Lung Cancer Mortality in the Mayo Lung Project: Impact of Extended Follow-up

Marcus, Pamela M.; Bergstralh, Erik J.; Fagerstrom, Richard M.; Williams, David E.; Fontana, Robert S.; Taylor, William F.; Prorok, Philip C.

doi:10.1093/jnci/92.16.1308

Cited by 479 publications

(288 citation statements)

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“…The current analysis did not change anyone's cause of death; hence, another mortality analysis would add nothing to what was reported recently by Marcus et al 6 Redoing the survival analysis (excluding the questionable diagnoses) would be problematic, because not all incidents were reviewed. Furthermore, survival analysis is an inappropriate outcome of a screening trial, because it is subject to lead-time bias.…”

Section: Discussionmentioning

confidence: 82%

“…Overdiagnosis is a term that pathologists may take issue with, but it is a term used by Marcus et al 6 that has become prominent in the literature to explain the discrepancy between survival benefit in the absence of mortality benefit. For the most part, the original diagnoses were confirmed on this subset of patients, which included 105 of the original 366 patients.…”

Section: Discussionmentioning

confidence: 99%

“…5 Recently, Marcus and colleagues performed an extended mortality follow-up of the Mayo Lung Project participants, resulting in a median follow-up of 20 years. 6 For patients who were diagnosed with lung carcinoma before July 1983 (the date the randomized trial closed), survival still was better in the screened group compared with the control group (P ϭ 0.0039) even after 20 years of follow-up. However, lung carcinoma mortality was similar (4.4 per 1000 person years in the screened arm vs. 3.9 per 1000 person years in the control arm; P ϭ 0.09).…”

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confidence: 99%

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Pathologic review of the Mayo Lung Project

Colby

Tazelaar

Travis

et al. 2002

Cancer

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BACKGROUNDIn the Mayo Lung Project Screening Trial, there were more carcinomas identified in the screened group compared with the control group. The screened group had better survival, but there was no difference in lung carcinoma mortality between the screened group and the control group. The purpose of this study was to review all available original pathology from the trial to determine whether overdiagnosis (carcinomas that do not result in the death of the patient) or misdiagnosis of lung carcinoma may explain this discrepancy.METHODSAll available lung pathology slides from patients who underwent surgery at the Mayo Clinic were reviewed independently by three blinded lung pathologists. Tumors were classified according to the 1999 World Health Organization criteria. In addition, agreement among the pathologists was assessed.RESULTSAmong 106 patients who underwent surgery at the Mayo Clinic, slides were available for review from 105 patients, including 77 slides from the screened group and 28 slides from the control group. The original diagnosis of carcinoma was confirmed in all patients. In 7 patients (6.7%), there was unanimous agreement that the lesion was preinvasive (carcinoma in situ), and these lesions all were from the screened group. In 90 patients (85.5%), there was unanimous agreement that the tumors were invasive. In 8 patients (7.8%), there was some disagreement between the observers about whether lesions were invasive or preinvasive; 7 of these 8 lesions were from the screened group. The level of agreement among pathologists for invasive carcinomas was > 94% for all comparisons, and the κ statistic ranged from 0.67 (substantial agreement) to 0.84 (almost perfect agreement). There was good agreement among the pathologists about tumor cell type with the κ statistic ≥ 0.65.CONCLUSIONSThe histologic diagnosis of carcinoma was confirmed for all 105 slides that were reviewed. The results of this study indicate that misdiagnosis does not explain the increased numbers of carcinomas identified in the screened group. The increased numbers of in situ carcinomas in the screened group resulted in increased numbers of squamous carcinomas in the screened group compared with the control group and may have contributed to the better survival. It is possible that carcinoma in situ accounted for some instances of overdiagnosis. Cancer 2002;95:2361–5. © 2002 American Cancer Society.DOI 10.1002/cncr.10930

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Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Pathologic review of the Mayo Lung Project

