Advances in Barrett’s Esophagus and Esophageal Adenocarcinoma
2005; Elsevier BV; Volume: 128; Issue: 6 Linguagem: Inglês
10.1053/j.gastro.2005.03.032
ISSN1528-0012
Autores Tópico(s)Gastric Cancer Management and Outcomes
ResumoDespite advances in diagnosis and therapy, esophageal adenocarcinoma remains an aggressive and usually lethal tumor. This review focuses on the epidemiology of esophageal adenocarcinoma and its presumed precursor lesion, Barrett’s esophagus; the pathogenesis of the cancer; advances in treatment of adenocarcinoma and Barrett’s esophagus; and strategies for cancer prevention. Emphasis is placed on recent literature. Although the absolute number of cases of adenocarcinoma in the United States is still small, the incidence of this cancer has increased dramatically in the last 40 years, and adenocarcinoma is now the predominant form of esophageal cancer in this country. Recent evidence suggests that Barrett’s esophagus is more prevalent in asymptomatic individuals than previously appreciated. The pathogenesis of Barrett’s esophagus is poorly understood. Given that some subjects will have repeated bouts of severe erosive esophagitis and never develop Barrett’s esophagus, host factors must play an important role. The utility of neoadjuvant radiation and chemotherapy in those with adenocarcinoma, although they are widely practiced, is not of clear benefit, and some authorities recommend against it. Ablative therapies, as well as endoscopic mucosal resection, hold promise for those with superficial cancer or high-grade dysplasia. Most series using these modalities feature relatively short follow-up, and longer-term data will be necessary to better describe the effects of these therapies. The value of chemoprevention in subjects with dysplastic Barrett’s esophagus by use of cyclooxygenase 2 inhibitors, nonsteroidal anti-inflammatory drugs, or proton pump inhibitors is unknown. Similarly, although endoscopic screening is widely practiced, its value in patients with chronic gastroesophageal reflux disease symptoms is of unproven value, and recommending bodies are divided as to its practice. Despite advances in diagnosis and therapy, esophageal adenocarcinoma remains an aggressive and usually lethal tumor. This review focuses on the epidemiology of esophageal adenocarcinoma and its presumed precursor lesion, Barrett’s esophagus; the pathogenesis of the cancer; advances in treatment of adenocarcinoma and Barrett’s esophagus; and strategies for cancer prevention. Emphasis is placed on recent literature. Although the absolute number of cases of adenocarcinoma in the United States is still small, the incidence of this cancer has increased dramatically in the last 40 years, and adenocarcinoma is now the predominant form of esophageal cancer in this country. Recent evidence suggests that Barrett’s esophagus is more prevalent in asymptomatic individuals than previously appreciated. The pathogenesis of Barrett’s esophagus is poorly understood. Given that some subjects will have repeated bouts of severe erosive esophagitis and never develop Barrett’s esophagus, host factors must play an important role. The utility of neoadjuvant radiation and chemotherapy in those with adenocarcinoma, although they are widely practiced, is not of clear benefit, and some authorities recommend against it. Ablative therapies, as well as endoscopic mucosal resection, hold promise for those with superficial cancer or high-grade dysplasia. Most series using these modalities feature relatively short follow-up, and longer-term data will be necessary to better describe the effects of these therapies. The value of chemoprevention in subjects with dysplastic Barrett’s esophagus by use of cyclooxygenase 2 inhibitors, nonsteroidal anti-inflammatory drugs, or proton pump inhibitors is unknown. Similarly, although endoscopic screening is widely practiced, its value in patients with chronic gastroesophageal reflux disease symptoms is of unproven value, and recommending bodies are divided as to its practice. Because of its rapidly increasing incidence over the last 40 years, esophageal adenocarcinoma has gone from a somewhat esoteric disease entity to the predominant form of esophageal cancer in the United States. Although still a