Cancer screening with multicancer detection tests: A translational science review.

Multicancer detection (MCD) tests use a single, easily obtainable biospecimen, such as blood, to screen for more than one cancer concurrently. MCD tests can potentially be used to improve early cancer detection, including cancers that currently lack effective screening methods. However, these tests have unknown and unquantified benefits and harms. MCD tests differ from conventional cancer screening tests in that the organ responsible for a positive test is unknown, and a broad diagnostic workup may be necessary to confirm the location and type of underlying cancer. Among two prospective studies involving greater than 16,000 individuals, MCD tests identified those who had some cancers without currently recommended screening tests, including pancreas, ovary, liver, uterus, small intestine, oropharyngeal, bone, thyroid, and hematologic malignancies, at early stages. Reported MCD test sensitivities range from 27% to 95% but differ by organ and are lower for early stage cancers, for which treatment toxicity would be lowest and the potential for cure might be highest. False reassurance from a negative MCD result may reduce screening adherence, risking a loss in proven public health benefits from standard-of-care screening. Prospective clinical trials are needed to address uncertainties about MCD accuracy to detect different cancers in asymptomatic individuals, whether these tests can detect cancer sufficiently early for effective treatment and mortality reduction, the degree to which these tests may contribute to cancer overdiagnosis and overtreatment, whether MCD tests work equally well across all populations, and the appropriate diagnostic evaluation and follow-up for patients with a positive test.

Diagnostic follow-up of indeterminate pulmonary nodules in the Medicare population.

BACKGROUND: Management of indeterminate pulmonary nodules (IPNs) is associated with redistribution of lung cancer to earlier stages, but most subjects with IPNs do not have lung cancer. The burden of IPN management in Medicare recipients was assessed. METHODS: Surveillance, Epidemiology, and End Results-Medicare data were analyzed for IPNs, diagnostic procedures, and lung cancer status. IPNs were defined as chest computed tomography (CT) scans with accompanying International Classification of Diseases (ICD) codes of 793.11 (ICD-9) or R91.1 (ICD-10). Two cohorts were defined: persons with IPNs during 2014-2017 comprised the IPN cohort, whereas those with chest CT scans without IPNs during 2014-2017 comprised the control cohort. Excess rates of various procedures due to reported IPNs over 2 years of follow-up (chest CT, positron emission tomography [PET]/PET-CT, bronchoscopy, needle biopsy, and surgical procedures) were estimated using multivariable Poisson regression models comparing the cohorts adjusted for covariates. Prior data on stage redistribution associated with IPN management were then used to define a metric of excess procedures per late-stage case avoided. RESULTS: Totals of 19,009 and 60,985 subjects were included in the IPN and control cohorts, respectively; 3.6% and 0.8% had lung cancer during follow-up. Excess procedures per 100 persons with IPNs over a 2-year follow-up were 63, 8.2, 1.4, 1.9, and 0.9 for chest CT, PET/PET-CT, bronchoscopy, needle biopsy, and surgery, respectively. Corresponding excess procedures per late-stage case avoided were 48, 6.3, 1.1, 1.5, and 0.7 based on an estimated 1.3 late-stage cases avoided per 100 IPN cohort subjects. CONCLUSIONS: The metric of excess procedures per late-stage case avoided can be used to measure the benefits-to-harms tradeoff of IPN management.

Changes in uptake of stool-based colorectal cancer screening during the Covid-19 pandemic.

