Screening recommendations should be based off all-cause mortality
The claim that cancer screening saves lives is based on fewer deaths due to the target cancer. Vinay Prasad and colleagues argue that reductions in overall mortality should be the benchmark and call for higher standards of evidence for cancer screening Despite growing appreciation of the harms...
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"Using disease specific mortality as a proxy for overall mortality deprives people of information about their chief concern:
reducing their risk of dying. Although some people may have personal reasons for wanting to avoid a specific diagnosis, the burden falls on providers to provide clear information about both
disease specific and overall mortality and to ensure that the overall goal of healthcare—to improve quantity and quality of life—is not undermined.
Discrepancies between disease specific and overall mortality were found in direction or magnitude in seven of 12 randomised trials of cancer screening.
Despite reductions in disease specific mortality in the majority of studies, overall mortality was unchanged or increased. In cases where both mortality rates were reduced the improvement was larger in overall mortality than in disease specific mortality. This suggests an imbalance in non-disease specific deaths, which warrants examination and explanation. A systematic review of meta-analyses of cancer screening trials found that three of 10 (33%) showed reductions in disease specific mortality and that none showed reductions in overall mortality.
Such “off-target deaths” are particularly likely among screening tests associated with
false positive results, overdiagnosis of non-harmful cancers, and detection of incidental findings. For example, prostate specific antigen (PSA) testing yields numerous false positive results, which contribute to over one million prostate biopsies a year. Prostate biopsies are associated with
serious harms, including admission to hospital and death. Moreover, men diagnosed with prostate cancer are more likely to
have a heart attack or commit suicide in the year after diagnosis14 or to die of complications of treatment for cancers that may never have caused symptoms.
The overall effect of cancer screening on mortality is more complex than a disease specific endpoint can capture, owing to the harms of further testing, overdiagnosis, and overtreatment. Realisation of this has led to reversal or abandonment of a number of screening campaigns, including chest radiography screening for lung cancer, urine testing for neuroblastoma, and PSA for prostate cancer. Screening for lung cancer and neuroblastoma increased diagnoses and harms
without decreasing disease specific mortality. PSA screening increased harms
without changing overall mortality; disease specific mortality remains debated."