Abstract Background: National Comprehensive Cancer Network guidelines have recommended metastatic colorectal cancer patients (mCRC pts) undergo BRAF, KRAS, NRAS, and microsatellite instability/mismatch repair deficiency (MSI/MMR) testing since 2015. Previous studies have reported molecular testing rates from academic and community cancer centers, but there is a lack of information on testing rates in community health systems (HS) which account for approximately half of US cancer care. Methods: Tumor molecular testing rates were assessed in a first stage analysis for pts with mCRC in HS, in order to inform a second stage analysis focused on treatment decisions and pt outcomes. For the first stage analysis, we randomly selected 200 pts (50 pts from each of 4 HS sites) diagnosed with mCRC between 1/1/2015 and 9/1/2020. The 200 pts were identified through technology-enabled curation, followed by retrospective review performed by certified tumor registrars. An anticipated cohort of 1000 evaluable pts is planned for the second stage analysis. Results: 53% of pts were tested for all four biomarkers at some point during their care (Table). Pts more likely to have been tested include those: from HS Site 1 (P = 4.2x10-5); age <65 years old at mCRC diagnosis (P = 0.014); and with commercial insurance (P = 0.015). Among pts tested, the median times from metastatic diagnosis to BRAF, KRAS, and NRAS testing results were 35, 33, and 34 days, respectively. Conclusion: This first stage analysis of molecular testing in mCRC pts revealed variation in testing rates by site, biomarker, and patient characteristics, which may in part be explained by the implementation of a precision medicine testing program at HS Site 1. A second stage analysis assessing the impact of biomarker testing on treatment decisions and pt outcomes will be guided by this initial characterization of testing rates and possible confounders. Biomarker testing rates among metastatic colorectal patients across four health system sitesSite 1 (n=50)Site 2 (n=50)Site 3 (n=50)Site 4 (n=50)BRAF tested43 (86%)25 (50%)24 (48%)26 (52%)Count (%)KRAS tested44 (88%)35 (70%)32 (64%)35 (70%)Count (%)NRAS tested42 (84%)23 (46%)26 (52%)30 (60%)Count (%)MSI/MMR tested49 (98%)37 (74%)44 (88%)44 (88%)Count (%)All biomarkers tested40 (80%)19 (38%)20 (40%)26 (52%)Count (%) Citation Format: Chenan Zhang, Mahder Teka, Francesca F. Coutinho, Joseph R. Burkhart, Louise E. Widmer, Ronda G. Broome, Mary T. Tran, Michael A. Thompson, Antony M. Ruggeri, Jennifer J. Godden, James L. Weese, Douglas J. Reding, Anna B. Berry, Yanina Natanzon, Thomas D. Brown. Staged analysis of standard of care tumor molecular testing among patients with metastatic colorectal cancer in the community health system setting [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2618.

BACKGROUND The benefits of endoscopic testing for colorectal-cancer screening are uncertain. We evaluated the effect of screening with flexible sigmoidoscopy on colorectal-cancer incidence and mortality. METHODS From 1993 through 2001, we randomly assigned 154,900 men and women 55 to 74 years of age either to screening with flexible sigmoidoscopy, with a repeat screening at 3 or 5 years, or to usual care. Cases of colorectal cancer and deaths from the disease were ascertained. RESULTS Of the 77,445 participants randomly assigned to screening (intervention group), 83.5% underwent baseline flexible sigmoidoscopy and 54.0% were screened at 3 or 5 years. The incidence of colorectal cancer after a median follow-up of 11.9 years was 11.9 cases per 10,000 person-years in the intervention group (1012 cases), as compared with 15.2 cases per 10,000 person-years in the usual-care group (1287 cases), which represents a 21% reduction (relative risk, 0.79; 95% confidence interval [CI], 0.72 to 0.85; P<0.001). Significant reductions were observed in the incidence of both distal colorectal cancer (479 cases in the intervention group vs. 669 cases in the usual-care group; relative risk, 0.71; 95% CI, 0.64 to 0.80; P<0.001) and proximal colorectal cancer (512 cases vs. 595 cases; relative risk, 0.86; 95% CI, 0.76 to 0.97; P=0.01). There were 2.9 deaths from colorectal cancer per 10,000 person-years in the intervention group (252 deaths), as compared with 3.9 per 10,000 person-years in the usual-care group (341 deaths), which represents a 26% reduction (relative risk, 0.74; 95% CI, 0.63 to 0.87; P<0.001). Mortality from distal colorectal cancer was reduced by 50% (87 deaths in the intervention group vs. 175 in the usual-care group; relative risk, 0.50; 95% CI, 0.38 to 0.64; P<0.001); mortality from proximal colorectal cancer was unaffected (143 and 147 deaths, respectively; relative risk, 0.97; 95% CI, 0.77 to 1.22; P=0.81). CONCLUSIONS Screening with flexible sigmoidoscopy was associated with a significant decrease in colorectal-cancer incidence (in both the distal and proximal colon) and mortality (distal colon only). (Funded by the National Cancer Institute; PLCO ClinicalTrials.gov number, NCT00002540.).

