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Prehabilitation and rehabilitation for surgically treated lung cancer patients
Journal of Cancer Research and Practice xxx (2017) 1e6
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Review Article
Prehabilitation and rehabilitation for surgically treated lung cancer patients Tung-Chou Li a, b, Ming-Chung Yang a, Ailun Heather Tseng c, Henry Hsin-Chung Lee c, d, e, * a
Department of Physical Medicine and Rehabilitation, Cathay General Hospital, Taipei, Taiwan School of Medicine, Fu Jen Catholic University, Taipei, Taiwan c Department of Surgery, Hsinchu Cathay General Hospital, Hsinchu, Taiwan d Department of Surgery, Cathay General Hospital, Taipei, Taiwan e Graduate Institute of Translational and Interdisciplinary Medicine, College of Health Sciences & Technology, National Central University, Taoyuan, Taiwan b
a r t i c l e i n f o
a b s t r a c t
Article history: Received 22 March 2017 Received in revised form 1 June 2017 Accepted 1 June 2017 Available online xxx
According to the published data, lung cancer was the most common and deadly malignancy between 2002 and 2008 in Taiwan, with a significant difference between the 5-year survival rate of patients who underwent surgery and those who did not receive surgical intervention. The anatomic resection with radical lymph node dissection is a curative treatment for lung cancer. Although there is insufficient evidence to support the routine functional assessment before surgery, the assessment of exercise capacity before surgery is considered pivotal in the management of patients with lung cancer, both for prognostic and therapeutic reasons. Prehabilitation could improve exercise capacity, and might increase the number of inoperable-to-operable patients and reduce postoperative morbidity and mortality. Furthermore, rehabilitation after surgery approach seems to improve patient physical performance and quality of life. Despite advances in research over the past decade on the role of rehabilitation in patients with lung resection, only a few physicians incorporate this type of treatment into the daily care of lung cancer patients. Therefore, the integration of rehabilitation with medical optimization in the perisurgical period deserves to receive more attention by clinicians to elucidate the most comprehensive interventions. © 2017 The Chinese Oncology Society. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords: Lung cancer Surgery Prehabilitation Rehabilitation Exercise
1. Introduction Lung cancer is the most common and deadly malignancy in Taiwan, the cause of an estimated 33,919 new cases between 2002 and 2008. Although the 5-year survival rate is only 15.9%, the overall survival rate is as high as 60.7% in patients whose tumors are confined to the primary site at time of diagnosis. Unfortunately, this number only accounts for just 12.5% of the patients, and only 16.4% patients received surgical resection with a median survival of 13.2 months.1 Anatomic resection with radical lymph node dissection is a curative treatment for lung cancer. There is a significant difference between the 5-year survival rate of patients who underwent surgery (57.2%) and those who did not receive surgical intervention
* Corresponding author. Department of Surgery, Hsinchu Cathay General Hospital, No. 678, Sec. 2, Zhonghua Rd., East Dist., Hsinchu City 30060, Taiwan. E-mail address: [email protected] (H.H.-C. Lee). Peer review under responsibility of The Chinese Oncology Society.
(7.5%), according to the published data in Taiwan. Patients who underwent lobectomy have a higher 5-year survival rate compared with patients who underwent other surgical procedures.1 Given the relatively poor prognosis for patients with lung cancer who cannot be treated surgically, every effort should be made to increase the number of patients eligible for surgery. Approximately 73% of men and 53% of women are diagnosed with chronic obstructive pulmonary disease (COPD) along with lung cancer.2 These patients often have hyperinflation and increased labored breathing which leads to decreased activity levels, subsequent muscle deconditioning and poor exercise tolerance. Surgery in these patients can be associated with increased risk of morbidity and mortality after lung resection.3 For lung cancer patients with no underlying chronic respiratory disease, physical symptom burden, fatigue and performance status may have a negative effect on general function and poor postoperative outcomes.4,5 The benefits of pulmonary rehabilitation in COPD are welldocumented. Advances in research over the past decade, particularly supporting the use of exercise training, have rapidly
http://dx.doi.org/10.1016/j.jcrpr.2017.06.001 2311-3006/© 2017 The Chinese Oncology Society. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).
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progressed the role of rehabilitation in lung resected patients. This review article discusses the preoperative assessment of patients awaiting lung cancer surgery and the potential role of rehabilitation associating with the number of patients eligible for tumor resection. Finally, the impact of pulmonary rehabilitation on surgical outcomes during and after surgery are reviewed. 2. Preoperative evaluation Surgical options in cases of lung cancer include pneumonectomy, lobectomy or sub-lobar resection, and are available for patients who are eligible for surgery. The advantages of limited pulmonary resection are in part the ability to preserve a greater amount of lung volume and reducing the risk of physiological impairment after surgery. Although surgery is the best option for treating patients with early-stage non-small-cell lung cancer (NSCLC), abnormal pulmonary function still occurs in patients with potentially resectable tumors. These patients may be at an increased risk of both immediate perioperative complications and long-term disability following surgical resection.6 The level of acceptable risk for postoperative complications is somewhat subjective, and efforts persist to ensure the best predictive tests and define the threshold values necessary for minimizing surgical risk. Consequently, in considering whether the patient should undergo curative-intent surgical resection of lung cancer, the possible shortterm perioperative risk from comorbid cardiopulmonary disease and the long-term risk of pulmonary disability must be balanced against the possible risk of reduced survival if an oncological suboptimal treatment strategy is chosen. The task of the preoperative assessment is to identify patients at an increased risk of both perioperative complications and long-term disability from lung cancer. This assessment is essential to allow communication between clinicians and their patients about treatment options and risks, so that informed decisions can be made. Preoperative functional evaluation is deemed necessary for all types of operations. Diffusing capacity of the lung (DLCO), one of the most clinically valuable tests of lung function, was established for predicting postoperative complications in patients with normal Forced Expiratory Volume in One Second (FEV1). The clinicians should not ignore the assessment of exercise capacity and Maximum Oxygen Uptake (VO2 max), which has been proven to be inversely correlated with post-operative morbidity and mortality, as shown by the guidelines laid down by the European Respiratory Society and the European Society of Thoracic Surgeons joint task force. The suggested tests include measurement of preoperative pulmonary function, calculation of predicted postoperative pulmonary function, measures of gas exchange, and exercise testing.7 In 2013, the American College of Chest Physicians provided a guideline to the preoperative physiological assessment of patients being considered for surgical resection of lung cancer.6 It has been recommended that patients must be assessed by a multidisciplinary team before operation, regardless of age. During the preoperative period, optimal medical care for patients who have chronic respiratory disease should include smoking cessation, optimal pharmacologic and oxygen therapy when indicated, and prompt treatment of exacerbations. Patients with lung cancer are predisposed to atherosclerotic cardiovascular disease because of cigarette smoking, and the prevalence of underlying coronary artery disease is about 11e17%.8,9 The risk of major postoperative cardiac complications, including myocardial ischemia, pulmonary edema, ventricular fibrillation or primary cardiac arrest and cardiac-related death, is about 2e3% following lung resection.8,9 As a consequence, a preoperative cardiovascular risk assessment should be first performed. The Thoracic Revised Cardiac Risk Index (ThRCRI) is the preferred risk scoring tool to assess cardiac risk in