PURPOSE: Colorectal cancer (CRC) screening is underutilized and endoscopic colon screening includes a number of barriers that were exacerbated by the Covid-19 pandemic. At-home stool-based screening (SBS) increased during the pandemic and potentially reached eligible adults hesitant to be screened by endoscopy. The purpose of this analysis was to examine the change in uptake of SBS during the pandemic among adults not screened within guidelines by endoscopy. METHODS: We used data from the 2019 and 2021 National Health Interview Surveys to estimate uptake of SBS among adults aged 50-75 years, without a previous diagnosis of CRC and without guideline-concordant endoscopic screening. We also examined provider recommendations for screening tests. To examine if changes in uptake differed during the pandemic by demographic and health characteristics, we combined survey years and ran logistic regression models with an interaction term for each factor and survey year. RESULTS: In our study population, SBS increased 74% overall from 2019 to 2021 (8.7% to 15.1%; p < 0.001), with the largest percent increase among those aged 50-52 years (3.5% to 9.9%; p < 0.001). Among those aged 50-52 years, the ratio of endoscopy to SBS changed from 83%/17% in 2019 to 55%/45% in 2021. Cologuard was the only screening test where recommendations by healthcare providers significantly increased from 2019 (10.6% to 16.1%; p = 0.002). CONCLUSIONS: Use and recommendations for SBS increased substantially during the pandemic. Increased awareness among patients could potentially improve future CRC screening rates if uptake of SBS occurs among those unable or unwilling to be screened by endoscopy.

Cervical cancer screening and predictors of screening by diabetes status.

PURPOSE: Women with diabetes have lower survival rates after a cervical cancer diagnosis compared to women without diabetes. Pap smears and human papilloma virus (HPV) testing are highly effective screening tests for cervical cancer, therefore, it is important to know the prevalence of guideline-concordant screening among women with diabetes and understand if their predictors of screening differ. The purpose of this analysis was to assess guideline-concordant cervical cancer screening and predictors by diabetes status. METHODS: We used the 2019 National Health Interview Survey data, limited to women aged 21-65 years without a previous diagnosis of cancer, a hysterectomy, or diagnosed with diabetes in the year prior to the survey. We considered the Pap and HPV tests together and concordance as being tested within the past 3 years as part of a routine exam. We calculated weighted, adjusted prevalence, and prevalence ratios (PRs) of screening concordance comparing women with diabetes to those without. RESULTS: The unadjusted prevalence of concordant screening was 66.5% for women with diabetes compared to 73.3% for women without diabetes (PR = 0.91 95% CI 0.84-0.98). In the fully adjusted model adjusting for factors known to be associated with diabetes and access to healthcare, the association was attenuated and no longer statistically significant (PR = 0.96 95% CI 0.89-1.04). CONCLUSION: Cervical cancer screening concordance was lower in women with diabetes compared to those without overall but the deficit appears to be due primarily to underlying differences in sociodemographic characteristics and access to healthcare and not diabetes independently.

Differences in the relationship between diabetes and prostate cancer among Black and White non-Hispanic men.

PURPOSE: Studies finding lower incidence rates of prostate cancer among men with diabetes have been primarily conducted in White non-Hispanic (WNH) populations. The purpose of this analysis is to compare the relationship between diabetes and prostate cancer among Black (BNH) and White non-Hispanic men. METHODS: We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data from 2011 to 2015 to compare incidence rates and tumor characteristics between BNH and WNH men by diabetes status. Age-adjusted incidence rates and corresponding rate ratios (RR) by diabetes status were calculated overall and by tumor grade, stage, and PSA level separately for BNH and WNH men. We used multivariable logistic regression to compare tumor characteristics among men with prostate cancer in the numerator, both within and across race/ethnic groups. RESULTS: Overall age-adjusted incidence rates were significantly lower in men with diabetes compared to those without among WNH men [RR = 0.88 95% Confidence Interval (CI) 0.86-0.90] but there was no difference in rates by diabetes status among BNH men (RR = 1.01 95% CI 0.96-1.07). Men with diabetes were less likely to be diagnosed with distant-staged tumors compared to those without diabetes in both race/ethnic groups but the magnitude of difference by diabetes status was greater in BNH [Odds Ratio (OR) = 0.52 95% CI 0.42-0.64] than WNH (OR = 0.88 95% CI 0.81-0.95) men (p-value for interaction < 0.001). CONCLUSION: The relationship between diabetes and prostate cancer differed between BNH and WNH men. The differences could have implications in evaluating the effectiveness of prostate cancer screening in men with diabetes across racial/ethnic subgroups.

Other and All-Cause Mortality among Men Diagnosed with Prostate Cancer in the PLCO Trial.

