Reduced Pancreatic Cancer Survival During COVID-19 Pandemic

Pancreatic Cancer: Pancreatic CancerEven before the COVID-19 pandemic, pancreatic ductal adenocarcinoma (PDAC) had the worst prognosis of any of the common cancers, with only a quarter of patients still alive 1 year from diagnosis.1 Given the unprecedented disruption to health care services during the pandemic,2 it is perhaps unsurprising that pancreatic cancer outcomes would have worsened, with a growing body of evidence to support this hypothesis. The more important questions, rather, are what was the extent of and reasons for this impact, and what lessons can we learn to plan for future health care disruptions to minimize “collateral damage”? We recently published results from our British single-center study, suggesting a halving of median survival for PDAC patients diagnosed during the pandemic compared to a comparable pre-pandemic cohort. In real terms, this represented a 4-month reduction in median survival.3 Our findings are validated by a North American study, which found an increased proportion of patients presenting at later stages and a reduction of 2 months in overall survival in those diagnosed with metastatic PDAC during the pandemic compared with before the pandemic.4 Several other studies have demonstrated the negative effects of COVID-19 on PDAC diagnosis and management. A Spanish study compared changes in PDAC diagnoses and treatment as a result of the pandemic and found a trend towards prolonged time to diagnosis and delayed treatment with a statistically significant increase in those presenting with Stage III/IV disease.5 McKay et al surveyed the impact of COVID-19 on 29 UK pancreatic cancer centers during the first phase of the pandemic and found reduced diagnostic investigations and a change in treatment pathways, with access to invasive diagnostic procedures (e.g., ERCP and laparoscopy) particularly affected. There was a 40 percent reduction in the use of surgical resection compared with a 2019 baseline and approximately a quarter of centers changed treatment regimens from surgery to neoadjuvant treatment for resectable disease.6 Data from a separate study from our center showed that, during the early pandemic, one-third of preferred hepatopancreatobiliary MDT recommendations for surgery were altered due to concerns regarding patient risk from COVID-19 during treatment or due to the presumed balance of risk and benefit in patients with borderline performance status.7 What might be driving this consistent reduction in patient outcomes? This may relate to either direct or indirect effects of COVID-19, with indirect effects mediated through changes in the nature of the disease or patient at the time of diagnosis or changes to diagnostic or management pathways. Reduced survival during the pandemic may directly relate to excess mortality due to COVID-19 infection. While larger datasets would be valuable in fully evaluating any effect, in our study we did not identify a significant proportion of deaths from COVID-19 in the “pandemic” cohort and found the overall reduction in survival was unaffected after exclusion of the small number of cases.3 Two-week wait referrals in England for upper-gastrointestinal malignancies from primary care fell by 65 percent compared with 2019 during the pandemic, inevitably leading to delays in diagnosis and treatment.8 PDAC often presents indolently with vague symptoms and any reduction in primary care contact could shift diagnosis to a later stage of disease. Surgical resection offers the only possibility of a cure in PDAC,9 but is only appropriate in early-stage disease. Therefore, any delays in diagnosis risk restriction of treatment options and a reduction in overall survival.3,4 This is supported by the evidence showing that referral pathways and treatment regimens have changed during the pandemic.3-7 The results of the studies to date suggesting the substantial impact of the COVID-19 pandemic on PDAC are very concerning. Although most of the existing research conducted on COVID-19 and PDAC are from small datasets, we must not ignore the alarm bells ringing. Confirmation of these findings with larger, more geographically diverse studies will enable petitioning of policy makers to both acknowledge the negative impact of COVID-19 on PDAC outcomes and implement strategies to mitigate the impact of future pandemics. While we can already see some of the impact in PDAC due to its poor prognosis, the impact across other tumor sites, where survival is generally longer, may not yet be evident. We suggest that the impact of COVID-19 upon PDAC should act as a warning for other malignancies, where further time may be required for the negative impact of COVID-19 to be seen. The COVID-19 pandemic strained not only health care systems, but policy makers and governments as well. Decisions were made without the benefit of time or evidence to consider their wider impact; for example, dramatically altered public health messaging that encouraged patients to minimize their contact with health care to avoid overwhelming the system. As more evidence emerges of the effects of these decisions not just on PDAC, but on outcomes in other cancers, the alarm bells are likely to ring ever louder and must not be ignored. ALEXANDRA BRODEY is in the Department of Oncology at Oxford University Hospitals NHS Foundation Trust. OLIVER MADGE, MRCP(UK), is in the Ambulatory Assessment Unit at Oxford University Hospitals NHS Foundation Trust. SHIVAN SIVAKUMAR, MRCP(UK), PhD, is in the Department of Oncology at Oxford University Hospitals NHS Foundation Trust and the Department of Oncology at the University of Oxford. MATTHEW J. BOTTOMLEY, MRCP(UK), DPhil, is in the Ambulatory Assessment Unit at Oxford University Hospitals NHS Foundation Trust and the Nuffield Department of Medicine at University of Oxford.Alexandra Brodey: Alexandra BrodeyOliver Madge, MRCP(UK): Oliver Madge, MRCP(UK)Shivan Sivakumar, MRCP(UK), PhD: Shivan Sivakumar, MRCP(UK), PhDMatthew J. Bottomley, MRCP(UK), DPhil: Matthew J. Bottomley, MRCP(UK), DPhil