Does preoperative pulmonary rehabilitation/physiotherapy improve patient outcomes following lung resection?

Summary

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was whether preoperative physiotherapy (pulmonary prehabilitation) is beneficial for patients undergoing lung resection. Altogether 177 papers were found using the reported search, of which 10 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. A meta-analysis by Li et al. showed that patients who received a preoperative rehabilitation programme (PRP) had reduced incidence of postoperative pulmonary complications (PPCs) (odds ratio 0.44, 95% CI 0.27–0.71), reduced length of stay (LOS) (−4.23 days, 95% CI −6.14 to −2.32 days) and improved 6-min walking distance (71.25 m, 95% CI 39.68–102.82) and peak oxygen uptake consumption (VO² peak) (3.26, 95% CI 2.17–4.35). A meta-analysis by Steffens et al. showed that PPCs were reduced in patients with PRP (relative risk 0.49, 95% CI 0.33–0.73) and reduced LOS (−2.86 days, 95% CI −5.40 to −0.33). The results of 3 additional meta-analyses, 4 randomized controlled trials and 1 observational study all provide further support to PRP in enhanced recovery after surgery and the improvement in exercise capacity. We conclude that PRP improves exercise capacity in patients undergoing surgical resection for lung cancer. Moderate quality evidence supports preoperative exercise providing significant reduction in PPCs and hospital LOS. Referral to exercise programmes should be considered in patients awaiting lung resection, particularly those deemed borderline for suitability for surgical resection.

INTRODUCTION

A best evidence topic was constructed according to a structured protocol. This is fully described in the ICVTS [1]. This is an update of a previous best evidence topic on the subject by Nagarajan et al. [2].

THREE-PART QUESTION

In [patients undergoing lobectomy] is [preoperative pulmonary rehabilitation/physiotherapy] of benefit in [improving preoperative exercise capacity and reducing post-operative morbidity and length of stay (LOS)]?

CLINICAL SCENARIO

A 60-year-old female patient is presented at the lung cancer multi-disciplinary meeting with biopsy-proven T1cN0M0 squamous cell carcinoma of the left lower lobe. She is a life-long smoker with a poor exercise tolerance. She has a forced expiratory volume in 1 s (FEV1) <40% and a diffusing capacity of the lungs for carbon monoxide of 45%. The surgical team deem her suitable, albeit borderline, for a video-assisted thoracoscopic left lower lobectomy and discuss if there is anything that can be done preoperatively to optimize her postoperative recovery. Pulmonary rehabilitation/physiotherapy improves exercise tolerance in patients with chronic obstructive pulmonary disease (COPD). Does the same strategy improve exercise capacity and reduce post-operative morbidity and length of stay in patients undergoing lung resection? You resolve to check the literature for evidence.

SEARCH STRATEGY

Medline 2010 to November 2020 using PubMed interface, publications in English language: (physiotherapy OR pulmonary rehabilitation OR prehabilitation OR training) AND (preoperative) AND (lung cancer) AND (lung resection OR lobectomy).

A secondary search of Embase was performed, without the identification of further papers suitable for inclusion as best evidence.

SEARCH OUTCOME

A total of 177 papers were found using the primary reported search. From these, 10 papers were identified that provided the best evidence to answer the question. These are presented in Table 1.

Table 1:

Best evidence papers

Author, date, journal and countryStudy type(level of evidence)	Patient group	Outcomes	Key results	Comments
Li et al. (2019), Cancer Manag Res, China [3] Meta-analysis (level I)	404 patients from 7 RCTs - Group I: n = 192, preoperative exercise - Group C: n = 232, standard care	PPCs	Reported 6/7 RCTs: Group I OR 0.44, 95% CI 0.27–0.71 (I2 = 0, P = 0.0001)	The type, duration, and intensity of exercise varied among the studies
		LOS	Reported 5/7 RCTs: SMD −4.23 days, 95% CI −6.14 to −2.32 days
		Exercise capacity - 6MWD - VO2 peak	Reported 3/7 RCTs: SMD 71.25, 95% CI 39.68 − 102.82 SMD 3.26, 95% CI 2.17–4.35
Steffens et al. (2018), Br J Sports Med, UK [4] Meta-analysis (level I)	432 patients from 6 studies 332 patients from 4 RCTs and 1 qRCT in meta-analysis - Group I: n = 165, preoperative exercise - Group C: n = 167, standard care	PPCs	Pooled effect of 4/5 trials (n = 288): RR 0.49, 95% CI 0.33–0.73	The definition of postoperative complication varied between included trials Moderate quality evidence using the GRADE approach
		LOS	Reported 5/5 RCTs: MD −2.86 days, 95% CI −5.40 to −0.33
Cavalheri and Granger (2017), Cochrane, Australia [5] Meta-analysis (level I)	158 patients from 5 RCTs - Group I: n = 81, preoperative exercise - Group C: n = 77, standard care	PPCs	Reported 4/5 RCTs: RR 0.33, 95% CI 0.17–0.61	Deemed low-quality evidence Intention-to-treat analysis was only reported in 2 studies Two studies were excluded where authors could not be contacted to clarify details required for inclusion
		LOS	Reported 4/5 RCTs: MD −4.24 days, 95% CI −5.43 to −3.06 days
		Exercise capacity - 6MWD - FVC	Reported 2/5 RCTs (n = 81): MD 18.23 m, 95% CI 8.50–27.96 m MD 2.97% predicted, 95% CI 1.78–4.16% predicted
Ni et al. (2017), China [6] Meta-analysis (level I)	6 studies of various types - 3 RCTs, 1 CT and 2 SGTs Group I: n = 112 preoperative exercise Group C: n = 111 standard care	PPCs	Reported 4/6 studies (n = 185) OR was 0.33 (95% CI = 0.15–0.74, P = 0.007)	Patients with NSCLC only Only 1 RCT provided data on 6MWD
		LOS	Reported 4/6 studies (n = 185): Decrease in LOS of −4.98 days (95% CI = −6.22 to −3.74) after exercise training (P < 0.00001)
		Exercise capacity - 6MWD	Reported 3/6 studies: 6MWD increased 39.95 m (95% CI = 5.31–74.6) P = 0.02, (I2 = 0%)
Sebio Garcia et al. (2016), Interact CardioVasc Thorac Surg [7] Meta-analysis (level I)	1189 patients with lung cancer from 21 studies - Group I: n = 595, preoperative exercise - Group C: n = 594, standard care	PPCs	Pooled effect 5/21 studies: RR = 0.55; 95% CI 0.34–0.89	Lung resection mostly by open thoracotomy Included non-RCTs and observational studies
		LOS	Pooled effect 7/21 studies: MD = −4.83, 95% CI −5.90 to −3.76
		Exercise capacity - FEV1 - FVC	Pooled effect 10/21 studies: SMD = 0.27, 95% CI 0.11–0.42 Pooled effect 8/21 studies: SMD = 0.38, 95% CI 0.14–0.63
Liu et al. (2020), Anesth Analg, China [8] Randomized controlled trial (RCT) (level II)	73 patients with NSCLC undergoing VATs lobectomy Group I: n = 37, prehabilitation group Group C: n = 36, control group	PPCs	No difference between groups Group I: 4 PPCs Group C: 5 PPCs	Small patient group Only VATs patients were included The baseline pulmonary functions of both groups were within the normal level
		LOS	No difference between groups Group I: 5 days Group C: 5 days
		Exercise capacity: 6MWD FVC	Prehabilitation intervention improved 6MWD: Mean difference between group I and group C: +60.9 months, 95% CI 32.4–89.5, P < 0.001 0.35L higher in group I, 95% CI 0.05–0.66, P = 0.21
Rispoli et al. (2020), Tumori, Italy [9] Observational study (level III)	59 patients with mild COPD who underwent lobectomy for cancer and underwent preoperative rehabilitation Group A: n = 13 <3 sessions per week Group B: n = 46 >3 sessions per week	Exercise capacity: 6MWD FEV1	Only group B patients showed significant improvement in 6MWD Group B: 28% increase (±7.9), P = 0.001 Group A: 19% (±3.5), P = 0.23 Only group B patients showed significant improvement in FEV1 Group B: 8.2% increase (±0.7), P = 0.004 Group A: 2.7% (±0.3), P = 0.67	Small patient group Included only patients with COPD
		PPCs	Group A presented higher number of PPCs Group A: 6 Group B: 3, P = 0.0005 Multivariate analysis showed the number of weekly rehabilitation sessions was only independent predictive prognostic factor, P = 0.001
Laurent et al. (2020), Eur J Phys Rehabil Med, France [10] RCT (level II)	26 patients eligible for NSCLC resection Group T: n = 14 Preoperative respiratory muscle training + chest physical therapy Group C: n = 12 Chest physical therapy	Exercise capacity: Minute VE l min−1 ET seconds	Group T: +15(±)16 Group C: −2(±)17, P = 0.004 Group T: +299(±)199 Group C: −5 (±) 371, P = 0.001	Potential bias: Evaluators not blinded to allocation groups Limited sample of patients
		PPCs	Group T: 2 Group C: 10, P = 0.037
		LOS	No difference between groups. Group T: 7.6 ± 3.3 Group C: 8.5 ± 4.7
Lai et al. (2019), Ann Transl Med, China [11] Randomized trial (level II)	68 patients with NSCLC undergoing VATs lobectomy Intervened group (Group I): n = 34, Preoperative physical training Controlled group (Group C): n = 34, Routine preoperative preparation	PPCs	Group I: 11.8% (4/34) Group C: 35.3 % (12/34), P = 0.022	Participants were from single study centre Only patients with predicted postoperative FEV1 < 60% included in study
		LOS	Group I: 5 (4–7) Group C: 8 (7–10), P ≤ 0.001
		Exercise capacity: 6MWD	Group I: 22.6 ± 27 Group C: 2.7 ± 27.6 Between-group difference: 19.9 months, 95% CI 6.7–33.2, P = 0.004
		QOL	Emotional function of EORTC-QLQ-30 significantly improved in Group I: Z value = 3.363, P = 0.001
Bhatia and Kayser (2019), J Rehabil Med, Switzerland [12] RCT (level II)	151 patients with NSCLC stage IIIA or less, who underwent surgical resection Group UC: n = 77 Group PH: n = 74	Exercise capacity: 6MWD VO2 peak	20% increase in Group PH, 95% CI 14–26, P < 0.001 6MWD declined in group UC 14% increase in group PH, 95% CI 3–26, P = 0.004 VO2 peak decreased in Group UC	22% of patients had an ASA score of 3–4, making adherence in this trial challenging