PURPOSE: Men with prostate cancer have high cause-specific survival, and most deaths are from other causes. This study aimed to investigate other and all-cause mortality in a large cancer screening cohort. MATERIALS AND METHODS: From the PLCO (Prostate, Lung, Colorectal and Ovarian) Cancer Screening Trial cohort, we selected men diagnosed with prostate cancer from 1994-2014. We examined other and all-cause survival by prostate cancer risk level, defined as the D'Amico categories for localized disease (low, intermediate and high risk) plus nonlocalized disease. We developed 3 Cox proportional hazards models to assess the relationship between risk level and survival. Model I controlled for age, race, study arm and diagnosis year. Model II additionally controlled for other demographic and medical history factors. Model III additionally controlled for initial treatment. RESULTS: Of 76,672 men in PLCO and 10,859 prostate cancer cases, 9,248 (85.2%) had known prostate cancer risk level (mean±SD age 70.4±6.2 years). Median followup time from diagnosis was 10.8 years (IQR 6.8-15.0). Of 3,318 deaths 81% were from other causes. Compared to the low risk group, other-cause mortality HRs were 1.13 (95% CI 1.04-1.23), 1.35 (95% CI 1.21-1.50) and 1.63 (95% CI 1.35-1.97) for intermediate risk, high risk and advanced disease, respectively, in model II. Model III HRs were similar to model II except for advanced disease, where the HR decreased to 1.35. CONCLUSIONS: Other-cause survival was greater in lower vs higher risk disease, even after controlling for lifestyle characteristics and comorbidities. Further research is needed to identify factors contributing to this higher other-cause mortality to help mitigate the risk.

Opioid and Other Medication Use and General Health Status in a Cohort of Older Adults.

OBJECTIVE: The aim of this study was to determine whether the use of opioids and other medications in a cohort of older adults was associated with self-reported health status. METHODS: Among participants in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Screening Trial linked to Medicare Part D claims data and answering a quality-of-life questionnaire, we examined the relationship between medication use over a 5-year period and various self-reported health status variables assessed several years later, including overall health status (STATUS) and trouble with activities of daily living (TADL). Multivariable logistic regression was used to estimate odds ratios (ORs) for the health status variables and metrics of medication use, including >60-day use, and for opiates, chronic use, with models controlling for demographics (model I), additionally for chronic conditions (model II), and additionally for other medication use (model III). RESULTS: The study cohort included 22,844 PLCO participants (56% women, 90% non-Hispanic whites); 4.2% had chronic opioid use and 12.5% used for >60 days. Fair-poor STATUS was reported in 37.9% of participants with chronic opioid use versus 15.0% of participants without (p < 0.001). ORs for chronic opioid use for fair-poor STATUS (compared to good-excellent) were significantly elevated in all models but decreased from model I (OR = 3.6; 95% CI :3.1-4.1) to model II (OR = 2.7; 95% CI :2.3-3.1) to model III (OR = 2.1; 95% CI :1.8-2.5). ORs for TADL were generally similar to those for STATUS. Other drug classes also had significantly elevated model III ORs for fair-poor versus good-excellent STATUS (range 1.1-1.6). CONCLUSION: Frequent use of various medication classes correlated with measures of future health status in an elderly population, with opioids having the strongest association. The magnitude of the association decreased after controlling for concurrent chronic conditions but remained elevated. Future research should consider how the use of opioids and other medications impact measures of health-related quality of life.

Healthcare Access, Utilization, and Preventive Health Behaviors by Eligibility for Lung Cancer Screening.

