Abstract
Whilst the benefit of detecting and removing cancer precursors in the cervix and the large bowel is unequivocally documented, the balance between benefit and harm due to screening for early detection of breast and prostate cancer remains uncertain after 30–50 years of randomized control trials (RCTs). Concomitantly, traditional RCTs become increasingly unfeasible due to low compliance, contamination of control groups, difficulties to enroll screening naïve individuals, and prohibitively high costs. Therefore, we have systematically reviewed pros and cons with alternative study designs to quantify screening effectiveness. Whilst traditional RCTs should remain gold standard whenever feasible, observational cohort and case–control studies are unlikely to provide the valid evidence needed for health policy decisions. Instead, we advocate two methodological approaches that are novel in assessment of cancer screening effectiveness. One—the difference-in-difference design, well established in health policy and public health research—has a sophisticated ecologic design which unfortunately is feasible only in few countries. Another implies that sequential RCTs become embedded whenever population-based screening programs are implemented.
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References
Laara E, Day NE, Hakama M. Trends in mortality from cervical cancer in the Nordic countries: association with organised screening programmes. Lancet. 1987;1(8544):1247–9.
Gustafsson L, Ponten J, Zack M, Adami HO. International incidence rates of invasive cervical cancer after introduction of cytological screening. Cancer Causes Control. 1997;8(5):755–63.
Adami HO, Baron JA, Rothman KJ. Ethics of a prostate cancer screening trial. Lancet. 1994;343(8903):958–60.
Bretthauer M, Kaminski MF, Loberg M, et al. Population-based colonoscopy screening for colorectal cancer: a randomized clinical trial. JAMA Intern Med. 2016;176(7):894–902.
Autier P, Boniol M. Mammography screening: a major issue in medicine. Eur J Cancer. 2018;90:34–62.
Andriole GL, Crawford ED, Grubb RL 3rd, et al. Prostate cancer screening in the randomized prostate, lung, colorectal, and ovarian cancer screening trial: mortality results after 13 years of follow-up. J Natl Cancer Inst. 2012;104(2):125–32.
Holme Ø, Kalager M, Bretthauer M, Adami HO, Helsingen L, Løberg M. Ongoing trials will not determine the comparative effectiveness of colorectal cancer screening tests. Gastroenterology. 2020. https://doi.org/10.1053/j.gastro.2020.02.071.
Kalager M, Tamimi RM, Bretthauer M, Adami HO. Prognosis in women with interval breast cancer: population based observational cohort study. BMJ. 2012;345:e7536.
Holmberg LH, Tabar L, Adami HO, Bergstrom R. Survival in breast cancer diagnosed between mammographic screening examinations. Lancet. 1986;8497(2):27–30.
Andrae B, Andersson TM, Lambert PC, et al. Screening and cervical cancer cure: population based cohort study. BMJ. 2012;344:e900.
Jodal H, Løberg M, Holme O, et al. Mortality from post-screening (interval) colorectal cancers is comparable to cancers from unscreened patients: a randomized sigmoidoscopy trial. Gastroenterology. 2018;155(1787–94):e3.
Adami HO, Csermely P, Veres DV, et al. Are rapidly growing cancers more lethal? Eur J Cancer. 2017;72:210–4.
Gustafsson L, Adami HO. Natural history of cervical neoplasia: consistent results obtained by an identification technique. Br J Cancer. 1989;60(1):132–41.
Loberg M, Kalager M, Holme O, Hoff G, Adami HO, Bretthauer M. Long-term colorectal-cancer mortality after adenoma removal. N Engl J Med. 2014;371(9):799–807.
Welch HG, Black WC. Overdiagnosis in cancer. J Natl Cancer Inst. 2010;102(9):605–13.
Adami HO. The prostate cancer pseudo-epidemic. Acta Oncol. 2010;49(3):298–304.
Barratt A. Overdiagnosis in mammography screening: a 45 year journey from shadowy idea to acknowledged reality. BMJ. 2015;350:h867.
Autier P, Boniol M, Koechlin A, Pizot C, Boniol M. Effectiveness of and overdiagnosis from mammography screening in the Netherlands: population based study. BMJ. 2017;359:j5224. https://doi.org/10.1136/bmj.j5224.
Kalager M, Adami HO, Bretthauer M, Tamimi RM. Overdiagnosis of invasive breast cancer due to mammography screening: results from the Norwegian screening program. Ann Intern Med. 2012;156(7):491–9.
Brawley OW. Accepting the existence of breast cancer overdiagnosis. Ann Intern Med. 2017;166(5):364–5.
IARC. Colorectal cancer screening. Handb Cancer Prev. 2019;17:1–300.
Breast cancer screening. Vainio H, Bianchini F, editors. Lyon: IARC Press; 2002.
Phillips N, Coldman A. Comparison of nonbreast cancer incidence, survival and mortality between breast screening program participants and nonparticipants. Int J Cancer. 2008;122(1):197–201.
Cuzick J, Edwards R, Segnan N. Adjusting for non-compliance and contamination in randomized clinical trials. Stat Med. 1997;16(9):1017–29.
Duffy S, Cuzick J, Tabar L, et al. Correcting for non-compliance bias in case–control studies to evaluate cancer screening programmes. J R Stat Soc Ser C Appl Stat. 2008;51:235–43.
Schneeweiss S, Rassen JA, Glynn RJ, Avorn J, Mogun H, Brookhart MA. High-dimensional propensity score adjustment in studies of treatment effects using health care claims data. Epidemiology. 2009;20(4):512–22.
Carter JL, Coletti RJ, Harris RP. Quantifying and monitoring overdiagnosis in cancer screening: a systematic review of methods. BMJ. 2015;350:g7773.
Wing C, Simon K, Bello-Gomez RA. Designing difference in difference studies: best practices for public health policy research. Ann Rev Publ Health. 2018;39:453–69.
Kalager M, Zelen M, Langmark F, Adami HO. Effect of screening mammography on breast-cancer mortality in Norway. N Engl J Med. 2010;363(13):1203–10.
Olsen AH, Lynge E, Njor SH, et al. Breast cancer mortality in Norway after the introduction of mammography screening. Int J Cancer. 2013;132(1):208–14.
Kalager M, Bretthauer M. Improving cancer screening programs. Science. 2020;367(6474):143–4.
Hakama M, Pukkala E, Heikkila M, Kallio M. Effectiveness of the public health policy for breast cancer screening in Finland: population based cohort study. BMJ. 1997;314(7084):864–7.
Pitkaniemi J, Seppa K, Hakama M, et al. Effectiveness of screening for colorectal cancer with a faecal occult-blood test, in Finland. BMJ Open Gastroenterol. 2015;2(1):e000034.
Cancer Registry of Norway. HPV i primærscreening. Available at: www.kreftregisteret.no/en/screening/Cervical-Cancer-Screening-Programme/Helsepersonell/screeningstrategi-og-nasjonale-retningslinjer/hpv-i-primarscreening/.
Kaminski MF, Kraszewska E, Rupinski M, Laskowska M, Wieszczy P, Regula J. Design of the polish colonoscopy screening program: a randomized health services study. Endoscopy. 2015;47(12):1144–50.
Ioannidis JP. Why most published research findings are false. PLoS Med. 2005;2(8):e124.
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Adami, HO., Bretthauer, M. & Kalager, M. Assessment of cancer screening effectiveness in the era of screening programs. Eur J Epidemiol 35, 891–897 (2020). https://doi.org/10.1007/s10654-020-00684-7
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DOI: https://doi.org/10.1007/s10654-020-00684-7