Collateral effects of the COVID-19 pandemic on endocrine treatments for breast and prostate cancer in the UK: implications for bone health (preprint)

BackgroundThe COVID-19 pandemic affected cancer screening, diagnosis and treatment pathways. This study examined the impact of the pandemic on incidence and trends of endocrine treatments in patients with breast or prostate cancer; and endocrine treatment-related side-effects. MethodsPopulation-based cohort study using UK primary care Clinical Practice Research Datalink (CPRD) GOLD database. There were 13,701 newly diagnosed breast cancer patients and 12,221 prostate cancer patients with [≥]1-year data availability since diagnosis between January 2017-June 2022. Incidence rates (IR) and incidence rate ratios (IRR) were calculated across multiple time periods before and after lockdown to examine the impact of changing social restrictions on endocrine treatments and treatment-related outcomes, including osteopenia, osteoporosis and bisphosphonate prescriptions. ResultsIn patients with breast cancer, aromatase inhibitor prescriptions increased during lockdown compared to pre-pandemic (IRR: 1.22 [95% Confidence Interval: 1.11-1.34]), followed by a decrease post-first lockdown (IRR: 0.79 [95%CI: 0.69-0.89]). In patients with prostate cancer, first-generation antiandrogen prescriptions increased compared to pre-pandemic (IRR: 1.23 [95% CI: 1.08-1.4]). For breast cancer patients on aromatase inhibitors, diagnoses of osteopenia, osteoporosis and bisphosphonate prescriptions were reduced across all lockdown periods compared to pre-pandemic (IRR range: 0.31-0.62). ConclusionDuring the first two years of the pandemic, newly diagnosed breast and prostate cancer patients were prescribed more endocrine treatments compared to pre-pandemic, due to restrictions on hospital procedures replacing surgeries with bridging therapies. But breast cancer patients had fewer diagnoses of osteopenia and osteoporosis, and bisphosphonate prescriptions. These patients should be followed up in the coming years for signs of bone thinning. Evidence of poorer management of treatment-related side-effects will allow us to determine whether there is a need to better allocate resources to patients at high risk for bone-related complications.

The impact of the COVID-19 pandemic on short-term cancer survival in the United Kingdom: a cohort analysis (preprint)

Objectives: The COVID-19 pandemic profoundly affected healthcare systems and patients. There is a pressing need to comprehend the collateral effects of the pandemic on non-communicable diseases. Here we examined the impact of the COVID-19 pandemic on short-term cancer survival in the United Kingdom (UK). We hypothesised that short-term survival from nine cancers would be reduced during the pandemic, particularly cancers that benefit from screening and early detection (e.g., breast and colorectal cancer). Design: Population-based cohort study. Setting: Electronic health records from UK primary care Clinical Practice Research Datalink (CPRD) GOLD database. Participants: There were 12,259,744 eligible patients aged [≥]18 years with [≥]one year of prior history identified from January 2000 to December 2021. Main outcome measures: We estimated age-standardised incidence rates (IR) and short-term (one- and two-year) survival of several common cancers (breast, colorectal, head and neck, liver, lung, oesophagus, pancreatic, prostate, and stomach cancer) from 2000 to 2019 (in five-year strata) compared to 2020 to 2021 using the Kaplan-Meier method. Results: Apart from pancreatic cancer, IRs decreased for all cancers in 2020 and recovered to different extents in 2021. Short-term survival improved for most cancers between 2000 to 2019, but then declined for those diagnosed in 2020 to 2021.This was most pronounced for colorectal cancer, with one-year survival falling from 79.3% [95% confidence interval: 78.5%-80.1%] in 2015 to 2019 to 76.3% [74.6%-78.1%] for those diagnosed in 2020 to 2021. Conclusion: Short-term survival for many cancers was impacted by the management of the COVID-19 pandemic in the UK. This decline was most prominent for colorectal cancer, with reductions in survivorship equivalent to returning to mortality seen in the first decade of the 2000s. These results illustrate the need for an immediate and well-funded investment in resolving the current backlog in cancer screening and diagnostic procedures in the UK National Health Service to improve patient outcomes.

