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doi:10.1016/S1470-2045(03)01167-7

  1. 1. For personal use. Only reproduce with permission from The Lancet. THE LANCET Oncology Vol 4 August 2003 http://oncology.thelancet.com 481 In the absence of medical contraindications to surgery, resection is the mainstay of treatment for localised oesophageal cancer. Advancements in preoperative staging and imaging, anaesthesia delivery, surgical technique, and postoperative care, now enable the surgeon to safely operate on patients with oesophageal tumours and to tailor the procedure on the basis of performance status, tumour location, and extent of disease. During the past 10 years, several “minimally invasive” techniques, which aim to limit the extent of resection, have been introduced; these procedures are currently being investigated for use in both staging and treatment of oesophageal malignant diseases. Despite these accomplishments however, overall 5-year survival remains disappointing: less than 25% of patients live for 5 years after oesophagectomy. For patients with locally or regionally advanced disease (stage IIa, IIb, III, and IVa), combining several treatment approaches, either with or without surgery, can result in good objective responses and, in some patients, durable survival. The role of surgery in such combined modality approaches is still evolving and some investigators have challenged its worth. To provide a definitive review of the issues involved, we outline the types of surgery used to treat cancer of the oesophagus and summarise the available data about their effectiveness. Clinical outcomes, the value of preoperative chemo- radiotherapy, and the use of surgery are all considered. Lancet Oncol 2003; 4: 481–88 During the past two decades, an epidemiological shift has occurred—adenocarcinoma has surpassed squamous-cell carcinoma as the most common histological type of oesophageal cancer in both the USA and western Europe.1–4 These countries have also experienced a parallel increase in the incidence of gastro-oesophageal reflux disease and development of Barrett’s metaplasia;5,6 the frequency, severity, and duration of reflux symptoms correlate with an increased risk of oesophageal adenocarcinoma.7 Furthermore, owing to the link between obesity and reflux disease, the increasing prevalence of obesity in the USA may also be contributing to the climbing incidence of oesophageal adenocarcinoma.8–10 This alarming increase has made therapeutic management of oesophageal carcinoma an urgent issue. The question of which treatment approach is the most appropriate is much debated, but since the number of well-controlled prospective randomised trials is small, efforts to resolve this controversy have been mostly unsuccessful. Resection is still standard treatment for patients with localised oesophageal cancer who do not have medical contraindications to surgery (figure 1). Advances in non- invasive imaging, preoperative staging, anaesthesia, and postoperative pain control, combined with refinements in surgical technique and postoperative care, have enabled experienced centres to reduce operative mortality rates to below 5%.11–13 There are various techniques for attempting curative resection of oesophageal cancer and surgery has traditionally been viewed as the most effective way of ensuring both locoregional control and long-term survival. Therefore, extending the limits of resection (ie, use of radical ReviewSurgery for oesophageal cancer PCW is a Surgical Oncology Fellow in the Department of Surgery, University of Chicago, IL, USA. MCP is a Professor of Surgery and Chief of Surgical Oncology in the Department of Surgery, University of Chicago, IL, USA. Correspondence: Prof Mitchell C Posner, Department of Surgery, University of Chicago, 5841 S. Maryland Avenue, MC 5031, Chicago, IL 60637, USA. Tel: +1 773 834 0156. Fax: +1 773 702 0564. Email: mposner@surgery.bsd.uchicago.edu The role of surgery in the management of oesophageal cancer Peter C Wu and Mitchell C Posner Figure 1. Transhiatal oesophagectomy. The oesophagus and mobilised stomach are delivered from the abdominal cavity. The tumour can be visualised in the distal oesophagus (top). The resected portion shows an ulcerated oesophageal adenocarcinoma (bottom).
