Use of the Decipher genomic classifier among men with prostate cancer in the United States.

BACKGROUND: Management of localized or recurrent prostate cancer since the 1990s has been based on risk stratification using clinicopathological variables, including Gleason score, T stage (based on digital rectal exam), and prostate-specific antigen (PSA). In this study a novel prognostic test, the Decipher Prostate Genomic Classifier (GC), was used to stratify risk of prostate cancer progression in a US national database of men with prostate cancer. METHODS: Records of prostate cancer cases from participating SEER (Surveillance, Epidemiology, and End Results) program registries, diagnosed during the period from 2010 through 2018, were linked to records of testing with the GC prognostic test. Multivariable analysis was used to quantify the association between GC scores or risk groups and use of definitive local therapy after diagnosis in the GC biopsy-tested cohort and postoperative radiotherapy in the GC-tested cohort as well as adverse pathological findings after prostatectomy. RESULTS: A total of 572 545 patients were included in the analysis, of whom 8927 patients underwent GC testing. GC biopsy-tested patients were more likely to undergo active active surveillance or watchful waiting than untested patients (odds ratio [OR] =2.21, 95% confidence interval [CI] = 2.04 to 2.38, P < .001). The highest use of active surveillance or watchful waiting was for patients with a low-risk GC classification (41%) compared with those with an intermediate- (27%) or high-risk (11%) GC classification (P < .001). Among National Comprehensive Cancer Network patients with low and favorable-intermediate risk, higher GC risk class was associated with greater use of local therapy (OR = 4.79, 95% CI = 3.51 to 6.55, P < .001). Within this subset of patients who were subsequently treated with prostatectomy, high GC risk was associated with harboring adverse pathological findings (OR = 2.94, 95% CI = 1.38 to 6.27, P = .005). Use of radiation after prostatectomy was statistically significantly associated with higher GC risk groups (OR = 2.69, 95% CI = 1.89 to 3.84). CONCLUSIONS: There is a strong association between use of the biopsy GC test and likelihood of conservative management. Higher genomic classifier scores are associated with higher rates of adverse pathology at time of surgery and greater use of postoperative radiotherapy.In this study the Decipher Prostate Genomic Classifier (GC) was used to analyze a US national database of men with prostate cancer. Use of the GC was associated with conservative management (ie, active surveillance). Among men who had high-risk GC scores and then had surgery, there was a 3-fold higher chance of having worrisome findings in surgical specimens.

Radon and lung cancer in the pooled uranium miners analysis (PUMA): highly exposed early miners and all miners.

OBJECTIVES: Radon is a ubiquitous occupational and environmental lung carcinogen. We aim to quantify the association between radon progeny and lung cancer mortality in the largest and most up-to-date pooled study of uranium miners. METHODS: The pooled uranium miners analysis combines 7 cohorts of male uranium miners with 7754 lung cancer deaths and 4.3 million person-years of follow-up. Vital status and lung cancer deaths were ascertained between 1946 and 2014. The association between cumulative radon exposure in working level months (WLM) and lung cancer was modelled as the excess relative rate (ERR) per 100 WLM using Poisson regression; variation in the association by temporal and exposure factors was examined. We also examined analyses restricted to miners first hired before 1960 and with <100 WLM cumulative exposure. RESULTS: In a model that allows for variation by attained age, time since exposure and annual exposure rate, the ERR/100 WLM was 4.68 (95% CI 2.88 to 6.96) among miners who were less than 55 years of age and were exposed in the prior 5 to <15 years at annual exposure rates of <0.5 WL. This association decreased with older attained age, longer time since exposure and higher annual exposure rate. In analyses restricted to men first hired before 1960, we observed similar patterns of association but a slightly lower estimate of the ERR/100 WLM. CONCLUSIONS: This new large, pooled study confirms and supports a linear exposure-response relationship between cumulative radon exposure and lung cancer mortality which is jointly modified by temporal and exposure factors.

Lung Cancer and Radon: Pooled Analysis of Uranium Miners Hired in 1960 or Later.

BACKGROUND: Despite reductions in exposure for workers and the general public, radon remains a leading cause of lung cancer. Prior studies of underground miners depended heavily upon information on deaths among miners employed in the early years of mine operations when exposures were high and tended to be poorly estimated. OBJECTIVES: To strengthen the basis for radiation protection, we report on the follow-up of workers employed in the later periods of mine operations for whom we have more accurate exposure information and for whom exposures tended to be accrued at intensities that are more comparable to contemporary settings. METHODS: We conducted a pooled analysis of cohort studies of lung cancer mortality among 57,873 male uranium miners in Canada, Czech Republic, France, Germany, and the United States, who were first employed in 1960 or later (thereby excluding miners employed during the periods of highest exposure and focusing on miners who tend to have higher quality assessments of radon progeny exposures). We derived estimates of excess relative rate per 100 working level months (ERR/100 WLM) for mortality from lung cancer. RESULTS: The analysis included 1.9 million person-years of observation and 1,217 deaths due to lung cancer. The relative rate of lung cancer increased in a linear fashion with cumulative exposure to radon progeny (ERR/100 WLM=1.33; 95% CI: 0.89, 1.88). The association was modified by attained age, age at exposure, and annual exposure rate; for attained ages <55 y, the ERR/100 WLM was 8.38 (95% CI: 3.30, 18.99) among miners who were exposed at ≥35 years of age and at annual exposure rates of <0.5 working levels. This association decreased with older attained ages, younger ages at exposure, and higher exposure rates. DISCUSSION: Estimates of association between radon progeny exposure and lung cancer mortality among relatively contemporary miners are coherent with estimates used to inform current protection guidelines. https://doi.org/10.1289/EHP10669.

