Lorenz D. Oncologic esophageal resection and reconstruction: Open, hybrid, minimally invasive or robotic? Chirurg 2017;88:496-502. [Crossref] [PubMed]
- Li C, Ferri LE, Mulder DS, et al. An enhanced recovery pathway decreases duration of stay after esophagectomy. Surgery 2012;152:606-14; discussion 614-6. [Crossref] [PubMed]
- Munitiz V, Martinez-de-Haro LF, Ortiz A, et al. Effectiveness of a written clinical pathway for enhanced recovery after transthoracic (Ivor Lewis) oesophagectomy. Br J Surg 2010;97:714-8. [Crossref] [PubMed]
- Schmidt HM, El Lakis MA, Markar SR, et al. Accelerated Recovery Within Standardized Recovery Pathways After Esophagectomy: A Prospective Cohort Study Assessing the Effects of Early Discharge on Outcomes, Readmissions, Patient Satisfaction, and Costs. Ann Thorac Surg 2016;102:931-9. [Crossref] [PubMed]
- Carli F, Gillis C, Scheede-Bergdahl C. Promoting a culture of prehabilitation for the surgical cancer patient. Acta Oncol 2017;56:128-33. [Crossref] [PubMed]
- Minnella EM, Bousquet-Dion G, Awasthi R, et al. Multimodal prehabilitation improves functional capacity before and after colorectal surgery for cancer: a five-year research experience. Acta Oncol 2017;56:295-300. [Crossref] [PubMed]
- Yoshida N, Baba Y, Shigaki H, et al. Preoperative Nutritional Assessment by Controlling Nutritional Status (CONUT) is Useful to estimate Postoperative Morbidity After Esophagectomy for Esophageal Cancer. World J Surg 2016;40:1910-7. [Crossref] [PubMed]
- Elliott JA, Doyle SL, Murphy CF, et al. Sarcopenia: Prevalence, and Impact on Operative and Oncologic Outcomes in the Multimodal Management of Locally Advanced Esophageal Cancer. Ann Surg 2017. [Epub ahead of print]. [Crossref] [PubMed]
- Sinclair R, Navidi M, Griffin SM, et al. The impact of neoadjuvant chemotherapy on cardiopulmonary physical fitness in gastro-oesophageal adenocarcinoma. Ann R Coll Surg Engl 2016;98:396-400. [Crossref] [PubMed]
- Jack S, West MA, Raw D, et al. The effect of neoadjuvant chemotherapy on physical fitness and survival in patients undergoing oesophagogastric cancer surgery. Eur J Surg Oncol 2014;40:1313-20. [Crossref] [PubMed]
- Gockel I, Niebisch S, Ahlbrand CJ, et al. Risk and Complication Management in Esophageal Cancer Surgery: A Review of the Literature. Thorac Cardiovasc Surg 2016;64:596-605. [Crossref] [PubMed]
- Low DE, Alderson D, Cecconello I, et al. International Consensus on Standardization of Data Collection for Complications Associated With Esophagectomy: Esophagectomy Complications Consensus Group (ECCG). Ann Surg 2015;262:286-94. [Crossref] [PubMed]
- Derogar M, Orsini N, Sadr-Azodi O, et al. Influence of major postoperative complications on health-related quality of life among long-term survivors of esophageal cancer surgery. J Clin Oncol 2012;30:1615-9. [Crossref] [PubMed]
- Rutegård M, Lagergren J, Rouvelas I, et al. Population-based study of surgical factors in relation to health-related quality of life after oesophageal cancer resection. Br J Surg 2008;95:592-601. [Crossref] [PubMed]
- Djärv T, Lagergren J, Blazeby JM, et al. Long-term health-related quality of life following surgery for oesophageal cancer. Br J Surg 2008;95:1121-6. [Crossref] [PubMed]
- Gockel I, Gönner U, Domeyer M, et al. Long-term survivors of esophageal cancer: disease-specific quality of life, general health and complications. J Surg Oncol 2010;102:516-22. [Crossref] [PubMed]
- Pouwels S, Fiddelaers J, Teijink JA, et al. Preoperative exercise therapy in lung surgery patients: A systematic review. Respir Med 2015;109:1495-504. [Crossref] [PubMed]
- Coats V, Maltais F, Simard S, et al. Feasibility and effectiveness of a home-based exercise training program before lung resection surgery. Can Respir J 2013;20:e10-6. [Crossref] [PubMed]
- Minnella EM, Awasthi R, Gillis C, et al. Patients with poor baseline walking capacity are most likely to improve their functional status with multimodal prehabilitation. Surgery 2016;160:1070-9. [Crossref] [PubMed]
- Chen BP, Awasthi R, Sweet SN, et al. Four-week prehabilitation program is sufficient to modify exercise behaviors and improve preoperative functional walking capacity in patients with colorectal cancer. Support Care Cancer 2017;25:33-40. [Crossref] [PubMed]
- van Adrichem EJ, Meulenbroek RL, Plukker JT, et al. Comparison of two preoperative inspiratory muscle training programs to prevent pulmonary complications in patients undergoing esophagectomy: a randomized controlled pilot study. Ann Surg Oncol 2014;21:2353-60. [PubMed]
- Dettling DS, van der Schaaf M, Blom RL, et al. Feasibility and effectiveness of pre-operative inspiratory muscle training in patients undergoing oesophagectomy: a pilot study. Physiother Res Int 2013;18:16-26. [Crossref] [PubMed]
- Valkenet K, Trappenburg JC, Gosselink R, et al. Preoperative inspiratory muscle training to prevent postoperative pulmonary complications in patients undergoing esophageal resection (PREPARE study): study protocol for a randomized controlled trial. Trials 2014;15:144. [Crossref] [PubMed]
- Pfirrmann D, Tug S, Brosteanu O, et al. Internet-based perioperative exercise program in patients with Barrett's carcinoma scheduled for esophagectomy [iPEP - study] a prospective randomized-controlled trial. BMC Cancer 2017;17:413. [Crossref] [PubMed]