  2. 2. For personal use. Only reproduce with permission from The Lancet. THE LANCET Oncology Vol 4 August 2003 http://oncology.thelancet.com482 procedures) is considered reasonable for improving overall outcome. Proponents of en bloc oesophagectomy with extended lymphadenectomy claim lower recurrence rates and increased survival in patients with locally and regionally advanced lesions.14–17 However, few appropriately designed clinical trials have examined the effectiveness of this approach compared with less radical procedures. There have been consistent reports of median survival times of 12–24 months and 5-year survival of less than 25% for patients who undergo oesophagectomy alone. These results prompted a re- evaluation of the role of surgical resection for oesophageal cancer. Critics argue that if the extent of surgery is not the most crucial determinant of survival, then more “patient friendly” approaches should be used. A recent development is the use of minimally invasive techniques, which incorporate thoracoscopic or laparoscopic manoeuvers, for both the staging and treatment of oesophageal malignant diseases. Theoretically, these procedures should provide equivalent outcomes to radical surgery and reduce postoperative morbidity, mortality, and length of stay in hospital. However, prospective randomised trials of preoperative chemoradiotherapy have not definitively shown that this approach has benefits over surgery alone. High rates of objective tumour response with chemoradiotherapy (25% complete response and 60–70% partial pathological response) suggest that surgery may now be considered an adjuvant treatment. This view has been reinforced by trial results indicating that the proportion of patients who survive for 5 years after receiving chemoradiation without surgery is comparable to that reported with surgery alone.18 As a consequence, many investigators and clinicians have begun to question the necessity of surgical intervention. Less invasive methods of treatment, for example, endoscopic oesophageal stent placement and photodynamic or laser therapy, are now being used instead of surgery for relief of the symptoms of dysphagia in the palliative setting.19–22 This development provides the impetus for oncologists to question the role of resection in oesophageal cancer and to challenge the use of surgical intervention in this disease. In this review, we aim to describe the concepts, issues, data, and trends associated with the role of surgery in the management of carcinoma of the oesophagus, and provide guidelines for survival intervention in multimodality treatment strategies. For the purposes of this paper, we define carcinoma of the oesophagus as tumours of the gastro-oesophageal junction either with or without Barrett’s changes. Tumours of the gastric cardia are a separate entity not specifically addressed here, although the determination of site of origin of lesions in this region is often not possible. We recognise that adenocarcinoma and squamous-cell carcinoma of the oesophagus are disparate diseases and, therefore, should be addressed with separate treatment. Unfortunately, this distinction has been blurred in most trials so both histological types are generally studied and managed in a similar way. Where possible and appropriate, we have noted the histological types being assessed. Our recommendations are weighted towards the management of adenocarcinoma of the middle and distal oesophagus, because this pathological entity is most common in the USA. Extent of surgery There is considerable debate about whether modification of operative techniques, eg, reducing radicality or residual disease, can substantially change the outcome. Issues which Review Surgery for oesophageal cancer Table 1. Randomised controlled trials comparing transthoracic (TTE) with transhiatal (THE) oesophagectomy N Pulmonary Anastamotic leak (%) Postoperative Median survival 5-year survival (%) Ref complications mortality (%) (months) TTE THE TTE THE p TTE THE p TTE THE p TTE THE p TTE THE p 114 106 57 27 <0·001 16 14 NS 4 2 NS 24 21·6 NS 39 29 NS 23 19 20 N/A N/A N/A N/A N/A N/A 0 0 NS 13·5 16 NS N/A N/A N/A 24 16 16 50 25 N/A 12·5 12·5 NS 6·3 6·3 NS N/A N/A NA N/A N/A N/A 25 35 32 20 19 NS 9 6 NS 8·6 6·3 NS 12.0 16 NS N/A N/A N/A 26 N/A, not applicable; NS, non significant Figure 2. Extent of lymph node dissection for a standard esophagectomy (left) and for a three- field lymphadenectomy.