patients undergoing noncardiac surgical procedures.10 The risk score was based on weight values of high-risk surgery as follows (including lobectomy or pneumonectomy): 1.5 points; previous ischemic heart disease: 1.5 points; previous stroke or transient ischemic attack: 1.5 points; and serum creatinine 2 mg/dL: 1 point. Patients with ThRCRI 2 or any cardiac condition requiring medication or a newly suspected cardiac condition or limited exercise tolerance (inability to climb two flights of stairs) should be referred for a cardiac consultation and noninvasive testing, and the treatment results should be noted in these patients (Fig. 1).10 The next step is to assess FEV1 and DLCO. The Predicted PostOperative (ppo) lung functions should be calculated by the operation methods. For pneumonectomy candidates, ventilation/ perfusion scan (V/Q scan) method was suggested to calculate the ppo values of FEV1 or DLCO (ppo values ¼ preoperative values (1 fraction of total perfusion for the resected lung), where the preoperative values are taken as the best measured postbronchodilator values. For lobectomy patients, ppo values of FEV1 or DLCO was calculated by segmental counting (ppo values ¼ preoperative values (1 e y/z), where the preoperative values are taken as the best measured postbronchodilator value, y is the number of functional or unobstructed lung segments to be removed and z is the total number of functional segments. If both the percent of ppoFEV1 and ppoDLCO values are greater than 60%, the patient is considered to be at low risk. This indicates that the expected risk of mortality is below 1% for perioperative death and cardiopulmonary complications following resection, and major anatomic resections including pneumonectomy can be safely performed. No further tests are required in this group. If either the percent ppoFEV1 or the percent of ppoDLCO are within 30e60% of predicted values, a low technology exercise test (e.g. stair climb test or shuttle walk test) should be performed. If either stair climbing test is greater than 22 m or shuttle walk distance greater than 400 m, patients are regarded as at low risk of anatomic resection. A formal cardiopulmonary exercise test is indicated when the percent of ppoFEV1 or ppoDLCO <30%, or when the performance of the stair-climbing test or the shuttle walk test is not satisfactory. On the other hand, VO2 max >20 mL/kg/min or at 75% indicates a low risk. If VO2 max is between 10 and 20 mL/kg/min or 35e75%, the patients will be considered moderate risk which implies that the morbidity and mortality rates may vary according to the values of split lung functions, exercise tolerance and extent of resection. The risks and benefits of the operation should be thoroughly discussed with the patient. The actual risks are affected by patient factors (comorbidities, age), structural aspects (center volume, specialization), process factors (management of complications) and surgical access (thoracotomy vs. minimally invasive). Conversely, VO2 max <10 mL/kg/min or 35% predicted indicates a high risk of mortality which may be higher than 10%. This will cause considerable risk of severe cardiopulmonary morbidity and residual functional loss. At this point, patients should be advised about alternative surgical (minor resections or minimally invasive surgery) or nonsurgical options. For patients who are considered for surgery but have a high risk outcome, a preoperative or postoperative pulmonary rehabilitation is recommended.6 In patients with lung cancer being considered for surgery who undergo neoadjuvant therapy, it is suggested that repeated pulmonary functional testing with diffusion capacity be performed after completion of neoadjuvant therapy.6 3. Preoperative rehabilitation Severe pulmonary function impairment was considered inoperable in approximately 37% of patients with anatomically resectable lung cancer.11 The surgical morbidity and mortality rates for
Please cite this article in press as: Li T-C, et al., Prehabilitation and rehabilitation for surgically treated lung cancer patients, Journal of Cancer Research and Practice (2017), http://dx.doi.org/10.1016/j.jcrpr.2017.06.001
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Fig. 1. Physiologic evaluation resection algorithm. Abbreviation: ACC: American College of Cardiology; AHA: American Heart Association; CABG: coronary artery bypass graft surgery; CPET: cardiopulmonary exercise test; PCI: percutaneous coronary intervention; ppoDLCO: predicted postoperative diffusing capacity for carbon monoxide; ppoFEV1: predicted postoperative forced expiratory volume in 1 s; SCT: stair climb test; SWT: shuttle walk test; ThRCRI: thoracic revised cardiac risk index; VO2max: maximal oxygen consumption.
patients at an acceptable risk of perioperative complications were 31.6% and 4.3%, respectively, whereas those at high risk were 83.3% and 33.3%, respectively.12 Acknowledging the severity of this problem allows clinicians to develop a more effective preoperative management strategies that could better prepare patients for surgery. Prehabilitation exercise should be undertaken prior to surgery or treatment for two primary reasons. The first is to optimize the physical status and overall medical stability before surgery and reduce postoperative morbidity in operable patients. Two systemic reviews and one meta-analysis study concluded that pre-surgical interventions based on moderate-to-intense aerobic exercise in lung cancer patients undergoing lung resection could improve pulmonary function (Force Vital Capacity (FVC) and FEV1) and functional capacity significantly before surgery, reduce postoperative morbidity (risk ratios ¼ 0.45) and in-hospital length of stay (LOS) (mean difference ¼ 4.83). However, interventions performed only during the postoperative period did not seem to reduce postoperative pulmonary complications (PPCs) or LOS. Since physical training programs differed in every study, it was not possible to identify the best preoperative intervention due to the paucity of clinical trials in this area.13e15 The second reason is to increase the percentage of operable
cases by improving the physical status of a patient who was initially considered inoperable due to cardiopulmonary impairment to become a candidate for potentially curative surgery. As earlier discussed, exercise capacity might discriminate between patients who can and cannot tolerate surgery, thereby allowing a greater number of patients to receive a potentially curative operation. Two studies evaluated the role of short-term preoperative pulmonary rehabilitation on exercise capacity for inoperable patients to sufficiently improve their physical status surgery. In the prospective observational study,16 the recruitment criteria were patients with COPD alone or with lung cancer, and subjects whose VO2 max cardiopulmonary exercise test was less than or equal to 15 mL/kg/ min. Overall, 12 patients fulfilled the inclusion criteria, who completed the preoperative rehabilitation that consisted of 1 ½ hour sessions daily, five sessions per week for four weeks. The program included breathing and coughing techniques, incentive spirometry exercises and cycling. After training, the patients' exercise performances were significantly improved. The mean VO2 max had increased to 2.8 mL/kg/min, whereas the pulmonary function test and diffuse lung capacity were unchanged. Also, 11 of the patients underwent lobectomy with no postoperative mortality noted, and the mean hospital stay was 17 days. Postoperative pulmonary complication happened in eight patients. In another pilot
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study,17 eight lung cancer patients who were inoperable due to poor pulmonary function underwent a four-week preoperative rehabilitationdfive daily sessions, 3 h each, every weekd including incremental symptom-limited aerobic exercise, breathing exercises, and educational sessions. All of the patients improved their exercise capacity as it affects clinical criteria for surgery, and were subsequently operated on with no mortality and a morbidity of 25%. Functional parameters measured before and after preoperative rehabilitation demonstrated a significant increase in FVC, both in terms of volume (þ0.44 l) and percentage of that predicted (þ12.9%). Similar improvements, although to a lesser extent, were observed for FEV1. General performance in the 6-min walk test (6 MWT) improved by 47.4%. The strong correlation between prehabilitation values and the indices of FEV1, 6 MWT, and arterial oxygen tension (paO2) after surgical treatment indicated that patients who had the worst initial pulmonary function and exercise capacity received the most benefits from pulmonary rehabilitation. Although preoperative rehabilitation may have a strong impact on survival if additional patients are qualified for curative resection, yet strong evidence remains lacking to support the regimens for patients who have lung cancer. This may be due to, in part, the relatively brief period of time between cancer diagnosis and surgery, which does not typically allow a 4e8 weeks rehabilitation