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Journal of Clinical Oncology, Vol 22, No 20 (October 15), 2004: pp. 4202-4208 © 2004 American Society of Clinical Oncology. DOI: 10.1200/JCO.2004.11.102 Quality of Life After Transhiatal Compared With Extended Transthoracic Resection for Adenocarcinoma of the EsophagusFrom the Departments of Medical Psychology and Surgery, Academic Medical Center, Amsterdam; and Department of Surgery, Erasmus Medical Center, Rotterdam, the Netherlands Address reprint requests to A.G.E.M. de Boer, MD, Coronel Institute, Academic Medical Center, Meibergdreef 15, 1105 AZ Amsterdam, the Netherlands; e-mail: A.G.deBoer{at}amc.uva.nl
PURPOSE: To assess 3 years of quality of life in patients with esophageal cancer in a randomized trial comparing limited transhiatal resection with extended transthoracic resection. PATIENTS AND METHODS: Quality-of-life questionnaires were sent at baseline and at 5 weeks; 3, 6, 9, and 12 months; and 1.5, 2, 2.5, and 3 years after surgery. Physical and psychological symptoms, activity level, and global quality of life were assessed with the disease-specific Rotterdam Symptom Checklist. Generic quality of life was measured with the Medical Outcomes Study Short Form-20. RESULTS: A total of 199 patients participated. Physical symptoms and activity level declined after the operation and gradually returned toward baseline within the first year (P < .01). Psychological well-being consistently improved after baseline (P < .01), whereas global quality of life showed a small initial decline followed by continuous gradual improvement (P < .01). Quality of life stabilized in the second and third year. Three months after the operation, patients in the transhiatal esophagectomy group (n = 96) reported fewer physical symptoms (P = .01) and better activity levels (P < .01) than patients in the transthoracic group (n = 103), but no differences were found at any other measurement point. For psychological symptoms and global quality of life, no differences were found at any follow-up measurement. A similar pattern was found for generic quality of life. CONCLUSION: No lasting differences in quality of life of patients who underwent either transhiatal or transthoracic resection were found. Compared with baseline, quality of life declined after the operation but was restored within a year in both groups.
The incidence of adenocarcinoma of the distal esophagus and gastric cardia is increasing, and long-term survival after potentially curative surgery is approximately 20%.1,2 Curative esophageal resection may be carried out by either the transhiatal or the transthoracic technique.3 Transhiatal surgery aims to decrease early postoperative morbidity and mortality by performing a relatively limited cervico-abdominal (transhiatal) resection without formal lymphadenectomy. Transthoracic surgery aims at improving the cure rate by performing a combined cervico-thoraco-abdominal resection, in which the tumor and adjacent structures are dissected via a thoracotomy, together with a lymph node dissection of the posterior mediastinum and the upper abdomen (transthoracic esophagectomy with extended en bloc lymphadenectomy). Our earlier results showed that, after a median follow-up of 4.7 years, 70% of the patients died after transhiatal resection, and 60% died after transthoracic resection (P = .12). Although the difference in survival was not statistically significant, there was a trend toward a survival benefit with the transthoracic esophagectomy at 5 years; disease-free survival was 27% in the transhiatal esophagectomy group compared with 39% in the transthoracic esophagectomy group (95% confidence limits for the difference, –1%, 24%).3 Subgroup analyses showed that the long-term benefit of transthoracic esophagectomy is more substantial in patients with esophageal tumors (5-year survival advantage, 17%; 95% confidence limits, –3%, 37%) than in patients with junctional or cardiac tumors (5-year survival advantage, 1%).4 In addition to survival data, the measurement of outcome in esophageal cancer therapy requires information on quality of life.5,6 A potentially curative esophageal resection is a major operation with severe physical, emotional, and social effects, and therefore, both types of resection may have serious negative consequences for the patients' short-term and long-term quality of life.7-12 Recognizing such treatment burden, researchers are increasingly studying the quality of life of patients with esophageal cancer,13 but no long-term quality of life in a clinical trial of esophageal patients has been reported. This long-term quality of life would include the total impact of the two surgical techniques on the quality of life over a long period of time, purposely including the effects of possible additional treatments or of disease recurrence. Considering the balanced results of the survival data, the effects of the operations on the quality of life become even more important because a trade-off might have to be made between potential survival benefit and potential better quality of life. The aim of this study is to compare the quality of life of patients with esophageal cancer who underwent a limited transhiatal resection compared with patients those who underwent an extended transthoracic resection in the context of a randomized study.