  3. 3. For personal use. Only reproduce with permission from The Lancet. THE LANCET Oncology Vol 4 August 2003 http://oncology.thelancet.com 483 remain particularly controversial are the optimum surgical approach, the extent of lymph-node dissection, and the value of using minimally invasive techniques. Transthoracic vs transhiatal resection The two most common surgical approaches for curative resection of oesophageal cancer are transthoracic (TTE) and transhiatal (THE) oesophagectomy. Proponents of TTE claim it gives direct visualisation and thorough dissection of perigastric/perioesophageal nodal tissue and thoracic oesophagus thereby ensuring complete tumour removal and minimising the potential for occult residual disease and tumour spillage. The direct transthoracic approach substantially reduces the risk of injury to adjacent structures including the azygos vein, thoracic duct, aorta, and bronchus. However, supporters of THE claim that it is oncologically equivalent (with a similar poor outcome) to TTE, minimises respiratory complications, reduces the lethal complications of mediastinitis due to anastamotic leakage, and shortens the duration of the operation leading to decreased morbidity and mortality. Four randomised controlled trials comparing the outcome of patients who underwent TTE or THE have been published (table 1).23–26 Three of these phase III trials24–26 had very small sample sizes so no definitive conclusions can be drawn from their data. In all three trials, postoperative morbidity and mortality rates were similar for both groups and overall survival was unaffected by choice of surgical approach. A fourth trial from the Netherlands23 involved 220 patients with adenocarcinoma of the mid or distal oesophagus who were randomly assigned to undergo either TTE or THE. Significantly more lymph nodes were dissected from patients in the TTE group (31 vs 16, p <0·001); however, there was no difference between the groups in terms of how radical the procedures were: the numbers of R0, R1, and R2 resections were equivalent. A significantly higher incidence of pulmonary complications, and increased time in both intensive-care unit and hospital were recorded for patients who underwent the transthoracic approach, but there was no difference in postoperative mortality between the two procedures. At a median follow-up of 4·7 years there were no significant differences in survival, for median, 5-year disease- free, overall, and quality-adjusted values. The investigators noted a trend toward improvements in disease-free and overall survival benefit at 5 years with TTE; the survival curves began to separate at 3 years. In addition, two meta-analyses27,28 reviewing over 65 studies published between 1986 and 1999 that compared TTE and THE have been published. Both series concluded that overall perioperative complications and survival at 3 or 5 years did not differ significantly between transthoracic and transhiatal procedures. There was a significantly higher perioperative mortality rate for patients who underwent TTE whereas those patients treated wtih THE had a higher incidence of anastamotic leak, anastamotic stricture, and recurrent laryngeal nerve injury. Mortality rates varied considerably between the two procedures from 0 to 27·8% in the two previously described meta-analyses. Centres with most experience of oesophageal resection had mortality rates of below 5%. There is now mounting evidence to support the notion that outcome is directly related to volume of operations for complex oncological procedures. Three studies using Medicare-linked databases for reimbursed oesophagectomies have shown significantly improved outcomes and lower mortality rates in those centres designated as high-volume hospitals with regard to oesophageal resection.29-31 It can therefore safely be concluded that both transthoracic and transhiatal approaches to oesophageal resection are safe in experienced hands, and neither technique is superior. Lymphadenectomy Although in recent years postoperative mortality has declined and rates of complete resection have improved, 5-year survival after oesophagectomy procedures seldom exceeds 25%. Owing to extensive submucosal lymphatic drainage of the oesophagus, nearly 80% of patients