In 2013, the US Preventive Services Task Force recommended low-dose computed tomography screening for smokers at high risk of lung cancer; however, use remains low. Efforts to promote lung cancer screening need to consider how receptive this population is to preventive healthcare and cancer screening. In addition, because of demonstrated heterogeneity in behaviors by smoking status, interventions may need to differ among eligible high-risk subgroups. To assess the engagement of high-risk smokers in other preventive healthcare behaviors, we examined healthcare use, including non-lung cancer screening, and healthcare provider discussions regarding screening by eligibility for lung cancer screening. We used the 2015 National Health Interview Survey to assess smoking history, healthcare use, cancer screening, vaccinations, and healthcare provider discussions regarding non-lung cancer screening. We calculated weighted prevalence estimates and prevalence ratios comparing eligible and ineligible current and former smokers to never smokers. Eligible current and former smokers had significantly different healthcare utilization and screening concordance compared to never smokers and to each other. Compared to never smokers, eligible current smokers were significantly less likely to be concordant with breast, colorectal, and cervical cancer screening while eligible former smokers were only less likely to be concordant with breast cancer screening. Eligible current smokers were less likely to report physician discussions about non-lung screening tests. Provider discussions about screening and engagement in preventive healthcare differed among current and former smokers eligible for lung cancer screening. Intervention efforts to increase lung cancer screening levels will likely need to differ as well.

Contribution of Surveillance Colonoscopy to Colorectal Cancer Prevention.

BACKGROUND & AIMS: The contribution of surveillance colonoscopy, as opposed to that of initial colonoscopy examination, to prevention of colorectal cancer (CRC) is uncertain. We estimated the preventive effect of surveillance colonoscopy by applying the recently developed metric of adenoma dwell time avoided needed to prevent 1 CRC case (DTA). METHODS: We followed subjects in the prostate, lung, colorectal and ovarian (PLCO) cancer screening trial who underwent colonoscopies following positive findings from sigmoidoscopies (colonoscopy cohort, n = 15,935) for CRC incidence for 10 years. The number and timing of adenomas removed during surveillance were measured in a subset (n = 3492) of patients and extrapolated to the entire cohort to estimate the total avoided adenoma dwell time. A previously determined DTA value of 612 dwell years was applied to estimate the number of CRC cases prevented by surveillance. Proportional reduction in CRC was computed as CP/(CO+CP), where CO and CP are observed and estimated prevented cases, respectively. RESULTS: In the colonoscopy cohort of the PLCO, 2882 subjects had advanced adenomas (AAs), 572 had 3 or more non-advanced adenomas (NAA3+), 4496 had 1-2 non-advanced adenomas (NAA1-2), and 7985 had no adenoma (NA). The mean number of subsequent colonoscopy examinations over 10 years were 1.80 for subjects with AAs, 1.63 for subjects with NAA3+, and 1.46 for subjects with NAA1-2. Average years of avoided adenoma dwell time per subject were 4.0 for subjects with AAs, 5.5 for subjects with NAA3+, and 2.4 for subjects with NAA1-2. There were 56 cases of CRC in subjects with AAs, 4 cases of CRC in subjects with NAA3+, and 33 cases of CRC in subjects with NAA1-2. Estimated proportional reductions in CRC incidence were 25.0% in subjects with AAs (95% CI, 16%-34%), 34.4% in subjects with NAA1-2 (95% CI, 25%-40%), and 30.4% overall (in subjects with AAs, NAA3+, or NAA1-2; 95% CI, 25%-40%). Absolute CRC incidence reductions were 7.1 per 10,000 PY in subjects with AAs and 4.1 per 10,000 PY in subjects with NAA1-2. CONCLUSIONS: Using the recently developed metric of DTA, we estimated that surveillance colonoscopy in the PLCO colonoscopy cohort during 10 years of follow up prevented 30% of CRC cases. Because the methodology for estimation is indirect, the true effect is uncertain.

Examining the relationship between diabetes and prostate cancer through changes in screening guidelines.