The NCI imbedded the notion of comprehensive quality control and assurance (CQA) in the design concept for the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. PLCO implemented a comprehensive, adaptable quality assurance and control program to span more than 20 years of data collection, coordinate multiple institutions and committees, and integrate a wide variety of complex protocols. CQA concepts, practices, and procedures traced through all aspects of trial management, governance, and operations of PLCO. The driving force behind CQA in PLCO was scientific and clinical credibility of trial data and findings. CQA as implemented in PLCO was operationally analogous to the concept of Total Quality Management (TQM) described in the management literature. This paper describes CQA actualization in PLCO.

Biomedical research cannot succeed without funding, knowledgeable staff, and appropriate infrastructure. There are however equally important but intangible factors that are rarely considered in planning large multidisciplinary endeavors or evaluating their success. The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial required extensive collaborations between individuals from many fields, including clinicians, clinical trialists, and administrators; it also addressed questions across the spectrum of cancer prevention and control. In this manuscript, we examine the experiences and opinions of trial staff regarding the building of successful relationships in PLCO. We summarize, in narrative form, data collected using open-ended questionnaires that were administered to the National Cancer Institute project officers, coordinating center staff, screening center principal investigators, and screening center coordinators in 2015, about 3 years after publication of the final primary trial manuscript. Trust, respect, listening to others, and in-person interaction were frequently mentioned as crucial to building successful relationships.

Objectives Occupational exposure to chlorinated aliphatic solvents has been associated with an increased cancer risk, including brain cancer. However, many of these solvents remain in active, large-volume use. We evaluated glioma risk from non-farm occupational exposure (ever/never and estimated cumulative exposure) to any of the six chlorinated solvents-carbon tetrachloride, chloroform, methylene chloride, trichloroethylene, tetrachloroethylene or 1,1,1-trichloroethane-among 798 cases and 1175 population-based controls, aged 18-80 years and non-metropolitan residents of Iowa, Michigan, Minnesota and Wisconsin. Methods Solvent use was estimated based on occupation, industry and era, using a bibliographic database of published exposure levels and exposure determinants. Unconditional logistic regression was used to calculate ORs adjusted for frequency matching variables age group and sex, and age and education. Additional analyses were limited to 904 participants who donated blood specimens (excluding controls reporting a previous diagnosis of cancer) genotyped for glutathione-S-transferases GSTP1, GSTM3 and GSTT1. Individuals with functional GST genes might convert chlorinated solvents crossing the blood-brain barrier into cytotoxic metabolites.Results Both estimated cumulative exposure (ppm-years) and ever exposure to chlorinated solvents were associated with decreased glioma risk and were statistically significant overall and for women. In analyses comparing participants with a high probability of exposure with the unexposed, no associations were statistically significant. Solvent-exposed participants with functional GST genes were not at increased risk of glioma.Conclusions We observed no associations of glioma risk and chlorinated solvent exposure. Large pooled studies are needed to explore the interaction of genetic pathways and environmental and occupational exposures in glioma aetiology.

We tested the hypothesis that genes involved in the alcohol oxidation pathway modify the association between alcohol intake and breast cancer. Subjects were women aged 55–74 at baseline from the screening arm of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Incident breast cancers were identified through annual health surveys. Controls were frequency matched to cases by age and year of entry into the trial. A self-administered food frequency questionnaire queried frequency and usual serving size of beer, wine or wine coolers, and liquor. Three SNPs in genes in the alcohol metabolism pathway were genotyped: alcohol dehydrogenase 2, alcohol dehydrogenase 3, and CYP2E1. The study included 1,041 incident breast cancer cases and 1,070 controls. In comparison to non-drinkers, the intake of any alcohol significantly increased the risk of breast cancer, and this risk increased with each category of daily alcohol intake (OR 2.01, 95% CI 1.14, 3.53) for women who drank three or more standard drinks per day. Stratification by genotype revealed significant gene/environment interactions. For the ADH1B gene, there were statistically significant associations between all levels of alcohol intake and risk of breast cancer (all OR > 1.34 and all lower CI > 1.01), while for women with the GA or AA genotype, there were no significant associations between alcohol intake and risk of breast cancer. Alcohol intake, genes involved in alcohol metabolism and their interaction increase the risk of breast cancer in post-menopausal women. This information could be useful for primary care providers to personalize information about breast cancer risk reduction.