rare cause of cancer death internationally, esophageal adenocarcinoma has become a significant health concern in Western countries. Given the poor prognosis associated with the disease, a better understanding of the pathogenesis of the disease and the factors associated with increased risk is essential. Also, strategies for prevention of esophageal adenocarcinoma are hotly contested.The following review will focus on new developments in the field of Barrett’s esophagus (BE) and esophageal adenocarcinoma. Given the myriad aspects of these disease states, an exhaustive review of all that is known about them is beyond the scope of this article. Therefore, this work will concentrate on the epidemiology of the disease states, the pathogenesis of the cancer, advances in treatment, and strategies for cancer prevention. Special emphasis will be placed on recent data, with effort to place these data in the context of our knowledge of BE and esophageal adenocarcinoma.Epidemiology of Barrett’s esophagus and esophageal adenocarcinomaThe incidence of esophageal adenocarcinoma in the United States has increased approximately 300%–500% in the last 40 years.1Daly J.M. Karnell L.H. Menck H.R. National Cancer Data Base report on esophageal carcinoma.Cancer. 1996; 78: 1820-1828Crossref PubMed Scopus (248) Google Scholar, 2Bytzer P. Christensen P.B. Damkier P. Vinding K. Seersholm N. Adenocarcinoma of the esophagus and Barrett’s esophagus a population-based study.Am J Gastroenterol. 1999; 94: 86-91Crossref PubMed Scopus (210) Google Scholar, 3Devesa S.S. Blot W.J. Fraumeni Jr, J.F. Changing patterns in the incidence of esophageal and gastric carcinoma in the United States.Cancer. 1998; 83: 2049-2053Crossref PubMed Scopus (1474) Google Scholar Although previous misclassification of some esophageal adenocarcinomas as gastric cardia tumors may be in part responsible for the noted increase, it does not likely explain the entire increase. If misclassification were to explain all of the increase, a concomitant decrease in the number of gastric cardia tumors might be expected over the same time period. The opposite is true; the incidence of gastric cardia tumors has not decreased and may have actually increased over this period.4Corley D.A. Kubo A. Influence of site classification on cancer incidence rates an analysis of gastric cardia carcinomas.J Natl Cancer Inst. 2004; 96: 1383-1387Crossref PubMed Scopus (55) Google Scholar, 5Nguyen A.M. Luke C.G. Roder D. Comparative epidemiological characteristics of oesophageal adenocarcinoma and other cancers of the oesophagus and gastric cardia.Asian Pac J Cancer Prev. 2003; 4: 225-231PubMed Google ScholarLess clear is the trend in the incidence of BE. Because BE is thought to be the precursor lesion to most or all cases of adenocarcinoma of the esophagus, increases in cancer might be expected to be preceded by increases in the incidence of BE. Longitudinal single-center studies do show an increase in diagnosis of BE over the past several decades.6Conio M. Cameron A.J. Romero Y. Branch C.D. Schleck C.D. Burgart L.J. et al.Secular trends in the epidemiology and outcome of Barrett’s oesophagus in Olmsted County, Minnesota.Gut. 2001; 48: 304-309Crossref PubMed Scopus (171) Google Scholar, 7Hurschler D. Borovicka J. Neuweiler J. Oehlschlegel C. Sagmeister M. Meyenberger C. et al.Increased detection rates of Barrett’s oesophagus without rise in incidence of oesophageal adenocarcinoma.Swiss Med Wkly. 2003; 133: 507-514PubMed Google Scholar However, this increasing trend mirrors the increasing use of upper endoscopy. It may, therefore, mean that the increased incidence of BE described in these studies is due to increased opportunity for detection, as well as the increasing appreciation of BE as a risk factor for cancer, as opposed to a true increase in prevalence.The increasing trend in esophageal adenocarcinoma closely resembles the epidemic increase in obesity in the US population.8Kuczmarski R.J. Flegal K.M. Campbell S.M. Johnson C.L. Increasing prevalence of overweight among US adults. The National Health and Nutrition Examination Surveys, 1960 to 1991.JAMA. 1994; 272: 205-211Crossref PubMed Google Scholar, 9Mokdad A.H. Serdula M.K. Dietz W.H. Bowman B.A. Marks J.S. Koplan J.P. The spread