who undergo surgery have positive lymph nodes. Nodal involvement is the single most important prognostic factor in oesophageal cancer for both locoregional and systemic recurrence after complete resection.32–35 FDG-PET36 and sentinel-lymph-node mapping37 have been used in efforts to improve clinical staging of lymph-node involvement, and immunohistochemical staining38 has been used to refine tumour detection. Radical en bloc resections involving dissection of the cervical, superior mediastinal, and celiac-axis lymph nodes have been reported to reduce the rate of locoregional recurrence and increase long-term survival in patients who undergo oesophagectomy. Proponents of three-field lymph- node dissections argue that up to 30% of patients with mid or distal oesophageal cancers have cervical lymph-node metastases.39–41 Despite the potential benefits of this approach for staging oesophageal disease more accurately, whether it results in improved local control and survival is less clear. Several non-randomised series from single institutions have been reported;15–17, 42–44 the authors suggest survival is improved by use of extended lymphadenectomy, with acceptable morbidity and low associated mortality (figure 2). However, many of these studies are hindered by small sample sizes, confounding the effects of additional non-surgical treatment, and comparison to historical controls. Therefore, any claims that radical lymph-node dissection alone is reponsible for better outcome are speculative. One recent single-institution study in the USA involved 80 consecutive patients who underwent oesophagectomy with radical lymph-node dissection. 5-year overall survival was 51% better than that for historical controls, with no difference in operative mortality and reasonable morbidity.45 30% of patients in this study were upstaged as a result of extended lymphadenectomy, as has been reported in the Japanese experience.39,46,47 Only one prospective randomised trial has been done to compare extended lymphadenectomy and conventional procedures in 62 patients with resectable squamous-cell cancer of the thoracic oesophagus.48 Despite the fact that radical lymph-node dissection operations are more lengthy and cause greater blood loss than conventional methods, postoperative mortality is not significantly different. In this small, single-institution series, patients who ReviewSurgery for oesophageal cancer
  4. 4. For personal use. Only reproduce with permission from The Lancet. THE LANCET Oncology Vol 4 August 2003 http://oncology.thelancet.com484 were assigned to undergo extended lymphadenectomy were more likely to survive for 5 years that patients who underwent conventional lymphadenectomy (66·2% vs 48%) and were less likely to have disease recurrence (12·9% vs 24·1%). Neither difference was statistically significant however. Furthermore, patients in this trial were subsequently randomised to receive either chemo- radiotherapy or chemotherapy alone after the operation, which confuses the interpretation of this trial’s results. Lymph-node dissection certainly provides more accurate pathological staging of disease so stage migration may explain some of the “improved” outcomes reported in many series.23,49 This point underscores the importance of carefully designed randomised controlled studies to find out if therapeutic benefit can be attributed to extended lymphadenectomy for oesophageal cancer. At present, such a claim cannot be justified. Minimally invasive oesophagectomy Since improved outcomes have not consistently been shown with radical procedures, further refinements in surgical technique are unlikely to have a substantial impact on this disease. Meanwhile, many investigators have begun to explore more “patient friendly” procedures with the hope of obtaining equivalent oncological outcome while reducing morbidity and mortality. Non-surgical techniques such as endoscopic mucosal resection are being applied for tumours limited to the mucosa and may, with further study, prove to be an effective alternative to oesophagectomy.50,51 Recently, minimally invasive techniques of oesophageal resection have been used. These procedures incorporate various combinations of laparoscopy, thoracoscopy, and hand- assisted manoeuvers. Minimally invasive surgery offers many theoretical advantages including minimising postoperative pain, reducing length of stay in intensive-care units and hospital, and decreasing overall cost. These factors improve quality of care and outcome, enabling patients to regain a normal lifestyle quickly. Hand-assisted laparoscopic techniques can reliably mimic open oesophagectomy and may be the ideal bridge between open and totally laparoscopic or thoracoscopic procedures, thereby reducing the need for surgeons to be specialist in oesophageal procedures. 