Appendix B. Selected Screening Services and USPSTF Recommendations
Appendix A. Search terms
Psychological Harms / Search terms (Medline)Prostate Cancer / Prostate cancer*[tw] OR prostatic cancer*[tw] OR Prostatic Neoplasms[Mesh] OR prostate specific antigen[tw] OR PSA[tw]) AND (screening*[tw] OR early diagnosis[tw] OR early detection[tw] OR biops*[tw] OR surveillance[tw] OR watchful waiting[tw]) AND (depress*[tw] OR distress[tw] OR stress*[tw] OR worry[tw] OR fear*[tw] OR anxiet*[tw] OR quality of life[tw] OR mental health[tw] OR mental disorders[tw] OR psycholog*[tw] OR psychosocial[tw] OR well being[tw] OR uncertainty[tw] OR emotion*[tw] OR false positive*[tw] OR harm*[tw] OR adverse effect*[tw] OR complication*[tw])
Lung Cancer / (Lung cancer*[tw] OR Lung Neoplasms[Mesh]) AND (screening*[tw] OR early diagnosis[tw] OR early detection[tw] OR biops*[tw] OR surveillance[tw] OR watchful waiting[tw]) AND (depress*[tw] OR distress[tw] OR stress*[tw] OR worry[tw] OR fear*[tw] OR anxiet*[tw] OR quality of life[tw] OR mental health[tw] OR mental disorders[tw] OR psycholog*[tw] OR psychosocial[tw] OR wellbeing[tw] OR well-being[tw] OR uncertainty[tw] OR emotion*[tw] OR false positive*[tw] OR harm*[tw] OR adverse effect*[tw] OR complication*[tw])
Abdominal Aortic Aneurysm / (Abdominal aortic aneurysm[tw] OR Aortic Aneurysm, Abdominal[Mesh]) AND (screening*[tw] OR early diagnosis[tw] OR early detection[tw] OR biops*[tw] OR surveillance[tw] OR watchful waiting[tw]) AND (depress*[tw] OR distress[tw] OR stress*[tw] OR worry[tw] OR fear*[tw] OR anxiet*[tw] OR quality of life[tw] OR mental health[tw] OR mental disorders[tw] OR psycholog*[tw] OR psychosocial[tw] OR well being[tw] OR uncertainty[tw] OR false positive*[tw] OR emotion*[tw] OR harm*[tw] OR adverse effect*[tw] OR complication*[tw])
Osteoporosis / ((osteoporosis[tw] OR osteopenia[tw] OR bone density[tw] OR bone mineral density[tw]) AND (screen*[tw] OR early diagnosis[tw] OR early detection[tw] OR densitometry[tw]OR absorptiometry[tw] OR DEXA[tw] OR DXA[tw]) AND (depress*[tw] OR stress*[tw] OR distress [tw] OR worry[tw] OR fear*[tw] OR anxiet*[tw] OR quality of life[tw] OR mental health[tw] OR mental disorders[tw] OR psycholog*[tw] OR well being[tw] OR psychosocial[tw] OR uncertainty[tw] OR emotion*[tw])) NOT (animals NOT humans)
Carotid Artery Stenosis / (Carotid artery stenos*[tw] OR carotid stenos*[tw] OR Carotid Stenosis[Mesh]) AND (screening*[tw] OR early diagnosis[tw] OR early detection[tw] OR biops*[tw] OR surveillance[tw] OR watchful waiting[tw]) AND (depress*[tw] OR distress[tw] OR stress*[tw] OR worry[tw] OR fear*[tw] OR anxiet*[tw] OR quality of life[tw] OR mental health[tw] OR mental disorders[tw] OR psycholog*[tw] OR psychosocial[tw] OR well being[tw] OR uncertainty[tw] OR false positive*[tw] OR emotion*[tw] OR harm*[tw] OR adverse effect*[tw] OR complication*[tw])