of the obesity epidemic in the United States, 1991–1998.JAMA. 1999; 282: 1519-1522Crossref PubMed Scopus (1508) Google Scholar Additionally, obesity has been strongly associated as a risk factor for esophageal adenocarcinoma, even after controlling for the severity of reflux symptoms.10Lagergren J. Bergstrom R. Nyren O. Association between body mass and adenocarcinoma of the esophagus and gastric cardia.Ann Intern Med. 1999; 130: 883-890Crossref PubMed Google Scholar, 11Chow W.H. Blot W.J. Vaughan T.L. Risch H.A. Gammon M.D. Stanford J.L. et al.Body mass index and risk of adenocarcinomas of the esophagus and gastric cardia.J Natl Cancer Inst. 1998; 90: 150-155Crossref PubMed Google Scholar These 2 facts have led authorities to suggest a causal relationship between trends of increasing obesity and resultant esophageal adenocarcinoma in the US population.12Engel L.S. Chow W.H. Vaughan T.L. Gammon M.D. Risch H.A. Stanford J.L. et al.Population attributable risks of esophageal and gastric cancers.J Natl Cancer Inst. 2003; 95: 1404-1413Crossref PubMed Google Scholar, 13Wei J.T. Shaheen N. The changing epidemiology of esophageal adenocarcinoma.Semin Gastrointest Dis. 2003; 14: 112-127PubMed Google Scholar, 14El Serag H.B. The epidemic of esophageal adenocarcinoma.Gastroenterol Clin North Am. 2002; 31 (viii): 421-440Abstract Full Text Full Text PDF PubMed Scopus (73) Google Scholar Although such a relationship is certainly plausible, no causal chain has been definitely proven, and changes in other environmental exposures over the last 50 years may account for all or part of the observed increase.One recent important contribution to this field has been the demonstration of the prevalence of BE in asymptomatic populations. BE has long been recognized as a possible complication of chronic reflux disease. However, 40% or more of esophageal adenocarcinoma is found in subjects without previous symptoms of reflux15Lagergren J. Bergstrom R. Lindgren A. Nyren O. Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma.N Engl J Med. 1999; 340: 825-831Crossref PubMed Scopus (1778) Google Scholar, 16Farrow D.C. Vaughan T.L. Sweeney C. Gammon M.D. Chow W.H. Risch H.A. et al.Gastroesophageal reflux disease, use of H2 receptor antagonists, and risk of esophageal and gastric cancer.Cancer Causes Control. 2000; 11: 231-238Crossref PubMed Scopus (142) Google Scholar, 17Chow W.H. Finkle W.D. McLaughlin J.K. Frankl H. Ziel H.K. Fraumeni Jr, J.F. The relation of gastroesophageal reflux disease and its treatment to adenocarcinomas of the esophagus and gastric cardia.JAMA. 1995; 274: 474-477Crossref PubMed Google Scholar—an observation that is inconsistent with the theory that BE arises from gastroesophageal reflux disease (GERD) and is the predisposing lesion to adenocarcinoma. This apparent contradiction may be at least partially explained by recent prevalence data of BE in asymptomatic populations. Gerson et al18Gerson L.B. Shetler K. Triadafilopoulos G. Prevalence of Barrett’s esophagus in asymptomatic individuals.Gastroenterology. 2002; 123: 461-467Abstract Full Text Full Text PDF PubMed Scopus (279) Google Scholar performed upper endoscopy on 110 subjects with no or negligible GERD symptoms who were presenting for colorectal cancer screening. The surprising and somewhat unsettling finding in this primarily Veterans Administration Medical Center cohort was that almost 25% of those with no GERD symptoms harbored BE, and 8% of the subjects had long-segment disease (>3 cm). Other groups19Rex D.K. Cummings O.W. Shaw M. Cumings M.D. Wong R.K. Vasudeva R.S. et al.Screening for Barrett’s esophagus in colonoscopy patients with and without heartburn.Gastroenterology. 2003; 125: 1670-1677Abstract Full Text Full Text PDF PubMed Scopus (219) Google Scholar, 20DeVault K.R. Ward E.M. Wolfsen H.C. Loeb D.S. Krishna M. Hemminger L.L. et al.Barrett’s esophagus is common in older patients undergoing screening colonoscopy regardless of gastroesophageal reflux symptoms (abstr).Gastroenterology. 