Patients Eligible patients with histologically confirmed adenocarcinoma of the distal esophagus or gastric cardia involving the mid-to-distal esophagus without evidence of distant dissemination and/or local irresectability were randomly assigned to undergo transhiatal esophagectomy or transthoracic esophagectomy with extended en bloc lymphadenectomy. Patients were included between April 1994 and February 2000, in two academic medical centers. The study was approved by the medical ethics committees. Patients had to be older than 18 years of age and in adequate physical condition as indicated by their assignment to American Society of Anesthesiologists class I or II.14 Exclusion criteria were previous or coexisting cancer, neoadjuvant chemotherapy or radiation therapy, recurrent laryngeal nerve palsy, and the impossibility to construct a gastric tube. After written informed consent, randomization took place 2 to 4 weeks before the operation. Details of the design, surgery, pathologic examination, and clinical results of this trial have been reported earlier.3
Quality-of-Life Measurement Disease-specific quality of life was measured by the Rotterdam Symptom Checklist (RSCL), an extensively validated self-report questionnaire designed for use with cancer patients.15 We adapted the original RSCL by adding nine physical symptoms specific to esophageal carcinoma (dysphagia, loss of taste, weight loss, early satiety, blown up feeling, hoarseness, pain behind the chest bone, food not going down, and nocturnal coughing) and omitting seven less relevant physical items (burning eyes, dry mouth, hair loss, shivering, tingling hands or feet, painful muscles, and lower back pain).12 The adapted RSCL contained 41 items, covering 25 physical symptom items (eg, lack of appetite and hoarseness), seven psychological symptom items (eg, anxiety and depressed mood), eight items on activity level (eg, walking and shopping), and one item measuring global quality of life. The adapted RSCL has recently been validated.16 The instrument showed good convergent and discriminant validity and was highly responsive to change. Answers were rated on a 4-point response scale, except for the global quality-of-life item, which was assessed on a 7-point scale. All raw scales were linearly converted to a 0 to 100 scale, with higher scores indicating better quality of life. Generic quality of life was measured with the Medical Outcomes Study Short Form-20 (MOS SF-20), a reliable and valid standardized measure17 containing 20 items measuring health perceptions, physical functioning, role functioning, social functioning, mental health, energy, and bodily pain. The MOS SF-20 was scored on a 5-point scale. All raw scales were linearly converted to a 0 to 100 scale, with higher scores indicating higher levels of quality of life, except for bodily pain. Clinical data included tumor location, postoperative complications, artificial ventilation time, hospital stay, overall survival, and disease-free survival.
Statistical Analysis Baseline quality-of-life scores were compared between treatment groups using the Student's t test. Next, we compared the preoperative baseline scores with the follow-up quality-of-life measurements (5 weeks; 3, 6, 9, and 12 months; and 1.5, 2, 2.5, and 3 years after surgery) using univariate repeated-measurement analyses reporting the time effect and the time by treatment group interaction effect. To investigate the quality of life of long-term survivors, a univariate repeated-measurement analysis was performed on the data of those patients who survived at least 2 years after the operation. Analyses were performed with both the nonimputed and imputed data. Results did not vary between the two methods, and therefore, only the results based on the imputed data will be shown.