Overdiagnosis / Search terms (Medline)
Prostate Cancer / (“Prostatic neoplasms”[Mesh] OR “prostate cancer”[tw])
AND (screening[tw] OR mass screening[Mesh] OR early diagnosis[tw] OR prostate specific antigen[tw]) OR PSA [tw]
AND (overdiagnos*[tw] OR over-diagnos*[tw] OR overdetect*[tw] OR over-detect*[tw])
Lung Cancer / (Lung cancer*[tw] OR Lung Neoplasms[Mesh]) AND (screening[tw] OR mass screening[Mesh] OR early diagnosis[tw] OR prostate specific antigen[tw] OR PSA [tw] OR biops*[tw]) AND (overdiagnos*[tw] OR over diagnos*[tw] OR overdetect*[tw] OR over detect*[tw] OR insignifican*[tw]) AND (rate[tw] OR frequency[tw] OR incidence[tw] OR prevalence[tw] OR epidemiology[subheading])
Abdominal Aortic Aneurysm / (Abdominal aortic aneurysm[tw] OR Aortic Aneurysm, Abdominal[Mesh]) AND (screening[tw] OR mass screening[Mesh] OR early diagnosis[tw] OR biops*[tw]) AND (overdiagnos*[tw] OR over diagnos*[tw] OR overdetect*[tw] OR over detect*[tw] OR insignifican*[tw]) AND (rate[tw] OR frequency[tw] OR incidence[tw] OR prevalence[tw] OR epidemiology[subheading])
Osteoporosis / (osteoporosis [MeSH] OR osteoporosis[tw] OR osteopenia[tw]) AND (overdiagnos*[tw] OR over diagnos*[tw] OR overdetect*[tw] OR over detect*[tw] OR diagnostic errors[mesh] OR misdiagnos*[tw] OR misinterpret*[tw]) AND (rate[tw] OR frequency[tw] OR incidence[tw] OR prevalence[tw] OR epidemiology[subheading])
Carotid Artery Stenosis / (Carotid artery stenos*[tw] OR carotid stenos*[tw] OR Carotid Stenosis[Mesh]) AND (screening[tw] OR mass screening[Mesh] OR early diagnosis[tw] OR biops*[tw]) AND (overdiagnos*[tw] OR over diagnos*[tw] OR overdetect*[tw] OR over detect*[tw] OR insignifican*[tw]) AND (rate[tw] OR frequency[tw] OR incidence[tw] OR prevalence[tw] OR epidemiology[subheading])
Appendix B. Selected screening services and USPSTF recommendations
Screening Service (Year of Most Recent USPSTF Review) / USPSTF RecommendationsProstate Cancer (2011) / D: Recommends against PSA-based screening for prostate cancer.
Lung Cancer (2013) / B: Recommends annual screening for lung cancer with low-dose computed tomography (LDCT) in persons at high risk for lung cancer based on age and smoking history.
Abdominal Aortic Aneurysm (2014) / B: Recommends one-time screening for abdominal aortic aneurysm (AAA) by ultrasonography in men aged 65 to 75 who have ever smoked. C: No recommendation for or against screening in men aged 65-75 who have never smoked. D: Recommends against screening in women
Osteoporosis (2010) / B: Recommends screening for osteoporosis in women aged 65 years or older and in younger women whose fracture risk is equal to or greater than that of a 65-year-old white woman who has no additional risk factors.I: Insufficient evidence to assess screening in men.
Carotid Artery Stenosis (2014)* / D: Recommends against screening for carotid artery stenosis in the general adult population.
