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Age-related differences in colon and rectal cancer survival have been observed, even after accounting for differences in background mortality. To determine to what extent stage, tumour site, or histology could contribute to these differences, we estimated 1-year relative survival (RS) age stratified by these factors. Colon and rectal cancer cases diagnosed between 2012 and 2016 and followed up until 2017 were retrieved from 18 United States Surveillance Epidemiology and End Results cancer registries. For colon cancer, 1-year RS ranged from 87.8% [95% Confidence Interval: 87.5-88.2] in the 50–64-year-old age group to 62.3% [61.3-63.3] in the 85–99-year-old age group and for rectal cancer ranged from 92.3% [91.8-82.7] to 65.0% [62.3-67.5]. With respect to stage, absolute differences in RS between 50–64-year-old and 75–84-year-old in RS increased with increasing stage (from 6 [5-7] %-points in localized disease to 27 [25-29] %-points in distant disease) and were the highest for cancers of unknown stage (>28%-points). With respect to topography, age-related differences in survival were smallest for those in right-sided colon (8 [7-9] %-points) and largest for tumours of the colon without topography further specified (25 [21-29] %-points). While age-related differences in survival varied by histology and tumour site, the overall age-related differences in survival could not be explained by differences in distribution of these factors by age, consistent with a hypothesis that stage at diagnosis or treatment are more likely drivers. Incorporating data on geriatric conditions such as frailty and comorbidity would support further understanding of the age gap in colon and rectal cancer survival.

Background Simple blood tests can play an important role in identifying patients for cancer investigation. The current evidence base is limited almost entirely to tests used in isolation. However, recent evidence suggests combining multiple types of blood tests and investigating trends in blood test results over time could be more useful to select patients for further cancer investigation. Such trends could increase cancer yield and reduce unnecessary referrals. We aim to explore whether trends in blood test results are more useful than symptoms or single blood test results in selecting primary care patients for cancer investigation. We aim to develop clinical prediction models that incorporate trends in blood tests to identify the risk of cancer. Methods Primary care electronic health record data from the English Clinical Practice Research Datalink Aurum primary care database will be accessed and linked to cancer registrations and secondary care datasets. Using a cohort study design, we will describe patterns in blood testing (aim 1) and explore associations between covariates and trends in blood tests with cancer using mixed-effects, Cox, and dynamic models (aim 2). To build the predictive models for the risk of cancer, we will use dynamic risk modelling (such as multivariate joint modelling) and machine learning, incorporating simultaneous trends in multiple blood tests, together with other covariates (aim 3). Model performance will be assessed using various performance measures, including c-statistic and calibration plots. Discussion These models will form decision rules to help general practitioners find patients who need a referral for further investigation of cancer. This could increase cancer yield, reduce unnecessary referrals, and give more patients the opportunity for treatment and improved outcomes.

Background:Prostate cancer is an important cause of death worldwide. The number of years of life lost (YLL) due to prostate cancer is a metric of the toll of prostate cancer and using projections of demographic changes, can be used to measure future burden. Methods:Prostate cancer mortality data by country and world region was retrieved from the Global Cancer Observatory and the World Health Organization mortality data set, and life expectancy was from the United Nations Department of Economic and Social Affairs. We estimated YLL as the difference between age at death in people with prostate cancer and remaining life expectancy for people of the same age in the general population. We also estimated the age-standardized YLL rates per 100,000 males over 50 and the average annual percentage change in YLL rates over the period 2000–2019 and the number of YLL for the year 2040 by applying population projections to the 2020 YLL rates. Results:In 2020, 3.5 million person-years of life were lost due to prostate cancer in males over 50, and 40% of YLL were in those aged over 75. Age-standardized rates varied greatly between and within regions. Over the last two decades, rates of YLL have increased in many Asian and African countries while they have decreased in northern American and European countries. Globally, YLL are anticipated to double by 2040 to reach 7.5 million, with the greatest increases in Africa, Asia, and Latin America and the Caribbean. Conclusion:There are wide variations in the burden of prostate cancer globally as measured by YLL. The burden of prostate cancer is projected to increase over time and appears to be highest in Sub-Saharan Africa, Eastern Europe, and Latin America and the Caribbean. It will be critical to plan and implement programs to reduce the burden of prostate cancer globally.

