A Cost-Effectiveness Analysis of Lung Cancer Screening with Low-Dose Computed Tomography and a Diagnostic Biomarker

Background The Lung Computed Tomography Screening Reporting and Data System (Lung-RADS) reduces the false-positive rate of lung cancer screening but introduces prolonged periods of uncertainty for indeterminate findings. We assess the cost-effectiveness of a screening program that assesses indeterminate findings earlier via a hypothetical diagnostic biomarker introduced in place of Lung-RADS 3 and 4A guidelines. Methods We evaluated the performance of the US Preventive Services Task Force (USPSTF) recommendations on lung cancer screening with and without a hypothetical non-invasive diagnostic biomarker using a validated microsimulation model. The diagnostic biomarker assesses the malignancy of indeterminate nodules, replacing Lung-RADS 3 and 4A guidelines, and is characterized by a varying sensitivity profile that depends on nodule’s size, specificity, and cost. We tested the robustness of our findings through univariate sensitivity analyses. Results A lung cancer screening program per the USPSTF guidelines that incorporates a diagnostic biomarker with at least medium sensitivity profile and 90% specificity, that costs ≤$250, is cost-effective with an incremental cost-effectiveness ratio lower than $100,000 per quality-adjusted life year, and improves lung cancer-specific mortality reduction while requiring fewer screening exams than the USPSTF guidelines with Lung-RADS. A screening program with a biomarker costing ≥$750 is not cost-effective. The health benefits accrued and costs associated with the screening program are sensitive to the disutility of indeterminate findings and specificity of the biomarker, respectively. Conclusions Lung cancer screening that incorporates a diagnostic biomarker, in place of Lung-RADS 3 and 4A guidelines, could improve the cost-effectiveness of the screening program and warrants further investigation.

Real-World Utilization of Androgen Deprivation Therapy-Intensification Among Older Canadian Men with de Novo Metastatic Prostate Cancer

Background Despite the wealth of evidence demonstrating the efficacy of treatment intensification beyond androgen deprivation therapy (ADT) among patients with de novo metastatic castration-sensitive prostate cancer (mCSPC), little is known of its real-world utilization. This study examined the real-world uptake of ADT treatment intensification among older men in a large Canadian province. Methods We performed a retrospective population-based cohort study using province-wide linked administrative data in Ontario, Canada. Patients 66 years and older with de novo mCSPC were included and their treatment with conventional ADT-based regimens, ADT plus next-generation androgen receptor-axis-targeted therapy (ARAT), and ADT plus docetaxel were identified and stratified by time. Results From 2014 to 2019, 3556 patients were identified with de novo mCSPC. Most patients (n = 2794, 78.6%) were treated with a conventional ADT regimen while 399 (11.2%) patients received ADT intensification with docetaxel and 52 (1.5%) patients received abiraterone acetate plus prednisone (AA+P). In a time-stratified analysis of ADT intensification before and after the pivotal AA+P trial (LATITUDE), AA+P uptake increased from 0.5% to 3.0% while docetaxel use dropped from 12.0% to 10.0%. The median survival of the study population was 18 months (IQR = 10–31). Conclusion The majority of patients with de novo mCSPC are treated with ADT alone in the Canadian real-world setting, despite randomized clinical trial evidence of benefit with the use of ADT-intensified regimens. As ADT treatment intensification is substantially under-used, better understanding the barriers to treatment and targeted education to address these are needed.

Endogenous Circulating Sex Hormone Concentrations and Colon Cancer Risk in Postmenopausal Women: A Prospective Study and Meta-Analysis

Background Observational studies have consistently reported that postmenopausal hormone therapy use is associated with lower colon cancer risk. However, epidemiological studies examining the associations between circulating concentrations of endogenous estrogens and colorectal cancer have reported inconsistent results. Methods We investigated the associations between circulating concentrations of estrone, estradiol, free estradiol, testosterone, free testosterone, androstenedione, dehydroepiandrosterone (DHEA), progesterone, and sex hormone binding globulin (SHBG) with colon cancer risk in a nested case–control study of 1,028 postmenopausal European women (512 colon cancer cases, 516 matched controls) who were non-current users of exogenous hormones at blood collection. Multivariable conditional logistic regression models were used to compute odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate the association between circulating sex hormones and colon cancer risk. We also conducted a dose-response meta-analysis of prospective studies of circulating estrone and estradiol with colorectal, colon, and rectal cancer risk in postmenopausal women. All statistical tests were 2-sided. Results In the multivariable model, a non-statistically significant positive relationship was found between circulating estrone and colon cancer risk (OR per log2-1 unit increment = 1.17, 95%CI = 1.00–1.38; ORquartile4-quartile1 = 1.33, 95%CI = 0.89–1.97, Ptrend = 0.20). Circulating concentrations of estradiol, free estradiol, testosterone, free testosterone, androstenedione, DHEA, progesterone, and SHBG were not associated with colon cancer risk. In the dose-response meta-analysis, no clear evidence of associations were found between circulating estradiol, and estrone concentrations with colorectal, colon, and rectal cancer risk. Conclusion Our observational and meta-analysis results do not support an association between circulating concentrations of endogenous sex hormones and colon or rectal cancer in postmenopausal women.