*Draft evidence report
Appendix C. Study characteristics for 5 screening servicesPsychological Harms of Prostate Cancer Screening
Source / Subjects / Study Type / Outcomes of Interest (Instrument or Data Source) / Comparisona (Time Points) / Frequency/Burdenb
Screening Test/Workup
Archer and Hayter, 20061 / 7 men aged 50-69 years, from a general practice / Qualitative / Men’s reactions to an equivocal PSA result (Interviews) / None / Burden
Bratt et al., 20032 / 57 men aged 40-73 years, from families with history of PrCa / Longitudinal / Anxiety, depression, & cancer-related distress (HADS; IES) / Change over time (day of screening; 4-6 weeks later) / Both
Brindle et al., 20063 / 569 men aged 50–69 years, recruited for ProtecT / Longitudinal / Anxiety, depression, and HRQoL (HADS; SF-36) / Change over time (before screening and before biopsy) / Both
Carlsson et al., 20074 / 1,781 men aged ≥50 years, enrolled in ERSPC / Longitudinal / Anxiety (items on study-specific questionnaire) / Change over time (before PSA results; awaiting biopsy) / Both
Chapple et al., 20075 / 50 men aged 52-75 years, recruited from urologists, general practitioners & support groups / Qualitative / Men’s experiences before, during, & after biopsy (Interviews) / None / Burden
Cormier et al., 20026 / 220 brothers or sons of men with PrCa / Longitudinal / HRQoL; anxiety (SF-36; STAI) / Change over time (before PSA test; before results; after normal result) / Both
Evans et al., 20077 / 28 men aged 40-75 years, from 6 Welsh general practices / Qualitative / Men’s responses to screening process (Interviews) / None / Burden
Macefield et al., 2010c8 / 330 men aged 50-69 years, participating in ProtecT / Longitudinal / Distress (POMS-SF; IES) / Change over time (PSA screening; during clinic visit for biopsy; after receiving normal biopsy result; 12 weeks after negative result) / Both
Macefield et al., 20099 / 4,198 men aged 50–69 years, recruited for ProtecT / Longitudinal / Anxiety (HADS) / Change over time (PSA test; time of biopsy) / Burden
Medd et al., 200510 / 31 men, aged 47-91 years, referred to biopsy clinic / Cross-sectional/ qualitative / Men’s experiences before, during, & after biopsy (Study-specific questionnaire and interviews) / None / Both
Oliffe, 2004d 11 / 14 men aged 46-74 years, recruited from support groups or advertising / Qualitative / Experiences of testing, work-up and diagnosis (Interviews) / None / Burden
Taylor et al., 200212 / 136 men, mean age 58.5 years, registered for free screening at 2 hospital-based sites / Longitudinal / Avoidant or intrusive cancer-related thoughts (IES; MHI-5) / Change over time (before screening; 1 week after normal result) / Both
False-Positive Results
Fowler et al., 200613 / 285 men, mean age 61 years, from 3 hospital primary practices / Longitudinal / PrCA-related thoughts and worry (Study-specific questionnaire) / Change over time (6 weeks, 6 months, and 1 year after normal PSA test or normal biopsy) / Both
Ishihara et al., 2006c14 / 141 men aged ≥50 years, enrolled from hospital outpatient list / Longitudinal / HRQoL (SF-36) / Age- and gender-adjusted SF-36 Japanese national norms, plus
change over time within subjects
(before biopsy; after results) / Burden
Katz et al., 200715 / 210 men, aged 52-70 years, from university hospitals and primary care practices / Cross-sectional / Anxiety; HRQoL; PrCa-related worry and perceived susceptibility (SF-36; SAI-6; study-specific items) / Primary care patients with PSA
findings in the reference range / Burden
McGovern et al., 200416 / 16 men, aged 55-74 years, enrolled in the PLCO / Qualitative / Responses to a false-positive screening test (Focus groups) / None / Burden
McNaughton-Collins et al., 200417 / 400 men, mean age 60 years, from 3 hospital primary care practices / Cross-sectional / PrCA-related thoughts and worry (Study-specific questionnaire) / Primary care patients with PSA
findings in the reference range / Both
Perczek et al., 2002c 18 / 101 men, mean age 66.7 years, at VA Medical Centers / Longitudinal / Distress (POMS) / Change over time (before & after biopsy) / Burden
Diagnosis (Labeling)