12005 Background: Radiotherapy-related adverse effects such as the development of subsequent neoplasms cause significant morbidity among prostate cancer survivors. Advances in radiotherapy techniques, including intensity-modulated radiation therapy (IMRT) and proton beam radiotherapy (PBRT), have aimed to reduce exposure to adjacent healthy tissues to reduce adverse effects. Initial reports based on small sample sizes and limited follow up (through 2011) have suggested reduced risks for subsequent colon and rectal cancers following IMRT compared to 3D conformal radiotherapy (CRT) for prostate cancer patients, but not for subsequent bladder cancer. We sought to extend previous reports with larger sample size and longer follow up. Methods: We conducted a retrospective cohort study within the linked database of Surveillance, Epidemiology and End Results (SEER) cancer registries and Medicare claims. The cohort included men diagnosed with first primary non-metastatic prostate cancer at ages 66-84 during 2002-2011; received initial IMRT, PBRT, or CRT; and survived without developing a second primary cancer ≥5 years after diagnosis (follow up through 2016). Cox regression models estimated risks of second primary solid tumors after IMRT and PBRT vs CRT, adjusting for age at prostate cancer diagnosis, tumor grade, race, Charlson comorbidity score, and receipt of initial prostate cancer therapy. Results: The cohort (median follow-up = 8.4 years) included 51,020 patients, of whom 19,536 received CRT alone, 29,868 received IMRT without PBRT, and 1,616 received PBRT. Compared to patients who received CRT (n = 1,348, 7.0%), both IMRT (n = 1,289, 4.3%; hazard ratio [HR] = 0.87; 95% confidence interval [CI], 0.80-0.95) and PBRT (n = 83, 5.1%; HR = 0.77; 95% CI 0.62-0.97) showed a decrease in risk of developing any second solid malignancy. In analyses by second cancer type, risks of colon cancer (HR = 0.70; 95%CI, 0.52-0.94) and bladder cancer (HR = 0.79; 95%CI, 0.65-0.97) were significantly lower after IMRT than CRT, whereas no association was observed for anorectal cancers (HR = 1.00; 95%CI, 0.65-1.53). Further investigation by time since prostate cancer diagnosis revealed a time-dependent decrease after IMRT compared to CRT in risk for bladder cancer (HRs = 0.94, 0.87, 0.61 for 5-7.4, 7.5-9.9, and 10+ years respectively) and anorectal cancer (HRs = 1.22, 0.97, 0.78), whereas the opposite trend was observed for colon cancer (HRs = 0.70, 0.68, 1.05). Conclusions: In this large cohort with increased follow-up time compared with previous reports, we observed reduced risk of colon and bladder cancer with IMRT overall, as well as time-dependent patterns for bladder and anorectal cancer that were consistent with improved tumor targeting. Further research is needed with larger sample sizes to evaluate long-term effects after PBRT. Our study supports the value of quantifying adverse effects as radiotherapy techniques evolve.

Malignant tumors of the central nervous system in adults comprise a heterogeneous group of malignancies, the largest subgroups comprising astrocytomas, ependymomas, and oligodendrogliomas. Glioblastomas are the most common tumor type, and they have dismal prognosis. Due to differences in cell type of origin, as well as pathogenesis, it is plausible that their etiology also differs between tumor types. The etiology of malignant CNS tumors is largely unknown and no occupational risk factors have been definitively identified. High doses of ionizing radiation increase the risk, but in occupational settings the dose levels appear too small to result in discernible excesses. Several studies have assessed possible effect of extremely low frequency and radiofrequency electromagnetic fields, but the results are inconsistent. Increased brain tumor risk has been reported in agricultural workers, but no specific exposure has been linked to them. Pesticides have been analyzed in several studies without showing a clear increase in risk. acceptedVersion