Recent Trends in the Epidemiology of Esophageal Cancer

Transcription

1 ANNALS OF CLINICAL AND LABORATORY SCIENCE, Vol. 26, No. 6 Copyright 1996, Institute for Clinical Science, Inc. Recent Trends in the Epidemiology of Esophageal Cancer Comparison of Epidermoidand Adenocarcinomas* TERENCE N. MOYANA, M.B. and MICHELE JANOSKI Department of Pathology, Royal University Hospital and College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada ABSTRACT This was a retrospective study of 306 consecutive patients with esophageal carcinoma seen at the Saskatoon Cancer Center from 1970 to 1992, making an annual incidence of approximately 2.7 percent per 100,000 population. The two main cancer types were (1) epidermoid carcinoma (199 patients or 69 percent), and (2) adenocarcinoma (81 patients or 28 percent). At the time of diagnosis, all patients had advanced disease with >60 percent having extra-esophageal spread. Patient management was conventional with radiotherapy, surgery, chemotherapy, or combinations thereof being the mainstay of treatment. After a mean follow-up of 13 months, 82 percent of the patients had died of disease, 11 percent of other causes, and none were cured of disease. An analysis of the time trends showed an increasing incidence of both epidermoid carcinomas and adenocarcinomas, particularly the latter. There was a preponderance of distally located tumors in either group. The reasons for these trends in the pathobiology of esophageal carcinoma are not fully understood at this time. Introduction Cancer of the esophagus is characterized by marked variations in incidence in different parts of the world.1 2,3 4 How * Send reprint requests to: Terence N. Moyana, M.B., Department of Pathology, Royal University H ospital, 103 H ospital D rive, Saskatoon, SK, Canada, S7N 0W8. ever, even within a given country, significant differences in the epidemiology of this cancer have b een observed between various regions or counties.1,2,3 These differences become even more accentuated if esophageal cancer is stratiified into its two major histologic subtypes, namely, epidermoid carcinoma and adenocarcinoma. Recently, there has been a growing body of literature attesting to the dramatic increase in esopha /96/ $01.20 Institute for Clinical Science, Inc.

2 geal adenocarcinoma that has occurred over the last few decades and is still apparently unabated.5,6,7 With regard to epidermoid cancer, some regions have witnessed an increase while others have seen a decrease.1,2,3,4 The reasons for these changes are not entirely clear. However, the foregoing epidemiologic features of esophageal cancer suggest that environmental factors may be important in its pathogenesis. In the present study, the clinical and pathologic features of patients with esophageal carcinoma seen at the Saskatchewan Cancer Clinic were studied with a view to comparing our findings with those of other investigators. The population of this province has remained relatively stable at approximately 1 million over the last 50 years,8 and there is a comprehensive Provincial Cancer Registry to which all physicians are required to register every patient diagnosed with cancer.9 Given the fact that virtually all health care costs incurred by cancer patients are covered by the provincial health care insurance, as well as the unremitting nature of established esophageal carcinoma, there is reason to believe that the numbers of esophageal carcinoma patients herein described closely reflect this disease as it occurs in this region. It is also hoped that the data base so created in this study could form a baseline from which to monitor possible future trends in the pathobiology of esophageal cancer in this region. EPIDEMIOLOGY OF ESOPHAGEAL CANCER 4 81 Materials and Methods The case records of the Saskatchewan Cancer Clinic were searched for all cases of patients diagnosed with esophageal cancer from the beginning of 1970 to the end of With regard to the esophagogastric region, tumors that were predominantly located on the proximal side were regarded as being of esophageal origin, whereas those on the distal side were considered gastric; the latter were excluded from the study. Of the cases that were considered to have originated from the esophagus, be this proximal, middle or distal, approximately half were registered with the Saskatoon branch of the C linic. This branch covers the approximately 500,000 residents in the northern half of the province;8 the esophageal carcinoma patients from this latter group are the subject of this report. The computer data-base identified 306 such patients. The health record charts of these patients were then pulled out and reviewed in detail using a check-list that had been prepared in advance. The pathology reports of all the patients were reviewed, and, when necessary for the sake of clarification, the slides were retrieved and re-examined. The cases were further stratified into the two major histologic types, namely, epidermoid carcinoma and adenocarcinoma, based on the predominant morphologic pattern. The minor histologic types of carcinoma were excluded from the study. From the data-base of th ese 306 patients, 10 patients were excluded because the diagnosis of esophageal cancer had been made predominantly on clinical and radiologic grounds without a (definitive) tissue diagnosis. Some of these patients had been deemed unsuitable for en doscopic biop sy eith er because they had terminal disease or were too much of a risk to undergo the procedure; in others, the biopsies were inconclusive and had not been repeated. Another 16 cases were excluded because the tumors were either anaplastic or did not fit into either of the two main histologic cell types. All in all, this left 280 cases for further study. These cases were comprised of 199 epidermoid carcinomas and 81 adenocarcinomas, and they were analysed for various clinicopathologic features (table I).

