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.
There are two chief reasons why cancer screening might reduce disease specific mortality without significantly reducing overall mortality. Firstly, studies may be underpowered to detect a small overall mortality benefit. Secondly, disease specific mortality reductions may be offset by deaths due to the downstream effects of screening.
Underpowered studies lead to uncertainty and assumptions of benefit rather than scientific evidence of benefit. In the 30 year follow-up of the Minnesota Colon Cancer Control Study, which assessed annual fecal occult blood testing, there were 128 deaths from colon cancer per 10 000 participants in the screened group and 192 per 10 000 in the control arm—a statistically significant difference of 64 deaths per 10 000. But there was a difference of only two overall deaths between the screened arm (7111 deaths per 10 000) and the control arm (7109 deaths per 10 000; P=0.97). Hazard ratios and Kaplan Meier curves corroborate this finding of no mortality difference. For 80% power to detect a difference in overall mortality of 64 deaths per 10 000 (assuming the disease specific benefit was not offset by other deaths), the trial would have needed to be about five times as large.
However, meta-analyses of fecal occult blood testing have shown a slight increase in deaths unrelated to colorectal cancer associated with screening, which implies that downstream effects of screening may partially or wholly negate any disease specific gains.
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 diagnosis 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.
Key Players In This New Effort Include:
*Nobody is going to cure cancer in a year," Brawley [American Cancer Society's chief medical officer Dr. Otis Brawley] said. "I don't think anybody going to cure cancer in a decade.*
The promise: cure. The reality: more funding for extraordinary profit-generators.