52 The hand-assisted approach preserves the advantages of open procedures by offering tactile sensation or feedback, and improved hand-eye co- ordination, while maintaining the benefits of a minimally invasive procedure. The surgeon’s ability to “feel” the tumour during the procedure helps ensure wide-field dissection and adequate surgical margins. Proponents of minimally invasive approaches argue that mediastinal exposure is improved and lymph-node dissection is made easier by use of laparoscopic or thoracoscopic techniques. Initial studies have shown that minimally invasive oesophagectomy can often be done relatively quickly, with minimum blood loss, variable hospital stay, and no substantial increase in operative morbidity or mortality over conventional oesophagectomy techniques (table 2).52–56 Lymph-node retrieval seems adequate and comparable to that achieved during open oesophageal resection. However, despite the fact that incisions are smaller, multiple body compartments (abdomen, mediastinum, thorax, and neck) are still disturbed, which is the major contributing factor to the morbidity and mortality associated with oesophagectomy. Indeed, this may negate the theoretical advantages of a “minimally” invasive approach. In conclusion, no scientifically generated data is currently available to support significant advantages of the minimally invasive approach for oesophagectomy over the open technique. Numerous issues remain unresolved regarding the clinical usefulness of minimally invasive oesophageal resection. These include: the optimum approach; applicability to general surgeons; cost-effectiveness; proof of advantages over open techniques; and the role of minimally invasive oesophagectomy in combined modality therapy. When analysing a new technology, it is important to distinguish between perceived and actual benefits and, in the case of minimally invasive oesophagectomy, controlled comparative studies will be essential for determining its true value. At present this procedure remains an investigational approach for cancer of the oesophagus. Review Surgery for oesophageal cancer Table 2. Meta-analysis of trials comparing transthoracic (TTE) versus transhiatal (THE) oesophagectomy N Pulmonary complications (%) Anastamotic leak (%) Postoperative mortality (%) 5-year survival (%) Ref TTE THE RR (CI) TTE THE RR (CI) TTE THE RR (CI) TTE THE RR (CI) 7527 18·7 12·7 1·47 7·2 13·6 0·53 9·2 5·7 1·60 23·0 21·7 1·06 27 (1·29-1·68) (0·45-0·63) (1·89-1·42) (1·18-0·96) 5483 25·0 24·0 N/A 10·0 16·0 N/A 9·5 6·3 N/A 26·0 24·0 N/A 28 RR (CI), relative risk (confidence interval); N/A, not applicable. Table 3. Results of minimally invasive oesophagectomy N Operative Blood loss Lymph nodes Hospital Complications (%) Mortality (%) Ref time (min) (mL) dissected stay (days) Respiratory Cardiac Anastamotic leak 77 450 N/A 16 7 18·2 13·0 9·1 0 54 18 364 297 10.8 11·3 16·7 N/A 11·0 0 55 9 390 290 6 6·4 55·6 N/A 0·0 0 53 N/A, not applicable.
  5. 5. For personal use. Only reproduce with permission from The Lancet. THE LANCET Oncology Vol 4 August 2003 http://oncology.thelancet.com 485 Surgery as part of combined modality therapy The equivalence between incidence and mortality rates in the USA for oesophageal cancer4 and the failure of surgery alone to alter this pattern means that many oncologists favour combined modality therapy. As a consequence, chemo- radiotherapy, either with or without surgery, is the most widely used treatment for patients with oesophageal cancer in the USA.57 We have chosen to critically analyse the data from available clinical trials to find out whether this trend in treatment is justified or requires further study. The role of resection as a component of