COPD: chronic obstructive pulmonary disease; ET: endurance time; FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; LOS: length of stay; 6MWD: 6-min walking distance; MD: mean difference; NSCLC: non-small-cell lung cancer; OR: odds ratio; PPCs: postoperative pulmonary complications (); PH: prehabilitation; QOL: quality of life; RCT: randomized controlled trial; RR: relative risk; SMD: standardized mean difference; UC: usual care; VE: ventilation; ASA: American Society of Anaesthesiology; CI: confidence interval; VATs: video-assisted thoracoscopic surgery; SGTs: single group trials; qRCT: quasi randomised controlled trial; CT: controlled trial.

RESULTS

A total of 10 papers were included to provide best evidence on this topic. Five meta-analyses provide the strongest level of evidence (level I), with the most contemporary study published in 2019. A further 4 randomized trials and an observational study have been included for discussion as they represent more recent data not included in the meta-analyses.

Li et al. [3] in 2019 performed a meta-analysis of 404 patients from 7 randomized controlled trials (RCTs) on the impact of preoperative exercise therapy on surgical outcomes in lung cancer patients, with or without COPD. Along with being the most recent meta-analysis published, this study also performed a subgroup analysis on patients with COPD, a patient group with a high incidence of lung cancer. From pooled data from 6 of the 7 studies, they found patients receiving preoperative exercise training had a statistically significant lower incidence of postoperative pulmonary complications (PPCs), with an odds ratio of 0.44 compared to standard care. The heterogeneity of this result was acceptable (I² = 0, P < 0.0001). In 5 studies that reported postoperative pneumonia, there was no reduction in postoperative pneumonia rates in those receiving preoperative exercise before lung cancer resection. The length of stay in patients receiving preoperative exercise training was shorter with a standardized mean difference of minus 4.23 days (P = 0.02). Further subgroup analysis of patients with COPD and lung cancer simultaneously found no benefit of preoperative exercise intervention in the incidence of PPCs but did see a similar reduction in LOS. Patients receiving preoperative exercise before surgery reported an improved exercise capacity with an increase in the 6-min walking distance (6MWD) and a higher VO² peak; however, no significant difference in pulmonary function was observed. Li et al. provided some evidence that preoperative exercise enhanced recovery after surgery for patients with lung cancer and COPD.