3 4 8 2 MOYANA AND JANOSKI TABLE I Comparison of Epidermoid Carcinoma and Adenocarcinoma Epidemoid Carcinoma Patients (%) Adenocarcinoma Patients (%) Total Number 199(68.6) 81 (27.9) Males-Females: Ratio 145:54; 2.69:1 70:11; 6.36:1 Age range: Mean (years) 33-96; ; 70 Major clinical symptoms: Dysphagia 160 (80) 58 (72; Odynophagia 152 (76) 57 (70) Loss of weight 51 (26) 33 (41) Vomiting 24 (12) 12(15) Regurgitation 21 (11) 13 (16) Hematemesis 7(4) 4(5) Anatomic site: Upper third 28(15) 0 Middle third 73 (37) 11 (14) Lower third 95 (48) 70 (86) Staging: Confined to esophagus 72 (36) 33(41) Peri-esophageal spread 59 (30) 9(11) Distant spread and/or to other organs 68 (34) 39 (48) Management: Esophagectomy and chemotherapy 27(14) 11 (14) Radiotherapy and chemotherapy 112(56) 26 (32) Combination of previous 2 21 (10) 6(7) Chemotherapy alone 2(1) 6(7) Simple palliation 37(19) 32 (40) Follow-up period: Range; (months) 0-158(14) 0-72 (9) Outcome: Alive and well 0 0 Alive with disease 11(5) 6(7) Died of disease 159 (80) 70 (87) Died of other causes 28 (14) 4(5) Lost to follow-up 1 (1) 1 (1) Risk factors: Smoking Alcohol 51 7 Barrett's esophagus 1 11 Dysplasia 4 3 Oropharyngeal cancer 5 2 Other Gl cancers 4 1 Esophageal polyps 1 0 Achalasia 2 1 Diverticula 2 0 Post-gastrectomy 4 3

4 Results E p i d e r m o i d C a r c in o m a This group (table I) was comprised of 199 patients with a male-to-female ratio of 3:1. The age range was 33 to 96 years with a mean of 70. The clinical symptomatology was dominated by dysphagia and odynophagia. The most common location of the tumors was the distal third of the esophagus. Staging using clinical, radiologic, and pathologic means revealed that 36 percent of cases were confined to the esophagus while the rest had already spread beyond the esophagus. The major modes of patient management were radiotherapy and/or esophagectomy with or without chemotherapy. Some of the more advanced cancers were managed by simple palliative measures such as the insertion of indwelling esophageal tubes. The mean follow-up was 14 months, and 80 percent of patients had died of disease whereas 14 percent died of other causes. An analysis of the risk factors revealed that a significant history of smoking or alcohol intake were the most common risk factors. A d e n o c a r c in o m a This group (table I) was composed of 81 patients with a male-to-female ratio of 6:1. The age range was 45 to 95 years with a mean of 70. The major clinical symptoms were dysphagia and odynophagia. The majority of tumors were located in the distal third of the esophagus whereas none were in the proximal third. Approximately 60 percent of the tumors had spread beyond the esophagus at the time of diagnosis. The major modalities of treatment were esophagectomy and/or radiotherapy with or without chemotherapy. More advanced cases were similarly simply managed by palliative measures such as insertion of indw elling intra-esophageal tubes. The EPIDEMIOLOGY OF ESOPHAGEAL CANCER mean follow-up was 9 months with 87 percent of the patients dying of disease. The most common risk factors were a significant history of smoking and Barrett s esophagus. Discussion An analysis of our results reveals some interesting features regarding the epidermiology of esophageal carcinoma. Based on these findings, the overall incidence of biopsy-proven esophageal carcinoma was approximately 2.7 per 100,000 persons per annum. This is comparable with the findings from some of the low-risk regions in the U.S.A.1,4 The relatively high proportion of adenocarcinomas in this study is also in accord with the recently described trends in the U.S.A. and western Europe.1,5,6,7,10,11 This is in marked contrast to the high incidence areas (50 to >100 cases per 100,000 population) of the world, such as parts of China, Iran, and South Africa where epidermoid carcinomas constitute more than 90 percent of the esophageal cancers.1,2,3,12,13,14 Furthermore, our results show an apparent increase in the incidence of not only adenocarcinoma but also epidermoid carcinoma (figure 1) although the increase in adenocarcinoma is more prominent. The reasons for this increase are not altogether clear but may be due in part to better diagnostic modalities, such as newer medical imaging techniques and fiberoptic endoscopy as well as the increased utilization of these modalities. However, the differential increase in the number of adenocarcinomas over epidermoid carcinomas suggests that there is more to this than simp ly im p rovem en ts in d ia g n o s tic armamentaria and/or increased use of upper gastroin testin al en d o sco p y. Although the overall population numbers in this province have remained relatively unchanged,18 the composition may have somewhat changed over the years owing