Arredondo et al., 200419 / 383 men, largely >55 years old, enrolled in CaPSURE / Longitudinal / HRQoL during WW (RAND SF-36) / Change over time (6-months intervals, up to 5 years after diagnosis) / Burden
Bailey et al., 200720 / 10 men, aged 64-88 years, attending urology clinic at a tertiary care medical center / Qualitative / Uncertainty during WW (Interviews) / None / Burden
Batista-Miranda et al., 200321 / 60 men awaiting treatment & 21 controls; aged 49-74 years / Cross-sectional / PrCA-specific QoL (FACT-P validation study) / Age-matched controls attending urology clinic but w/o PrCa dx / Burden
Bill-Axelson et al., 201122 / 72,613 men with PrCa (mean age at study entry 71.1 years) and 217,839 age-matched men without PrCa / Longitudinal / Psychiatric hospitalization; outpatient visits; use of antidepressant medication (Swedish registry data) / Age-matched population controls / Frequency
Bill-Axelson et al., 201023 / 128 suicides among 77,439 men with PrCa / Longitudinal / Suicide (Swedish registry data) / Age-standardized suicide rate in the general population / Frequency
Bisson et al., 200224 / 88 men aged 48-78 years, attending a joint urology/oncology clinic / Cross-sectional / Depression; anxiety; distress; QoL (GHQ30; HADS; IES; EORTC-QOL-30) / Scores were compared to published criteria for “caseness” / Frequency
Burnet et al., 200725 / 100 men (mean age 67.1 years) from outpatient clinics / Cross-sectional / Anxiety & depression during AS (HADS) / Normative HADS data from a large non-clinical sample / Both
Daubenmeier et al., 200626 / 93 men (mean age intervention group 64.8 years, controls 66.5 years) enrolled in RCT on effects of lifestyle changes on PrCa progression / Longitudinal / HRQoL during AS (SF-36; Perceived Stress Scale) / Change over time (baseline & 12 months later) / Burden
Ervik et al., 201027 / 10 men, aged >55 years, from urology/endocrinology clinics / Qualitative / Reactions to diagnosis (Interviews) / None / Burden
Fall et al., 200928 / 136 suicides among 168,584 men with PrCa (mean age at diagnosis 73.4 years), out of 4,305,358 men followed 1961-2004 / Longitudinal / Suicide (Swedish registry data) / Men without PrCa / Frequency
Fang et al., 201029 / 148 suicides among 342,497 men (mean age at diagnosis 70.2 years) with PrCa / Longitudinal / Suicide (National Death Index) / Age-, calendar period-, and state-matched suicide rates from the general population / Frequency
Fransson et al., 200930 / 27 men, aged 65-88 years at study entry, with localized disease, recruited for RCT comparing WW to RT / Longitudinal / HRQoL (EORTC-QLQ-30) during WW / Change over time (between 4 & 10 years of follow-up) / Burden
Hedestig et al., 200331 / 7 men, aged 62-69 years, selected from a PrCa registry / Qualitative / Worry, fear, & uncertainty during WW (Interviews) / None / Burden
Johansson et al., 201132 / 167 men, aged 45-75 years, randomly assigned to WW in SPCG-4 / Longitudinal / QoL; anxiety; depression (Study-specific questionnaire) / Population-based control group matched for region and age; also within-subjects change at 2 follow-up points 9 years apart / Both
Kelly, 200933 / 14 men, aged 59-83 years, from outpatient clinics / Qualitative / Impact of diagnosis on body image (Interviews) / None / Burden
Korfage et al., 200634 / 52 men, aged 60–74 years, enrolled in ERSPC / Longitudinal / HRQoL (SF-36; EQ-5D) / Change over time (before & after diagnosis) / Burden
Kronenwetter et al., 200535 / 26 men, aged 50-85 years, participating in the Prostate Cancer Lifestyle Trial (PCLT) / Qualitative / Reactions to diagnosis (Interviews) / None / Burden
Oliffe et al., 200936 / 25 men, aged 48-77 years, referred by physicians / Qualitative / AS-related uncertainty (Interviews) / None / Burden
Oliffe, 200637 / 35 men, aged 46-87 years, recruited from PrCa support groups or advertising / Qualitative / Reactions to diagnosis (Interviews) / None / Burden
Reeve et al., 201238 / 163 Medicare beneficiaries, mean age 75.1 years / Longitudinal / HRQoL & major depression during conservative management (SF-36; Diagnostic Interview Schedule items from MHOS) / Matched non-cancer controls / Both