OBJECTIVE:To quantify outcomes of individuals diagnosed and treated for prostate cancer in a single institution.DESIGN:Retrospective electronic chart abstraction.SETTING:Marshfield Clinic, the largest private multispecialty group practice in Wisconsin, and one of the largest in the United States, provides health care services annually to approximately 385,000 unique patients through 1.8 million annual patient encounters.PARTICIPANTS:Individuals within the Marshfield Clinic cancer registry who had been diagnosed with prostate cancer between 1960 and 2009.METHODS:Electronic chart abstraction from the cancer registry and the electronic medical record was conducted (N=6,181). Data abstracted included age at diagnosis; stage and grade of tumor; prostate specific antigen (PSA) values before, at, and after diagnosis; initial cancer treatment; follow-up time; subsequent cancer treatments; evidence of metastasis; age of death; and cause of death, if known.RESULTS:The average age of prostate cancer diagnosis has decreased from 70-71 years in the 1960's and 1970's to an average age at diagnosis of 67 years in the 2000's (P<0.001). This decrease in age occurred within the decades of implementation of PSA screening. Approximately 74% of men diagnosed with prostate cancer within the PSA screening era had at least one PSA test, and the presence of a PSA test did not appear to change treatment outcome. Age, grade, and stage were the biggest predictors of prostate cancer outcome. There was no difference in event-free survival between current treatment types (radical prostatectomy, brachytherapy, photon treatment, or intensity-modulated radiation therapy) (2003 or later) when stratified by age (greater than 85%, 5-year event-free survival P=0.85); however, more events occurred with older external beam radiation treatment regimens (1993-2003) (70% to 75%, 5-year event-free survival P=0.001).CONCLUSION:Individuals diagnosed and treated for prostate cancer within the Marshfield Clinic comprehensive care setting follow national trends with a decreased age of diagnosis since the advent of PSA screening. Outcomes for individuals treated within the Clinic system are also comparable to national trends.

BACKGROUND:Understanding glioma etiology requires determining which environmental factors are associated with glioma. Upper Midwest Health Study case-control participant work histories collected 1995-1998 were evaluated for occupational associations with glioma. "Exposures of interest" from our study protocol comprise our a priori hypotheses. MATERIALS AND METHODS:Year-long or longer jobs for 1,973 participants were assigned Standard Occupational Classifications (SOC) and Standard Industrial Classifications (SIC). The analysis file includes 8,078 SIC- and SOC-coded jobs. For each individual, SAS 9.2 programs collated employment with identical SIC-SOC coding. Distributions of longest "total employment duration" (total years worked in jobs with identical industry and occupation codes, including multiple jobs, and non-consecutive jobs) were compared between cases and controls, using an industrial hygiene algorithm to group occupations. RESULTS:Longest employment duration was calculated for 780 cases and 1,156 controls. More case than control longest total employment duration was in the "engineer, architect" occupational group [16 cases, 10 controls, odds ratio (OR) 2.50, adjusted for age group, sex, age and education, 95% confidence interval (CI) 1.12-5.60]. Employment as a food processing worker [mostly butchers and meat cutters] was of borderline significance (27 cases, 21 controls, adjusted OR: 1.78, CI: 0.99-3.18). CONCLUSIONS:Among our exposures of interest work as engineers or as butchers and meat cutters was associated with increased glioma risk. Significant associations could be due to chance, because of multiple comparisons, but similar findings have been reported for other glioma studies. Our results suggest some possible associations but by themselves could not provide conclusive evidence.