program. This issue may hinder the translation of evidence supporting prehabilitation into clinical practice. Furthermore, it is currently recommended for already operable patients not to delay surgery in order to undertake prehabilitation, but instead use the time waiting to deliver prehabilitation. The European Respiratory Society and the European Society of Thoracic Surgeons have published evidence-based guidelines on the use of physical therapy programs in lung cancer patients. The suggestions were that exercise training may improve surgical risk and/or recovery, symptom control, and possibly, risk of dying following a lung cancer diagnosis.7 4. Perioperative rehabilitation Rehabilitation in the immediate postoperative period aims to reduce PPCs, prevent deconditioning and facilitate early and safe discharge. A PPC is defined as any pulmonary sequelae occurring during the post-operative period and resulting in significant dysfunction, adversely affecting the clinical course.18 The problems that were encountered included pneumonia, atelectasis, acute respiratory failure, need for reintubation, pulmonary edema, bronchospasm, pneumothorax and prolonged air leaks. Currently, the known independent risk factors for PPC are age 75 years, body mass index 30 kg/m2, Anesthesia Physical Classification System scored 3, smoking history and COPD.3 Despite the improvement in surgical techniques and perioperative management, PPCs still occur in 3.9%e32.5% of patients with lung cancer who have undergone surgical resection.19e21 PPCs are a major cause of morbidity, mortality, prolonged hospital stay, and the increased cost of care.20 One study examined the feasibility of high frequency chest wall oscillation therapy immediately after pulmonary lobectomy in lung cancer patients compared to conventional chest physiotherapy. The chest wall oscillation group had a better and quicker recovery of pulmonary function (including FEV1 and oxygenation) than the conventional chest physiotherapy group. No unexpected complications, such as hemodynamic deterioration, bleeding or chest tube or wound problems associated with oscillation therapy were detected.22 A quasi-experimental study attempted to evaluate the effects of an intensive postoperative respiratory exercise in patients undergoing lobectomy; 90% of the 208 participants had lung cancer. The control group received standard care and the experimental group received an additional daily physiotherapy program that
focused on respiratory exercises until discharge. A significant improvement in terms of PPCs was detected in both the control (20.6%) and experimental group (6.6%), with a median LOS of 14 and 12 days in control and experimental groups, respectively. In addition, both the physiotherapy program and percentage of FEV1 were identified as protective factors for the development of PPCs in lobectomy procedure according to the logistic regression model.21 Another randomized single-blind clinical trial found that no difference was apparent in the PPC rate or LOS for patients treated with prophylactic targeted respiratory physiotherapy (deep breathing and coughing, mobilization, progressive shoulder/ thoracic mobility exercises) plus the usual care compared to usual care alone. The usual care included a clinical pathway with early mobilization.19 However, the study was conducted in a single hospital in New Zealand. The results cannot be extrapolated for the entire population, thus execution of this treatment should be used with caution. A systematic review investigated the efficacy of perioperative respiratory physiotherapy in patients undergoing pulmonary resection for lung cancer in terms of PPC incidence, postoperative recovery of pulmonary function and LOS.14 Studies were included if they were randomized controlled trials, compared two or more perioperative physiotherapy interventions or compared one intervention with no intervention. Two studies investigated the efficacy of interventions that started preoperatively and then continued after surgery23,24; four studies assessed postoperative interventions only.19,24e26 The rehabilitation program includes incentive spirometry, breathing and coughing exercises, sustained maximal inspirations, active cycle of breathing techniques, intermittent positive pressure breathing, flutter, positive pressure devices and shoulder/thoracic cage exercise. The authors found that pre-surgical interventions based on moderate-to-intense aerobic exercise in patients undergoing lung resection improved functional capacity and reduced postoperative morbidity, whereas interventions performed only during the postoperative period did not seem to reduce PPCs or LOS. However, it was noted that the results of the substantial heterogeneity in the interventions across the studies were inconsistent.14 Recent improvements in pain management and the increasing use of video-assisted thoracic surgery changed the postoperative clinical pathways. There is a lack of strong evidence to support the routine use of prophylactic targeted pulmonary rehabilitation interventions immediately after lung resection surgery. 5. Postoperative rehabilitation Although surgery is the main curative therapy for lung cancer, the procedure can directly cause a reduction in pulmonary functional reserve and exercise capacity proportional to the extent of resection. The problems might be more severe in those undergoing multimodality treatments or who have co-morbidity. Across various studies, indices such as FEV1, FVC, TLC, DLCO and VO2 peak are negatively affected by thoracic surgery.22,27e29 Patients with lung cancer who underwent segmentectomy had better pulmonary function after surgery than those who underwent lobectomy at 3e12 months postoperatively. However, a marginally significant benefit was observed in segmentectomy group for anaerobic threshold when compared to lobectomy.27e30 There was a positive and significant correlation between the number of resected segments versus loss of both FVC and FEV1 at six months.30 The loss of lung function also varied significantly with the location of the resection, comorbidity and methods of operation. For example, resection of an emphysematous portion of the lung will probably result a reduced loss of function. Patients with COPD typically experience smaller declines in FEV1 after lobectomy than
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those without COPD.27,30 Declines in DLCO and VO2 peak are more variable, with the reported decrease of 3e20% in those with COPD, and 0e21% in those without the disease. Such reduction persisted up to three years after surgery, while the values still remained lower than the preoperative values.31 When divided lobectomy into two groups: the upper lobectomy (UL) group and the lower lobectomy (LL) group, FVC of the LL group decreased more significantly from two weeks to six months after the operation compared with the UL group. There were no differences at 12 months after resection between the two groups nor in FEV1.28 A recent study showed that the actual percent-of-predicted FEV1 and DLCO one month after surgery were almost equal to the predicted postoperative value, and the number continued to increase significantly six to 12 months after training. However, no improvement was observed on the same actual pulmonary functional tests in subjects with COPD, or in those who underwent thoracotomy or received adjuvant chemotherapy after one year of training.32 In light of those factors that contribute to muscle deconditioning, and ultimately to physical inactivity, the training exercise should play a key role in preventing or at least mitigating the harmful effects of surgery. Rehabilitation following surgery aims to restore physical status and to maximize function, physical activity, psychological status and health-related quality of life. Nevertheless, only a few studies on this topic have been performed and are generally based on a small number of patients. In 2014, a systematic review aimed to synthesize all available evidence with regard to exercise intervention for patients who were surgically treated for NSCLC.33 The results illustrated only 20 studies across the spectrum being considered eligible for the review, and most selected studies were observational single group trials. Generally, rehabilitation programs are supervised, which range from 4 to 14 weeks in an outpatient setting, although inpatient and home-based programs have also been used. A majority of the studies included both aerobic (walking, treadmill and/or stationary cycle) and resistance training components. Other components such as breathing exercises, dyspnea management, balance exercises and limb stretches were used occasionally; however, the independent contribution of these training components to the resultant outcomes is unknown. The authors found that the outcomes measured in pulmonary function, including FEV1, DLCO and FVC, showed insignificant results for all pulmonary function measures in six