2004; 126: 680AGoogle Scholar have found that lesser, but still substantial, proportions of asymptomatic individuals have BE (Table 1). Currently unknown is whether these asymptomatic individuals with BE have the same increased risk of cancer that has been shown in previous, symptomatic cohorts that have been followed up longitudinally.Table 1Prevalence of BE in Asymptomatic CohortsStudyYearPatient populationnPrevalence of BEPrevalence of long-segment BEGerson et al18Gerson L.B. Shetler K. Triadafilopoulos G. Prevalence of Barrett’s esophagus in asymptomatic individuals.Gastroenterology. 2002; 123: 461-467Abstract Full Text Full Text PDF PubMed Scopus (279) Google Scholar2002Veterans Administration medical center11025%7%Rex et al19Rex D.K. Cummings O.W. Shaw M. Cumings M.D. Wong R.K. Vasudeva R.S. et al.Screening for Barrett’s esophagus in colonoscopy patients with and without heartburn.Gastroenterology. 2003; 125: 1670-1677Abstract Full Text Full Text PDF PubMed Scopus (219) Google Scholar2003University hospital5565.6%0.36%DeVault et al20DeVault K.R. Ward E.M. Wolfsen H.C. Loeb D.S. Krishna M. Hemminger L.L. et al.Barrett’s esophagus is common in older patients undergoing screening colonoscopy regardless of gastroesophageal reflux symptoms (abstr).Gastroenterology. 2004; 126: 680AGoogle Scholar2004Academic practice13812.3NRNR, not reported. Open table in a new tab Also unknown is the exact risk of cancer in subjects with BE. Initial reports pegged this risk at 1% or more per year. More recent reports and a meta-analysis have suggested this risk to be approximately half that amount.21O’Connor J.B. Falk G.W. Richter J.E. The incidence of adenocarcinoma and dysplasia in Barrett’s esophagus report on the Cleveland Clinic Barrett’s Esophagus Registry.Am J Gastroenterol. 1999; 94: 2037-2042PubMed Google Scholar, 22Drewitz D.J. Sampliner R.E. Garewal H.S. The incidence of adenocarcinoma in Barrett’s esophagus a prospective study of 170 patients followed 4.8 years.Am J Gastroenterol. 1997; 92: 212-215PubMed Google Scholar, 23Conio M. Blanchi S. Lapertosa G. Ferraris R. Sablich R. Marchi S. et al.Long-term endoscopic surveillance of patients with Barrett’s esophagus. Incidence of dysplasia and adenocarcinoma: a prospective study.Am J Gastroenterol. 2003; 98: 1931-1939Crossref PubMed Scopus (154) Google Scholar, 24Shaheen N.J. Crosby M.A. Bozymski E.M. Sandler R.S. Is there publication bias in the reporting of cancer risk in Barrett’s esophagus?.Gastroenterology. 2000; 119: 333-338Abstract Full Text Full Text PDF PubMed Google Scholar Of course, these analyses provide rough estimates based on accumulated data from cohorts for multiple years. It is quite possible (perhaps even likely) that cancer risk is unevenly spread in any given subject’s “Barrett’s lifetime.” For instance, it may be that the initial period immediately after the development of the BE is a critical time in which a subgroup of subjects experience rapid progression through degrees of dysplasia to cancer. Conversely, perhaps nondysplastic BE of 10 years’ duration is at very little, if any, risk of progression. Because the exact time of development of BE in subjects diagnosed with the condition is unknown, we have no data as to cancer risk as a function of the duration of preceding BE.Pathogenesis of Barrett’s esophagus and cancerBE is thought to be a sequela of chronic reflux disease. Subjects with chronic reflux disease seem to harbor BE 5%–15% of the time.25Corder A.P. Jones R.H. Sadler G.H. Daniels P. Johnson C.D. Heartburn, oesophagitis and Barrett’s oesophagus in self-medicating patients in general practice.Br J Clin Pract. 1996; 50: 245-248PubMed Google Scholar, 26Winters Jr, C. Spurling T.J. Chobanian S.J. Curtis D.J. Esposito R.L. Hacker III, J.F. et al.Barrett’s esophagus. A prevalent, occult complication of gastroesophageal reflux disease.Gastroenterology. 1987; 92: 118-124PubMed Google Scholar, 27Csendes A. Smok G. Burdiles P. Quesada F. Huertas C. Rojas J. et al.Prevalence of Barrett’s esophagus by endoscopy and histologic studies a prospective evaluation of 306 control subjects and 376 patients with symptoms of gastroesophageal reflux.Dis Esophagus. 