5 4 8 4 MOYANA AND JANOSKI Trends in the incidence of esophageal carcinoma F ig u r e 1. Trends in the incidence of esophageal cancer from 1970 to [open squares and solid lines-epid erm o id carcinoma; dark circles and dashed lines adenocarcinoma]. o> o> G) Year to human migration; but this is difficult to measure. It is possible that this may have partly influenced the cancer trends. For both squamous cell carcinoma and adenocarcinoma, the clinical symptomatology was dominated by dysphagia and odynophagia, as is to be expected for relatively advanced esophageal cancers.2,4 With regard to the topographic site of these tumors, almost 50 percent of the epidermoid carcinomas were located in the distal third, whereas the middle third is generally reported as their commonest location.15 The preponderance of adenocarcinomas in the distal third is in accord with their pathogenetic origin from Barrett s esophageus and dysplasia.16,17,18 The staging of the disease was based on a combination of clinical, radiologic, and pathologic evaluations. In over 60 percent of cases, the cancer had already spread beyond the confines of the esophagus. In the remaining 38 percent, the cancer had spread to involve the muscularis propria. Thus, if esophageal cancer were to be defined along the same lines as gastric carcinoma,19 then all the cases in this study w ould be defined as advanced. The reasons for the late presentation of esophageal cancer patients are well-known2,15 and relate to (1) the high distensibility of the esophageal wall thus making dysphagia and odynophagia late symptoms, (2) the richly arborizing longitudinal and circumferential submucosal lymphatic plexuses that facilitate dissemination of the cancer, and (3) the absence of a serosa around most of the esophagus, thus aiding tumor spread. The late presentation of esophageal cancer patients also limits the treatment options and partly accounts for the dismal prognosis of this cancer.2,4,15 In general, total esophagectomy is the treatment of choice for early disease; however, in the current study, all the cases had spread at least to involve the muscle wall. Not surprisingly, after a mean follow-up period of 13 months, 82 percent of the patients had died of the disease, 11 percent of other causes, while only 6 percent were alive with the disease; no patients were reported to have been cured. The challenge is thus prevention or early detection of the disease. Indeed, much work is presently being devoted to studying dis

