Correspondence to: Patrick S. Romano, M.D., Ph.D., Department of Medicine and Pediatrics, University of California at Davis Medical Center, 4150 V St., Suite 2400, Sacramento, CA 95817 (e-mail: psromano{at}ucdavis.edu).
Newschaffer et al. (1) reported recently on a population-based analysis of causes of death among elderly Virginians with prostate cancer and benign prostatic hypertrophy (BPH). Radical prostatectomy was associated with statistically nonsignificantly lower odds of having prostate cancer as the reported cause of death (odds ratio [OR] = 0.77; 95% confidence interval [CI] = 0.42 to 1.40) among 1179 decedents with a history of prostate cancer, but statistically nonsignificantly higher odds of dying of other cancers (OR = 1.47; 95% CI = 0.85 to 2.56), relative to men with a history of BPH (excluding men whose deaths were attributed to prostate cancer). These surprising findings have important implications because of the unexplained 2.8% annual increase in prostate cancer mortality between 1987 and 1991 and the subsequent 1.2% (1991 to 1994) to 4.4% (1994 to 1997) annual decrease (2). Could the dramatic changes in radical prostatectomy utilization, from 10% of eligible patients in 1983 to 37% in 1992 and 35% in 1995 (3), partially account for the apparent increase in mortality until 1991 or the subsequent "premature" decline (4) (based on an estimated lead time of 57 years) (5)? Yes, if radical prostatectomy independently affects the likelihood that the death of a man with prostate cancer will be attributed to that cancer.
This hypothesis is not inconsistent with the data of Newschaffer et al., because the authors severely restricted their study sample by requiring that a prostate cancer case appear in both the Virginia Cancer Registry and the Medicare inpatient claims dataset. Any case of prostate cancer that was not diagnosed or initially treated as an inpatient was ineligible for inclusion. Indeed, even cases diagnosed as inpatients were ineligible if the diagnosis was established after discharge (e.g., by pathologic examination of transurethral prostatectomy fragments) and the discharge abstract was not amended when this information became available. The limited number of diagnosis fields available on Medicare Part A claims from 1987 to 1989 probably also had an adverse impact on case ascertainment. Cooper et al. (6) recently reported that prostate cancer was the least likely of six major cancer sites to be captured in Medicare inpatient data. Only 63% of Surveillance, Epidemiology, and End Results (SEER)1identified prostate cancer cases had a Medicare inpatient diagnosis of prostate cancer; linking Part B claims boosted this percentage to 88%. The sensitivity of inpatient claims data for prostate cancer has steadily decreased, from 84% in 1984 to 46% in 1993.
The loss of 37% of all prostate cancer cases in the source population could have introduced substantial selection bias into the analyses of Newschaffer et al. Their own prior work shows that very few of these "lost" cases received aggressive treatment (and probably none had radical prostatectomy) (7). These lost deaths were probably less likely to be attributed to prostate cancer than the deaths of men with a cancer-related hospitalization. If we assume that all prostate cancer patients initially treated with radical prostatectomy were retained in the sample of Newschaffer et al., then the magnitude of selection bias can be estimated by SB0/SA0, where SB0 is the probability of selection among conservatively managed patients whose deaths were later attributed to other causes and SA0 is the probability of selection among conservatively managed patients whose deaths were later attributed to prostate cancer. A plausible selection ratio of 0.5 would lead to a corrected adjusted odds ratio of 1.54 for surgery in Table 2 (1). In other words, the adjusted odds of prostate cancer as the underlying cause of death could be similar to the adjusted odds that Newschaffer et al. describe for other cancer causes of death. Such a labeling effect could partially explain the temporal concurrence between increased prostate cancer mortality before 1991 and increased utilization of radical prostatectomy. It might also explain the puzzling association between surgical treatment of prostate cancer and death due to other cancers (if some prostate cancer deaths were misattributed to other cancers).
NOTES
1 SEER is a set of geographically defined, population-based, central cancer registries in the United States, operated by local nonprofit organizations under contract to the National Cancer Institute (NCI). Registry data are submitted electronically without personal identifiers to the NCI on a biannual basis, and the NCI makes the data available to the public for scientific research.
REFERENCES
1
Newschaffer CJ, Otani K, McDonald MK, Penberthy LT. Causes of death in elderly prostate cancer patients and in a comparison nonprostate cancer cohort. J Natl Cancer Inst 2000;92:61321.
2 Ries LA, Wingo PA, Miller DS, Howe HL, Weir HK, Rosenberg HM, et al. The annual report to the nation of the status of cancer, 19831997, with a special section on colorectal cancer. Cancer 2000;88:2398424.[Medline]
3 Stanford JL, Stephenson RA, Coyle LM, Cerhan J, Correa R, Eley JW, et al. Prostate cancer trends 19731995, SEER Program, National Cancer Institute. NIH Publ. No. 994543. Bethesda (MD); 1999.
4
Etzioni R, Legler JM, Feuer EJ, Merrill RM, Cronin KA, Hankey BF. Cancer surveillance series: interpreting trends in prostate cancerpart III: quantifying the link between population-specific prostate-specific antigen testing and recent declines in prostate cancer mortality. J Natl Cancer Inst 1999;91:10339.
5 Hugosson J, Aus G, Becker C, Carlsson S, Eriksson H, Lilja H, et al. Would prostate cancer detected by screening with prostate-specific antigen develop into clinical cancer if left undiagnosed? A comparison of two population-based studies in Sweden. BJU Int 2000;85:107884.[Medline]
6 Cooper GS, Yuan Z, Stange KC, Dennis LK, Amini SB, Rimm AA. The sensitivity of Medicare claims data for case ascertainment of six common cancers. Med Care 1999;37:43644.[Medline]
7 McClish DK, Penberthy L, Whittemore M, Newschaffer C, Woolard D, Desch CE, et al. Ability of Medicare claims data and cancer registries to identify cancer cases and treatment. Am J Epidemiol 1997;145:22733.[Abstract]
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