2000; 13: 5-11Crossref PubMed Scopus (57) Google Scholar However, it is unclear why some subjects develop severe recurrent erosive esophagitis and never develop BE, whereas others with relatively few symptoms and little or no inflammatory disease on upper endoscopy develop long segments of severely dysplastic disease. It has been suggested that a genetic predisposition to the development of BE might be a necessary prerequisite to the disease. However, to date, a “Barrett’s gene” (or genes) has remained elusive. Several groups have attempted to study the heritability of BE as presumptive evidence of a genetic contribution to the disease. Family cohort studies have shown that BE occurs in family groups more frequently than would be expected by chance.28Chak A. Lee T. Kinnard M.F. Brock W. Faulx A. Willis J. et al.Familial aggregation of Barrett’s oesophagus, oesophageal adenocarcinoma, and oesophagogastric junctional adenocarcinoma in Caucasian adults.Gut. 2002; 51: 323-328Crossref PubMed Scopus (88) Google Scholar However, if there is a Barrett’s gene, the penetrance of the phenotype must be low, because most first-degree relatives of those with BE do not have BE themselves.29Romero Y. Cameron A.J. Schaid D.J. McDonnell S.K. Burgart L.J. Hardtke C.L. et al.Barrett’s esophagus prevalence in symptomatic relatives.Am J Gastroenterol. 2002; 97: 1127-1132Crossref PubMed Google ScholarExactly where the progenitor cells leading to BE arise is a matter of debate. Studies using cell markers suggested that BE arose from pluripotent cells found in the esophagus, which, in the presence of an acidic milieu, developed into columnar epithelium.30Boch J.A. Shields H.M. Antonioli D.A. Zwas F. Sawhney R.A. Trier J.S. Distribution of cytokeratin markers in Barrett’s specialized columnar epithelium.Gastroenterology. 1997; 112: 760-765Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar, 31Shields H.M. Rosenberg S.J. Zwas F.R. Ransil B.J. Lembo A.J. Odze R. Prospective evaluation of multilayered epithelium in Barrett’s esophagus.Am J Gastroenterol. 2001; 96: 3268-3273Crossref PubMed Google Scholar Recent work from Sarosi et al,32Sarosi G. Brown G. Jaiswal K. Lee E. Crook T. Sousa R. et al.Reflux-damaged epithelium is replaced by cells derived from the bone marrow in a rat model of Barrett’s esophagus (abstr).Gastroenterology. 2004; 126: 307AGoogle Scholar however, support an alternative explanation. Using a rodent model of BE, this group was able to show that the progenitor cells for BE arose in the animal’s bone marrow. The mechanism by which these cells differentiate and the factors leading to the propagation of columnar instead of squamous mucosa are still largely unknown.BE is thought to progress through stages of dysplasia to cancer, and, indeed, one of the strongest known predictors of cancer risk in the setting of BE is the degree of dysplasia. Subjects with nondysplastic BE and low-grade dysplasia have low rates of progression, whereas those with high-grade dysplasia (HGD) may experience disease progression at rates higher than 10% per year. 33Miros M. Kerlin P. Walker N. Only patients with dysplasia progress to adenocarcinoma in Barrett’s oesophagus.Gut. 1991; 32: 1441-1446Crossref PubMed Google Scholar, 34Reid B.J. Levine D.S. Longton G. Blount P.L. Rabinovitch P.S. Predictors of progression to cancer in Barrett’s esophagus baseline histology and flow cytometry identify low- and high-risk patient subsets.Am J Gastroenterol. 2000; 95: 1669-1676PubMed Google Scholar Additionally, surgical series show concurrent undetected cancer in the resection specimen in 50% or more of patients with HGD.35Falk G.W. Rice T.W. Goldblum J.R. Richter J.E. Jumbo biopsy forceps protocol still misses unsuspected cancer in Barrett’s esophagus with high-grade dysplasia.Gastrointest Endosc. 1999; 49: 170-176Abstract Full Text Full Text PDF PubMed Scopus (188) Google Scholar, 36Cameron A.J. Carpenter H.A. Barrett’s esophagus, high-grade dysplasia, and early adenocarcinoma a pathological study.Am J Gastroenterol. 1997; 92: 586-591PubMed Google Scholar, 37Heitmiller R.F. Redmond M. Hamilton S.R. Barrett’s esophagus with high-grade dysplasia. An indication for prophylactic esophagectomy.Ann Surg. 1996; 224: 66-71Crossref PubMed Scopus (262) Google Scholar It has been more recently appreciated, however, that the progression through grades of dysplasia is neither orderly nor inexorable. Indeed, subjects may jump from nondysplastic BE straight to HGD or cancer without an intervening detectable low-grade dysplasia phase.38Schnell T.G. Sontag S.J. Chejfec G. Aranha G. Metz A. O’Connell S. et al.Long-term nonsurgical management of Barrett’s esophagus with high-grade dysplasia.Gastroenterology. 