To assess the clinical meaning of statistically significant results, we used the distribution-based approach18 by calculating an effect size (
Because of multiple testing, only P
Of the total of 220 patients who were randomly assigned to the treatment groups, 199 patients were included in the quality-of-life study. Fourteen patients were enrolled onto the study before the quality-of-life substudy had started, and seven patients were not sent baseline questionnaires because of administrative error. There were no statistically significant differences between the treatment groups in percentage of patients who were included in the quality-of-life study and patients who were enrolled earlier or were not sent baseline questionnaires (P = .96). There were no significant differences between the groups at baseline in terms of demographic characteristics or tumor location (Table 1). Eighty-six (90%) of 96 patients in the transhiatal esophagectomy group and 100 (97%) of 103 patients in the transthoracic esophagectomy group underwent the planned procedure. Transhiatal resection was associated with fewer pulmonary complications, a shorter duration of mechanical ventilation, and shorter stays in the intensive-care unit or medium-care unit and in the hospital (Table 1).3
In both treatment groups, attrition rates were high, and the number of patients remaining on study at 3 years was 26 in the transhiatal group versus 27 in the transthoracic group. Nevertheless, the percentage of questionnaires returned from patients for quality-of-life assessment remained fairly high, from 95% for both groups at baseline and 1 year of follow-up down to 74% in the transhiatal group and 78% in the transthoracic group at the 2.5 year follow-up measurement (Table 2). The number of patients who did not return the questionnaire because they were too ill was relatively high in the first 3 months after the operation and then declined. No differences in completion rates between the two groups were found at any measurement point.
Physical symptoms and activity level declined after the operation in both groups but improved in the first year of follow-up (P < .01) and then stabilized at baseline level (Fig 1A and 1B). Psychological symptoms showed a consistent improvement after baseline (P < .01) in the first year after the esophagectomy and then stabilized (Fig 1C), whereas global quality of life showed a small initial decline, followed by gradual improvement above the initial level (P < .01; Fig 1D).
At 3 and 6 months after the operation, the patients in the transhiatal esophagectomy group reported significantly less physical symptoms than patients in the transthoracic esophagectomy group (both P = .01;  2 = 0.033 and 0.039, respectively), and at 3 months, they also showed better activity levels (P = .002; 2 = 0.05). No statistically significant differences were found at any other measurement point, and no differences at any follow-up measurement compared with baseline were detected in psychological symptoms and global quality of life between the two groups. Inspection of the individual items in the physical symptoms scale showed that the statistically significant difference between the groups could be equally contributed to the original and the added physical symptoms items. Analyses of generic quality of life as measured by the MOS SF-20 revealed a similar pattern. Quality of life declined sharply shortly after the operation, especially for physical functioning, social functioning, and role functioning (Fig 2A to 2G) in both groups. However, within 6 to 9 months, quality-of-life scores returned to baseline level.
Better quality of life was found for the transhiatal esophagectomy group at 5 weeks for pain (P = .01; 2 = 0.033); at 3 months for physical functioning (P = .01; 2 = 0.032), energy (P < .001; 2 = 0.064), and mental functioning (P = .001; 2 = 0.063); at 9 months for mental functioning (P = .005; 2 = 0.056), at 1.5 years for energy (P = .007; 2 = 0.064) and mental functioning (P = .006; 2 = 0.067); and at 2 years for energy (P = .01; 2 = 0.062). For health perceptions, social functioning, and role functioning, no statistically significant differences were found at any time point. For the 98 patients who survived longer than 2 years after the operation, quality of life values showed a similar pattern to those of the total group (data not shown). Again, physical symptoms and activity level decreased substantially after the operation in both groups and then slowly recovered over time to baseline level, whereas psychological symptoms and global quality of life showed a steady increase from baseline.
