Eur J Cardiothorac Surg 2003;23:805-810
© 2003 Elsevier Science NL
The effect of age on the outcome of surgical treatment for carcinoma of the oesophagus and gastric cardia
J.S. Rahamim,
G.J. Murphy*,
Y. Awan,
M. Junemann-Ramirez
Department of Cardiothoracic Surgery, Derriford Hospital, Derriford Road, Plymouth PL6 8DH, UK
Received 8 November 2002;
received in revised form 15 January 2003;
accepted 16 January 2003.
* Corresponding author. Tel.: +44-1752-777111; fax: +44-1752-763830
e-mail: gavinmurphy{at}hotmail.com
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Abstract
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Objective: The aim of this study was to examine the effect of age on the outcome of surgical treatment for carcinoma of the oesophagus and gastric cardia. Methods: From 1979 to 1999, 596 patients underwent gastro-oesophagectomy with two-field lymph node clearance for cancer under the care of a single surgeon. The clinicopathologic characteristics and survival of patients aged between 45 and 63 years (n=198, Group 1), 63 and 71 years (n=199, Group 2) and 71 and 89 years (n=199, Group 3) were compared. Results: Thirty-day mortality for the first 300 patients (1979–1993) in this consecutive series was 5, 8 and 18% for Groups 1, 2 and 3, respectively, and 6, 6 and 6% for Groups 1, 2 and 3, respectively, in the second consecutive 296 patients (1993–1999, P=0.006, 
2). Tumours were poorly differentiated in 55.7, 59.1 and 53.4% of patients in Groups 1, 2 and 3, respectively, for 1979–1993 and 64.7, 53.2 and 40.2% of tumours in Groups 1, 2 and 3, respectively, for 1993–1999 (P=0.02, 2). Adjuvant therapy was significantly more common in younger patients (P=0.006, 2). Five-year survival in the first period was 22, 15 and 11% for Groups 1, 2 and 3, respectively, (P=0.02 log–rank) and 18, 16 and 14% for Groups 1, 2 and 3 in the second period (P=NS, log–rank). Conclusions: Elderly patients now have equivalent short and long-term outcomes compared to younger patients following gastro-oesophagectomy. Five-year survival, even in younger patients receiving adjuvant therapy remains poor, however, at approximately 20%. New therapeutic modalities are required to improve long-term survival following surgical treatment of gastro-oesophageal carcinoma.
Key Words: Gastro-oesophagectomy • Oesophageal carcinoma
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1. Introduction
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The incidence of carcinoma of the oesophagus and gastric cardia has increased dramatically over recent years [1,2] as has the peak age of incidence of the disease [3]. This has led to an increase in the number of elderly patients referred for surgical treatment. However, the effect of advanced age on outcome following gastro-oesophagectomy remains unclear. Various studies have reported poorer short-term and long-term outcomes in the elderly following oesophagectomy [4–6] and have led to the suggestion that elderly patients may benefit from less radical or even non-surgical treatment [7]. Conversely, more recent studies report improved results in patients above 70 years of age associated with refinements in perioperative care [8–10]. Younger age at presentation has also been reported to affect long-term survival in some studies [11], but not others [12–14]. This has been attributed to more advanced or aggressive disease at presentation [12]. However, this also remains controversial [15].
The aim of this study was to examine the effect of age on the outcome of surgical treatment for carcinoma of the oesophagus and gastric cardia at a single high volume centre and to assess whether this has changed over time.
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2. Patients and methods
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2.1. Study design
Between November 1979 and December 1999, 596 patients with carcinoma of the oesophagus and gastric cardia underwent surgical resection at Derriford Hospital under the care of a single surgeon. Clinicopathological and outcome data were collected prospectively and survival data were obtained from the SouthWest Cancer Registry database and hospital records. To facilitate a comparison of clinicopathological characteristics and outcomes between patients of different age groups, the cohort was artificially separated into three groups of approximately 200 patients covering the ages 45–63 years (median 57, n=198, Group 1), 63–71 years (median 67, n=199, Group 2) and 71–89 years (median 75, n=199, Group 3), respectively. These groups were chosen to enable statistical comparison with group sizes large enough to facilitate comparison of long-term survival.
2.2. Surgery
All patients had detailed preoperative risk assessments based on history of chronic lung, heart, liver and renal diseases, chest roentgenogram, electrocardiogram, spirometry and haematological tests. Severe pulmonary dysfunction, defined as forced expiratory volume at 1 s less than 1 l, cardiac dysfunction defined as unstable angina, congestive cardiac failure or recent myocardial infarction (within 3 months), liver dysfunction defined as history of cirrhosis or chronic hepatitis were considered contraindications to surgery. Procedure type was determined by site of lesion and histological tumour type. Combined left thoracotomy and laparotomy was used for carcinoma of the gastric cardia. However, later the Ivor Lewis procedure was performed for these tumours as well as for carcinomas of the lower and middle third of the oesophagus. The three stages McKeowns procedure was performed for tumours in the upper half of the oesophagus. Total pharyngo–laryngo gastro-oesophagectomy was performed for carcinomas of the cervical and very proximal thoracic oesophagus (n=22). However, these patients represent a separate clinicopathological group and have not been included in this analysis. Radical resection with two-level lympadenectomy (paracardial, left gastric, lesser curve, coeliac, splenic and common hepatic, paraoesophageal, hilar, subcarinal, paratracheal and aortopulmonary window nodes resected with lymphatic duct left in situ) was performed in every case and gastrointestinal tract continuity was re-established with a posterior mediastinal gastric tube interposition in all cases. Anastomoses in the thoracic cavity were performed with a single layer stapled anastomoses using a circular stapling device with single layer sutured anastomoses in the neck. More recently, a two-layer intrathoracic anastomosis has been performed. Following formation of the stapled anastomosis a second layer of four partial thickness horizontal mattress sutures between the serosal surfaces of the oesophagus and the stomach approximately 2 cm from the suture line are performed, inkwelling the anastomoses within a cuff of the stomach tube. A pyloromyotomy or Heinke–Mikulicz pyloroplasty was performed with pyloroplasty closure using two layers of continuous absorbable suture material. Patients were routinely extubated in theatre and transferred to the ward postoperatively. Enteral feeding was recommenced if a postoperative gastromiro swallow demonstrated no evidence of leak (4 days (stapled) and 7 days (sutured)). In general, intrathoracic leaks from the gastric tube and anastomosis were treated surgically, whereas anastomotic leaks in the neck were treated conservatively. Anastomotic stricture was defined as readmission for flexible oesophagoscopy and passage of an oesophageal bougie because of postoperative dysphagia or poor weight gain. Twelve percent of patients received adjuvant (n=71) and 3% received neoadjuvant (n=19) treatments during the study. Patients were enrolled in several multicentre trials over this time period resulting in a variation in treatment protocols. However, in general, treatment involved two to six cycles of 5-flourouracil and cisplatin therapy with or without concomitant radiotherapy (40–60 Gy).
2.3. Statistical analysis
Probability of survival was estimated using Kaplan–Meier analysis and included all operative mortality as well as all deaths related and unrelated to cancer. Differences between survival curves were assessed by the log–rank test. All data were assessed for normality of distribution and equality of variance. Student's t test and ANOVA were used to compare normally distributed data. Categorical data were compared using Pearson's chi-squared test. All data analysis was performed using the SPSS for Windows, Version 9.0 (Chertsey, UK) software package.
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3. Results
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3.1. Clinicopathological characteristics
There was no difference in the male:female ratio between the three groups with no significant difference in the duration of symptoms prior to surgery or proportion of patients who reported significant weight loss prior to surgery (Table 1). There was a significantly higher proportion of poorly differentiated tumours in the younger age group. However, there was no significant difference between the groups in terms of TNM staging (American Joint Committee on Cancer Classification, AJCC) [16] or in the number of tumour positive lymph nodes or positive to normal lymph node ratio between the groups (Table 1). There were a significant proportion of patients with inadequate pathological staging attributed to non-systematic pathological reporting in patients early in the series (1979–1982). However, there was no significant difference across the groups in this respect. There was also no difference in the distribution of histological tumour types across the age groups (Table 2).
3.2. Surgery
There was no difference in the extent of surgical resection across the age groups (Table 3) or in the proportion of patients who underwent a drainage procedure or a two-layer anastomosis. A significantly higher proportion of patients in the younger age group received adjuvant therapy and to a lesser extent neoadjuvant therapy. There was no difference in the proportion of patients with poorly differentiated tumours that received adjuvant therapy (n=34, 14%), compared to moderately (n=27, 17%) or well (n=7, 13.5%) differentiated tumours (P=NS, 2).
3.3. Morbidity and mortality
There was a significantly higher incidence of respiratory complications, arrythmias and laryngeal nerve palsy in older patients (Table 4). There was also a higher 30-day mortality in older compared to younger patients (P<0.05, 2). Hospital stay was significantly different between the groups (ANOVA P<0.05, Table 4). However, on post hoc testing (Bonferroni) the difference was significant between Groups 1 and 2 (P=0.02), but not between Groups 1 and 3 (P=NS). The rate of readmission for dilatation of an anastomotic stricture was higher in younger patients (P<0.05, 2).
3.4. Long-term survival
The 5-year survival rate was 21, 16 and 13% for Groups 1, 2 and 3, respectively (Fig. 1
), log–rank P=0.008). Median survival for all patients was 13 months. There was improved early survival in Group 1, following which the survival curve was parallel to those of Groups 2 and 3. On Cox multivariate analysis (Table 5) degree of tumour differentiation and serious postoperative complications (pneumonia, myocardial infarct, pulmonary embolus) were found to be independent predictors of long-term survival. There was a statistical trend (P<0.1) towards adjuvant therapy and age group as independent predictors of long-term survival. However, these did not reach significance (P<0.05).
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Fig. 1. Cumulative long-term survival for each patient group: Group 1 (circle), Group 2 (triangle) and Group 3 (square). There was a significant difference in survival betwen the three groups with an increase in long-term survival associated with decreasing median age. There was a difference in early survival following which the three survival curves were parallel. Number of patients at risk over time is presented in the table given above.
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3.5. Changes in age-related outcomes over time
Thirty-day mortality for the first 300 patients (1979–1993) in this consecutive series was 5, 8 and 18% for Groups 1, 2 and 3, respectively, and 6, 6 and 6% for Groups 1, 2 and 3, respectively, in the second consecutive 296 patients (1993–1999, P=0.006, 2). There were minor changes in the ratios of postoperative complications across the groups with a reduction in the proportion of postoperative dysrythmias in the elderly group between 1993 and 1999 (P=0.006, 2) and an increase in the proportions of anastomotic leaks in the younger groups in the latter period (P=0.09, 2). The incidence of postoperative pneumonia did not change between 1979–1993 and 1993–1999 (P=NS, 2).
Tumours were poorly differentiated in 55.7, 59.1 and 53.4% of patients in Groups 1, 2 and 3, respectively, in the first time period and in 64.7, 53.2 and 40.2% of tumours in Groups 1, 2 and 3, respectively, in the second period (P=0.02, 2). Five-year survival in the first period was 22, 15 and 11% for Groups 1, 2 and 3, respectively (P=0.02 log–rank) and 18, 16 and 14% for Groups 1,2 and 3 in the second period (P=NS, log–rank).
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4. Discussion
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The principal finding of this retrospective cohort study is that overall long-term survival decreased with increasing patient age following surgery for cancer of the oesophagus and gastric cardia. Over the last 6 years of the study, 30-day mortality in elderly patients fell to that of other age groups and significant differences in long-term survival between different age groups for the period 1979–1993 were no longer present between 1993 and 1999. There was an increase in the proportion of poorly differentiated tumours in young patients as well as a higher prevalence of adjuvant therapy in younger patients in the latter period. Adjuvant therapy was significantly more common in younger patients and on multivariate analysis there was a statistical trend for adjuvant therapy to be an independent predictor of long-term survival.
Several retrospective studies have demonstrated that equivalent short-term outcomes can be achieved in the elderly compared to younger patients [9,10]. In an apparent contradiction, however, other centres report significantly worse outcomes following gastro-oesophagectomy for cancer of the oesophagus or gastric cardia in the elderly [4,5]. This study demonstrates that whilst in a large retrospective cohort, where 20 years of data are considered, the latter is true but when only those procedures performed within the last decade are considered the former is true. This reflects the improvement in overall outcomes following gastro-oesophagectomy for cancer over the last ten years [17] and demonstrates that this improvement in short-term outcome is most evident in the elderly population. Transthoracic oesophagectomy with two-field lymph node dissection is not, therefore, associated with increased mortality or reduced long-term survival in the elderly. This contrasts with a contemporary series of transthoracic oesophagectomy with three-field lymph node dissection where age greater than 65 years was found to significantly increase perioperative mortality [18]. Increased age may, therefore, remain as a relative contraindication to extensive neck dissection.
Higher postoperative morbidity and mortality in the elderly has been attributed to greater cardiorespiratory risk factors preoperatively [5,8], and in particular, to a significantly higher proportion of respiratory complications, the most common cause of postoperative death in patients undergoing oesophagectomy [5]. Respiratory complications did not decrease in the elderly with time in this cohort, as has been reported by others [5,8] although this can be attributed to the low overall incidence of postoperative pneumonia compared to other studies. Low respiratory morbidity is, in our opinion, related to the policy of early extubation of patients, thereby promoting early mobility and avoiding the disruption of pulmonary defence mechanisms associated with ventilation [19]. This low incidence of respiratory morbidity was achieved despite radical surgery incorporating thoracotomy in virtually every patient.
The reason for the reduction in 30-day mortality seen in elderly patients (1993–1999) is not readily apparent from data presented and is more probably due to a combination of different factors including increasing experience of the surgical team as well as better patient selection with time. Data on preoperative risk factors and resection rates were not recorded systematically and interpretation of this data would have benefited from comparison of these across the groups. This is a weakness of this study and can be attributed to our prospective data collection dating to the 1970s when these data were not recorded.
Whilst survival curves of all data for 1979–1999 suggest that long-term survival simply mirrors short-term survival, with parallel curves after the first 90 days for all three groups, analysis of changes between the first and second consecutive series of patients (1979–1993 and 1993–1999) demonstrate that 5-year mortality dropped in the younger age group and increased in the older age group between 1993 and 1999. This reflects both improved early survival in the elderly as well as an increase in poorly differentiated tumours in the younger group where tumour differentiation was seen to be a highly significant independent predictor of long-term outcome on multivariate analysis. This differs from the findings of Nazoe et al. [12] which report that oesophageal cancers in younger patients were more aggressive, but were not associated with reduced long-term survival. This was attributed to the better physical potential and nutritional condition in younger patients. The increased use of adjuvant therapy in young patients was not related to the aggressive nature of the tumour, but occurs due to the perception that younger patients with fewer cardio-respiratory risk factors will more readily tolerate chemo-radiotherapy [20] as well as the inevitable tendency to treat cancer more aggressively in the young. Disease-specific mortality data would undoubtedly have assisted in the interpretation of our results. However, given the frequent misreporting of deaths in the community as being disease or non-disease related this has not been included.
Overall long-term survival is the most reliable endpoint and this study demonstrates that elderly patients now have equivalent short- and long-term outcomes compared to younger patients following gastro-oesophagectomy. Coupled with the observation that increased age is not associated with a significantly lower quality of life following gastro-oesophagectomy [21] these data suggest that increased age should not be considered as a contraindication to radical curative surgery for cancer of the oesophagus and gastric cardia. Despite excellent short-term outcomes, long-term survival, even in young patients receiving adjuvant therapy remains poor at approximately 20%. New therapeutic modalities are required to improve long-term survival following surgical treatment of gastro-oesophageal carcinoma.
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Footnotes
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Presented in part to the Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland, Manchester, September 2002.
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Top
Abstract
1. Introduction