Siston et al., 200339 / 39 men, aged 47-84 years, from 5 VA Medical Centers / Longitudinal / Cancer-specific QoL during WW (EORTC-QLQ-30+3) / Change over time (after dx, 3 months & 12 months later) / Burden
Thong et al., 200940 / 71 men, aged ≥50 years, identified from a cancer registry / Cross-sectional / HRQoL during AS (SF-36; Quality of Life – Cancer Survivors) / Norms for Dutch adult males / Burden
van den Bergh et al., 201041 / 129 men, median age 64.6 years at diagnosis, participating in a prospective protocol-based AS program / Longitudinal / Anxiety & depression (CES-D, MAX-PC) / Change over time (2 time points during AS) / Both
Vasarainen et al., 201142 / 75 men, aged 60-69 years, enrolled in a prospective AS study (PRIAS) / Longitudinal / HRQoL (RAND-36) / Previously published norms for Finnish adult males / Burden
Notes: aUnless otherwise noted, in this column “change over time” refers to repeated measures within subjects. bWe defined frequency of harm as the number of people who suffer a specific harm per 1,000 people exposed to the possibility of that harm, or sufficient data to estimate the proportion. We defined burden as an indication of the physical or psychological effects experienced by the patient or family, such as its severity, anticipated duration, treatability, or effect on daily functioning. cAlso includes evidence on harms of diagnosis. dAlso includes evidence on harms of false positive results. Abbreviations (and type of instrument):(GENERAL) BDI = Beck Depression Inventory; CES-D = Center for Epidemiologic Studies Depression Scale; EQ-5D = A simple health outcomes survey devised by the EuroQol Group; GHQ30 = General Health Questionnaire; GTUS = Growth Through Uncertainty Scale; HADS = Hospital Anxiety & Depression Scale; HAI = Health Anxiety Inventory; MHI-5 = Mental Health Inventory; MHOS = Medicare Health Outcomes Survey; MUIS-C = Mishel Uncertainty in Illness Scale Community Form; POMS-SF = Profile of Mood States—Short Form; QoL = Quality of Life; RAND-36 = RAND 36-item Health Survey; SAI-6 = State Anxiety Index, short-form version; SF-36 = 36-Item Short Form Health Survey; STAI = State-Trait Anxiety Inventory. (CANCER –SPECIFIC) EORTC-QLQ-30 EORTC-QLQ-30+3= European Organization for Research and Treatment of Cancer Quality of Life questionnaire; FACT-P = Functional Assessment of Cancer Therapy—Prostate; IES = Impact of Event Scale; MAX-PC = Memorial Anxiety Scale for Prostate Cancer; QLI = Ferrans & Powers Quality of Life Index-Cancer Version; UCLA-PCI = UCLA Prostate Cancer Index. Other abbreviations: AS = Active Surveillance; CaPSURE = Cancer of the Prostate Strategic Urological Research Endeavor Health Survey; ERSPC = European Randomised Study of Screening for Prostate Cancer; HRQoL = Health-Related Quality of Life; PrCa = Prostate Cancer; PLCO = Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial; PRIAS = Prostate Cancer Research International: Active Surveillance study; ProtecT = Prostate Testing for Cancer and Treatment study; PSA = Prostate Serum Antigen test; RP = Radical prostatectomy; RT = Radiotherapy; SEER = Surveillance, Epidemiology and End Results program; SPCG-4 = Scandinavian Prostate Cancer Group Study Number 4; WW = Watchful Waiting
Overdiagnosis of Prostate Cancer
Author, Year / Study Type / Data/Population / Outcome(s) of Interest
Ciatto et al., 200543 / Follow-up of 2 pilot studies / 6890 participants in pilot screening studies from 1991 to 1994 / Observed excess incidence in screened subjects
Davidov & Zelin, 200444 / Modeling / Hypothetical; assumes that screened population is a random sample from general population / Probability of overdiagnosis
Draisma et al., 200945 / Modeling / SEER 9 population aged 50 – 84 years during 1985 – 2000 / Overdiagnosis rate
Graif et al., 200746 / Pathology/Imaging / 2,126 men with clinical stage T1c PCa treated with RRP from 1989 to 2005 / Possible overdiagnosis, defined as tumor volume less than 0.5 cm3, Gleason less than 7, clear surgical margins, and organ confined disease in the RRP specimen
