Patient reported outcomes (PROs) after minimally invasive and open esophagectomy

Introduction

As surgical morbidity and mortality continues to decrease, and surgeons are embarking on increasingly complex procedures, outcomes and other quality metrics are continually monitored and critiqued. As health care systems continue to evolve, emphasis on the reporting of these outcomes has undergone a paradigm shift, from one of physician reported outcomes alone, to one that includes patient reported outcomes (PROs). PROs assess certain interventions, and their effect on multiple reportable metrics, all from the perspective of the patient undergoing that specific intervention (1). As patient advocates from a surgical perspective, surgeons may use these data to select the most appropriate approach to surgery to help improve outcomes from the patient’s point of view, although utilization of PROs to make meaningful conclusions does remain an area of controversy (1,2).

An esophagectomy remains a procedure with a significant amount of inherent morbidity, and techniques and approaches that improve patient’s overall well-being and quality of life are advantageous. While the immediate goal of an esophagectomy for malignancy is an appropriate oncologic outcome, an equal goal is good quality of life postoperatively, but often the latter is erroneously overlooked. Patients with esophageal cancer who undergo treatments with curative intent have a significant number of quality of life altering symptoms (3). Improved quality of life after esophagectomy also can be a predictor of long term survival outcomes, and may predict improved outcomes to a better degree than functional status scoring systems (4-6).

Functional recovery, immediate and chronic pain, and physical, social, and emotional well-being are all are facets of complete perioperative recovery and represent targets for potential improvement after esophagectomy. Several instruments, primarily in the form of questionnaires, can be used to monitor these facets postoperatively from the patient’s perspective. The most extensively utilized ones for post esophagectomy patients are the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, EORTC QLQ-OES18, and Functional Assessment of Cancer Therapy-Esophageal (FACT-E) questionnaires coupled with patient reported pain scoring systems. These instruments contain quality of life measurements for general oncology issues, as well as esophageal components specific to esophageal quality of life concerns.

Minimally invasive approaches, whether laparoscopic and thoracoscopic alone or robotic assisted, seem to improve quality of life after esophagectomy when compared to similar open approaches. Analysis of the comparison of minimally invasive versus open esophagectomy (OE), from a quality of life perspective, will help to apply operative approaches to maximize PROs. For the purposes of this review, the focus will be on the randomized controlled trials available and higher quality large series, if applicable. Also, for the purposes of this review, MIE is defined as those approaches utilizing a complete laparoscopic and thoracoscopic approach, and hybrid approaches will not be discussed. Data for minimally invasive and robotic esophagectomies will be looked at separately in comparison to open, although robotic approaches represent a subset of the minimally invasive approach.

Minimally invasive esophagectomy (MIE) versus OE

The TIME trial was a randomized controlled trial comparing minimally invasive Ivor Lewis esophagectomy with thoracoscopy and laparoscopy with standard open approaches, and PROs were reported as secondary outcomes at 6 week patient follow up (7). In the MIE arm, short term quality of life outcomes were improved in SF-36 physical health component summary score, which primarily represents physical functioning, physical capabilities, pain, and general health (P=0.007), with the mental component summary scores statistically similar (P=0.806). By the EORTC-C30, global patient health was improved with MIE (P=0.020) and by EORTC-OES18, talking and pain scores were improved in MIE (P=0.008, P=0.002) (7). All of these short term quality of life outcomes differences persisted at one year follow up, with the exception of talking scores becoming statistically similar (8).

In another randomized trial, Hong et al. randomized patients to minimally invasive or OE (9). Using the EORTC QLQ-30 and OES-18, both groups had global quality of life and physical functioning declines, not unexpectedly. However, the MIE arm had improved global quality of life scores at 2 and 4 weeks, (P<0.001), improved physical functioning scores at 2, 4, and 8 weeks (P<0.001), and improved fatigue and pain symptom scores at 2, 4, 8, and 12 weeks. (P<0.001). Also, the MIE global quality of life scores nearly matched the preoperative levels (82.5±11.4 baseline vs. 82.1±10.5 at 12 weeks), while the OE cohort failed to return near baseline (83.3±10.9 baseline vs. 71.3±11.9). Also, pain and fatigue symptom scores at 12 weeks exceeded their baseline in the OE arm.