PURPOSE: Previous studies have found that men with diabetes are at reduced risk of prostate cancer compared to men without diabetes. The lower risk could be due to biologic differences and/or a diagnosis bias from use of the prostate-specific antigen (PSA) test as a screening and diagnostic tool. We sought to further examine the relationship between diabetes and incidence of prostate cancer and examine the potential impact of changes in PSA screening guidelines in 2008 and 2012. METHODS: We used 2004-2015 Surveillance, Epidemiology and End Results (SEER)-Medicare data and limited the study population to men aged 67-74 with at least 2 years of continuous enrollment. Using the 5% Medicare sample as the denominator and prostate cancer cases as the numerator, we calculated age-adjusted rate ratios (RR) in 2006-2011 and 2012-2015 by diabetes status, overall and by tumor grade. We used multivariable logistic regression to compare tumor characteristics by diabetes status. RESULTS: Men with diabetes had lower incidence rates of prostate cancer compared to men without diabetes in 2006-2011 [RR = 0.89 95% confidence interval (CI) 0.87-0.91] and 2012-2015 (RR = 0.92 95% CI 0.89-0.95) but the slight attenuation toward the null in 2012-2015 was primarily due to the change in RRs for low-grade tumors. CONCLUSION: We found differences in the risk and characteristics of prostate cancer by diabetes status and that some risks have changed over time as guidelines have changed. With lower PSA use in the more recent time-period, rates of low-grade tumors have become more similar by diabetes status.

Aspirin use and ovarian cancer risk using extended follow-up of the PLCO Cancer Screening Trial.

OBJECTIVE: Frequent use of aspirin has been associated with reduced ovarian cancer risk in observational studies, but it is unclear if only daily, low-dose aspirin confers a protective benefit. We examined associations between patterns of aspirin use and ovarian cancer risk among postmenopausal women in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. METHODS: Participants were enrolled in PLCO between 1993 and 2001 and followed for cancer outcomes through 2014. Detailed data on aspirin use (e.g., dose, frequency and duration) were ascertained via the supplemental questionnaire (SQX) administered in 2006-2007. We used Cox proportional hazards regression to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between aspirin use (defined as use ≥once/week) and incident ovarian cancer. We conducted analyses among all women in the study sample and stratified by age at the time of the SQX. RESULTS: There were 41,633 women included in this analysis, of whom 223 developed incident ovarian cancer. Overall, aspirin use was not significantly associated with ovarian cancer risk (HR: 0.93, 95% CI: 0.72-1.21). Among women <70 years, there was suggestion of an inverse association for daily use of aspirin (HR: 0.65, 95% CI: 0.40-1.05), low-dose aspirin (HR: 0.79, 95% CI: 0.51-1.24) and daily use of low-dose aspirin (HR: 0.64, 95% CI: 0.38-1.09). CONCLUSIONS: These findings suggest a potential modest effect of daily, low-dose aspirin in reducing ovarian cancer risk. However, effect estimates were imprecise given the small number of events, and further research will be needed to confirm and extend these findings.

Metastatic prostate cancer at diagnosis and through progression in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

BACKGROUND: The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial assessed the effect of screening with prostate-specific antigen and a digital rectal examination on prostate cancer mortality. Another endpoint of interest was the burden of total metastatic disease. METHODS: All men in PLCO were assessed for metastatic prostate cancer at diagnosis; men with clinical stage I/II disease were assessed for metastatic progression. The rate of total metastatic disease was defined as metastases found either at diagnosis or through progression divided by person-years (PYs) of follow-up for all men in the trial. Metastatic progression rates were computed among men with clinical stage I/II prostate cancer. Survival among men with metastases at diagnosis was compared with survival among men with metastatic progression. RESULTS: Among 38,340 men in the intervention arm and 38,343 men in the control arm in PLCO, there were 4974 and 4699 prostate cancer cases, respectively. The rates of total metastatic disease were 4.72 and 4.83 per 10,000 PYs in the intervention and control arms, respectively (rate ratio, 0.98; 95% CI, 0.81-1.18). The rates of metastatic progression among men with clinical stage I/II prostate cancer were 43.7 and 50.5 per 10,000 PYs in the intervention and control arms, respectively (P = .30). Prostate cancer-specific 5- and 10-year survival rates were significantly worse for men with metastatic progression (24% and 19%, respectively) than men with metastases at diagnosis (40% and 26%, respectively). CONCLUSIONS: Rates of total metastatic disease and metastatic progression were similar across arms in PLCO. Survival was worse for men with metastatic progression in comparison with those with metastatic disease at diagnosis.

Number of Adenomas Removed and Colorectal Cancers Prevented in Randomized Trials of Flexible Sigmoidoscopy Screening.