of the ten studies except only four studies reported an improved pulmonary function. All but one of the studies that used the 6 MWT test reported a significant increase in distance measured from baseline to post intervention, which increased from 28 m to 377 m. Studies focusing on the cardiopulmonary exercise test reported a significant increase in exercise capacity in three of the five studies, with VO2 max improving from 2.8 to 6.3 mL/kg/min. One study showed that the highest percentage of improvement was twice as long in the duration of intervention (eight weeks compared to four weeks). Studies that recruited patients who had impaired exercise capacity at baseline (VO2 max < 15 mL/kg/min) showed the most improvement in postexercise interventions.33 The Cochrane review on exercise after lung resection identified three randomized trials involving 178 participants.34 The metaanalysis found that exercise capacity was statistically greater in the exercise training group compared to the control group following lung resection for NSCLC. No between-group differences were observed in health-related quality of life (HRQoL) or FEV1. Evidence from the study suggested that exercise training, including aerobic and resistance exercises, may potentially increase exercise capacity in people following lung resection due to lung cancer. Although the quality of the evidence is low, referrals to exercise training or pulmonary rehabilitation programs should be considered. This is especially true for those with impairments in exercise
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capacity.34 Since the publication of the two review articles, three additional randomized trials that evaluated the role of postoperative rehabilitation in lung cancer patients were subsequently published. One was a prospective randomized controlled trial on 40 patients who were randomly assigned to one of four groups (three intervention groups and one control group). The postoperative exercise program comprised a supervised exercise program that involved resistance and high-intensity interval cardiorespiratory exercise, 2 h weekly for 12 weeks combined with individual counseling. The postoperative exercise was completed by 73% of the patients randomly assigned to this intervention. The study concluded that an early postoperative exercise program for patients with NSCLC was safe and feasible, but a preoperative home-based exercise program was not feasible for this population in a fast-track set up.35 Another study used a three-axis accelerometer for five to six days to measure the physical activity before and two months after surgery. Similar to the previous study, patients did not recover to the preoperative physical activity level two months after lung resection surgery. However, compared with the control group, there was an improvement in the postoperative physical activity level in patients, including older patients, who underwent outpatient pulmonary rehabilitation.36 The third study investigated the effects of high-intensity training (60 min, three times a week for 20 weeks) starting at five to seven weeks after surgery in the single-blind randomized controlled trial. The program included, among other standard postoperative care, 60 min, three times a week, 20 weeks strength and endurance training. After intervention, the authors concluded that the high intensity training was well-tolerated and induced a clinically significant increase in peak oxygen uptake during walking, DLCO, muscular strength, daily physical functioning and quality of life.37 The growing body of evidence suggests that rehabilitation following surgery is safe and well-tolerated, and is associated with improvements in physical and physiological outcomes. Exercise in this setting is not yet a routine clinical practice. Larger randomized control trials with excellent methodological quality, intention-totreat analysis and proper implementation are needed to confirm the efficacy of exercise intervention. Furthermore, strengthening of the meta-analyses are required in assisting the translation of evidence into routine clinical practice. 6. Conclusion Research on pulmonary rehabilitation supports the value of this treatment modality in a global approach to patients with lung cancer. The available evidence suggests that pulmonary rehabilitation is safe and feasible in lung cancer patients, and can be performed in a variety of situations. Although there is not enough evidence to support the routine functional assessment before surgery, the assessment of exercise capacity is considered pivotal in the management of patients with lung cancer, both for prognostic and therapeutic reasons. On the other hand, a sufficient amount of data is available to support the fact that prehabilitation could improve exercise capacity and reduce postoperative morbidity and mortality. There is also a clear rationale that the optimization of the preoperative fitness obtained through a rehabilitation program may make candidates for surgical resection for those patients who, despite anatomical resectability, were initially declared inoperable due to poor physical performance. The evidence provided will increase the number of inoperable-to-operable patients with lung cancer. Furthermore, rehabilitation after surgery could improve physical performance and quality of life, but the data were limited. To date, there is no consensus on the correct timing, duration and those components which should be part of the rehabilitation
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program. Further well-designed studies are needed to better define the benefits and optimization of the intervention. We look forward to improving outcomes with the widespread use of comprehensive pulmonary rehabilitation in lung cancer patients. Financial support None. Conflicts of interest The authors declare no conflicts of interest. References 1. Wang BY, Huang JY, Cheng CY, Lin CH, Ko J, Liaw YP. Lung cancer and prognosis in taiwan: a population-based cancer registry. J Thorac Oncol. 2013;8: 1128e1135. 2. Loganathan RS, Stover DE, Shi W, Venkatraman E. Prevalence of COPD in women compared to men around the time of diagnosis of primary lung cancer. Chest. 2006;129:1305e1312. 3. Agostini P, Cieslik H, Rathinam S, et al. Postoperative pulmonary complications following thoracic surgery: are there any modifiable risk factors? Thorax. 2010;65:815e818. 4. Doorenbos A, Given B, Given C, Verbitsky N. Physical functioning: effect of behavioral intervention for symptoms among individuals with cancer. Nurs Res. 2006;55:161e171. 5. Hopwood P, Stephens RJ. Depression in patients with lung cancer: prevalence and risk factors derived from quality-of-life data. J Clin Onco. 2000;18: 893e903. 6. Brunelli A, Kim AW, Berger KI, Addrizzo-Harris DJ. Physiologic evaluation of the patient with lung cancer being considered for resectional surgery: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143:e166Se190S. 7. Brunelli A, Charloux A, Bolliger CT, et al. ERS/ESTS clinical guidelines on fitness for radical therapy in lung cancer patients (surgery and chemo-radiotherapy). Eur Respir J. 2009;34:17e41. 8. Brunelli A, Cassivi SD, Fibla J, et al. External validation of the recalibrated thoracic revised cardiac risk index for predicting the risk of major cardiac complications after lung resection. Ann Thorac Surg. 2011;92:445e448. 9. Brunelli A, Varela G, Salati M, et al. Recalibration of the revised cardiac risk index in lung resection candidates. Ann Thorac Surg. 2010;90:199e203. 10. Lee TH, Marcantonio ER, Mangione CM, et al. Derivation and prospective validation of a simple index for prediction of cardiac risk of major noncardiac surgery. Circulation. 1999;100:1043e1049. 11. Baser S, Shannon VR, Eapen GA, et al. Pulmonary dysfunction as a major cause of inoperability among patients with non-small-cell lung cancer. Clin Lung Cancer. 2006;7:344e349. 12. Stanzani F, Paisani Dde M, Oliveira A, Souza RC, Perfeito JA, Faresin SM. Morbidity, mortality, and categorization of the risk of perioperative complications in lung cancer patients. J Bras Pneumol. 2014;40:21e29. 13. Mainini C, Rebelo PF, Bardelli R, et al. Perioperative physical exercise interventions for patients undergoing lung cancer surgery: what is the evidence? SAGE Open Med. 2016;4, 2050312116673855. 14. Rodriguez-Larrad A, Lascurain-Aguirrebena I, Abecia-Inchaurregui LC, Seco J. Perioperative physiotherapy in patients undergoing lung cancer resection. Interact Cardiovasc Thorac Surg. 2014;19:269e281. 15. Sebio Garcia R, Yanez Brage MI, Gimenez Moolhuyzen E, Granger CL, Denehy L. Functional and postoperative outcomes after preoperative exercise training in patients with lung cancer: a systematic review and meta-analysis. Interact Cardiovasc Thorac Surg. 2016;23:486e497. 16. Bobbio A, Chetta A, Ampollini L, et al. Preoperative pulmonary rehabilitation in patients undergoing lung resection for non-small cell lung cancer. Eur J Cardiothorac Surg. 2008;33:95e98.