Rituximab is an anti-CD20 monoclonal antibody that has demonstrated efficacy in patients with indolent and aggressive forms of non-Hodgkin’s lymphoma and has become part of the standard therapy for patients with B-cell malignancies. The study was designed to examine if rituximab increases the risk to develop non-neutropenic infection (NNI). Medical records of 202 patients diagnosed as follicular lymphoma or small lymphocytic lymphoma were reviewed. Negative binomial regression was used to estimate relative risk (RR) of NNI. Rituximab (n= 41) and non-rituximab (n= 161) groups had a total of 31.636 and 195.691 reviewed patient days, and recorded a total of 67 and 154 infections, respectively. Negative binomial regression analysis revealed significant effects for the treatment (rituximab vs. non-rituximab) and age (p< 0.01). The RRs of viral and bacterial NNI for rituximab group compared to nonrituximab group were 3.33 and 2.60, respectively; while the RRs for one year increment of age were 1.03 and 1.04, respectively. The time-to-first viral and bacterial NNI for rituximab group were significantly faster than non-rituximab group. Rituximab may increase the risk of NNI in patients with follicular lymphoma or small lymphocytic lymphoma.

PURPOSE:Within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), we assessed the long-term disease-specific functioning among prostate cancer (PCa) survivors versus noncancer controls, the impact of trial arm (screening/usual care) on functioning, and the effect of treatment modality on functioning. PATIENTS AND METHODS:PCa survivors (n = 529), 5 to 10 years postdiagnosis, were frequency-matched to noncancer controls (n = 514) for race, screening center, year of enrollment, and trial arm. Participants completed a telephone interview regarding PCa-specific symptomatology. Weights accounted for patient selection from the five PLCO screening centers. Propensity-score methods were used to balance groups of interest with respect to demographic and medical characteristics. RESULTS:Weighted linear regression analyses revealed poorer sexual and urinary function among PCa survivors compared with noncancer controls (P < .001). Trial arm was not significantly related to any outcome (P > .31). Compared with radical prostatectomy patients (n = 201), radiation-therapy patients (n = 110) reported better sexual (P < .05) and urinary (P < .001) functioning but poorer bowel outcomes (P < .05). Survivors who received treatment combinations including androgen deprivation (n = 207) reported significantly poorer hormone-related symptoms compared with radical prostatectomy patients (P < .05). CONCLUSION This study demonstrated the persistence of clinically significant, long-term PCa treatment-related sexual and urinary adverse effects up to 10 years postdiagnosis. To our knowledge, this was the first comparison of prostate-related dysfunction among screened survivors versus screened noncancer controls and indicated that these long-term problems were attributable to PCa treatment and not to aging or comorbidities. Finally, differences in long-term adverse effects between treatment modalities are particularly relevant for patients and clinicians when making treatment decisions.

An excess incidence of brain cancer in farmers has been noted in several studies. The National Institute for Occupational Safety and Health developed the Upper Midwest Health Study (UMHS) as a case–control study of intracranial gliomas and pesticide uses among rural residents. Previous studies of UMHS participants, using “ever-never” exposure to farm pesticides and analyzing men and women separately, found no positive association of farm pesticide exposure and glioma risks. The primary objective was to determine if quantitatively estimated exposure of pesticide applicators was associated with an increased risk of glioma in male and female participants.

CONTEXT:Screening for ovarian cancer with cancer antigen 125 (CA-125) and transvaginal ultrasound has an unknown effect on mortality.OBJECTIVE:To evaluate the effect of screening for ovarian cancer on mortality in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.DESIGN, SETTING, AND PARTICIPANTS:Randomized controlled trial of 78,216 women aged 55 to 74 years assigned to undergo either annual screening (n = 39,105) or usual care (n = 39,111) at 10 screening centers across the United States between November 1993 and July 2001. Intervention The intervention group was offered annual screening with CA-125 for 6 years and transvaginal ultrasound for 4 years. Participants and their health care practitioners received the screening test results and managed evaluation of abnormal results. The usual care group was not offered annual screening with CA-125 for 6 years or transvaginal ultrasound but received their usual medical care. Participants were followed up for a maximum of 13 years (median [range], 12.4 years [10.9-13.0 years]) for cancer diagnoses and death until February 28, 2010.MAIN OUTCOME MEASURES:Mortality from ovarian cancer, including primary peritoneal and fallopian tube cancers. Secondary outcomes included ovarian cancer incidence and complications associated with screening examinations and diagnostic procedures.RESULTS:Ovarian cancer was diagnosed in 212 women (5.7 per 10,000 person-years) in the intervention group and 176 (4.7 per 10,000 person-years) in the usual care group (rate ratio [RR], 1.21; 95% confidence interval [CI], 0.99-1.48). There were 118 deaths caused by ovarian cancer (3.1 per 10,000 person-years) in the intervention group and 100 deaths (2.6 per 10,000 person-years) in the usual care group (mortality RR, 1.18; 95% CI, 0.82-1.71). Of 3285 women with false-positive results, 1080 underwent surgical follow-up; of whom, 163 women experienced at least 1 serious complication (15%). There were 2924 deaths due to other causes (excluding ovarian, colorectal, and lung cancer) (76.6 per 10,000 person-years) in the intervention group and 2914 deaths (76.2 per 10,000 person-years) in the usual care group (RR, 1.01; 95% CI, 0.96-1.06).CONCLUSIONS:Among women in the general US population, simultaneous screening with CA-125 and transvaginal ultrasound compared with usual care did not reduce ovarian cancer mortality. Diagnostic evaluation following a false-positive screening test result was associated with complications. Trial Registration clinicaltrials.gov Identifier: NCT00002540.

