Delays in the initiation of cancer treatment were associated with higher all-cause mortality among patients with breast, lung, prostate and colon cancers in an analysis of data on more than 2.2 million patients enrolled in the National Cancer Database (NCDB).
Patients with colon cancer and non-small cell lung cancer (NSCLC) had the highest mortality associated with increased time-to-treatment in the cohort study, but longer time-to-treatment initiation was linked to higher mortality for all four cancers, “suggesting an indirect association between treatment deferral and mortality that may not become evident for years,” wrote researcher Eugene Cone, MD, of Brigham and Women’s Hospital, Boston, and colleagues, in JAMA Network Open.
They added that while the analysis involved patients treated between 2004 and 2015, the findings have practical implications during Covid-19 and beyond the pandemic.
“Our study has important policy implications for the current pandemic, for triage of cancer care in resource-limited settings, and for future crises, as health care may be affected by future natural disasters , pandemics, and supply chain constraints,” they wrote.
“Our analyses suggests a rank order for prioritizing which patient cases could still be performed in resource-limited settings and the order in which cases should be added back to the treatment schedule as resource limitations ease. Our initial analysis of these common cancers provides foundational evidence on these discussions.”
The study included 2,241,706 patients (mean age 63 [11.9] years, 1,268,794 [56.6%] women, 1,880,317 [83.9%] white): 1,165,585 (52.0%) with breast cancer, 853,030 (38.1%) with prostate cancer, 130,597 (5.8%) with NSCLC, and 92,494 (4.1%) with colon cancer.
The median time to treatment initiation (TTI) by cancer was 32 (21-48) days for breast, 79 (55-117) days for prostate, 41 (27-62) days for NSCLC, and 26 (16-40) days for colon.
Among the main study findings:
- The predicted 5-year and 10-year mortality rates associated with TTI were greatest for colon cancer (stage III 5 year predicted mortality with a TTI of 61-120 days of 38.9% versus 181-365 days, 47.6%).
- The predicted 5-year and 10-year mortality rates associated with TTI were lowest for low-risk prostate cancer patients treated within 60 days (4.9% and 17.3%, respectively).
- While analysis of all-stage prostate and breast did not reveal any association with delay, by-stage analysis demonstrated associations of high-risk and intermediate-risk prostate and stage I and II breast cancers with TTI of 61 to 120 days, and all-stage breast cancers with TTI greater than 121 days.
- Increasing TTI and advanced stage and risk was associated with greater predicted mortality across all cancers (eg, predicted mortality: stage III breast cancer at TTI 181-365 days, 32.7% vs stage 0 breast cancer at TTI 8-60 days, 9.6%). Sensitivity analysis using 30-day intervals found no difference in trends by disease.
Key study limitations cited by the researchers included the lack of data on reasons for treatment delay and the recognition that “drivers of increased TTIs in our patient cohort may differ from those in a pandemic.”
“Patients in our cohort may have confounding factors, which are linked to both worse outcomes and TTI, including low health literacy, poor access to care, and care at lower-quality hospitals, which could limit the generalizability of our findings,” they wrote. “All patients are exposed to resource limitations in pandemic conditions, including those who are unaffected by these confounders, though disparities in care persist for racial minority groups.”
Cone and colleagues wrote that they considered their analysis to be a “worst case scenario in estimating the effects of high times between diagnosis and treatment.”
“We believe bias in this direction to be preferable, however, as it is more useful for hospital administrators, clinicians, and policymakers to know the upper limit effect size for predicted mortality potentially associated with triage decisions, especially when compared with underestimation owing to best-case biased analyses.”
They concluded that their finding of a mortality benefit associated with a shorter duration of time from cancer diagnosis to treatment challenges current guidelines for the management of prostate cancer.
“Specifically, our data support only limited deferral for prostate cancer, with length of deferral dependent on risk stratification,” they wrote. “Future analyses will expand to other cancers, which may assist with treatment deferral decisions in resource-limited settings and provide a framework for prioritizing treatments as limitations ease.”
In accompanying commentary, Laura Van Metre Baum, MD, of Vanderbilt University School of Medicine, Nashville, and colleagues, wrote that the findings “draw attention to the importance of prioritizing timely cancer care, even during the Covid-19 pandemic,” which includes cancer screening.
“Primary care, the most important conduit for cancer screening and initial evaluation of new symptoms, has been the hardest hit economically and the most subject to profound disruption and restructuring during the current Covid-19 pandemic,” they wrote, adding that the pandemic may have long-term implications for access to timely care.
They noted that disparities in access to care and the treatment delays that result from them, “reflect inequities and inadequacies in the health care system.”
“Adequate investment in primary care could improve outcomes, given the cost-saving and mortality benefits of preventive care, early diagnosis and timely treatment and holistic, comprehensive management provided by a good primary care team,” they wrote, adding that “improvement in insurance coverage for cancer and other chronic conditions could alleviate the financial toxicity and accompanying trade-offs patients are forced to make between their health and their livelihood.”
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Delays in the initiation of cancer treatment were associated with higher all-cause mortality among patients with breast, lung, prostate and colon cancers.
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The study findings have policy implications for the current pandemic, for triage of cancer care in resource-limited settings, and for future crises, the researchers wrote.
Salynn Boyles, Contributing Writer, BreakingMED™
Principal researcher Quoc-Dien Trinh reported receiving research support from a Health Services Research pilot test grant from the Defense Health Agency and an unrestricted educational grant from the Vattikutti Urology Institute; he also reported receiving personal fees from Astellas Pharma, Bayer, Janssen Pharmaceuticals, Insightec, and Intuitive Surgical unrelated to this research.
Editorial writer Cardinale Smith reported receiving honoraria from Teva Pharmaceuticals unrelated to this research.
Cat ID: 22
Topic ID: 78,22,22,23,24,25,192,925