17. Cesario A, Ferri L, Galetta D, et al. Pre-operative pulmonary rehabilitation and surgery for lung cancer. Lung Cancer. 2007;57:118e119. 18. Sharafkhaneh A, Falk JA, Minai OA, Lipson DA. Overview of the perioperative management of lung volume reduction surgery patients. Proc Am Thorac Soc. 2008;5:438e441. 19. Reeve JC, Nicol K, Stiller K, et al. Does physiotherapy reduce the incidence of postoperative pulmonary complications following pulmonary resection via open thoracotomy? A preliminary randomised single-blind clinical trial. Eur J Cardiothorac Surg. 2010;37:1158e1166. 20. Rodriguez-Larrad A, Vellosillo-Ortega JM, Ruiz-Muneta C, AbeciaInchaurregui LC, Seco J. Postoperative respiratory exercises reduce the risk of developing pulmonary complications in patients undergoing lobectomy. Arch Bronconeumol. 2016;52:347e353. 21. Warner DO. Preventing postoperative pulmonary complications: the role of the anesthesiologist. Anesthesiology. 2000;92:1467e1472. 22. Park H, Park J, Woo SY, Yi YH, Kim K. Effect of high-frequency chest wall oscillation on pulmonary function after pulmonary lobectomy for non-small cell lung cancer. Crit Care Med. 2012;40:2583e2589. 23. Morano MT, Araujo AS, Nascimento FB, et al. Preoperative pulmonary rehabilitation versus chest physical therapy in patients undergoing lung cancer resection: a pilot randomized controlled trial. Arch Phys Med Rehabil. 2013;94: 53e58. 24. Benzo R, Wigle D, Novotny P, et al. Preoperative pulmonary rehabilitation before lung cancer resection: results from two randomized studies. Lung Cancer. 2011;74:441e445. 25. Agostini P, Naidu B, Cieslik H, et al. Effectiveness of incentive spirometry in patients following thoracotomy and lung resection including those at high risk for developing pulmonary complications. Thorax. 2013;68:580e585. 26. Arbane G, Tropman D, Jackson D, Garrod R. Evaluation of an early exercise intervention after thoracotomy for non-small cell lung cancer (NSCLC), effects on quality of life, muscle strength and exercise tolerance: randomised controlled trial. Lung Cancer. 2011;71:229e234. 27. Kim SJ, Lee YJ, Park JS, et al. Changes in pulmonary function in lung cancer patients after video-assisted thoracic surgery. Ann Thorac Surg. 2015;99: 210e217. 28. Macke RA, Schuchert MJ, Odell DD, Wilson DO, Luketich JD, Landreneau RJ. Parenchymal preserving anatomic resections result in less pulmonary function loss in patients with Stage I non-small cell lung cancer. J Cardiothorac Surg. 2015;10:49. 29. Seok Y, Jheon S, Cho S. Serial changes in pulmonary function after videoassisted thoracic surgery lobectomy in lung cancer patients. Thorac Cardiovasc Surg. 2014;62:133e139. 30. Harada H, Okada M, Sakamoto T, Matsuoka H, Tsubota N. Functional advantage after radical segmentectomy versus lobectomy for lung cancer. Ann Thorac Surg. 2005;80:2041e2045. 31. Nagamatsu Y, Maeshiro K, Kimura NY, et al. Long-term recovery of exercise capacity and pulmonary function after lobectomy. J Thorac Cardiovasc Surg. 2007;134:1273e1278. 32. Park TY, Park YS. Long-term respiratory function recovery in patients with stage I lung cancer receiving video-assisted thoracic surgery versus thoracotomy. J Thorac Dis. 2016;8:161e168. 33. Crandall K, Maguire R, Campbell A, Kearney N. Exercise intervention for patients surgically treated for Non-Small Cell Lung Cancer (NSCLC): a systematic review. Surg Oncol. 2014;23:17e30. 34. Cavalheri V, Tahirah F, Nonoyama M, Jenkins S, Hill K. Exercise training undertaken by people within 12 months of lung resection for non-small cell lung cancer. Cochrane Database Syst Rev. 2013:CD009955. 35. Sommer MS, Trier K, Vibe-Petersen J, et al. Perioperative rehabilitation in operable lung cancer patients (PROLUCA): a feasibility study. Integr Cancer Ther. 2016;15:455e466. 36. Maeda K, Higashimoto Y, Honda N, et al. Effect of a postoperative outpatient pulmonary rehabilitation program on physical activity in patients who underwent pulmonary resection for lung cancer. Geriatr Gerontol Int. 2016;16: 550e555. 37. Edvardsen E, Skjonsberg OH, Holme I, Nordsletten L, Borchsenius F, Anderssen SA. High-intensity training following lung cancer surgery: a randomised controlled trial. Thorax. 2015;70:244e250.
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Contents lists available at ScienceDirect
Journal of Cancer Research and Practice journal homepage: http://www.journals.elsevier.com/journal-of-cancerresearch-and-practice
Review Article
Prehabilitation and rehabilitation for surgically treated lung cancer patients Tung-Chou Li a, b, Ming-Chung Yang a, Ailun Heather Tseng c, Henry Hsin-Chung Lee c, d, e, * a
Department of Physical Medicine and Rehabilitation, Cathay General Hospital, Taipei, Taiwan School of Medicine, Fu Jen Catholic University, Taipei, Taiwan c Department of Surgery, Hsinchu Cathay General Hospital, Hsinchu, Taiwan d Department of Surgery, Cathay General Hospital, Taipei, Taiwan e Graduate Institute of Translational and Interdisciplinary Medicine, College of Health Sciences & Technology, National Central University, Taoyuan, Taiwan b
a r t i c l e i n f o
a b s t r a c t
Article history: Received 22 March 2017 Received in revised form 1 June 2017 Accepted 1 June 2017 Available online xxx
According to the published data, lung cancer was the most common and deadly malignancy between 2002 and 2008 in Taiwan, with a significant difference between the 5-year survival rate of patients who underwent surgery and those who did not receive surgical intervention. The anatomic resection with radical lymph node dissection is a curative treatment for lung cancer. Although there is insufficient evidence to support the routine functional assessment before surgery, the assessment of exercise capacity before surgery is considered pivotal in the management of patients with lung cancer, both for prognostic and therapeutic reasons. Prehabilitation could improve exercise capacity, and might increase the number of inoperable-to-operable patients and reduce postoperative morbidity and mortality. Furthermore, rehabilitation after surgery approach seems to improve patient physical performance and quality of life. Despite advances in research over the past decade on the role of rehabilitation in patients with lung resection, only a few physicians incorporate this type of treatment into the daily care of lung cancer patients. Therefore, the integration of rehabilitation with medical optimization in the perisurgical period deserves to receive more attention by clinicians to elucidate the most comprehensive interventions. © 2017 The Chinese Oncology Society. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords: Lung cancer Surgery Prehabilitation Rehabilitation Exercise
1. Introduction Lung cancer is the most common and deadly malignancy in Taiwan, the cause of an estimated 33,919 new cases between 2002 and 2008. Although the 5-year survival rate is only 15.9%, the overall survival rate is as high as 60.7% in patients whose tumors are confined to the primary site at time of diagnosis. Unfortunately, this number only accounts for just 12.5% of the patients, and only 16.4% patients received surgical resection with a median survival of 13.2 months.1 Anatomic resection with radical lymph node dissection is a curative treatment for lung cancer. There is a significant difference between the 5-year survival rate of patients who underwent surgery (57.2%) and those who did not receive surgical intervention
* Corresponding author. Department of Surgery, Hsinchu Cathay General Hospital, No. 678, Sec. 2, Zhonghua Rd., East Dist., Hsinchu City 30060, Taiwan. E-mail address: [email protected] (H.H.-C. Lee). Peer review under responsibility of The Chinese Oncology Society.