Although severe immune dysregulation is an established risk factor for non-Hodgkin lymphoma (NHL), it is unclear whether subclinical immune system function influences lymphomagenesis. To address this question, we conducted a nested case-control study within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial to investigate whether circulating levels of cytokines and other immune markers are associated with future risk of NHL. Selected cytokines [interleukin (IL)-4, IL-6, IL-10, and TNF-α] and other immune markers [soluble TNF receptor 1 (sTNF-R1), sTNF-R2, C-reactive protein, and sCD27] were measured in prediagnostic serum specimens from 297 incident NHL cases and 297 individually matched controls. ORs and 95% confidence intervals (CI) relating quartiles of analyte concentration to NHL risk were calculated by using conditional logistic regression. Statistically significant associations with increased NHL risk were observed for elevated serum levels of sTNF-R1 (quartile 4 vs. quartile 1: OR = 1.7, 95% CI: 1.1-2.8; P(trend) = 0.02) and sCD27 (OR = 5.3, 95% CI: 2.9-9.4; P(trend) < 0.0001). These associations remained in analyses of cases diagnosed longer than 6 years following blood collection (sTNF-R1: OR = 2.1, 95% CI: 1.0-4.0, P(trend) = 0.01; sCD27: OR = 4.1, 95% CI: 1.9-8.5, P(trend) = 0.0001). Elevated levels of IL-10, TNF-α and sTNF-R2 were also significantly associated with increased risk of NHL overall; however, these associations weakened with increasing time from blood collection to case diagnosis and were null for cases diagnosed longer than 6 years postcollection. Our findings for sTNF-R1 and sCD27, possible markers for inflammatory and B-cell stimulatory states, respectively, support a role for subclinical inflammation and chronic B-cell stimulation in lymphomagenesis.

CONTEXT:The effect on mortality of screening for lung cancer with modern chest radiographs is unknown.OBJECTIVE:To evaluate the effect on mortality of screening for lung cancer using radiographs in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.DESIGN, SETTING, AND PARTICIPANTS:Randomized controlled trial that involved 154,901 participants aged 55 through 74 years, 77,445 of whom were assigned to annual screenings and 77,456 to usual care at 1 of 10 screening centers across the United States between November 1993 and July 2001. The data from a subset of eligible participants for the National Lung Screening Trial (NLST), which compared chest radiograph with spiral computed tomographic (CT) screening, were analyzed.INTERVENTION:Participants in the intervention group were offered annual posteroanterior view chest radiograph for 4 years. Diagnostic follow-up of positive screening results was determined by participants and their health care practitioners. Participants in the usual care group were offered no interventions and received their usual medical care. All diagnosed cancers, deaths, and causes of death were ascertained through the earlier of 13 years of follow-up or until December 31, 2009.MAIN OUTCOME MEASURES:Mortality from lung cancer. Secondary outcomes included lung cancer incidence, complications associated with diagnostic procedures, and all-cause mortality.RESULTS:Screening adherence was 86.6% at baseline and 79% to 84% at years 1 through 3; the rate of screening use in the usual care group was 11%. Cumulative lung cancer incidence rates through 13 years of follow-up were 20.1 per 10,000 person-years in the intervention group and 19.2 per 10,000 person-years in the usual care group (rate ratio [RR]; 1.05, 95% CI, 0.98-1.12). A total of 1213 lung cancer deaths were observed in the intervention group compared with 1230 in usual care group through 13 years (mortality RR, 0.99; 95% CI, 0.87-1.22). Stage and histology were similar between the 2 groups. The RR of mortality for the subset of participants eligible for the NLST, over the same 6-year follow-up period, was 0.94 (95% CI, 0.81-1.10).CONCLUSION:Annual screening with chest radiograph did not reduce lung cancer mortality compared with usual care.TRIAL REGISTRATION:clinicaltrials.gov Identifier: NCT00002540.