BACKGROUND & AIMS: Screening for colorectal cancer (CRC) with sigmoidoscopy reduces CRC incidence by detecting and removing adenomas. The number needed to screen is a measure of screening efficiency, but is not directly associated with adenoma removal. We propose the following 2 new metrics for quantifying the relationship between adenoma removal and CRC prevented: number of adenomas needed to remove (NNR) and adenoma dwell time avoided (DTA). METHODS: We collected data from 4 randomized trials of sigmoidoscopy screening (1 in the United States and 3 in Europe) to assess NNR and DTA. For each trial, NNR was computed as the number of adenomas removed from subjects in the intervention group, divided by the number of CRCs prevented. DTA was computed similarly but taking into account the timing of adenoma removal. Combined results across trials were assessed using standard meta-analytic techniques. RESULTS: The estimated NNR for the PLCO (Prostate, Lung, Colorectal and Ovarian) trial was 74 (95% confidence interval [CI], 56-110), for the NORCCAP (Norwegian Colorectal Cancer Prevention) trial was 71 (95% CI, 44-174), for the SCORE (Screening for Colon Rectum) trial was 27 (95% CI, 14-135), and for the UKFSST (UK Flexible Sigmoidoscopy Screening Trial) was 36 (95% CI, 28-52). The combined estimate (meta-analysis) of NNR was 52 (95% CI, 36-93) assuming heterogeneity (P for heterogeneity = .014). DTA estimates among trials ranged from 278 to 730 years, with a combined estimate of 500 (95% CI, 344-833) years assuming heterogeneity (P for heterogeneity = .035), or 2 CRC cases prevented per 1000 adenoma dwell years avoided. The combined estimates of NNR and DTA restricted to advanced adenomas were 13 (95% CI, 9-22) and 122 (95% CI, 90-190) years, respectively. CONCLUSIONS: We collected data from 4 randomized trials of sigmoidoscopy screening for CRC to develop metrics of endoscopic efficiency, NNR and DTA, which are directly linked to adenoma detection and removal. They can be used to compare screening among endoscopic modalities and to more precisely measure adenoma to carcinoma transition rates.

Correction to: The relationship between diabetes, prostate-specific antigen screening tests, and prostate cancer.

In the original publication of the article, the categories of PSA levels among the subpopulation of men diagnosed with prostate cancer were published incorrectly in Table 4. The corrected Table 4 is given in this Correction.

Extended follow-up for prostate cancer incidence and mortality among participants in the Prostate, Lung, Colorectal and Ovarian randomized cancer screening trial.

OBJECTIVE: To examine prostate cancer (PCa) incidence and mortality by arm in the randomized Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial. PATIENTS AND METHODS: Patients aged 55-74 years at 10 screening centres were randomized between 1993 and 2001 to an intervention or usual care arm. Patients in the intervention arm received six annual prostate-specific antigen (PSA) tests and four annual digital rectal examinations. The patients were followed for PCa incidence and for mortality via active follow-up processes and by linkage to state cancer registries and the National Death Index. For cancers identified through active follow-up, trial abstractors recorded the mode of diagnosis (screen-detected, symptomatic, other). RESULTS: A total of 38 340 patients were randomized to the intervention arm and 38 343 to a usual care arm. The median follow-up for mortality was 16.9 (intervention) and 16.7 years (usual care). There were 333 (intervention) and 352 (usual care) PCa cancer deaths, giving rates (per 10 000 person-years) of 5.5 and 5.9, respectively, and a rate ratio (RR) of 0.93 (95% confidence interval [CI] 0.81-1.08; P = 0.38). The RR for overall PCa incidence was 1.05 (95% CI 1.01-1.09). The RRs by Gleason category were 1.17 (95% CI 1.11-1.23) for Gleason 2-6, 1.00 (95% CI 0.93-1.07) for Gleason 7 and 0.89 (95% CI 0.80-0.99) for Gleason 8-10 disease. By mode of detection, during the trial's screening phase, 13% of intervention arm vs 27% of usual care arm cases were symptomatic; post-screening, these percentages were 18% in each arm. CONCLUSION: After almost 17 years of median follow-up, there was no significant reduction in PCa mortality in the intervention compared with the usual care arm. There was a significant increase in Gleason 2-6 disease and a significant reduction in Gleason 8-10 disease in the intervention compared with the usual care arm.

