Dynamic prediction by landmarking with data from cohort subsampling designs.

The United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) recently reported a reduction in the average overall mortality among ovarian cancer patients screened with an annual sequential, multimodal strategy that tracked biomarker CA125 over time, where increasing serum CA125 levels prompted ultrasound. However, multiple cases were documented wherein serum CA125 levels were rising, but ultrasound screens were normal, thus delaying surgical intervention. A significant factor which could contribute to false negatives is that many aggressive ovarian cancers are believed to arise from epithelial cells on the fimbriae of the fallopian tubes, which are not readily imaged. Moreover, because only a fraction of metastatic tumors may reach a sonographically-detectable size before they metastasize, annual screening with ultrasound may fail to detect a large fraction of early-stage ovarian cancers. The ability to detect ovarian carcinomas before they metastasize is critical and future efforts towards improving screening should focus on identifying unique features specific to aggressive, early-stage tumors, as well as improving imaging sensitivity to allow for detection of tubal lesions. Implementation of a three-stage multimodal screening strategy in which a third modality is employed in cases where the first-line blood-based assay is positive and the second-line ultrasound exam is negative may also prove fruitful in detecting early-stage cases missed by ultrasound.

Commentary on 'Performance of ultrasound as a second line test to serum CA125 in ovarian cancer screening'.

US Trial shows no early mortality benefit from annual prostate cancer screening

PROSTATE SPECIFIC ANTIGEN BASED PROSTATE CANCER SCREENING: ACCUMULATING EVIDENCE OF EFFICACY BUT PERSISTENT UNCERTAINTY

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

Pathologic findings following false-positive screening tests for ovarian cancer in the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial

Purpose: Androgenic actions are thought to underlie the development of both male pattern baldness and prostate cancer. However, results from previous studies of the relationship between these two phenotypes have been inconsistent. Therefore, we investigated the association of male pattern baldness at age 45 years with overall and aggressive prostate cancer risk in a large, prospective cohort–the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Methods: We included 39,070 men, from the usual care and screening arms of the trial, who were cancer-free at start of follow-up. Hazard ratios (HRs) and 95% confidence intervals (95%CIs) were estimated using Cox proportional hazards regression models with age as the underlying time-scale. Results: During follow-up (median=2.78 years), 1,138 incident prostate cancer cases were diagnosed, 578 of which were aggressive (Gleason score ≥ 7, stage ≥ III, or fatal). Frontal + vertex balding at age 45 years, compared with no balding, was not associated with overall prostate cancer risk (HR=1.19, 95%CI: 0.98, 1.45), but was associated with increased risk of aggressive prostate cancer (HR=1.42, 95%CI: 1.10, 1.83). Adjustment for covariates did not significantly alter these estimates. Other classes of male pattern baldness were not associated with the overall or aggressive prostate cancer. Conclusion: Our analysis indicates that frontal + vertex balding at age 45 years increases the risk for future development of aggressive prostate cancer, and supports the possibility of overlapping pathogenesis. Citation Format: Cindy Ke Zhou, Ruth M. Pfeiffer, Sean D. Cleary, Heather J. Hoffman, Paul H. Levine, Lisa W. Chu, Ann W. Hsing, Michael B. Cook. Male pattern baldness increases the risk of aggressive prostate cancer: A prospective analysis of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3260. doi:10.1158/1538-7445.AM2014-3260

The ERSPC (European Randomized Study of Screening for Prostate Cancer) found that screening reduced prostate cancer mortality, but the PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial) found no reduction. To evaluate whether effects of screening on prostate cancer mortality relative to no screening differed between the ERSPC and PLCO. Cox regression of prostate cancer death in each trial group, adjusted for age and trial. Extended analyses accounted for increased incidence due to screening and diagnostic work-up in each group via mean lead times (MLTs), which were estimated empirically and using analytic or microsimulation models. Randomized controlled trials in Europe and the United States. Men aged 55 to 69 (ERSPC) or 55 to 74 (PLCO) years at randomization. Prostate cancer screening. Prostate cancer incidence and survival from randomization; prostate cancer incidence in the United States before screening began. Estimated MLTs were similar in the ERSPC and PLCO intervention groups but were longer in the PLCO control group than the ERSPC control group. Extended analyses found no evidence that effects of screening differed between trials (P= 0.37 to 0.47 [range across MLT estimation approaches]) but strong evidence that benefit increased with MLT (P= 0.0027 to 0.0032). Screening was estimated to confer a 7% to 9% reduction in the risk for prostate cancer death per year of MLT. This translated into estimates of 25% to 31% and 27% to 32% lower risk for prostate cancer death with screening as performed in the ERSPC and PLCO intervention groups, respectively, compared with no screening. The MLT is a simple metric of screening and diagnostic work-up. After differences in implementation and settings are accounted for, the ERSPC and PLCO provide compatible evidence that screening reduces prostate cancer mortality. National Cancer Institute.