Previous research has indicated that treatment staff often underestimate the informational needs of cancer patients. In this study, the authors determined the total number of information sources obtained and used to influence treatment decisions, and the clinical and demographic factors associated with the use of specific sources of information in cancer patients. Participants were identified by the statewide cancer registry and diagnosed in 2004 with breast, colorectal, lung, or prostate cancer. A self-administered mailed questionnaire elicited cancer treatments, demographics, and information sources used to make treatment decisions. Of those surveyed, 1,784 (66%) participated and responded to all questions regarding information use. Over 69% of study participants reported obtaining information from a source other than the treatment staff. Significant predictors of using additional information sources included younger age, higher income, higher education, complementary and alternative medicine (CAM) use, and reporting shared decision making (all p values <.01). Participants with a college degree were more likely to use the Internet (OR 3.7; 95% CI 1.5–9.0) and scientific research reports (OR 3.3; 95% CI 1.6–6.9) to influence treatment decisions compared with those without a high school degree. Support group use to influence treatment decisions was not associated with socioeconomic variables but did vary by cancer type and CAM use. The sources of information study participants obtained and used to influence treatment decisions varied strongly by socioeconomic and demographic variables. These findings provide a deeper understanding of the information needs of cancer patients and have implications for dissemination strategies that can minimize disparities in access to cancer information.

BACKGROUND & AIMS:The recommended timing of surveillance colonoscopy for individuals with adenomatous polyps is based on adenoma histology, size, and number. The burden and cost of surveillance colonoscopy are significant. The aim of this study was to examine the use of surveillance colonoscopy on a community-wide basis. METHODS:We retrospectively queried participants in the Prostate, Lung, Colorectal, and Ovarian Cancer screening trial in 9 US communities about use of surveillance colonoscopy. Subjects whose initial colonoscopy showed advanced adenoma (AA), nonadvanced adenoma (NAA), or no adenoma (NA) findings were included. Colonoscopy examinations were confirmed by reviewing colonoscopy reports. RESULTS:Of 3876 subjects selected for inquiry, 3627 (93.6%) responded. The cumulative probability of a surveillance colonoscopy within 5 years was 58.4% (n = 1342) in the AA group, 57.5% in those with >or=3 NAAs (n = 117), 46.7% in those with 1-2 NAAs (n = 905), and 26.5% (n = 1263) in subjects with NAs. Within 7 years, 33.2% of subjects with AAs received >or=2 surveillance examinations versus 26.9% for those with >or=3 NAAs, 18.2% for those with 1 or 2 NAAs, and 10.4% for those with NAs. Incomplete colonoscopy, family history of colorectal cancer, or interval adenomatous findings could explain only a minority of surveillance colonoscopy in low-risk subjects. CONCLUSIONS:In community practice, there is substantial overuse of surveillance colonoscopy among low-risk subjects and underuse among subjects with AAs. Interventions to better align use of surveillance colonoscopy with risk for advanced lesions are needed.

OBJECTIVE:The purpose of this study was to measure the occurrence and natural history of simple ovarian cysts in a cohort of older women.STUDY DESIGN:Simple cysts were ascertained among a cohort of 15,735 women from the intervention arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial through 4 years of transvaginal ultrasound screening.RESULTS:Simple cysts were seen in 14% of women the first time that their ovaries were visualized. The 1-year incidence of new simple cysts was 8%. Among ovaries with 1 simple cyst at the first screen, 54% retained 1 simple cyst, and 32% had no cyst 1 year later. Simple cysts did not increase risk of subsequent invasive ovarian cancer.CONCLUSION:Simple ovarian cysts are fairly common among postmenopausal women, and most cysts appear stable or resolve by the next annual examination. These findings support recent recommendations to follow unilocular simple cysts in postmenopausal women without intervention.