Developing a survivorship care plan (SCP) delivery process for patients and primary care providers serving poor, rural, and minority patients with cancer.

BACKGROUND: Survivorship care plans (SCPs) summarize patients' treatment and act as an education and communication tool between oncologists and primary care providers (PCPs). But creation and delivery of SCPs are challenging, labor intensive, and costly. The University of New Mexico Comprehensive Cancer Center (UNM CCC) treats a poor, rural, and minority patient population, and our purpose was to implement and evaluate a process to create and deliver SCPs to patients and PCPs. METHODS: Providers placed an electronic SCP order, basic information was imported, and staff compiled treatment details. Flagged SCPs were then ready for delivery, providers approved of and delivered the SCP at the next encounter, and the SCP was sent to the PCP. RESULTS: By April 2020, 283 SCPs were ordered, 241 (85.2%) were created by the designated staff, and 97 (34.2%) were given to patients after definitive therapy for breast cancer (59.1%), gynecological cancers (10.8%), prostate cancer (7.4%), colorectal cancer (5.1%), and lymphomas (4.8%). Of 97 SCPs eligible to be sent to PCPs, 75 (77.3%) were mailed or sent via EMR. Of the 41 (48.9%) SCPs sent via mail or fax, only 8 (8.3%) were received and 5 (5.2%) integrated. CONCLUSIONS: This study shows that SCPs can be delivered to patients in a poor, rural, and minority patient population but that PCP receipt and integration of SCPs are poor. Future efforts need to ensure that an oncologist to PCP education and communication tool is able reach and be integrated by PCPs.

PUMA - pooled uranium miners analysis: cohort profile.

OBJECTIVES: Epidemiological studies of underground miners have provided clear evidence that inhalation of radon decay products causes lung cancer. Moreover, these studies have served as a quantitative basis for estimation of radon-associated excess lung cancer risk. However, questions remain regarding the effects of exposure to the low levels of radon decay products typically encountered in contemporary occupational and environmental settings on the risk of lung cancer and other diseases, and on the modifiers of these associations. These issues are of central importance for estimation of risks associated with residential and occupational radon exposures. METHODS: The Pooled Uranium Miner Analysis (PUMA) assembles information on cohorts of uranium miners in North America and Europe. Data available include individual annual estimates of exposure to radon decay products, demographic and employment history information on each worker and information on vital status, date of death and cause of death. Some, but not all, cohorts also have individual information on cigarette smoking, external gamma radiation exposure and non-radiological occupational exposures. RESULTS: The PUMA study represents the largest study of uranium miners conducted to date, encompassing 124 507 miners, 4.51 million person-years at risk and 54 462 deaths, including 7825 deaths due to lung cancer. Planned research topics include analyses of associations between radon exposure and mortality due to lung cancer, cancers other than lung, non-malignant disease, modifiers of these associations and characterisation of overall relative mortality excesses and lifetime risks. CONCLUSION: PUMA provides opportunities to evaluate new research questions and to conduct analyses to assess potential health risks associated with uranium mining that have greater statistical power than can be achieved with any single cohort.

Breast cancer survival, survival disparities, and guideline-based treatment.

PURPOSE: The role of appropriate therapy in breast cancer survival and survival disparities by race/ethnicity has not been fully elucidated. We investigated whether lack of guideline-recommended therapy contributed to survival differences overall and among Hispanics relative to non-Hispanic white (NHW) women in a case-cohort study. METHODS: The study included a 15% random sample of female invasive breast cancer patients diagnosed from 1997 to 2009 in 6 New Mexico counties and all deaths due to breast cancer-related causes. Information was obtained from comprehensive medical chart reviews. National Comprehensive Cancer Network (NCCN®) guideline-recommended treatment was assessed among white women aged < 70 who were free of contraindications for recommended therapy, had stage I-III tumors, and survived ≥ 12 months. Hazard ratios (HRs) and 95% confidence intervals (CIs) for breast cancer death were estimated using Cox proportional hazards models. RESULTS: Included women represented 4635 patients and 449 breast cancer deaths. Women who did not receive radiotherapy (HR 2.3; 95% CI 1.2-4.4) or endocrine therapy (HR 2.0; 95% CI 1.0-4.0) as recommended by guidelines had an increased risk of breast cancer death, relative to those treated appropriately. Receipt of guideline-recommended therapy did not differ between Hispanic and NHW women for chemotherapy (84.2% vs. 81.3%, respectively), radiotherapy (89.2% vs. 91.1%), or endocrine therapy (89.2% vs. 85.8%), thus did not influence Hispanic survival disparities. CONCLUSIONS: Lack of guideline-recommended radiotherapy or endocrine therapy contributed to survival as strongly as other established prognostic indicators. Hispanic survival disparities in this population do not appear to be attributable to treatment differences.