2001; 120: 1607-1619Abstract Full Text Full Text PDF PubMed Google Scholar Alternatively, subjects with HGD may undergo apparent regression of the disease and spend months or even years with no detectable dysplasia whatsoever. Data on disease progression in BE are compromised by our random-sampling endoscopic biopsy techniques. Almost all the data available on progression rates in BE are from studies using a random biopsy method. Even groups that use jumbo forceps and 1-cm, 4-quadrant biopsies leave the vast majority of the mucosa unsampled. It is difficult to know what percentage of apparent disease regression is real and what is due to random sampling error missing small or mosaic areas of more advanced dysplasia. Although more sophisticated methods of sampling BE by using vital stains or magnification of mucosal crypt patterns have been described,39Kiesslich R. Hahn M. Herrmann G. Jung M. Screening for specialized columnar epithelium with methylene blue chromoendoscopy in patients with Barrett’s esophagus and a normal control group.Gastrointest Endosc. 2001; 53: 47-52Abstract Full Text Full Text PDF PubMed Scopus (92) Google Scholar, 40Canto M.I. Setrakian S. Petras R.E. Blades E. Chak A. Sivak Jr, M.V. Methylene blue selectively stains intestinal metaplasia in Barrett’s esophagus.Gastrointest Endosc. 1996; 44: 1-7Abstract Full Text Full Text PDF PubMed Google Scholar, 41Canto M.I. Setrakian S. Willis J. Chak A. Petras R. Powe N.R. et al.Methylene blue-directed biopsies improve detection of intestinal metaplasia and dysplasia in Barrett’s esophagus.Gastrointest Endosc. 2000; 51: 560-568Abstract Full Text Full Text PDF PubMed Google Scholar, 42Sharma P. Weston A.P. Topalovski M. Cherian R. Bhattacharyya A. Sampliner R.E. Magnification chromoendoscopy for the detection of intestinal metaplasia and dysplasia in Barrett’s oesophagus.Gut. 2003; 52: 24-27Crossref PubMed Scopus (224) Google Scholar these methods have not been broadly adopted because of cost, increased time requirements, and lack of sufficient evidence of the effects of the methods on important outcomes.Advances in treatmentNeoadjuvant and surgical therapy for cancerThe prognosis for esophageal adenocarcinoma remains dismal, with a 5-year survival for all comers of approximately 20%.43Sihvo E.I. Luostarinen M.E. Salo J.A. Fate of patients with adenocarcinoma of the esophagus and the esophagogastric junction a population-based analysis.Am J Gastroenterol. 2004; 99: 419-424Crossref PubMed Scopus (43) Google Scholar, 44Victorzon M. Tolonen P. Kohonen M. Salmo M. Outcome of surgery for oesophageal carcinoma in a low volume centre, with and without preoperative chemoradiotherapy.Scand J Surg. 2004; 93: 37-42PubMed Google Scholar, 45Hagen J.A. DeMeester S.R. Peters J.H. Chandrasoma P. DeMeester T.R. Curative resection for esophageal adenocarcinoma analysis of 100 en bloc esophagectomies.Ann Surg. 2001; 234: 520-530Crossref PubMed Scopus (243) Google Scholar This poor result is due in part to the advanced stage of the cancer when it is usually diagnosed. More than 50% of those with this cancer present with stage III or IV disease.45Hagen J.A. DeMeester S.R. Peters J.H. Chandrasoma P. DeMeester T.R. Curative resection for esophageal adenocarcinoma analysis of 100 en bloc esophagectomies.Ann Surg. 2001; 234: 520-530Crossref PubMed Scopus (243) Google Scholar, 46Eloubeidi M.A. Desmond R. Arguedas M.R. Reed C.E. Wilcox C.M. Prognostic factors for the survival of patients with esophageal carcinoma in the U.S. the importance of tumor length and lymph node status.Cancer. 2002; 95: 1434-1443Crossref PubMed Scopus (211) Google Scholar However, some recent strides have been made in elucidating the best care for those with adenocarcinoma.After initial enthusiasm for neoadjuvant chemotherapy as an adjunct to surgery, a well-performed randomized controlled trial showed that neoadjuvant chemotherapy before resection does not improve survival.47Kelsen D.P. Ginsberg R. Pajak T.F. Sheahan D.G. Gunderson L. Mortimer J. et al.Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer.N Engl J Med. 1998; 339: 1979-1984Crossref PubMed Scopus (778) Google Scholar More promising have been the results of studies combining neoadjuvant chemotherapy with radiation therapy. Unblinded studies of neoadjuvant chemoradiation showed that approximately 25% of those undergoing therapy achieved a complete response and that those undergoing therapy had improved survival compared with historical controls.48Forastiere A.A. Orringer M.B. Perez-Tamayo C. Urba S.G. Zahurak M. Preoperative chemoradiation followed by transhiatal esophagectomy for carcinoma of the esophagus final report.J Clin Oncol. 1993; 11: 1118-1123Crossref PubMed Google Scholar, 49Posner M.C. Gooding W.E. Landreneau R.J. Rosenstein M.M. Clarke M.R. Peterson M.S. et al.Preoperative chemoradiotherapy for carcinoma of the esophagus and gastroesophageal junction.Cancer J Sci Am. 1998; 4: 237-246PubMed Google Scholar, 50Bates B.A. Detterbeck F.C. Bernard S.A. Qaqish B.F. Tepper J.E. Concurrent radiation therapy and chemotherapy followed by esophagectomy for localized esophageal carcinoma.J Clin Oncol. 1996; 14: 156-163Crossref PubMed Google Scholar Given these data, prospective randomized studies have been conducted comparing multimodality therapy with surgery alone. These trials have given somewhat conflicting data. Walsh et al51Walsh T.N. Noonan N. Hollywood D. Kelly A. Keeling N. Hennessy T.P. A comparison of multimodal therapy and surgery for esophageal adenocarcinoma.N Engl J Med. 1996; 335: 462-467Crossref PubMed Scopus (1248) Google Scholar randomized 113 patients with adenocarcinoma to undergo either surgery alone or neoadjuvant chemotherapy and radiation with surgery afterward. The chemotherapy regimen was 5-fluorouracil and cisplatin based, and 40 Gy of radiation was delivered. These investigators found a significant downstaging of tumors in the multimodality group; fewer subjects in this group had stage III or IV disease at the time of surgery. Additionally, 3-year survival was improved in the multimodality group (32% vs 6%), and median survival was significantly longer in the multimodality group (16 vs 11 months). Weaknesses of this study included the poor rate of survival in the surgery monotherapy group, as well as the inclusion of some gastric cardia cancers in the study group.A second study performed at University of Michigan showed less conclusive data.52Urba S.G. Orringer M.B. 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: 305-313PubMed Google Scholar This randomized controlled trial of 100 patients with both squamous cell carcinoma and adenocarcinoma of the esophagus compared surgery vs radiation combined with a chemotherapy regimen of 5-fluorouracil, cisplatin, and vinblastine. Unlike the study by Walsh et al,51Walsh T.N. Noonan N. Hollywood D. Kelly A. Keeling N. Hennessy T.P. A comparison of multimodal therapy and surgery for esophageal adenocarcinoma.N Engl J Med. 1996; 335: 462-467Crossref PubMed Scopus (1248) Google Scholar this study showed only an insignificant trend toward improved survival at 3 years in the multimodality group (30% vs 16%; P = .15). The absolute difference between the groups, although not statistically significant, is certainly clinically significant, but the study was not powered to detect relatively small absolute differences in survival.Given the conflicting nature of the data, as well as the shortcomings of the studies considering this question, many centers continue to practice multimodality neoadjuvant therapy for subjects with adenocarcinoma of the esophagus. Although some authorities have divergent points of view53Malthaner R.A. Wong R.K. Rumble R.B. Zuraw L. Neoadjuvant or adjuvant therapy for resectable esophageal cancer a clinical practice guideline.BMC Cancer. 2004; 4: 67Crossref PubMed Scopus (24) Google Scholar, 54Stahl M. Adjuvant chemoradiotherapy in gastric cancer and carcinoma of the oesophago-gastric junction.Onkologie. 2004; 27: 33-36Crossref PubMed Scopus (9) Google Scholar and although other data suggest no benefit from neoadjuvant therapy in the setting of esophageal adenocarcinoma,55Donington J.S. Miller D.L. Allen M.S. Deschamps C. Nichols III, F.C. Pairolero P.C. Preoperative chemoradiation therapy does not improve early survival after esophagectomy for patients with clinical stage III adenocarcin
Referência(s)