You have accessJournal of UrologyProstate Cancer: Epidemiology and Natural History I1 Apr 2010131 COMPARISON OF RISK ESTIMATES OF FACTORS ASSOCIATED WITH PROSTATE CANCER INCIDENCE AND MORTALITY BETWEEN SCREENED AND CONTROL ARMS IN THE PLCO TRIAL Amanda Black, Robert Grubb, Tim Church, Douglas Reding, Grant Izmirlian, Thomas Hickey, Jerome Mabie, Thomas Riley, Lawrence Ragard, Philip Prorok, Christine Berg, David Crawford, and Gerald Andriole Amanda BlackAmanda Black Bethesda, MD More articles by this author , Robert GrubbRobert Grubb St. Louis, MO More articles by this author , Tim ChurchTim Church Minneapolois, MN More articles by this author , Douglas RedingDouglas Reding Marshfield, WI More articles by this author , Grant IzmirlianGrant Izmirlian Bethesda, MD More articles by this author , Thomas HickeyThomas Hickey Rockville, MD More articles by this author , Jerome MabieJerome Mabie Rockville, MD More articles by this author , Thomas RileyThomas Riley Rockville, MD More articles by this author , Lawrence RagardLawrence Ragard Rockville, MD More articles by this author , Philip ProrokPhilip Prorok Bethesda, MD More articles by this author , Christine BergChristine Berg Bethesda, MD More articles by this author , David CrawfordDavid Crawford Denver, CO More articles by this author , and Gerald AndrioleGerald Andriole St. Louis, MO More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.182AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The PLCO trial demonstrated an increased rate of prostate cancer (CaP) incidence due to screening without a reduction in mortality. One explanation is that PSA screening detects many non-lethal cancers. Focusing on CaP incidence may result in the attenuation of the estimate of risk for factors important in CaP development. Therefore, we hypothesized that risk estimates for factors associated with CaP would be attenuated in the screening arm compared to the control arm, whereas risk factors associated with CaP-specific mortality (PCSM) would be the same for both screened and unscreened populations. METHODS From 1993-2001, 76,345 men aged 55-74 were randomized to receive annual PSA and DRE screening or usual care. Subjects self reported a number of health and lifestyle factors thought to be important in carcinogenesis at study entry. 31,638 and 29,867 men in the screened and control arms, respectively, had sufficient data for inclusion. The mean age of the population was 62.7 years at randomization. Overall 5,531 men were diagnosed with CaP, 1,812 (2.9%) men had aggressive CaP(Gleason ≥ 7, Stage ≥ IV) and 141 (0.23%) men died of CaP. Cox proportional hazards modeling was used to estimate the association of various factors associated with developing any CaP, aggressive CaP and lethal CaP. RESULTS Age, race and family history were all associated with CaP and aggressive CaP (see Table). Age and race were also associated with PCSM. Diabetes demonstrated a decreased risk of CaP diagnosis in both arms. Race was strongly associated with PCSM; the risk estimate was greater in the control arm men than in men who were in the intervention arm. Table. Multivariable analysis of risk factors for any, aggressive (Gleason ≥ 7, Clinical Stage ≥ IV) and lethal CaP Control Arm Risk Factors Any CaP Aggressive CaP Lethal CaP Age (Years) 1.04* (1.03 to 1.05) 1.07* (1.06 to 1.08) 1.15* (1.10 to 1.20) Race (White / Black) 1.82* (1.54 to 2.14) 2.28* (1.78 to 2.91) 4.30* (2.14 to 8.46) BMI <25kg/m2/ ≥40kg/m2 0.97 (0.63 to 1.49) 1.23 (0.65 to 2.33) 1.89 (0.25 to 14.38) Height (inches) 1.01 (1.01 to 1.03) 1.02 (1.00 to 1.05) 1.04 (0.95 to 1.13) Diabetes (Yes / no) 0.78* (0.67 to 0.91) 0.79 (0.62 to 1.02) 0.61 (0.24 to 1.53) Fam Hx CaP (Yes / no) 1.67* (1.47 to 1.89) 1.72* (1.40 to 2.10) 1.69 (0.81 to 3.53) Smoker (Never / Ever) 0.90* (0.83 to 0.98) 1.01 (0.88 to 1.15) 1.44 (0.85 to 2.43) Screened Arm Risk Factors Any CaP Aggressive CaP Lethal CaP Age (Years) 1.04* (1.04 to 1.05) 1.06* (1.05 to 1.08) 1.11* (1.06 to 1.16) Race (White / Black) 1.72* (1.48 to 2.00) 2.15* (1.69 to 2.75) 2.50* (1.07 to 5.78) BMI <25kg/m2/ ≥40kg/m2 0.71 (0.46 to 1.13) 1.12 (0.60 to 2.12) 2.11 (0.28 to 16.00) Height (inches) 1.00 (1.01 to 1.02) 1.00 (0.99 to 1.04) 1.06 (0.97 to 1.15) Diabetes (Yes / no) 0.71* (0.62 to 0.83) 0.90 (0.71 to 1.13) 0.47 (0.17 to 1.32) Fam Hx CaP (Yes / no) 1.60* (1.43 to 1.79) 1.61* (1.31 to 1.96) 0.86 (0.35 to 2.12) Smoker (Never / Ever) 0.89* (0.83 to 0.96) 0.75* (0.66 to 0.86) 0.68 (0.42 to 1.07) CONCLUSIONS Estimates of risk factors associated with CaP incidence were not significantly different in the screened and control arms of the PLCO trial. It is possible that PSA testing within the control arm caused the convergence of the risk estimates. Further investigation is needed into the increased risk of black men for developing any CaP, aggressive CaP and lethal CaP. © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e53-e54 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Amanda Black Bethesda, MD More articles by this author Robert Grubb St. Louis, MO More articles by this author Tim Church Minneapolois, MN More articles by this author Douglas Reding Marshfield, WI More articles by this author Grant Izmirlian Bethesda, MD More articles by this author Thomas Hickey Rockville, MD More articles by this author Jerome Mabie Rockville, MD More articles by this author Thomas Riley Rockville, MD More articles by this author Lawrence Ragard Rockville, MD More articles by this author Philip Prorok Bethesda, MD More articles by this author Christine Berg Bethesda, MD More articles by this author David Crawford Denver, CO More articles by this author Gerald Andriole St. Louis, MO More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Mutagen challenge and DNA repair assays have been used in case-control studies for nearly three decades to assess human cancer risk. The findings still engender controversy because blood was drawn after cancer diagnosis so the results may be biased, a type called 'reverse causation'. We therefore used Epstein-Barr virus-transformed lymphoblastoid cell lines established from prospectively collected peripheral blood samples to evaluate lung cancer risk in relation to three DNA repair assays: alkaline Comet assay, host cell reactivation (HCR) assay with the mutagen benzo[a]pyrene diol epoxide and the bleomycin mutagen sensitivity assay. Cases (n = 117) were diagnosed with lung cancer between 0.3 and 6 years after blood collection and controls (n = 117) were frequency matched on calendar year and age at blood collection, gender and smoking history; all races were included. Case and control status was unknown to laboratory investigators. In unconditional logistic regression analyses, statistically significantly increased lung cancer odds ratios (OR(adjusted)) were observed for bleomycin mutagen sensitivity as quartiles of chromatid breaks/cell [relative to the lowest quartile, OR = 1.2, 95% confidence interval (CI): 0.5-2.5; OR = 1.4, 95% CI: 0.7-3.1; OR = 2.1, 95% CI: 1.0-4.4, respectively, P(trend) = 0.04]. The magnitude of the association between the bleomycin assay and lung cancer risk was modest compared with those reported in previous lung cancer studies but was strengthened when we included only incident cases diagnosed more than a year after blood collection (P(trend) = 0.02), supporting the notion the assay may be a measure of cancer susceptibility. The Comet and HCR assays were unrelated to lung cancer risk.