In the largest propensity matched cohort study of MIE vs. OE in the literature, Wang et al. compared 444 MIE patients to 444 OE and included analysis on quality of life using the EORTC QLQ-30 and OES-18 questionnaires (10). Analysis included measurements to 24 months post operatively. MIE patients had improved global quality of life at 1, 3, 6, and 12 months (P<0.001), improved physical function at 1, 3, 6, and 12 months (P<0.001), less fatigue symptoms at 1, 3, 6, and 12 months (P<0.001), less pain symptoms at 1, 3, and 6 months (P<0.001) and less dyspnea symptoms at 1, 3, and 6 months (P<0.001). Beyond those time periods noted, there was no statistically significant difference in scores up to 24 months. Also, type of surgical approach, whether minimally invasive or open, independently had a positive impact of patients post-operative quality of life scores, with age and neoadjuvant therapy having a negative impact.

It is important to note, that nearly all minimally invasive techniques for esophagectomy use the Ivor Lewis or McKeown approach. Minimally invasive, or laparoscopic, transhiatal esophagectomy has been attempted by some surgeons with varying opinions. Some have advocated its use in distal esophageal cancers (11), while others have reported poor visibly leading to inadequate lymph node dissection and difficulty with hemostasis (12). Overall, laparoscopic transhiatal esophagectomy is associated with fewer complications and shorter hospital stays (13). Nevertheless, there are currently no known randomized studies strictly comparing a minimally invasive transhiatal esophagectomy to conventional OE in the setting of esophageal cancer. In a randomized study by Fontan and colleagues, minimally invasive laparoscopic esophagectomy was compared to open transhiatal esophagectomy in patients with megaesophagus in the setting of achalasia (14). A total of 30 patients were included, with 15 in each group. Dysphagia, overall pain, and in-hospital complications were analyzed, and with a mean follow-up time of 33 months, no statistically significant difference was identified. One death was reported in each group. Also, although there have been numerous studies comparing open transhiatal esophagectomy to other open approaches that include a transthoracic component, no randomized studies comparing minimally invasive tranhiatal esophagectomies to other minimally invasive approaches have been reported.

Robotic assisted minimally invasive esophagectomy (RAMIE) versus open

While robotic assisted surgery is essentially a subset of minimally invasive surgery, its comparison as a unique surgical approach in comparison to open should be evaluated as well. While high quality data for robotic approaches compared to open remains less robust in comparison with minimally invasive approaches, data is maturing in favor of the robotic assisted approaches. However, it is important to note that robotic assisted techniques and approaches vary in the literature, with the only completely robotic approach published by Sarkaria and colleagues (15-17).

In the only randomized control trial in this arena, the recently published ROBOT trial compared robotic esophagectomy versus open, and in the trial, PROs were evaluated, but it was not a primary endpoint of the trial (18). Mean overall postoperative pain scores were less in RAMIE vs. OE (P<0.001) and in 11 of 14 days, daily mean pain scores were statistically significantly less in the RAMIE arm. Using the EORTC-QLQC30, both discharge and 6-week health related quality of life and physical functioning were both statistically improved after RAMIE compared to OE (P=0.02 to 0.049)

Sarkaria et al. evaluated quality of life outcomes for RAMIE or OE utilizing the FACT-E questionnaire in a prospective fashion (19). This includes a total score and subset scores for physical, social, emotional, and functional, and esophageal-specific well-being. Overall, there was no difference in the total FACT-E scores between RAMIE or OE (P=0.84), or in any specific subset (P=0.49 to P>0.95). Both approaches to surgery yielded lower physical well-being scores at 1 month (P<0.001), with improvement at 4 months (P≤0.001), but without returning to baseline (P=0.011); findings for emotional well-being scores were similar. Importantly, RAMIE compared to OE had lower pain scores (P=0.005) and pain interfering with daily activity scores (P=0.002) in the early post-operative period. For both RAMIE and OE, pain scores significantly improved at each measured period to 4 months.