Steffens et al. [4] in 2018 performed a meta-analysis of patients undergoing lung cancer surgery in 5 trials (n = 332), of which 4 were RCTs and 1 quasi RCT. This meta-analysis included 3 further RCTs not included by Li et al. This was a study of the effect of preoperative exercise in patients with cancer undergoing surgical resection, with a subgroup analysis of those with lung cancer. The strongest evidence and recommendations from this study came from patients with lung cancer who underwent preoperative exercise, in comparison to other groups of patients undergoing oncological surgery.

PPC rates were reduced by 48% in the preoperative exercise group and length of stay was reduced by almost 3 days. Most of the preoperative exercise interventions investigated in the included trials incorporated aerobic and respiratory muscle training exercises. Results suggested a dose–response relationship, with trials performing a large number of exercise sessions per week reporting a larger effect size. Pooling estimates (I² = 0) provided moderate quality of evidence of a significant effect favouring preoperative pulmonary rehabilitation over control on PPCs and LOS.

Cavalheri and Granger [5] in 2017 performed a Cochrane review and meta-analysis of preoperative exercise for patients with non-small-cell lung cancer (NSCLC) from 5 RCTs (n = 158). This study was included as best evidence due to the strict methodological and reporting standards of Cochrane review, along with the inclusion of the primary outcome of intercostal catheter duration in meta-analysis. Using data from 4 trials (I² = 0), the authors found that preoperative exercise training conferred a 67% reduction in the risk of developing PPCs (P = 0.0004), a 4-day reduction in postoperative LOS (P = 0.00001) and improved preoperative 6MWD. Of the 3 studies that assessed FEV1 none reported a change with preoperative exercise, however, meta-analysis demonstrated that FVC improved by 2.97% more in the exercise group than control group. Further to this, there was a 3-day reduction in intercostal catheter duration in the preoperative exercise training group (P = 0.001). Due to significant risk of bias of the included studies and small sample sizes, authors rated the quality of evidence as low.

Ni et al. [6] in 2017 performed a meta-analysis of 15 studies of various types of patients with NSCLC treated with lung resection. Similar to other included meta-analyses, this study measured the primary end-points of post-operative LOS and PPCs. A fundamental difference, however, was that this meta-analysis also measured and assessed the secondary parameter of quality of life outcomes of patients who underwent preoperative exercise. Of the included trials, 6 studied the effect of preoperative exercise training on patient recovery and exercise capacity. In the pooled analysis of 4 studies, they found that preoperative exercise training shortened LOS, with a mean difference of −4.98 days (P < 0.00001) and also decreased PPCs with an odds ratio of 0.33. No heterogeneity was apparent among these studies (I² = 0%). Four weeks of preoperative exercise training improved exercise capacity in 3 studies, with 39.95 m increased in 6MWD (P < 0.00001). There was no heterogeneity among these studies. This meta-analysis also suggests exercise training conferred an improved quality of life for these patients. On the EORTC-QLQ-30 the dyspnoea score was lower (mean difference −14.3 points, 95% CI −20 to −8.6, P < 0.00001) after exercise. Ni et al. provided evidence that preoperative exercise may shorten LOS, reduce PPCs and increase exercise capacity in surgical patients with NSCLC.