combined modality treatment for oesophageal cancer is now being scrutinised and its superiority challenged. Preoperative combined modality treatment Phase III trials in which patients are randomised to either preoperative radiotherapy or surgery alone have not shown a survival benefit for combined therapy (table 3).58-62 This result is not surprising however, since both radiotherapy and surgery address local regional disease alone, yet the vast majority of patients die from systemic recurrence. The results of trials exploring the addition of chemotherapy to resection are conflicting (table 4).63–67 Two large multi-institutional prospective randomised trials of preoperative chemotherapy vs a surgical control have been reported.63,64 An intergroup trial64 in the USA showed that survival was equivalent between patients assigned induction chemotherapy (fluorouracil and cisplatin) and resection, and those treated with surgery alone. A similar trial by the UK Medical Research Council63 noted a significant median and 3-year survival benefit for patients randomised to preoperative fluorouracil with cisplatin compared with surgery alone. Although a direct comparison of several variables between the two trials suggests differences in total dose of drug, percentage of intended chemotherapy cycles that were delivered, and percentage of patients randomised to combined modality who actually underwent resection, we are still left with inexplicable disparate outcomes in these two trials and, therefore, the worth of preoperative chemotherapy remains questionable. Recognition of the need for improved local regional control, and also of the fact most patients succumb to distant disease, has prompted many investigators to explore preoperative chemoradiotherapy in an attempt to improve outcome. There have been three prospective randomised trials comparing induction chemoradiotherapy plus oesophagectomy with oesophagectomy alone (table 5). At face value, one of the studies68 showed a survival benefit with combined modality therapy although the other two studies69,70 showed equivalent median and 3-year survival between the groups. As with all clinical studies, each of these trials has its supporters and detractors providing evidence to support their own bias regarding the utility of combined modality therapy. The positive study by Walsh and colleagues68 has been criticised as a small, single-institution study with suboptimum preoperative staging and an extremely poor outcome in the surgical control group. Those who favour chemoradiotherapy point out that in the negative EORTC trial, 69 which showed an identical median survival between the two groups, there was a significant decrease in number of deaths from oesophageal ReviewSurgery for oesophageal cancer Table 4. Randomised controlled trials of preoperative radiotherapy versus surgery alone for oesophageal carcinoma N Histology Preoperative 5-year overall survival (%)* Ref radiotherapy Surgery Radiotherapy dose (Gy/time) plus surgery 176 SCC/AC 20/2 wk 17 9 58 108 SCC 35/4 wk 9† 21† 59 206 N/A 40/4 wk 30 35 60 208 SCC 33/12 d 9 10 61 124 SCC 39–45/8–12 d 11·5 9·5 62 *p=non-significant, †3-year overall survival. SCC, squamous-cell carcinoma; AC, adenocarcinoma. Table 5. Randomised controlled trials of preoperative chemotherapy vs surgery alone for oesophageal carcinoma N Histology Regimen Surgical mortality (%) Median survival (months) 2-year survival (%) Ref Surgery Chemotherapy p Surgery Chemotherapy p Surgery Chemotherapy p and surgery and surgery and surgery 802 SCC/AC 2 cycles of cisplatin plus 10·0 10·0 NS 13·3 16·8 NS 34 43 0·004 63 fluorouracil, then surgery 440 SCC/AC 3 cycles of cisplatin plus 6·0 6·0 NS 16·1 14·9 NS 37 35 NS 64 fluorouracil, then surgery and 2 cycles of cisplatin plus fluorouracil postoperatively 147 SCC 2 cycles of cisplatin plus 8·7 8·3 NS 13·8 16·2 NS 31 44 NS 65 fluorouracil, then surgery 75 SCC 3 cycles of cisplatin plus 10·0 19·0 N/A 10·0 10·0 NS N/A N/A N/A 66 fluorouracil then surgery 39 SCC 2 cycles of cisplatin plus 0·0 12·0 NS 9·0 9·0 NS N/A N/A N/A 67 bleomycin and vindesine, then surgery, and postoperative cisplatin and vindesine for 6 months SCC, squamous-cell carcinoma; AC, adenocarcinoma; NS, non-significant; N/A., not applicable.