Sugawara et al. also analyzed quality of life outcomes up to 24 months post operatively (20). RAMIE patients had higher physical and emotional function scores at 3, 6, and 18 months and 6, 18, and 24 months, respectively, compared to the open cohort. Generalized pain scores were lower in the RAMIE group at 3, 6, 12, and 24 months post-operatively, and esophageal specific pain scores were less at 3 and 18 months as well. Fatigue and insomnia at 24 months were less frequently reported in the RAMIE group. Importantly, this study is associated with significant bias due to the comparison of a robotic transhiatal approach with an open Ivor Lewis approach.

Similarly, as in traditional minimally invasive approaches, robotic assisted techniques for esophagectomy more commonly involve a transthoracic component as well. The studies regarding RAMIE above all include a transthoracic component during the esophagectomy, unless otherwise stated. There are currently a limited number of studies evaluating robotic transhiatal esophagectomies, none of which are randomized. Although some authors have reported similar oncologic results in robotic transhiatal resections compared to open (21,22), no study has reported PROs. Overall, further randomized perspective studies need to be performed to provide any definitive conclusions.

Conclusions

Based on the aforementioned studies, it appears that both minimally invasive esophagectomies, whether laparoscopic and thoracoscopic or robotic assisted approaches, offer significant benefits with regards to PROs in comparison to its open counterpart. These primarily represent improved functional recovery, quality of life, and improved pain, all facets which minimally invasive surgeons have emphasized as benefits of the approach. Overall, the weight of data supports the use of MIE from the perspective of improved post-operative quality of life, and more rapid return to preoperative baseline.

Acknowledgments

Funding: None.

Footnote

Provenance and Peer Review: This article was commissioned by the Guest Editor (Peter Kneuertz) for the series “Patient reported Outcomes in Thoracic Surgery: A new Frontier” published in Journal of Thoracic Disease. The article was sent for external peer review organized by the Guest Editor and the editorial office.