Gulati et al., 201047 / Modeling / Prostate Cancer Prevention Trial (PCPT) data / Percent overdiagnosed at 2 different PSA cut-offs
Heijnsdijk et al., 200948 / Modeling / Simulated cohort of 100 000 men (European standard population) / Cases overdetected per 100 screened men
Pashayan et al., 200949 / Modeling / ProtecT study plus UK national statistics and cancer registry data / Probability of overdiagnosis
Pelzer et al., 200850 / Pathology/Imaging / 1445 patients undergoing radical prostatectomy and with a PSA level <10 ng/mL / Over-diagnosis, defined as a pathological stage of pT2a and a Gleason score of <7 with no positive surgical margins
Telesca et al., 200851 / Modeling / SEER data, plus literature values for other parameters / Age- and ethnicity-specific overdiagnosis estimates
Tsodikov et al., 200652 / Modeling / SEER data from nine areas of the U.S. / Estimates of overdiagnosis by birth cohort
Welch & Albertsen, 200953 / Ecological / SEER and U.S. Census data / Percent overdiagnosed
Wu et al., 201254 / Modeling / Finnish arm of ERSPC / Absolute risk of overdetection
Abbreviations: ERSPC = European Randomized Study of Screening for Prostate Cancer; PrCA = Prostate cancer; PSA = Prostate Serum Antigen test; RRP = Radical Retropubic Prostactemy; SEER = Surveillance, Epidemiology and End Results program
Psychological Harms of Osteoporosis Screening
Source / Subjects / Study Type / Outcomes of Interest (Instrument or Data Source) / Comparisona
(Time Points) / Frequency/Burden?b
Screening Test
Emmett et al., 201255 / 31 women, aged ≥70-85 years, participating in screening arm of an RCT / Qualitative / Responses to screening (Interviews) / None / Burden
Green et al., 200656 / 24 women, aged 45-64 years, whose clinical consultations were recorded; 10 follow-up interviews / Qualitative / Responses to screening (Recorded clinical consultations; interviews) / None / Burden
Rimes et al., 200257 / 298 women, aged 32-73 years, recruited by advertising or word of mouth to participate in bone density measurement research / Longitudinal / Health anxiety; depression; perceived osteoporosis risk (HAI, STAI, BDI & osteoporosis-specific
questionnaire) / Change over time (before scanning, after results, and at 1 week and 3 month follow-up) / Burden
Diagnosis (Labeling)
Bianchi et al., 200558 / 62 women, aged 50-85 years, with uncomplicated primary OP / Cross-sectional / HRQoL & depression (QUALEFFO-41; Zung Depression Scale) / Women of comparable age with another chronic disease (hypothyroidism) / Both
Dennison et al., 201059 / 642 men (mean age 64.6 years) & women (mean age 66.6 years) traced through health services registry & enrolled in longitudinal study / Longitudinal / HRQoL (SF-36) / Osteoporotic, osteopenia, and normal subjects, compared before screening & 4 years later / Both
Salter et al., 201160 / 30 women, aged 70-85 years, purposively sampled from an RCT, recently screened, & told they were at higher risk of fracture (not formally diagnosed with OP) / Qualitative / “Risk-of-illness” experience (Interviews) / None / Burden
Notes: aUnless otherwise noted, in this column “change over time” refers to repeated measures within subjects. bWe defined frequency of harm as the number of people who suffer a specific harm per 1,000 people exposed to the possibility of that harm, or sufficient data for estimation of the proportion. We defined burden as an indication of the physical or psychological effects experienced by the patient or family, such as its severity, anticipated duration, treatability, or effect on daily functioning. Abbreviations (and type of instrument): (GENERAL) BARS = Beck Anxiety Rating Scale; BDI = Beck Depression Inventory; HADS = Hospital Anxiety & Depression Scale; HAI = Health Anxiety Inventory; HDRS = Hamilton Depression Rating Scale; SF-36 = 36-Item Short Form Health Survey (SF-36); STAI = State-Trait Anxiety Inventory. (OSTEOPOROSIS–SPECIFIC) Mini-OQOL = Osteoporosis Quality of Life scale; QUALEFFO-41 = Quality of life questionnaire of the European Foundation for Osteoporosis. Other abbreviations:HRQoL = Health-related quality of life; OP = osteoporosis; VFX = vertebral fracture