  6. 6. For personal use. Only reproduce with permission from The Lancet. THE LANCET Oncology Vol 4 August 2003 http://oncology.thelancet.com486 cancer in the preoperative chemoradiotherapy group. However, skeptics counter that combined modality therapy significantly increased postoperative mortality emphasising the toxicity of this aggressive approach. The authors of a negative trial from the University of Michigan70 reported equivalent median survival for patients treated with chemoradiotherapy and those who were assigned to surgery alone, but stated that there is a statistically non-significant trend toward improved survival with combined modality treatment, and that the trial was underpowered to detect a small, but potentially clinically meaningful, survival difference between the groups. The only way of resolving these conflicting results would be to design a large multi- institutional phase III trial of chemoradiotherapy plus surgery vs surgery alone. Such a trial was conceived of through the intergroup mechanism in the USA in October, 1997, but was prematurely closed after recruiting only 5% of the intended number of patients. The absence of benefit for preoperative chemoradio- therapy in the reported phase III trials means this approach should be considered investigational. A consistent finding in these three trials, as well as many phase II trials, is that 25% of patients treated with induction chemoradiotherapy have a complete pathological response with no residual tumour in samples of resected tissue after oesophagectomy. One would intuitively conclude that this group of patients does not require surgery, since it is difficult to comprehend how oesophagectomy offers any added benefit in this setting. By contrast, a number of phase II trials, including our own,71 show long-term survival for patients with residual disease in resected tissue after preoperative chemoradiotherapy, which suggests oesophagectomy is necessary for this cohort and their outcome would be compromised if residual tumour had been left in situ. Ideally, surgery should be directed towards patients who need oesophagectomy, so the risks of resection can be avoided in patients who would derive little benefit. A similar argument could be applied to chemoradiotherapy; however, our ability to predict tumour biology before initiation of treatment is, at best, limited. Definitive chemoradiotherapy The traditional role of surgery in the management of oesophageal cancer has further been challenged by the results of a phase III trial examining the usefulness of definitive chemoradiotherapy. In RTOG 8501,72 patients were randomised to receive chemoradiotherapy or radiotherapy alone; neither treatment group underwent surgery. The results imply that chemoradiotherapy is superior to radiotherapy—26% of patients in the combined modality group were alive at 5 years compared with no patients who received radiotherapy alone.18 The investigators appropriately point out that 5-year survival for patients who were treated with chemoradiotherapy was similar, or better, than that reported for patients who have surgery. However, persistent or recurrent local disease was present in about 40% of patients treated with chemoradiotherapy, suggesting that if surgery was also used, survival would be improved further. Obviously the only way to resolve this issue would be to design a randomised trial with surgery as the variable, ie, chemo- radiotherapy plus surgery vs definitive chemoradiotherapy alone. Although it was thought unlikely that a trial with this design would ever be initiated, such a trial was reported in abstract form at the 2002 Annual Meeting of the American Society of Clinical Oncology in Orlando, Florida. 73 Of the 455 patients who began chemoradiotherapy, 259 patients who had at least a partial response and no contraindication to further chemoradiotherapy or surgery were randomised to surgery or continuation of chemoradiotherapy. No difference was noted for 2-year survival or median survival between the two groups, although the 3-month mortality was significantly higher (9% vs 1%) in patients who underwent surgery as a component of their combined modality treatment. Although no definitive conclusions can be drawn from this trial since, at the present time, only the abstract is available for review, it again challenges the role of surgery as a mandatory therapeutic intervention for all patients with carcinoma of the oesophagus. Conclusions The management of oesophageal cancer will undoubtedly continue to evolve as improvements in technology, combined with a greater understanding of genomics and biology of tumours, better define effective therapeutic interventions and allow introduction of novel treatments into strategies for clinical management. The role of surgery is likely to change over time, but will continue as a primary, or secondary, treatment modality for a substantial number of patients with oesophageal cancer. In patients with confined disease (stage I and IIa), resection can be curative and the acceptable outcome achieved by surgeons who are experienced at oesophagectomy is unlikely to be challenged by other forms of therapy. Since the vast majority of patients with locally advanced disease who undergo chemoradiotherapy have residual disease in situ at completion of treatment, common sense dictates that surgery should be beneficial in achieving a long-term disease-free state. Conversely, it is difficult to contemplate how surgery would benefit patients who achieve a complete pathological response with combined modality therapy, and therefore, they should not be exposed to the risks associated with oesophageal resection. Unfortunately, at present, we are unable to Review Surgery for oesophageal cancer Table 6. Randomised controlled trials of neoadjuvant chemoradiation for oesophageal carcinoma N Histology Pathological Surgical mortality (%) Median survival (months) 3-year survival (%) Ref complete response (%) Surgery CMT p Surgery CMT p Surgery CMT p 100 SCC/AC 28·0 4·0 2·1 NS 17·6 16·9 NS 16·0 30·0 NS 70 282 SCC 26·0 3·6 12·3 0·012 18·6 18·6 NS 25·0 27·0 NS 69 113 AC 25·0 3·6 8·5 NS 11·0 16·0 0·01 6·0 32·0 0·01 68 SCC, squamous-cell carcinoma; AC, adenocarcinoma; CMT, combined modality therapy; NS, non-significant.