Breast cancer survivors who use estrogenic botanical supplements have lower serum estrogen levels than non users.

To measure the association between use of estrogenic botanical supplements and serum sex hormones in postmenopausal breast cancer survivors, a total 502 postmenopausal women were queried 2-3 years after breast cancer diagnosis about their use of botanical supplements, and supplements were categorized according to their estrogenic properties. Concurrently, a fasting blood sample was obtained for assay of estrone, estradiol, free estradiol, testosterone, free testosterone, dehydroepiandrosterone sulfate (DHEAS), and sex hormone-binding globulin. Adjusted means of the serum hormones were calculated by use of estrogenic supplements. Women reporting use of any estrogenic botanical supplement had significantly lower levels of estrone (20.8 vs. 23.6 pg/ml), estradiol (12.8 vs. 14.7 pg/ml), free estradiol (0.29 vs. 0.35 pg/ml), and DHEAS (47.7 vs. 56.2 microg/dl) compared to women reporting no use. Data from this cross-sectional study suggest the use of estrogenic botanical supplements may be associated with sex hormone concentrations in breast cancer survivors. Considering the high use of these supplements among breast cancer patients, further research is needed to clarify the relative estrogenicity/antiestrogenicity of these compounds and their relation with prognosis.

Toward a better understanding of the comparatively high prostate cancer incidence rates in Utah.

BACKGROUND: This study assesses whether comparatively high prostate cancer incidence rates among white men in Utah represent higher rates among members of the Church of Jesus Christ of Latter-day Saints (LDS or Mormons), who comprise about 70% of the state's male population, and considers the potential influence screening has on these rates. METHODS: Analyses are based on 14,693 histologically confirmed invasive prostate cancer cases among men aged 50 years and older identified through the Utah Cancer Registry between 1985 and 1999. Cancer records were linked to LDS Church membership records to determine LDS status. Poisson regression was used to derive rate ratios of LDS to nonLDS prostate cancer incidence, adjusted for age, disease stage, calendar time, and incidental detection. RESULTS: LDS men had a 31% (95% confidence interval, 26%-36%) higher incidence rate of prostate cancer than nonLDS men during the study period. Rates were consistently higher among LDS men over time (118% in 1985-88, 20% in 1989-92, 15% in 1993-1996, and 13% in 1997-99); age (13% in ages 50-59, 48% in ages 60-69, 28% in ages 70-79, and 16% in ages 80 and older); and stage (36% in local/regional and 17% in unstaged). An age- and stage-shift was observed for both LDS and nonLDS men, although more pronounced among LDS men. CONCLUSIONS: Comparatively high prostate cancer incidence rates among LDS men in Utah are explained, at least in part, by more aggressive screening among these men.

Incidental detection of population-based prostate cancer incidence rates through transurethral resection of the prostate.

OBJECTIVE: To provide an updated assessment of the influence transurethral resection of the prostate (TURP) has on incidental detection of prostate cancer and to characterize stage, histologic grade, and treatment patterns among these cases. METHODS: Analyses were based on 17,310 histologically confirmed prostate cancer cases ages 45 years and older recorded in the Utah Cancer Registry between 1980 and 1999 and 6426 TURP procedures recorded in the Utah Hospital Discharge Database from 1992 through 1999. An algorithm was developed for identifying TURP-detected prostate cancer incidence. RESULTS: Age-specific TURP-detected prostate cancer incidence rates tended to be flat between 1980 and 1990, decline through 1994, and then level off. Much of the decrease corresponds to the prostate-specific antigen (PSA) screening induced peak and subsequent fall in total prostate cancer incidence rates. Leveling off in the TURP-detected rates between 1994 and 1999 corresponds with a leveling off in the total prostate cancer incidence rates. The percentage of prostate cancer detected by TURP significantly increases with age, within each age group, but decreases over calendar years. For ages 45 years and older, the percentage of TURP-detected cases was 39.0% in 1980 to 1984, 33.9% in 1985 to 1989, 12.2% in 1990 to 1994, and 7.4% in 1995 to 1999. TURP-detected cases were significantly less likely to undergo radical prostatectomy or radiation therapy across age groups, despite having lower stage and histologic grade at diagnosis. CONCLUSION: TURP-detected prostate cancer rates have leveled off in the latter part of the 1990s, explaining about 10% of all detected cases. These cases have relatively good biologic potential and are less likely to pursue aggressive therapy.