The aim of this study was to compare the quality of life of patients with potentially curable esophageal cancer who underwent either a transhiatal resection or a transthoracic resection. Three months after the operation, the patients in the transhiatal esophagectomy group reported fewer physical symptoms and better activity levels, and at 6 months, they reported fewer physical symptoms. Yet, at later follow-up measurements, no differences were found. Analyses of generic quality-of-life indicators, such as physical functioning, social functioning, pain, and mental health, supported these findings. Again, we found that the quality of life of the transhiatal group was better 3 months after the operation, whereas differences fade after that point. However, inspection of the quality-of-life curves over time indicates that the quality-of-life scores of the transhiatal group were mostly above, and thus better than, those of the transthoracic group; although the differences were infrequently statistically significant at the P = .01 level, and the effect sizes were small. Thus, with a larger patient group or a less stringent significance level, more statistically significant differences might have been identified. In both groups, physical symptoms and global quality of life declined after the operation but then consistently increased over the first year of follow-up, whereas psychological symptoms showed a constant improvement after baseline in the first year after the esophagectomy and then stabilized. In line with our findings, earlier studies by Zieren et al,20 Blazeby et al,11 and Brooks et al13 also found that quality of life decreased after surgery but was restored within 620 to 911,13 months. An earlier study in 62 patients 3 months after surgery for esophageal cancer using the RSCL7 showed that the physical symptoms had increased, whereas the psychological symptoms had decreased, which is similar to our findings. The authors argued that these opposing developments might refer to the notion that these patients accept a great deal of physical discomfort in exchange for gaining an outlook on a longer life. With regard to the MOS SF-20, we compared the scores of our study group with those of other patients who underwent extensive lung transplantation surgery. Compared with the esophagectomy patients in this study, these lung transplantation patients showed worse MOS SF-20 scores 3 years postoperatively for physical functioning (50 v 73) and role functioning (53 v 73) but similar scores for mental health (75 v 80) and health perceptions (60 v 63).21 Measuring quality of life after an extensive operation, such as an esophagectomy, is important because of the possible harsh implications of surgery for the quality of life of the patients. Moreover, comparing the differences in quality of life after either a transhiatal or transthoracic operation is of great interest because a choice between the two treatment options proves to be difficult on medical grounds based on overall survival.3 However, no lasting differences in the quality of life of patients with esophageal cancer who underwent a transhiatal resection compared with patients who underwent a transthoracic resection were found. Therefore, we suggest, on the basis of subgroup analysis on tumor location,4 that transthoracic esophagectomy should be the standard treatment for otherwise fit patients with esophageal cancer, whereas transhiatal esophagectomy would be the preferred approach in patients with junctional or cardiac cancer. In this way, the chances of survival are optimized, whereas the additional decrease in quality of life directly after the transthoracic operation should fade after 6 months to a year. We conclude that there were no lasting differences in the quality of life of patients with esophageal cancer who underwent a transhiatal resection compared with patients who underwent a transthoracic resection. Baseline quality-of-life scores declined after the operation but were restored within a year in both treatment groups. Although quality-of-life scores of the transhiatal group were, as expected, generally better 3 months after the operation, differences faded after that point.
The authors indicated no potential conflicts of interest.
We thank C. Manshanden who acted as study coordinator at the beginning of the study, B. Wijnhoven and C. Buskens for their help collecting the quality-of-life questionnaires, and J. Tijssen, J. Kleijnen, and F. Oort for their advice.
This study was supported by grant No. 1996-041 from the Dutch Health Care Insurance Funds Council. Clinical data of this study have been published previously in Hulscher JBF, van Sandick JW, de Boer AGEM, et al: Extended transthoracic resection compared with limited transhiatal resection for adenocarcinoma of the esophagus. N Engl J Med 347:1662-1669, 2002. Authors' disclosures of potential conflicts of interest are found at the end of this article.