The benefit of screening for prostate cancer using prostate-specific antigen (PSA) testing and digital rectal examination (DRE) is uncertain and is under evaluation in a randomized prospective trial, the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Although the final results are several years away, the initial round of screening is complete. We describe the population enrolled in the PLCO trial, their baseline PSA and DRE screening results, and diagnostic follow-up results during the first year of follow-up. A total of 38,350 men were randomly assigned to the screening arm of the PLCO trial from November 1993 through June 2001. Men were advised to seek diagnostic follow-up from their primary care provider if their DRE was suspicious for cancer and/or if their serum PSA level was higher than 4 ng/mL. PLCO trial staff obtained records related to diagnostic follow-up. Compliance with both screening tests was high (more than 89%). At screening, 7.5% of men had a positive DRE (i.e., suspicious for cancer) and 7.9% had a PSA level higher than 4 ng/mL. Of the men with positive screening tests, 74.2% underwent additional diagnostic testing, and 31.5% underwent a prostatic biopsy within 1 year. Overall, 1.4% of the men in the screening arm were diagnosed with prostate cancer, the majority of whom had clinically localized cancer. These compliance, biopsy, and cancer detection rates appear to be representative of contemporary practice patterns. The PLCO trial is evaluating PSA- and DRE-based screening for prostate cancer in a clinically valid manner. Whether such screening will result in a reduction of prostate cancer mortality cannot be answered until the randomized comparison is completed.

Pathology tissue specimens with associated epidemiologic and clinical data are valuable for cancer research. The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial undertook a large-scale effort to create a public resource of pathology tissues from PLCO participants who developed a cancer during the trial. Formalin-fixed paraffin-embedded tissue blocks were obtained from pathology laboratories on a loan basis for central processing of tissue microarrays, with additional free-standing tissue cores collected for nucleic acid extraction. Pathology tissue specimens were obtained for prostate cancer (n = 1,052), lung cancer (n = 434), colorectal cancer (n = 675) and adenoma (n = 658), ovarian cancer and borderline tumors (n = 212), breast cancer (n = 870), and bladder cancer (n = 204). The process of creating this resource was complex, involving multidisciplinary teams with expertise in pathology, epidemiology, information technology, project management, and specialized laboratories. Creating the PLCO tissue resource required a multistep process, including obtaining medical records and contacting pathology departments where pathology materials were stored after obtaining necessary patient consent and authorization. The potential to link tissue biomarkers to prospectively collected epidemiologic information, screening and clinical data, and matched blood or buccal samples offers valuable opportunities to study etiologic heterogeneity, mechanisms of carcinogenesis, and biomarkers for early detection and prognosis. The methods and protocols developed for this effort, and the detailed description of this resource provided here, will be useful for those seeking to use PLCO pathology tissue specimens for their research and may also inform future tissue collection efforts in other settings. Cancer Epidemiol Biomarkers Prev; 25(12); 1635-42. ©2016 AACR.

Quality control of cancer screening examination procedures in the prostate, lung, colorectal and ovarian (PLCO) cancer screening trial

1791: The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial: Biopsy Rates and Cancer Characteristics of Initial (To) Screen (II)

Screening for breast cancer with mammography

Background: Some published studies on dietary fat and risk of pancreatic cancer suggest that dietary fat and specific fat sources may increase risk of pancreatic cancer. Methods: We examined the association between fat intake (measured by food frequency questionnaire) and pancreatic cancer risk among 111,416 participants in the PLCO Cancer Screening Trial using Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs). Results: There were 411 incident pancreatic cancer cases over the median 8.9 years of follow up. We observed an inverse association between saturated fat intake and pancreatic cancer risk comparing extreme quintiles (HR=0.64, 95% CI 0.46-0.88), but the association became weaker and non-significant when excluding individuals with <4 years of follow up to assess reverse causation HR=0.88 (95% CI 0.58-1.33). Total fat intake showed a similar pattern of association, while monounsaturated and polyunsaturated fat intakes and analysis by animal or plant source showed no association with risk. Conclusions: Despite more cases and longer follow up than most previous studies, our results do not suggest that higher fat consumption increases risk of pancreatic cancer. Lower fat intake in cases prior to diagnosis may reflect early manifestations of the disease (e.g. dyspepsia), and avoidance of fat which can exacerbate symptoms. Citation Format: Hannah E. Arem, Susan T. Mayne, Joshua Sampson, Harvey Risch, Rachael Z. Stolzenberg-Solomon. Dietary fat intake and risk of pancreatic cancer in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4809. doi:10.1158/1538-7445.AM2013-4809

Non-compliance with the initial screening exam visit in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial