Correspondence
Surgical Treatment of Esophageal Cancer
N Engl J Med 2003; 348:1177-1179March 20, 2003
- Article
To the Editor:
Hulscher and colleagues' success with transhiatal and transthoracic surgical approaches for esophageal carcinoma (median survival, 1.8 and 2.0 years, respectively) explains why they found no difference between the two procedures (Nov. 21 issue).1 Both participating institutions were high-volume centers for esophagectomy procedures (more than 50 per year), with a lower perioperative mortality rate (<4 percent) than that in the Medical Research Council trial (10 percent).2,3 Thus, over a six-year period, at least 600 such operations must have been conducted. However, the authors state that 263 patients were eligible. It is difficult to imagine that the rest of the esophagectomy procedures (those that were not eligible) were performed for squamous-cell carcinoma of the esophagus4 or a benign condition (which would be rare in the West) or failed to meet the eligibility criteria.
In addition, the attrition rate of nearly 16 percent is not explained. There must have been some upward stage migration in the transthoracic-esophagectomy group, since 69 percent of the patients in that group had advanced disease, as compared with only 57 percent in the transhiatal group (P<0.01). This may affect the analysis of overall survival. Although the trial did not set out to seek survival differences in patients with early esophageal carcinoma, readers may benefit from such information, especially when neoadjuvant treatment is being considered.2 The confounding effects on survival due to adjuvant chemotherapy (if received) are not highlighted.
4 ReferencesHemant M. Kocher, M.B., B.S.
Queen Elizabeth Hospital, London SE18 4QH, United Kingdom
hemant.kocher@kcl. ac. uk Paris P. Tekkis, M.B., B.S.
King's College Hospital, London SE5 9RS, United Kingdom1
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 2002;347:1662-1669
Full Text | Web of Science | Medline2
Medical Research Council Oesophageal Cancer Working Group
CrossRef | Web of Science | Medline3
Birkmeyer JD ,Siewers AE ,Finlayson EVA , et al. Hospital volume and surgical mortality in the United States. N Engl J Med 2002;346:1128-1137
Full Text | Web of Science | Medline4
Kocher HM ,Linklater K ,Patel S ,Ellul JP . Epidemiological study of oesophageal and gastric cancer in south-east England. Br J Surg 2001;87:1249-1257
CrossRef | Web of Science
To the Editor:
Hulscher et al. conclude that extended lymph-node dissection should be a standard component of esophagectomy. However, preoperative chemoradiotherapy may have a greater effect on outcome than extended lymphadenectomy and may obviate the need for extended lymphadenectomy. In many countries, the management of esophageal cancer includes chemotherapy and radiotherapy, and Hulscher and colleagues do not state what proportion of each group in their trial received postoperative adjuvant or salvage therapies that may have affected the calculation of costs or the survival curves.
Extended lymphadenectomy was associated with a 31 percent rate of local–regional failure, and the median survival rates were 1.8 and 2.0 years in the transhiatal- and transthoracic-esophagectomy groups, respectively. We and our colleagues at Johns Hopkins, in Baltimore, saw local–regional failure as a component of initial failure in only 8 of 90 patients (9 percent) treated with two consecutive protocols that included neoadjuvant radiotherapy with cisplatin, protracted venous infusion of fluorouracil, and administration of 44 Gy of external-beam radiation, followed by transhiatal esophagectomy and subsequent adjuvant chemotherapy.1,2 With this treatment approach, the median and disease-specific survival rates for all the enrolled patients were 2.9 years and 4.9 years, respectively, and the 5-year overall and disease-specific survival rates were 40 percent and 49 percent.
In their accompanying editorial, Kitajima and Kitagawa state that “systematic lymph-node dissection has a role in the curative treatment of esophageal cancer.”3 It appears that superior local control and survival are possible with neoadjuvant chemoradiotherapy, transhiatal esophagectomy, and postoperative chemotherapy.
3 ReferencesJonathan P.S. Knisely, M.D.
Barbara A. Burtness, M.D.
Ronald R. Salem, M.D.
Yale University School of Medicine, New Haven, CT 06520
jonathan.knisely@yale. edu 1
Heath EI ,Burtness BA ,Heitmiller RF , et al. Phase II evaluation of preoperative chemoradiation and postoperative adjuvant chemotherapy for squamous cell and adenocarcinoma of the esophagus. J Clin Oncol 2000;18:868-876
Web of Science | Medline2
Kleinberg L, Knisely JPS, Heitmiller R, et al. Mature survival results with preoperative cisplatin, protracted infusion 5-FU, and 44 Gy radiotherapy for esophageal cancer. Int J Radiat Oncol Biol Phys (in press).
3
Kitajima M ,Kitagawa Y . Surgical treatment of esophageal cancer -- the advent of the era of individualization. N Engl J Med 2002;347:1705-1709
Full Text | Web of Science | Medline
Author/Editor Response
Our conclusion cannot be interpreted as a general recommendation of transthoracic esophagectomy. Identification of subgroups that have relatively high long-term benefit helps translate the general outcome of the trial into individualized decision making. Because we expected site-specific treatment effects, randomization was stratified according to the tumor site. Although we recognize the limitations of subgroup analysis, the long-term benefit of transthoracic esophagectomy is more substantial in patients with esophageal tumors (five-year survival advantage, 17 percent; 95 percent confidence interval, –3 percent to 37 percent) than in patients with junctional or cardiac tumors (five-year survival advantage, 1 percent). Therefore, we now consider transthoracic esophagectomy standard treatment for otherwise fit patients with potentially curable esophageal cancer, whereas transhiatal esophagectomy is the preferred approach in patients with junctional or cardiac cancer.
So far, five of six randomized trials failed to show that neoadjuvant chemoradiotherapy was associated with a survival advantage. Outcomes in studies using historical controls are overestimated. Preoperative chemoradiotherapy is still considered experimental, with contradictory results reported from mostly underpowered trials.1 None of the patients in our study received either adjuvant or neoadjuvant therapy. Palliative external radiotherapy (in 29 patients) or chemotherapy (in 7) was used in some patients who had a symptomatic recurrence.
Of the 682 patients who underwent surgical tumor resection at the two institutions during the study period, 431 had adenocarcinoma, of whom 168 were excluded on the basis of predefined criteria, 34 refused to participate, and 9 were erroneously not asked to participate. Indeed, hospital volume is inversely related to early postoperative mortality.2 This partly explains the difference in mortality reported by us (<4 percent in-hospital mortality) and the Medical Research Council (10 percent within 30 days).
Lymphadenectomy leads to upward stage migration. However, this does not affect the base-line similarity of the randomized groups and thus does not affect the analysis of overall survival. Subgroup analysis of early stages (0 to IIB) combined showed a 19 percent five-year survival advantage after transthoracic esophagectomy, but this comparison is biased because of stage migration.
2 ReferencesJ. Jan B. van Lanschot, M.D.
Hugo W. Tilanus, M.D.
Huug Obertop, M.D.
Academic Medical Center, 1105 AZ Amsterdam, the Netherlands
j.j. vanlanschot@amc. uva. nl 1
Kelsen D . Preoperative chemoradiotherapy for esophageal cancer. J Clin Oncol 2001;19:283-285
Web of Science | Medline2
van Lanschot JJB ,Hulscher JBF ,Buskens CJ ,Tilanus HW ,ten Kate FJW ,Obertop H . Hospital volume and hospital mortality for esophagectomy. Cancer 2001;91:1574-1578
CrossRef | Web of Science | Medline
Author/Editor Response
We essentially agree with Knisely et al. that a multimodal approach is crucial to improve survival in patients with esophageal cancer. Concurrent chemoradiotherapy is a breakthrough for locally advanced and unresectable disease. However, the significance of neoadjuvant chemoradiotherapy in terms of local control and a survival benefit in patients with potentially resectable esophageal cancer is still controversial. Were it possible to perform curative resection, it would surely be hard to justify the risk of neoadjuvant chemoradiotherapy, including an increase in operative morbidity and late adverse effects. Of several randomized trials1-3 that compared neoadjuvant chemoradiotherapy followed by surgery with surgery alone, only one study, in which survival in the surgery-only group was very poor, showed an overall survival benefit associated with neoadjuvant chemoradiotherapy.1 The additional benefit of neoadjuvant chemoradiotherapy would necessarily depend to a certain degree on the quality of lymph-node dissection. From this point of view, the rationale for performing transhiatal esophagectomy is questionable.
Although we are not proposing that uniform extended lymph-node dissection be a standard component of esophagectomy, we do suggest that transhiatal esophagectomy is not always the best option as a surgical component. On the other hand, a complete response (according to pathological examination) after neoadjuvant chemoradiotherapy is a significant predictor of improved survival. Therefore, an individualized, multimodal therapeutic plan based on biologic information to predict the response to adjuvant therapy seems desirable.
3 ReferencesMasaki Kitajima, M.D.
Yuko Kitagawa, M.D.
Soji Ozawa, M.D.
Keio University, Tokyo 160-8582, Japan
kitajima@sc.itc. keio. ac. jp 1
Walsh TN ,Noonan N ,Hollywood D ,Kelly A ,Keeling N ,Hennessy TPJ . A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med 1996;335:462-467[Erratum, N Engl J Med 1999;341:384.]
Full Text | Web of Science | Medline2
Bosset J-F ,Gignoux M ,Triboulet J-P , et al. Chemoradiotherapy followed by surgery compared with surgery alone in squamous-cell cancer of the esophagus. N Engl J Med 1997;337:161-167
Full Text | Web of Science | Medline3
Ubra SG ,Orringer MB ,Turrisi A ,Iannettoni M ,Forastiere A ,Strawderman M . Randomized trial of preoperative chemoradiation versus surgery alone in patients with locoregional esophageal carcinoma. J Clin Oncol 2001;19:305-313
Web of Science | Medline
- Citing Articles (2)
Citing Articles
1
Takashi Ichikura, Kentaro Chochi, Hidekazu Sugasawa, Hidetaka Mochizuki. (2007) Proposal for a new definition of true cardia carcinoma. Journal of Surgical Oncology 95:7, 561-566
CrossRef2
T Lerut, W Coosemans, G Decker, P De Leyn, J Moons, P Nafteux, D Van Raemdonck. (2004) Extended surgery for cancer of the esophagus and gastroesophageal junction. Journal of Surgical Research 117:1, 58-63
CrossRef