1. Müller JM, Erasmi H, Stelzner M, et al: Surgical therapy of esophageal carcinoma. Br J Surg 77: 845-857, 1990[Medline]
2. Hulscher JBF, Tijssen JGP, Obertop H, et al: Transthoracic versus transhiatal resection for carcinoma of the esophagus: A meta-analysis. Ann Thorac Surg 72: 306-313, 2001
3. Hulscher JBF, van Sandick JW, de Boer AGEM, et al: Extended transthoracic resection compared with limited transhiatal resection for adenocarcinoma of the esophagus. N Engl J Med 347: 1662-1669, 2002 4. Van Lanschot JJB, Tilanus HW, Obertop H: Surgical treatment of esophageal cancer. N Engl J Med 348: 1178-1179, 2003 5. Langenhoff BS, Krabbe PFM, Wobbes T: Quality of life as an outcome measure in surgical oncology. Br J Surg 88: 643-652, 2001[CrossRef][Medline] 6. Gelfand GAJ, Finley RJ: Quality of life with carcinoma of the esophagus. World J Surg 18: 399-405, 1994[Medline] 7. Van Knippenberg FCE, Out JJ, Tilanus HW, et al: Quality of life in patients with resected esophageal cancer. Soc Sci Med 35: 139-145, 1992 8. Collard JM, Otte JB, Reynaer M, et al: Quality of life three years or more after esophagectomy for cancer. J Thorac Cardiovasc Surg 104: 391-394, 1992[Abstract]
9. McLarty AJ, Deschamps C, Trastek VF, et al: Esophageal resection for cancer of the esophagus: Long-term function and quality of life. Ann Thorac Surg 63: 1568-1572, 1997 10. Baba M, Ailou T, Natsugoe S, et al: Appraisal of ten-year survival following esophagectomy for carcinoma of the esophagus with emphasis on quality of life. World J Surg 21: 282-286, 1997[CrossRef][Medline] 11. Blazeby JM, Farndon JR, Donovan J, et al: A prospective longitudinal study examining the quality of life of patients with esophageal carcinoma. Cancer 88: 1781-1787, 2000[CrossRef][Medline] 12. De Boer AG, Genovesi PI, Sprangers MA, et al: Quality of life in long-term survivors after curative transhiatal oesophagectomy for oesophageal carcinoma. Br J Surg 87: 1716-1721, 2000[CrossRef][Medline] 13. Brooks JA, Kesler KA, Johnson CS, et al: Prospective analysis of quality of life after surgical resection for esophageal cancer: Preliminary results. J Surg Oncol 81: 185-194, 2002[CrossRef][Medline] 14. American Society of Anesthesiologists: ASA physical status classification system. Park Ridge, III: American Society of Anesthesiologists, 2002. http://www.asahq.org/clinical/physicalstatus.htm 15. de Haes JC, van Knippenberg FC, Neijt JP: Measuring psychological distress in cancer patients: Structure and application of the Rotterdam Symptom Checklist. Br J Cancer 62: 1034-1038, 1990[Medline] 16. De Boer AGEM, van Lanschot JJB, Stalmeier PFM, et al: Is a single-item visual analogue scale as valid, reliable and responsive as multi-item scales in measuring quality of life? Qual Life Res 13: 311-320, 2004[CrossRef][Medline] 17. Stewart AL, Hays RD, Ware JE: The MOS short-form general health survey: Reliability and validity in a patient population. Med Care 26: 724-735, 1988[Medline] 18. Lydick E, Epstein RS: Interpretation of quality of life changes. Qual Life Res 2: 221-226, 1993[CrossRef][Medline] 19. Cohen J: Statistical Power Analysis for the Behavioural Sciences (ed 2). Hillsdale, NY, Erlbaum, 1988 20. Zieren HU, Müller JM, Jacobi CA, et al: Adjuvant postoperative radiation therapy after curative resection of squamous cell carcinoma of the thoracic esophagus: A prospective randomized study. World J Surg 19: 444-449, 1995[CrossRef][Medline]
21. Gross CR, Savik K, Bolman M, et al: Long-term health status and quality of life outcomes of lung transplant recipients. Chest 108: 1587-1593, 1995 Submitted November 17, 2003; accepted July 21, 2004.
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Copyright © 2004 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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ABSTRACT
INTRODUCTION
2 tests were used to compare categoric data, and the Student's t test or the Mann-Whitney U test was used for continuous data. Missing data were handled in several ways. If a patient did not return a questionnaire because of a completely random reason (eg, the form was lost in the mail), we imputed the mean quality-of-life value of his or her treatment group (transhiatal of transthoracic esophagectomy) for a specific time point. We did not use the last observation forward approach because patients are expected to recover through the first year after the operation, so the previous observation might underestimate the true quality-of-life value. If a patient did not return a questionnaire because he or she was too ill (eg, caused by disease recurrence), we imputed the mean quality-of-life value of those patients in the same treatment group with disease recurrence who did return the questionnaire. No more than two values were imputed per patient. If a patient died, we did not impute a quality-of-life value. 
0.25). 