6 ease etiology and prevention, but it will take years before the results of these efforts can be fully evaluated.1,2 3, , 15,16,17,18,19,20 For early detection, fiberoptic endoscopy coupled with cytology screening and surveillance protocols for dysplasia are most useful.16,17,18 However, for w ide-scale use, issues of cost-effectiveness factor into these considerations. In this regard, identification of risk factors for the cancer is helpful in narrowing down the population who would most benefit from screening procedures and thus reducing costs. In this cohort, common risk factors for epidermoid carcinoma were a significant past history of smoking and/or drinking, and a past medical history of cancer of the upper aerodigestive tract or gastrointestinal tract. In addition to Barrett s esophagus and dysplasia, the latter risk factors were also important for adenocarcinoma. The fact that Barrett s esophagus was noted to be a precursor lesion in only 11 of the 81 adenocarcinoma patients suggests that, notwithstanding cost considerations, there is much potential for prevention or early detection of this cancer in patients with gastroesophageal reflux disease (GERD) since the pathogenesis of the cancer invokes GERD, Barrett s esophagus, and dysplasia as antecedent stages.5,6,7,16,17,18 Barrett s esophagus is associated with up to a 40-fold risk of developing adenocarcinoma above the general population.1 2,3,16,17,18 Efforts are also being made to determine the magnitude of the risk resulting from the other factors (table I).20 In summary, this is a retrospective study of esophageal cancer involving the northern half of Saskatchewan s population; the study period spanned 22 years. The results show that both epidermoid carcinomas and adenocarcinomas appear to be increasing in incidence, more so the adenocarcinomas. The latter also formed a disproportionately large percentage of EPIDEMIOLOGY OF ESOPHAGEAL CANCER the tumors when compared to the high incidence areas of esophageal carcinoma in the world. For both epidermoid carcinomas and adenocarcinomas, there was a preponderance of distally located tumors. Acknowledgments Thanks are extended to the Saskatchewan Cancer Foundation for its assistance in this project. References 1. Blot WJ. Esophageal cancer trends and risk factors. Semin Oncol 1994;21: Skinner DB, Belsey RH. Esophageal malignancies: incidence, etiology, presentation, and diagnosis. In: Management of esophageal disease. Philadelphia: WB Saunders Co. 1988: Schottenfeld D. Epidemiology of cancer of the esophagus. Semin Oncol 1994;11: Peacock JL, Keller JW, Asbury RF. Alimentary cancer. In: Rubin P, editor. Clinical oncology: a multidisciplinary approach for physicians and students, 7th ed. Philadelphia: WB Saunders Co., 1993: Pera M, Cameron AJ, Trastek VF, Carpenter HA, Zinsmeister AR. Increasing incidence of adenocarcinoma of the esophagus and esophagogastric junction. Gastroenterology 1993; 104: Blot WJ, Devesa SS, Kneller RW, Fraum eni JF Jr. Rising incidence of adenocarcinoma of the esophagus and gastric cardia. JAMA 1991;265: Hesketh PJ, Clapp RW, Doos WG, Spechler SJ. The increasing frequency of adenocarcinoma of the esophagus. Cancer 1989;64: Statistics Canada, demography division, population estimates section: intercensual annual estimates of population for census divisions and census metropolitan areas, Ottawa, Canada. 9. Saskatchewan cancer commission/foundation annual reports, , Regina, Saskatchewan. 10. Powell J, McConkey CC. Increasing incidence of adenocarcinoma of the gastric cardia and adjacent sites. Br J Cancer 1990;62: Oliver SE, Robertson CS, Logan RFA. Oesophageal cancer: A population-based study of survival after treatment. Br J Surg 1992;79: Munoz N, Lipkin M, Crespi M, W ahrendorf J, Grassi A, Shih-Hsien L. Proliferative abnormalities of the oesophageal epithelium of Chinese populations at high and low risk for oesophageal cancer. Int J Cancer 1985;36: Crespi M, Munoz N, Grassi A, Aramesh B, Amiri G, Mojtabai A. Oesophageal lesions in

7 4 8 6 MOYANA AND JANOSKI northern Iran: a premalignant condition? Lancet 1979;2: Mannell A, Murray W. Oesophageal cancer in South Africa. A review of 1926 cases. Cancer 1989;64: Law SYK, Fok M, Cheng SWK, Wong J. A comparison of outcome after resection for squamous cell carcinomas and adenocarcinomas of the esophagus and cardia. Surg Gynecol Obst 1992; 175: Geisinger KR, Teot LA, Richter JE. A comparative cytopathologic and histologic study of atypia, dysplasia and adenocarcinoma in Barrett s esophagus. Cancer 1992;69: Haggitt RC. Barrett s esophagus, dysplasia, and adenocarcinoma. Hum Pathol 1994;25: Hamilton SR, Smith RRL. The relationship betw een columnar epithelial dysplasia and invasive adenocarcinoma arising in Barrett s esophagus. Am J Clin Pathol 1987;87: Klimstra DS. Pathologic prognostic factors in esophageal carcinoma. Semin Oncol 1994;21: Cheng KK. The etiology of esophageal cancer in the Chinese. Semin Oncol 1994;21:411-5.