(7.5%), according to the published data in Taiwan. Patients who underwent lobectomy have a higher 5-year survival rate compared with patients who underwent other surgical procedures.1 Given the relatively poor prognosis for patients with lung cancer who cannot be treated surgically, every effort should be made to increase the number of patients eligible for surgery. Approximately 73% of men and 53% of women are diagnosed with chronic obstructive pulmonary disease (COPD) along with lung cancer.2 These patients often have hyperinflation and increased labored breathing which leads to decreased activity levels, subsequent muscle deconditioning and poor exercise tolerance. Surgery in these patients can be associated with increased risk of morbidity and mortality after lung resection.3 For lung cancer patients with no underlying chronic respiratory disease, physical symptom burden, fatigue and performance status may have a negative effect on general function and poor postoperative outcomes.4,5 The benefits of pulmonary rehabilitation in COPD are welldocumented. Advances in research over the past decade, particularly supporting the use of exercise training, have rapidly
http://dx.doi.org/10.1016/j.jcrpr.2017.06.001 2311-3006/© 2017 The Chinese Oncology Society. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).
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progressed the role of rehabilitation in lung resected patients. This review article discusses the preoperative assessment of patients awaiting lung cancer surgery and the potential role of rehabilitation associating with the number of patients eligible for tumor resection. Finally, the impact of pulmonary rehabilitation on surgical outcomes during and after surgery are reviewed. 2. Preoperative evaluation Surgical options in cases of lung cancer include pneumonectomy, lobectomy or sub-lobar resection, and are available for patients who are eligible for surgery. The advantages of limited pulmonary resection are in part the ability to preserve a greater amount of lung volume and reducing the risk of physiological impairment after surgery. Although surgery is the best option for treating patients with early-stage non-small-cell lung cancer (NSCLC), abnormal pulmonary function still occurs in patients with potentially resectable tumors. These patients may be at an increased risk of both immediate perioperative complications and long-term disability following surgical resection.6 The level of acceptable risk for postoperative complications is somewhat subjective, and efforts persist to ensure the best predictive tests and define the threshold values necessary for minimizing surgical risk. Consequently, in considering whether the patient should undergo curative-intent surgical resection of lung cancer, the possible shortterm perioperative risk from comorbid cardiopulmonary disease and the long-term risk of pulmonary disability must be balanced against the possible risk of reduced survival if an oncological suboptimal treatment strategy is chosen. The task of the preoperative assessment is to identify patients at an increased risk of both perioperative complications and long-term disability from lung cancer. This assessment is essential to allow communication between clinicians and their patients about treatment options and risks, so that informed decisions can be made. Preoperative functional evaluation is deemed necessary for all types of operations. Diffusing capacity of the lung (DLCO), one of the most clinically valuable tests of lung function, was established for predicting postoperative complications in patients with normal Forced Expiratory Volume in One Second (FEV1). The clinicians should not ignore the assessment of exercise capacity and Maximum Oxygen Uptake (VO2 max), which has been proven to be inversely correlated with post-operative morbidity and mortality, as shown by the guidelines laid down by the European Respiratory Society and the European Society of Thoracic Surgeons joint task force. The suggested tests include measurement of preoperative pulmonary function, calculation of predicted postoperative pulmonary function, measures of gas exchange, and exercise testing.7 In 2013, the American College of Chest Physicians provided a guideline to the preoperative physiological assessment of patients being considered for surgical resection of lung cancer.6 It has been recommended that patients must be assessed by a multidisciplinary team before operation, regardless of age. During the preoperative period, optimal medical care for patients who have chronic respiratory disease should include smoking cessation, optimal pharmacologic and oxygen therapy when indicated, and prompt treatment of exacerbations. Patients with lung cancer are predisposed to atherosclerotic cardiovascular disease because of cigarette smoking, and the prevalence of underlying coronary artery disease is about 11e17%.8,9 The risk of major postoperative cardiac complications, including myocardial ischemia, pulmonary edema, ventricular fibrillation or primary cardiac arrest and cardiac-related death, is about 2e3% following lung resection.8,9 As a consequence, a preoperative cardiovascular risk assessment should be first performed. The Thoracic Revised Cardiac Risk Index (ThRCRI) is the preferred risk scoring tool to assess cardiac risk in
patients undergoing noncardiac surgical procedures.10 The risk score was based on weight values of high-risk surgery as follows (including lobectomy or pneumonectomy): 1.5 points; previous ischemic heart disease: 1.5 points; previous stroke or transient ischemic attack: 1.5 points; and serum creatinine 2 mg/dL: 1 point. Patients with ThRCRI 2 or any cardiac condition requiring medication or a newly suspected cardiac condition or limited exercise tolerance (inability to climb two flights of stairs) should be referred for a cardiac consultation and noninvasive testing, and the treatment results should be noted in these patients (Fig. 1).10 The next step is to assess FEV1 and DLCO. The Predicted PostOperative (ppo) lung functions should be calculated by the operation methods. For pneumonectomy candidates, ventilation/ perfusion scan (V/Q scan) method was suggested to calculate the ppo values of FEV1 or DLCO (ppo values ¼ preoperative values (1 fraction of total perfusion for the resected lung), where the preoperative values are taken as the best measured postbronchodilator values. For lobectomy patients, ppo values of FEV1 or DLCO was calculated by segmental counting (ppo values ¼ preoperative values (1 e y/z), where the preoperative values are taken as the best measured postbronchodilator value, y is the number of functional or unobstructed lung segments to be removed and z is the total number of functional segments. If both the percent of ppoFEV1 and ppoDLCO values are greater than 60%, the patient is considered to be at low risk. This indicates that the expected risk of mortality is below 1% for perioperative death and cardiopulmonary complications following resection, and major anatomic resections including pneumonectomy can be safely performed. No further tests are required in this group. If either the percent ppoFEV1 or the percent of ppoDLCO are within 30e60% of predicted values, a low technology exercise test (e.g. stair climb test or shuttle walk test) should be performed. If either stair climbing test is greater than 22 m or shuttle walk distance greater than 400 m, patients are regarded as at low risk of anatomic resection. A formal cardiopulmonary exercise test is indicated when the percent of ppoFEV1 or ppoDLCO <30%, or when the performance of the stair-climbing test or the shuttle walk test is not satisfactory. On the other hand, VO2 max >20 mL/kg/min or at 75% indicates a low risk. If VO2 max is between 10 and 20 mL/kg/min or 35e75%, the patients will be considered moderate risk which implies that the morbidity and mortality rates may vary according to the values of split lung functions, exercise tolerance and extent of resection. The risks and benefits of the operation should be thoroughly discussed with the patient. The actual risks are affected by patient factors (comorbidities, age), structural aspects (center volume, specialization), process factors (management of complications) and surgical access (thoracotomy vs. minimally invasive). Conversely, VO2 max <10 mL/kg/min or 35% predicted indicates a high risk of mortality which may be higher than 10%. This will cause considerable risk of severe cardiopulmonary morbidity and residual functional loss. At this point, patients should be advised about alternative surgical (minor resections or minimally invasive surgery) or nonsurgical options. For patients who are considered for surgery but have a high risk outcome, a preoperative or postoperative pulmonary rehabilitation is recommended.6 In patients with lung cancer being considered for surgery who undergo neoadjuvant therapy, it is suggested that repeated pulmonary functional testing with diffusion capacity be performed after completion of neoadjuvant therapy.6 3. Preoperative rehabilitation Severe pulmonary function impairment was considered inoperable in approximately 37% of patients with anatomically resectable lung cancer.11 The surgical morbidity and mortality rates for
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Fig. 1. Physiologic evaluation resection algorithm. Abbreviation: ACC: American College of Cardiology; AHA: American Heart Association; CABG: coronary artery bypass graft surgery; CPET: cardiopulmonary exercise test; PCI: percutaneous coronary intervention; ppoDLCO: predicted postoperative diffusing capacity for carbon monoxide; ppoFEV1: predicted postoperative forced expiratory volume in 1 s; SCT: stair climb test; SWT: shuttle walk test; ThRCRI: thoracic revised cardiac risk index; VO2max: maximal oxygen consumption.