Secondary prostate cancer screening outcomes by race in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Screening Trial.

BACKGROUND: Despite disparities in prostate cancer incidence and mortality rates between black and white men, there is still insufficient data available to assess potential differences in the benefits and harms of prostate cancer screening by race. Although the Prostate, Lung, Colorectal, and Ovarian (PLCO) Screening Trial is underpowered to detect a difference by race in prostate-cancer specific mortality, because of the large study size, there are still sufficient numbers to examine secondary screening outcomes. The objective of this analysis is to examine whether differences exist between black and white participants with respect to screening false-positive rates, biopsy follow-up of men with positive screens, tumor characteristics, and overdiagnosis of prostate cancer. METHODS: Participants from the PLCO included men aged 55-74 years at baseline. Cancer diagnoses and deaths were identified through study update questionnaires, records of biopsy procedures, and linkage with the National Death Index. Cancer characteristics were obtained by medical abstractors. We used chi-squared tests to assess differences in false-positive rates, biopsy follow-up, and tumor characteristics. We used Cox proportional hazards models to compare incidence and mortality rates adjusting for age and survival rates adjusting for Gleason scores. RESULTS: Black men were slightly more likely (14.5%) to have a false-positive PSA test compared to white men (12.4%; P = 0.02) but less likely to have a false-positive digital rectal exam (DRE) (10.9% vs 14.2%, respectively; P < 0.001). Among all men who were screened, black men were significantly more likely to undergo a biopsy than white men (16.5% vs 13.8%, respectively [P = 0.003]) but there was no difference when limited to those with a positive PSA test. Prostate cancer tumors were more likely to be aggressive and to have metastasized in black men compared to white men. Disparities in incidence, mortality, and survival rates were comparable to those seen in population-based data. CONCLUSIONS: There was evidence that false-positive test results differed by race and screening test. Consistent with previous studies, cancer outcomes, and tumor characteristics were all more unfavorable in black men.

The efficacy of prostate-specific antigen screening: Impact of key components in the ERSPC and PLCO trials.

BACKGROUND: The European Randomized Study of Screening for Prostate Cancer (ERSPC) demonstrated that prostate-specific antigen (PSA) screening significantly reduced prostate cancer mortality (rate ratio, 0.79; 95% confidence interval, 0.69-0.91). The US Prostate, Lung, Colorectal, and Ovarian (PLCO) trial indicated no such reduction but had a wide 95% CI (rate ratio for prostate cancer mortality, 1.09; 95% CI, 0.87-1.36). Standard meta-analyses are unable to account for key differences between the trials that can impact the estimated effects of screening and the trials' point estimates. METHODS: The authors calibrated 2 microsimulation models to individual-level incidence and mortality data from 238,936 men participating in the ERSPC and PLCO trials. A cure parameter for the underlying efficacy of screening was estimated by the models separately for each trial. The authors changed step-by-step major known differences in trial settings, including enrollment and attendance patterns, screening intervals, PSA thresholds, biopsy receipt, control arm contamination, and primary treatment, to reflect a more ideal protocol situation and differences between the trials. RESULTS: Using the cure parameter estimated for the ERSPC, the models projected 19% to 21% and 6% to 8%, respectively, prostate cancer mortality reductions in the ERSPC and PLCO settings. Using this cure parameter, the models projected a reduction of 37% to 43% under annual screening with 100% attendance and biopsy compliance and no contamination. The cure parameter estimated for the PLCO trial was 0. CONCLUSIONS: The observed cancer mortality reduction in screening trials appears to be highly sensitive to trial protocol and practice settings. Accounting for these differences, the efficacy of PSA screening in the PLCO setting is not necessarily inconsistent with ERSPC results. Cancer 2018;124:1197-206. © 2017 American Cancer Society.