Colby

Tazelaar

Travis

et al. 2002

Cancer

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“…Nevertheless, within the category of male smokers these findings are largely representative of the community at large, since, with the exception of the prevalence screen, a sizable majority of subjects (approximately 75 percent) received their medical care outside of the Mayo Clinic (and largely outside of Minnesota, mostly in other Midwestern U. S. states). Though specific data documenting the states in which deaths occurred during active study follow-up were not available to us, additional National Death Index data collected as part of an analysis examining lung cancer mortality after active follow-up ended (in the years 1983 through 1996) [23] showed that over three quarters of deaths in study subjects occurring after 1983 took place outside Minnesota (E. Bergstralh, personal communication). Second, for a number of deaths no information was available to the mortality review committee other than the death certificate.…”

Section: Discussionmentioning

confidence: 99%

Death certificates provide an adequate source of cause of death information when evaluating lung cancer mortality: An example from the Mayo Lung Project

Doria-Rose

2009

Lung Cancer

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SummaryTo assess the accuracy of death certificates in assigning lung cancer as the underlying cause of death, death certificate data were compared to mortality review committee-determined causes of death among participants in the Mayo Lung Project. Further, the impact of death certificate misclassification on lung cancer mortality rates and Cox proportional hazards models was evaluated. The Mayo Lung Project (1971)(1972)(1973)(1974)(1975)(1976)(1977)(1978)(1979)(1980)(1981)(1982)(1983)) was a randomized, controlled trial of lung cancer screening; participants were male smokers aged 45 years and older who were seen as outpatients at the Mayo Clinic in Rochester, Minnesota. Overall there were 237 lung cancer deaths according to mortality review, and 224 according to the death certificate (sensitivity 88.6 percent, 95 percent confidence interval (CI): 83.9, 92.4; specificity 99.1 percent, 95 percent CI 98.6, 99.5). As compared to the mortality review committee's determination, the use of death certificate data resulted only in slight decreases to the calculated lung cancer mortality rates for each screening arm, and did not result in appreciable changes to hazard ratios for lung cancer mortality in Cox regression models. In these data, death certificates were sufficiently sensitive and specific such that their use did not result in a meaningful change to mortality-based outcomes.

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“…Early detection of disease that ultimately would not present clinically in some persons is a plausible harm of cancer screening, because it would lead to treatment, often invasive, of no clinical benefit. 1 To date, evidence suggests that "overdiagnosis" of this type is present in screening for prostate carcinoma, 2 breast carcinoma, 3 and lung carcinoma 4 and for neuroblastoma. 5 The advent of computed tomography (CT) screening raises the question of whether overdiagnosis may be clinically important for other solid organ malignancies.…”

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confidence: 99%

Screening computed tomography

Fenton

Weiss

2004

Cancer

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BACKGROUNDDespite uncertain benefits and harms, screening computed tomography (CT) is being marketed to consumers in the U.S. One plausible harm is the detection and treatment of renal carcinoma cases that otherwise would have remained clinically silent during the patient's lifetime.METHODSAfter estimating the prevalence of preclinical renal carcinoma using meta‐analysis of five series of asymptomatic, middle‐aged Americans who received CT screening, the authors divided the prevalence by U.S. incidence rates of clinical renal carcinoma among persons of similar age. This calculation would estimate the mean duration of the detectable preclinical period (the “sojourn time”) of renal carcinoma if the incidence of preclinical and clinical renal carcinoma were equivalent.RESULTSThe 5 series included 16,174 screenees (mean age range, 58–64 years; 61% male). The prevalence of asymptomatic renal carcinoma ranged from 0.11% to 0.76%; the pooled prevalence was 0.21% (95% confidence interval, 0.14–0.28%). The estimated mean sojourn time for renal carcinoma was between 3.7 years and 5.8 years among middle‐aged Americans.CONCLUSIONSBecause most renal carcinomas grow slowly during the preclinical period, the authors' estimated mean sojourn time did not seem unduly long. Therefore, the incidence rate of clinical renal carcinoma most likely is a reasonable surrogate for the incidence rate of preclinical renal carcinoma, implying that most renal carcinomas detected by CT screening among middle‐aged Americans are likely to progress to clinical diagnosis. Cancer 2004;100:986–90. © 2004 American Cancer Society.

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Lung Cancer Mortality in the Mayo Lung Project: Impact of Extended Follow-up

Cited by 479 publications

References 16 publications

Pathologic review of the Mayo Lung Project

Pathologic review of the Mayo Lung Project

Death certificates provide an adequate source of cause of death information when evaluating lung cancer mortality: An example from the Mayo Lung Project

Screening computed tomography

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