patients at an acceptable risk of perioperative complications were 31.6% and 4.3%, respectively, whereas those at high risk were 83.3% and 33.3%, respectively.12 Acknowledging the severity of this problem allows clinicians to develop a more effective preoperative management strategies that could better prepare patients for surgery. Prehabilitation exercise should be undertaken prior to surgery or treatment for two primary reasons. The first is to optimize the physical status and overall medical stability before surgery and reduce postoperative morbidity in operable patients. Two systemic reviews and one meta-analysis study concluded that pre-surgical interventions based on moderate-to-intense aerobic exercise in lung cancer patients undergoing lung resection could improve pulmonary function (Force Vital Capacity (FVC) and FEV1) and functional capacity significantly before surgery, reduce postoperative morbidity (risk ratios ¼ 0.45) and in-hospital length of stay (LOS) (mean difference ¼ 4.83). However, interventions performed only during the postoperative period did not seem to reduce postoperative pulmonary complications (PPCs) or LOS. Since physical training programs differed in every study, it was not possible to identify the best preoperative intervention due to the paucity of clinical trials in this area.13e15 The second reason is to increase the percentage of operable
cases by improving the physical status of a patient who was initially considered inoperable due to cardiopulmonary impairment to become a candidate for potentially curative surgery. As earlier discussed, exercise capacity might discriminate between patients who can and cannot tolerate surgery, thereby allowing a greater number of patients to receive a potentially curative operation. Two studies evaluated the role of short-term preoperative pulmonary rehabilitation on exercise capacity for inoperable patients to sufficiently improve their physical status surgery. In the prospective observational study,16 the recruitment criteria were patients with COPD alone or with lung cancer, and subjects whose VO2 max cardiopulmonary exercise test was less than or equal to 15 mL/kg/ min. Overall, 12 patients fulfilled the inclusion criteria, who completed the preoperative rehabilitation that consisted of 1 ½ hour sessions daily, five sessions per week for four weeks. The program included breathing and coughing techniques, incentive spirometry exercises and cycling. After training, the patients' exercise performances were significantly improved. The mean VO2 max had increased to 2.8 mL/kg/min, whereas the pulmonary function test and diffuse lung capacity were unchanged. Also, 11 of the patients underwent lobectomy with no postoperative mortality noted, and the mean hospital stay was 17 days. Postoperative pulmonary complication happened in eight patients. In another pilot
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study,17 eight lung cancer patients who were inoperable due to poor pulmonary function underwent a four-week preoperative rehabilitationdfive daily sessions, 3 h each, every weekd including incremental symptom-limited aerobic exercise, breathing exercises, and educational sessions. All of the patients improved their exercise capacity as it affects clinical criteria for surgery, and were subsequently operated on with no mortality and a morbidity of 25%. Functional parameters measured before and after preoperative rehabilitation demonstrated a significant increase in FVC, both in terms of volume (þ0.44 l) and percentage of that predicted (þ12.9%). Similar improvements, although to a lesser extent, were observed for FEV1. General performance in the 6-min walk test (6 MWT) improved by 47.4%. The strong correlation between prehabilitation values and the indices of FEV1, 6 MWT, and arterial oxygen tension (paO2) after surgical treatment indicated that patients who had the worst initial pulmonary function and exercise capacity received the most benefits from pulmonary rehabilitation. Although preoperative rehabilitation may have a strong impact on survival if additional patients are qualified for curative resection, yet strong evidence remains lacking to support the regimens for patients who have lung cancer. This may be due to, in part, the relatively brief period of time between cancer diagnosis and surgery, which does not typically allow a 4e8 weeks rehabilitation program. This issue may hinder the translation of evidence supporting prehabilitation into clinical practice. Furthermore, it is currently recommended for already operable patients not to delay surgery in order to undertake prehabilitation, but instead use the time waiting to deliver prehabilitation. The European Respiratory Society and the European Society of Thoracic Surgeons have published evidence-based guidelines on the use of physical therapy programs in lung cancer patients. The suggestions were that exercise training may improve surgical risk and/or recovery, symptom control, and possibly, risk of dying following a lung cancer diagnosis.7 4. Perioperative rehabilitation Rehabilitation in the immediate postoperative period aims to reduce PPCs, prevent deconditioning and facilitate early and safe discharge. A PPC is defined as any pulmonary sequelae occurring during the post-operative period and resulting in significant dysfunction, adversely affecting the clinical course.18 The problems that were encountered included pneumonia, atelectasis, acute respiratory failure, need for reintubation, pulmonary edema, bronchospasm, pneumothorax and prolonged air leaks. Currently, the known independent risk factors for PPC are age 75 years, body mass index 30 kg/m2, Anesthesia Physical Classification System scored 3, smoking history and COPD.3 Despite the improvement in surgical techniques and perioperative management, PPCs still occur in 3.9%e32.5% of patients with lung cancer who have undergone surgical resection.19e21 PPCs are a major cause of morbidity, mortality, prolonged hospital stay, and the increased cost of care.20 One study examined the feasibility of high frequency chest wall oscillation therapy immediately after pulmonary lobectomy in lung cancer patients compared to conventional chest physiotherapy. The chest wall oscillation group had a better and quicker recovery of pulmonary function (including FEV1 and oxygenation) than the conventional chest physiotherapy group. No unexpected complications, such as hemodynamic deterioration, bleeding or chest tube or wound problems associated with oscillation therapy were detected.22 A quasi-experimental study attempted to evaluate the effects of an intensive postoperative respiratory exercise in patients undergoing lobectomy; 90% of the 208 participants had lung cancer. The control group received standard care and the experimental group received an additional daily physiotherapy program that
focused on respiratory exercises until discharge. A significant improvement in terms of PPCs was detected in both the control (20.6%) and experimental group (6.6%), with a median LOS of 14 and 12 days in control and experimental groups, respectively. In addition, both the physiotherapy program and percentage of FEV1 were identified as protective factors for the development of PPCs in lobectomy procedure according to the logistic regression model.21 Another randomized single-blind clinical trial found that no difference was apparent in the PPC rate or LOS for patients treated with prophylactic targeted respiratory physiotherapy (deep breathing and coughing, mobilization, progressive shoulder/ thoracic mobility exercises) plus the usual care compared to usual care alone. The usual care included a clinical pathway with early mobilization.19 However, the study was conducted in a single hospital in New Zealand. The results cannot be extrapolated for the entire population, thus execution of this treatment should be used with caution. A systematic review investigated the efficacy of perioperative respiratory physiotherapy in patients undergoing pulmonary resection for lung cancer in terms of PPC incidence, postoperative recovery of pulmonary function and LOS.14 Studies were included if they were randomized controlled trials, compared two or more perioperative physiotherapy interventions or compared one intervention with no intervention. Two studies investigated the efficacy of interventions that started preoperatively and then continued after surgery23,24; four studies assessed postoperative interventions only.19,24e26 The rehabilitation program includes incentive spirometry, breathing and coughing exercises, sustained maximal inspirations, active cycle of breathing techniques, intermittent positive pressure breathing, flutter, positive pressure devices and shoulder/thoracic cage exercise. The authors found that pre-surgical interventions based on moderate-to-intense aerobic exercise in patients undergoing lung resection improved functional capacity and reduced postoperative morbidity, whereas interventions performed only during the postoperative period did not seem to reduce PPCs or LOS. However, it was noted that the results of the substantial heterogeneity in the interventions across the studies were inconsistent.14 Recent improvements in pain management and the increasing use of video-assisted thoracic surgery changed the postoperative clinical pathways. There is a lack of strong evidence to support the routine use of prophylactic targeted pulmonary rehabilitation interventions immediately after lung resection surgery. 5. Postoperative rehabilitation Although surgery is the main curative therapy for lung cancer, the procedure can directly cause a reduction in pulmonary functional reserve and exercise capacity proportional to the extent of resection. The problems might be more severe in those undergoing multimodality treatments or who have co-morbidity. Across various studies, indices such as FEV1, FVC, TLC, DLCO and VO2 peak are negatively affected by thoracic surgery.22,27e29 Patients with lung cancer who underwent segmentectomy had better pulmonary function after surgery than those who underwent lobectomy at 3e12 months postoperatively. However, a marginally significant benefit was observed in segmentectomy group for anaerobic threshold when compared to lobectomy.27e30 There was a positive and significant correlation between the number of resected segments versus loss of both FVC and FEV1 at six months.30 The loss of lung function also varied significantly with the location of the resection, comorbidity and methods of operation. For example, resection of an emphysematous portion of the lung will probably result a reduced loss of function. Patients with COPD typically experience smaller declines in FEV1 after lobectomy than