Conflicts of Interest: The authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-2019-pro-09). The series “Patient reported Outcomes in Thoracic Surgery: A new Frontier” was commissioned by the editorial office without any funding or sponsorship. Dr. JDL reports and owns stock in: Intuitive Surgical, Inc., Cigna Corp, and Proctor and Gamble. ISS serves as an unpaid editorial board member of Journal of Thoracic Disease from Sept 2018 to Aug 2020. Dr. ISS reports honoraria and/or grants for research/education/training, and/or consulting for Intuitive Surgical, Inc., On Target Laboratories, Cambridge Medical Robotics, and Auris Medical, all outside the scope of the submitted work. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of this work in ensuring that questions related to the accuracy or integrity of any part of this work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Rivera SC, Kyte DG, Aiyegbusi OL, et al. The impact of patient-reported outcome (PRO) data from clinical trials: a systematic review and critical analysis. Health Qual Life Outcomes 2019;17:156. [Crossref] [PubMed]
2. Straatman J, Joosten PJ, Terwee CB, et al. Systematic review of patient-reported outcome measures in the surgical treatment of patients with esophageal cancer. Dis Esophagus 2016;29:760-72. [Crossref] [PubMed]
3. Gupta V, Allen-Ayodabo C, Davis L, et al. Patient-Reported Symptoms for Esophageal Cancer Patients Undergoing Curative Intent Treatment. Ann Thorac Surg 2020;109:367-74. [Crossref] [PubMed]
4. van Heijl M, Sprangers MA, de Boer AG, et al. Preoperative and early postoperative quality of life predict survival in potentially curable patients with esophageal cancer. Ann Surg Oncol 2010;17:23-30. [Crossref] [PubMed]
5. Safieddine N, Xu W, Quadri SM, et al. Health-related quality of life in esophageal cancer: effect of neoadjuvant chemoradiotherapy followed by surgical intervention. J Thorac Cardiovasc Surg 2009;137:36-42. [Crossref] [PubMed]
6. Kidane B, Sulman J, Xu W, et al. Pretreatment quality-of-life score is a better discriminator of oesophageal cancer survival than performance status. Eur J Cardiothorac Surg 2017;51:148-54. [Crossref] [PubMed]
7. Biere SS, van Berge Henegouwen MI, Maas KW, et al. Minimally invasive versus open oesophagectomy for patients with oesophageal cancer: a multicentre, open-label, randomised controlled trial. Lancet 2012;379:1887-92. [Crossref] [PubMed]
8. Maas KW, Cuesta MA, van Berge Henegouwen MI, et al. Quality of Life and Late Complications After Minimally Invasive Compared to Open Esophagectomy: Results of a Randomized Trial. World J Surg 2015;39:1986-93. [Crossref] [PubMed]
9. Hong L, Zhang Y, Zhang H, et al. The short-term outcome of three-field minimally invasive esophagectomy for Siewert type I esophagogastric junctional adenocarcinoma. Ann Thorac Surg 2013;96:1826-31. [Crossref] [PubMed]
10. Wang H, Shen Y, Feng M, et al. Outcomes, quality of life, and survival after esophagectomy for squamous cell carcinoma: A propensity score-matched comparison of operative approaches. J Thorac Cardiovasc Surg 2015;149:1006-14; discussion 1014-5.e4. [Crossref] [PubMed]
11. Haisley KR, Abdelmoaty WF, Dunst CM. Laparoscopic Transhiatal Esophagectomy for Invasive Esophageal Adenocarcinoma. J Gastrointest Surg 2020. [Epub ahead of print]. [Crossref] [PubMed]
12. Levy RM, Wizorek J, Shende M, et al. Laparoscopic and thoracoscopic esophagectomy. Adv Surg 2010;44:101-16. [Crossref] [PubMed]
13. Gurusamy KS, Pallari E, Midya S, et al. Laparoscopic versus open transhiatal oesophagectomy for oesophageal cancer. Cochrane Database Syst Rev 2016;3:CD011390. [Crossref] [PubMed]
14. Fontan AJA, Batista-Neto J, Pontes ACP, et al. Minimally invasive laparoscopic esophagectomy vs. transhiatal open esophagectomy in achalasia: a randomized study. Arq Bras Cir Dig 2018;31:e1382. [Crossref] [PubMed]
15. Sarkaria IS, Latif MJ, Bianco VJ, et al. Early operative outcomes and learning curve of robotic assisted giant paraesophageal hernia repair. Int J Med Robot 2017;13. [Crossref] [PubMed]
16. Sarkaria IS, Rizk NP. Robotic-assisted minimally invasive esophagectomy: the Ivor Lewis approach. Thorac Surg Clin 2014;24:211-22. vii. [Crossref] [PubMed]
17. Sarkaria IS, Rizk NP, Grosser R, et al. Attaining Proficiency in Robotic-Assisted Minimally Invasive Esophagectomy While Maximizing Safety During Procedure Development. Innovations (Phila) 2016;11:268-73. [Crossref] [PubMed]
18. van der Sluis PC, van der Horst S, May AM, et al. Robot-assisted Minimally Invasive Thoracolaparoscopic Esophagectomy Versus Open Transthoracic Esophagectomy for Resectable Esophageal Cancer: A Randomized Controlled Trial. Ann Surg 2019;269:621-30. [Crossref] [PubMed]
19. Sarkaria IS, Rizk NP, Goldman DA, et al. Early Quality of Life Outcomes After Robotic-Assisted Minimally Invasive and Open Esophagectomy. Ann Thorac Surg 2019;108:920-8. [Crossref] [PubMed]
20. Sugawara K, Yoshimura S, Yagi K, et al. Long-term health-related quality of life following robot-assisted radical transmediastinal esophagectomy. Surg Endosc 2020;34:1602-11. [Crossref] [PubMed]
21. Washington K, Watkins JR, Jay J, et al. Oncologic Resection in Laparoscopic Versus Robotic Transhiatal Esophagectomy. JSLS 2019;23:e2019.00017.
22. Coker AM, Barajas-Gamboa JS, Cheverie J, et al. Outcomes of robotic-assisted transhiatal esophagectomy for esophageal cancer after neoadjuvant chemoradiation. J Laparoendosc Adv Surg Tech A 2014;24:89-94. [Crossref] [PubMed]