CORRESPONDENCE

Re: The Role of Overdiagnosis and Reclassification in the Marked Increase of Esophageal Adenocarcinoma Incidence

David Forman

Affiliation of author: Centre for Epidemiology and Biostatistics, University of Leeds, Arthington House, Cookridge Hospital, Hospital Lane, Leeds, UK

Correspondence to: David Forman, PhD, Professor of Cancer Epidemiology, University of Leeds, Centre for Epidemiology and Biostatistics, Arthington House, Cookridge Hospital, Hospital Lane, Leeds, LS16 6QB, UK (e-mail: d.forman{at}leeds.ac.uk).

Pohl and Welch consider whether the reported dramatic increase in esophageal adenocarcinoma represents a real increase in disease burden or whether it can be explained by artifacts introduced by classification problems and/or increased diagnostic intensity (1). Based on an analysis of the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) database, they conclude that the observed increase not only represents a true increase in disease but also that the rate of increase makes this cancer "the fastest rising malignancy in the United States." They show an approximate sixfold increase in incidence between 1973–1975 and 1999–2001, a rate substantially higher than that for other cancers known to be increasing in incidence (e.g., two- to threefold increases for melanoma and prostate cancer).

The authors dismiss reclassification of gastric cardia adenocarcinoma as an artifactual explanation for the increase in esophageal adenocarcinoma because incidence of the former is also increasing over time and, they argue, if the reclassification were to explain the increase in esophageal adenocarcinoma, cardia adenocarcinoma incidence should decrease. This is true if the entirety of the increase were to occur through reclassification, but changes over time in the approach to cardia adenocarcinoma classification could profoundly affect the magnitude of the increase in cancers in this region of the body. The esophagus and cardia are anatomically juxtaposed, and their respective tumors cannot be distinguished by microscopic pathology. It can be difficult, and sometimes impossible, to assign many tumors unambiguously to the stomach or the esophagus. After the growth in interest in esophageal adenocarcinoma, it is also likely that a potential bias is operating, such that, given uncertainty, surgeons and gastroenterologists may have become increasingly more prone to assign tumors at the gastroesophageal junction to the esophagus.

When making comparisons over time using routinely acquired data, it is prudent to combine results for adenocarcinoma at both the gastric cardia and the esophagus. By combining, the sixfold increase reported by Pohl and Welch between 1975 and 2001 reduces to less than threefold.

Pohl and Welch also fail to take into account overall trends in gastric cancer incidence, especially those for which subsite information is unavailable. Fig. 1 shows, using the same SEER data (2) and the same time period considered by Pohl and Welch, trends in gastric adenocarcinoma incidence separately for the cardia, other specified subsites, and unspecified for subsite. The most substantial change over time has been in unspecified gastric cancer, which has fallen from 3 to 1 case(s) per million people between 1975 and 2001. In 1975–1977, 42% of gastric cancers were unspecified for subsite compared with 27% in 1999–2001. This decline confirms a clinical view that in the 1970s and 1980s there was little interest in subsite classification and that gastric cancer was largely thought of as a single entity. Again, a growing interest in gastric cardia adenocarcinoma in the 1990s is likely to have led to an increase in subsite classification.



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Fig. 1. Stomach cancer incidence (age-adjusted to world standard population) by year of diagnosis and subsite, Surveillance, Epidemiology, and End Results. (SEER) 9 areas, male and female, 1975–2001. The SEER 9 areas include all new malignancies diagnosed within the states of Connecticut, Hawaii, Iowa, New Mexico, and Utah, and the cities of Atlanta, Detroit, San Francisco, and Seattle and represents approximately 10% of the U.S. population. Cancers of the cardia (diamonds), non-cardia specified cancers (squares), and overlapping/not otherwise specified cancers (triangles) are shown.

 
It is unclear what proportion of subsite unspecified gastric cancer may have been localized to the cardia region, but, if the proportion were the same as that for subsite-specified cancers, then the rate of cardia adenocarcinoma would increase only marginally between 1975 and 2001 (from 18 to 19 cases per million people). An estimate of the combined rate for both esophageal and cardia adenocarcinoma, corrected for unspecified cancer, would then be approximately 22 cases per million people in 1975 and 42 per million in 2001, a less than twofold increase. This increase is important but not nearly as dramatic as the results presented by Pohl and Welch.

REFERENCES

(1) Pohl H, Welch HG. The role of overdiagnosis and reclassification in the marked increase of esophageal adenocarcinoma incidence. J Natl Cancer Inst 2005;97:142–46.[Abstract/Free Full Text]

(2) Surveillance, Epidemiology, and End Results (SEER) Program. SEER*Stat Database: incidence—SEER 9 Regs Public-Use, November 2003 Sub (1973–2001), National Cancer Institute, DCCPS, Surveillance Research Program, Cancer Statistics Branch, released April 2004, based on the November 2003 submission. Available at http://www.seer.cancer.gov. [Communication from L. Ries.]



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