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those without COPD.27,30 Declines in DLCO and VO2 peak are more variable, with the reported decrease of 3e20% in those with COPD, and 0e21% in those without the disease. Such reduction persisted up to three years after surgery, while the values still remained lower than the preoperative values.31 When divided lobectomy into two groups: the upper lobectomy (UL) group and the lower lobectomy (LL) group, FVC of the LL group decreased more significantly from two weeks to six months after the operation compared with the UL group. There were no differences at 12 months after resection between the two groups nor in FEV1.28 A recent study showed that the actual percent-of-predicted FEV1 and DLCO one month after surgery were almost equal to the predicted postoperative value, and the number continued to increase significantly six to 12 months after training. However, no improvement was observed on the same actual pulmonary functional tests in subjects with COPD, or in those who underwent thoracotomy or received adjuvant chemotherapy after one year of training.32 In light of those factors that contribute to muscle deconditioning, and ultimately to physical inactivity, the training exercise should play a key role in preventing or at least mitigating the harmful effects of surgery. Rehabilitation following surgery aims to restore physical status and to maximize function, physical activity, psychological status and health-related quality of life. Nevertheless, only a few studies on this topic have been performed and are generally based on a small number of patients. In 2014, a systematic review aimed to synthesize all available evidence with regard to exercise intervention for patients who were surgically treated for NSCLC.33 The results illustrated only 20 studies across the spectrum being considered eligible for the review, and most selected studies were observational single group trials. Generally, rehabilitation programs are supervised, which range from 4 to 14 weeks in an outpatient setting, although inpatient and home-based programs have also been used. A majority of the studies included both aerobic (walking, treadmill and/or stationary cycle) and resistance training components. Other components such as breathing exercises, dyspnea management, balance exercises and limb stretches were used occasionally; however, the independent contribution of these training components to the resultant outcomes is unknown. The authors found that the outcomes measured in pulmonary function, including FEV1, DLCO and FVC, showed insignificant results for all pulmonary function measures in six of the ten studies except only four studies reported an improved pulmonary function. All but one of the studies that used the 6 MWT test reported a significant increase in distance measured from baseline to post intervention, which increased from 28 m to 377 m. Studies focusing on the cardiopulmonary exercise test reported a significant increase in exercise capacity in three of the five studies, with VO2 max improving from 2.8 to 6.3 mL/kg/min. One study showed that the highest percentage of improvement was twice as long in the duration of intervention (eight weeks compared to four weeks). Studies that recruited patients who had impaired exercise capacity at baseline (VO2 max < 15 mL/kg/min) showed the most improvement in postexercise interventions.33 The Cochrane review on exercise after lung resection identified three randomized trials involving 178 participants.34 The metaanalysis found that exercise capacity was statistically greater in the exercise training group compared to the control group following lung resection for NSCLC. No between-group differences were observed in health-related quality of life (HRQoL) or FEV1. Evidence from the study suggested that exercise training, including aerobic and resistance exercises, may potentially increase exercise capacity in people following lung resection due to lung cancer. Although the quality of the evidence is low, referrals to exercise training or pulmonary rehabilitation programs should be considered. This is especially true for those with impairments in exercise
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capacity.34 Since the publication of the two review articles, three additional randomized trials that evaluated the role of postoperative rehabilitation in lung cancer patients were subsequently published. One was a prospective randomized controlled trial on 40 patients who were randomly assigned to one of four groups (three intervention groups and one control group). The postoperative exercise program comprised a supervised exercise program that involved resistance and high-intensity interval cardiorespiratory exercise, 2 h weekly for 12 weeks combined with individual counseling. The postoperative exercise was completed by 73% of the patients randomly assigned to this intervention. The study concluded that an early postoperative exercise program for patients with NSCLC was safe and feasible, but a preoperative home-based exercise program was not feasible for this population in a fast-track set up.35 Another study used a three-axis accelerometer for five to six days to measure the physical activity before and two months after surgery. Similar to the previous study, patients did not recover to the preoperative physical activity level two months after lung resection surgery. However, compared with the control group, there was an improvement in the postoperative physical activity level in patients, including older patients, who underwent outpatient pulmonary rehabilitation.36 The third study investigated the effects of high-intensity training (60 min, three times a week for 20 weeks) starting at five to seven weeks after surgery in the single-blind randomized controlled trial. The program included, among other standard postoperative care, 60 min, three times a week, 20 weeks strength and endurance training. After intervention, the authors concluded that the high intensity training was well-tolerated and induced a clinically significant increase in peak oxygen uptake during walking, DLCO, muscular strength, daily physical functioning and quality of life.37 The growing body of evidence suggests that rehabilitation following surgery is safe and well-tolerated, and is associated with improvements in physical and physiological outcomes. Exercise in this setting is not yet a routine clinical practice. Larger randomized control trials with excellent methodological quality, intention-totreat analysis and proper implementation are needed to confirm the efficacy of exercise intervention. Furthermore, strengthening of the meta-analyses are required in assisting the translation of evidence into routine clinical practice. 6. Conclusion Research on pulmonary rehabilitation supports the value of this treatment modality in a global approach to patients with lung cancer. The available evidence suggests that pulmonary rehabilitation is safe and feasible in lung cancer patients, and can be performed in a variety of situations. Although there is not enough evidence to support the routine functional assessment before surgery, the assessment of exercise capacity is considered pivotal in the management of patients with lung cancer, both for prognostic and therapeutic reasons. On the other hand, a sufficient amount of data is available to support the fact that prehabilitation could improve exercise capacity and reduce postoperative morbidity and mortality. There is also a clear rationale that the optimization of the preoperative fitness obtained through a rehabilitation program may make candidates for surgical resection for those patients who, despite anatomical resectability, were initially declared inoperable due to poor physical performance. The evidence provided will increase the number of inoperable-to-operable patients with lung cancer. Furthermore, rehabilitation after surgery could improve physical performance and quality of life, but the data were limited. To date, there is no consensus on the correct timing, duration and those components which should be part of the rehabilitation
Please cite this article in press as: Li T-C, et al., Prehabilitation and rehabilitation for surgically treated lung cancer patients, Journal of Cancer Research and Practice (2017), http://dx.doi.org/10.1016/j.jcrpr.2017.06.001
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Please cite this article in press as: Li T-C, et al., Prehabilitation and rehabilitation for surgically treated lung cancer patients, Journal of Cancer Research and Practice (2017), http://dx.doi.org/10.1016/j.jcrpr.2017.06.001