The Impact of the UK COVID-19 Lockdown on the Screening, Diagnostics and Incidence of Breast, Colorectal, Lung and Prostate Cancer in the UK: a Population-Based Cohort Study (preprint)

Objectives: This study aimed to assess the impact of the COVID-19 lockdown on the screening and diagnosis of breast, colorectal, lung, and prostate cancer. The study also investigated whether the rates returned to pre-pandemic levels by December 2021. Design: Cohort study. Setting: Electronic health records from UK primary care Clinical Practice Research Datalink (CPRD) GOLD database. Participants: The study included individuals registered with CPRD GOLD between January 2017 and December 2021, with at least 365 days of prior observation. Main outcome measures: The study focused on screening, diagnostic tests, referrals and diagnoses of first-ever breast, colorectal, lung, and prostate cancer. Incidence rates (IR) were stratified by age, sex and region, and incidence rate ratios (IRR) were calculated to compare rates during and after lockdown with the reference period before lockdown. Forecasted rates were estimated using negative binomial regression models. Results: Among 5,191,650 eligible participants, the initial lockdown resulted in reduced screening and diagnostic tests for all cancers, which remained dramatically reduced across the whole observation period for almost all tests investigated. For cancer incidence rates, there were significant IRR reductions in breast (0.69), colorectal (0.74), and prostate (0.71) cancers. However, the reduction in lung cancer incidence (0.92) was non-significant. Extrapolating to the entire UK population, an estimated 18,000 breast, 13,000 colorectal, 10,000 lung, and 21,000 prostate cancer diagnoses were missed from March 2020 to December 2021. Conclusion: The national COVID-19 lockdown in the UK had a substantial impact on cancer screening, diagnostic tests, referrals and diagnoses. Although incidence rates started to recover after the lockdown, they remained significantly lower than pre-pandemic levels for breast and prostate cancers and associated tests. Delays in diagnosis are likely to have adverse consequences on cancer stage, treatment initiation, mortality rates, and years of life lost. Urgent strategies are needed to identify undiagnosed cases and address the long-term implications of delayed diagnoses.

The role of COVID-19 vaccines in preventing post COVID-19 thromboembolic and cardiovascular complications: a multinational cohort study (preprint)

ImportanceThe overall effects of vaccination on the risk of cardiac, and venous and arterial thromboembolic complications following COVID-19 remain unclear. ObjectiveWe studied the association between COVID-19 vaccination and the risk of acute and subacute COVID-19 cardiac and thromboembolic complications. DesignMultinational staggered cohort study, based on national vaccination campaign rollouts. SettingNetwork study using electronic health records from primary care records from the UK, primary care data linked to hospital data from Spain, and national insurance claims from Estonia. ParticipantsAll adults with a prior medical history of [≥]180 days, with no history of COVID-19 or previous COVID-19 vaccination at the beginning of vaccine rollout were eligible. ExposureVaccination status was used as a time-varying exposure. Vaccinated individuals were classified by vaccine brand according to the first dose received. Main OutcomesPost COVID-19 complications including myocarditis, pericarditis, arrhythmia, heart failure (HF), venous (VTE) and arterial thromboembolism (ATE) up to 1 year after SARS-CoV-2 infection. MeasuresPropensity Score overlap weighting and empirical calibration based on negative control outcomes were used to minimise bias due to observed and unobserved confounding, respectively. Fine-Gray models were fitted to estimate sub-distribution Hazard Ratios (sHR) for each outcome according to vaccination status. Random effect meta-analyses were conducted across staggered cohorts and databases. ResultsOverall, 10.17 million vaccinated and 10.39 million unvaccinated people were included. Vaccination was consistently associated with reduced risks of acute (30-day) and subacute post COVID-19 VTE and HF: e.g., meta-analytic sHR 0.34 (95%CI, 0.27-0.44) and 0.59 (0.50-0.70) respectively for 0-30 days, sHR 0.58 (0.48 - 0.69) and 0.71 (0.59 - 0.85) respectively for 90-180 days post COVID-19. Additionally, reduced risks of ATE, myocarditis/pericarditis and arrhythmia were seen, but mostly in the acute phase (0-30 days post COVID-19). ConclusionsCOVID-19 vaccination reduced the risk of post COVID-19 complications, including cardiac and thromboembolic outcomes. These effects were more pronounced for acute (1-month) post COVID-19 outcomes, consistent with known reductions in disease severity following breakthrough vs unvaccinated SARS-CoV-2 infection. RelevanceThese findings highlight the importance of COVID-19 vaccination to prevent cardiovascular outcomes after COVID-19, beyond respiratory disease. Key PointsO_ST_ABSQuestionC_ST_ABSWhat is the impact of COVID-19 vaccination to prevent cardiac complications and thromboembolic events following a SARS-CoV-2 infection? FindingsResults from this multinational cohort study showed that COVID-19 vaccination reduced risk for acute and subacute COVID-19 heart failure, as well as venous and arterial thromboembolic events following SARS-CoV-2 infection. MeaningThese findings highlight yet another benefit of vaccination against COVID-19, and support the recommendations for COVID-19 vaccination even in people at high cardiovascular risk.