Sebio Garcia et al. [7] in 2016 performed a meta-analysis of 21 studies of various types of lung cancer patients treated with exercise training prior to surgical resection. This study was the largest of the 5 meta-analyses, including the most participants, with a total of 1189 patients participating in the studies selected. They found that pooled estimates of effect sizes showed a significant increase for both FEV1 and FVC in patients that received preoperative exercise therapy. A significant reduction in LOS was identified in the intervention group of −4.83 days (P < 0.00001), along with a reduction in the rate of PPCs with a relative risk of 0.55 (P = 0.005). There was some heterogeneity with an I² of 27%. When patients without impaired pulmonary function were analysed separately, the relative risk for developing PPCs was not statistically significant. The results of this systematic review indicate that exercise-based intervention preoperatively improves exercise capacity and can reduce PPCs and LOS for those patients undergoing surgery for lung cancer.

Liu et al. [8] in 2020 performed an RCT with 73 patients, studying the impact of prehabilitation on perioperative functional capacity in patients undergoing VATs lobectomy for NSCLC. They found the average 6MWD was 60.9 m higher perioperatively in the prehabilitation group (n = 37) compared to the control group (95% CI, 32.4–89.5, P < 0.001). The FVC was also improved in the intervention group, found to be 0.35 l higher (95% CI, 0.05–0.66, P = 0.21). There were no further differences in lung function, disability and psychological assessment, LOS, PPCs and mortality between groups. This study demonstrated a prehabilitation program could improve perioperative functional capacity in patients undergoing VATs lobectomy for lung cancer.

Rispoli et al. [9] in 2020 performed a prospective, observational, single centre study of 59 patients with mild COPD who underwent lobectomy for cancer and underwent preoperative rehabilitation. All patients attended a preoperative rehabilitation program and were analysed in 2 groups depending on the sessions performed each week (<3 sessions or ≥3 sessions per week). The group that performed <3 sessions per week presented a higher number of PPCs (6 vs 3, P = 0.0005). Multivariate analysis showed the number of weekly rehabilitation sessions was the only independent predictive prognostic factor (P = 0.001). In this small study population, Rispoli et al. found that rehabilitation could reduce PPCs in those with mild to moderate COPD undergoing lobectomy for cancer and that patients should be motivated to perform at least 3 rehabilitation sessions each week.

Laurent et al. [10] in 2020 performed an RCT including 26 patients eligible for NSCLC resection, studying the impact of preoperative respiratory muscle endurance training. Those in the intervention group (n = 14) were found to have improved exercise capacity with increased minute ventilation [+15(±)16 vs −2(±)17, P = 0.004] and increased endurance time [+299(±)199 vs −5 (±)371, P = 0.001]. Those in the respiratory muscle endurance training group had a lower number of PPCs (2 vs 10, P = 0.037). There was, however, no difference in LOS between groups.

Lai et al. [11] in 2019 performed a randomized trial of 68 patients with NSCLC undergoing VATs lobectomy, to investigate the influence of preoperative physical training. In those that underwent preoperative physical training, they found a reduction in both PPCs (11.8% vs 35.3%, P = 0.022) and LOS (median 5 (4–7) vs 8 (7–10), P ≤ 0.001) along with an increase in 6MWD (19.9 months, 95% CI, 6.7–33.2, P = 0.004). The study found that preoperative physical training can improve cardiopulmonary tolerance, reduce PPCs and shorten in-hospital LOS.

Bhatia and Kayser [12] in 2019 performed an RCT of 151 patients with NSCLC stage IIIA or less, who underwent surgical resection and examined the effect of prehabilitation on exercise capacity. The prehabilitation group had an increased 6MWD (median 20%, 95% CI 14–26, P < 0.001) and improved VO² max (median 14%, 95% CI 3–26%, P = 0.004). Although 30% of patients in the rehabilitation group had COPD with dyspnoea at rest, the programme was found to be safe in this population of patients with the training well tolerated.

CLINICAL BOTTOM LINE

Preoperative exercise therapy improves exercise capacity in patients undergoing surgical resection for the management of lung cancer. Moderate quality evidence supports that preoperative exercise provides a significant reduction in PPCs and hospital LOS. Referrals to exercise programs should be considered in patients awaiting lung resection, particularly those patients deemed borderline for suitability for surgical resection. Further RCTs are needed to investigate the effect of preoperative exercise on mortality and the cost/benefit of this intervention.

Conflict of interest: none declared.

Reviewer information

Interactive CardioVascular and Thoracic Surgery thanks the anonymous reviewer(s) for their contribution to the peer review process of this article.