  7. 7. For personal use. Only reproduce with permission from The Lancet. THE LANCET Oncology Vol 4 August 2003 http://oncology.thelancet.com 487 accurately pinpoint those patients who require some kind of therapeutic intervention and those for who particular treatments should be avoided. However, it is likely that in the not too distant future, we will be able to establish a “genetic fingerprint” for each individual patient that will dictate the most efficacious therapeutic strategy in each setting. It is important for us to separate fact from fiction when assessing the effectiveness of therapeutic interventions and avoid the pitfalls inherent in personal bias. For example, although minimally invasive oesophagectomy has many theoretical benefits, its worth has not been vigorously examined and, therefore, the actual advantages over open oesophagectomy are unclear and unproven. Likewise, the widespread use of preoperative chemoradiotherapy on the basis of its presumed therapeutic benefit should be weighed against the insufficient evidence for an actual advantage over resection alone. The challenge for us is not to accept the status quo and to investigate new better options, but to do so in a scientifically sound way that leaves little doubt to the accuracy of therapeutic claims. In a disease where as many deaths occur as new cases are reported each year, no therapeutic option, including surgery, should be dogmatically accepted and defended. We should all continue to search for more effective applications of current treatments, and vigorously explore innovative alternatives which must be validated through the clinical-trial process. References 1 Blot WJ, Devesa SS, Kneller RW, Fraumeni JF, Jr. Rising incidence of adenocarcinoma of the esophagus and gastric cardia. JAMA 1991; 265: 1287–89. 2 Devesa SS, Blot WJ, Fraumeni JF, Jr. Changing patterns in the incidence of esophageal and gastric carcinoma in the United States. Cancer 1998; 83: 2049–53. 3 Blot WJ, McLaughlin JK. The changing epidemiology of esophageal cancer. Semin Oncol 1999; 26 (5 suppl 15): 2–8. 4 Jemal A, Thomas A, Murray T, Thun M. Cancer statistics, 2002. CA Cancer J Clin 2002; 52: 23–47. 5 Winters C Jr, Spurling TJ, Chobanian SJ, et al. Barrett’s esophagus. A prevalent, occult complication of gastroesophageal reflux disease. Gastroenterology 1987; 92: 118–24. 6 DeMeester TR. Esophageal carcinoma: current controversies. Semin Surg Oncol 1997; 13: 217–33. 7 Lagergren J, Bergstrom R, Lindgren A, Nyren O. Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med 1999; 340: 825–31. 8 Lagergren J, Bergstrom R, Nyren O. Association between body mass and adenocarcinoma of the esophagus and gastric cardia. Ann Intern Med 1999; 130: 883–90. 9 Chow WH, Blot WJ, Vaughan TL, et al. Body mass index and risk of adenocarcinomas of the esophagus and gastric cardia. J Natl Cancer Inst 1998; 90: 150–55. 10 Vaughan TL, Davis S, Kristal A, Thomas DB. Obesity, alcohol, and ReviewSurgery for oesophageal cancer Search strategy and selection criteria References for this review were identified by searches of PubMed. Search criteria included the terms “esophageal neoplasm”, “esophagectomy”, “transhiatal”, “transthoracic”, “minimally invasive surgery”, “laparoscopy” or “laparoscopic”, “thoracoscopy” or “thoracoscopic”, “radiotherapy”, “chemotherapy”, “chemoradiotherapy”, and “multimodality therapy”. Selected papers from the search results were retrieved and only papers involving human studies, published in English, were used for this review. tobacco as risk factors for cancers of the esophagus and gastric cardia: adenocarcinoma versus squamous cell carcinoma. 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