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Background: Prostate cancer screening with PSA has decreased the average age of prostate cancer detection and increased the number of men who undergo prostate biopsies. Currently two thirds of the prostate biopsies performed due to a high PSA test are negative for prostate cancer leading to unnecessary expense and distress for the individual. One way to decrease the unnecessary procedures associated with PSA screening would be to identify individuals who are at higher or lower risk of prostate cancer using newly discovered genetic and environmental risk factors. Aims: Using the males in the Personalized Medicine Research Project (PMRP) population that have had a PSA test, determine if genetic and environmental factors can be incorporated into the PSA screening model to better discriminate individuals who will have a diagnosis of prostate cancer from those with negative biopsies. Methods: All men in PMRP who have had a PSA test (N=4659) were genotyped for 12 polymorphisms that have been associated with prostate cancer in GWAS studies and an additional 52 polymorphisms that were associated with a number of diseases. We also included dietary history, particularly dairy intake if available for the individual. Results: A total of 935 of the 4659 men in the study have had a prostate biopsy with a positive biopsy rate of 34%. Using a panel of 12 previously identified polymorphisms; seven were significantly associated with prostate cancer in our population. Another three polymorphisms were found to be associated in our population (LPL rs328, NOS3 rs1799983, and PON2 rs7493). None of the tested polymorphisms were associated with the biopsy procedure. Individuals with 4 or fewer of the 10 associated risk alleles (17.33% of the population) were more likely to have a negative biopsy (OR 1.87 p=0.0017) while those individuals who have 8 or more associated risk alleles (11% of the population) were more likely to have a positive biopsy (OR 2.68). Conclusions: The PMRP population that has experienced at least one PSA screen is a viable population for testing new screening algorithms that incorporate genetic and environmental factors for better identification of prostate cancer risk. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3766.