ABSTRACT
Importance: Resource limitations because of pandemic or other stresses on infrastructure necessitate the triage of time-sensitive care, including cancer treatments. Optimal time to treatment is underexplored, so recommendations for which cancer treatments can be deferred are often based on expert opinion. Objective: To evaluate the association between increased time to definitive therapy and mortality as a function of cancer type and stage for the 4 most prevalent cancers in the US. Design, Setting, and Participants: This cohort study assessed treatment and outcome information from patients with nonmetastatic breast, prostate, non-small cell lung (NSCLC), and colon cancers from 2004 to 2015, with data analyzed January to March 2020. Data on outcomes associated with appropriate curative-intent surgical, radiation, or medical therapy were gathered from the National Cancer Database. Exposures: Time-to-treatment initiation (TTI), the interval between diagnosis and therapy, using intervals of 8 to 60, 61 to 120, 121 to 180, and greater than 180 days. Main Outcomes and Measures: 5-year and 10-year predicted all-cause mortality. Results: This study included 2â¯241â¯706 patients (mean [SD] age 63 [11.9] years, 1â¯268â¯794 [56.6%] women, 1â¯880â¯317 [83.9%] White): 1â¯165â¯585 (52.0%) with breast cancer, 853â¯030 (38.1%) with prostate cancer, 130â¯597 (5.8%) with NSCLC, and 92â¯494 (4.1%) with colon cancer. Median (interquartile range) 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. Across all cancers, a general increase in the 5-year and 10-year predicted mortality was associated with increasing TTI. The most pronounced mortality association was for colon cancer (eg, 5 y predicted mortality, stage III: TTI 61-120 d, 38.9% vs. 181-365 d, 47.8%), followed by stage I NSCLC (5 y predicted mortality: TTI 61-120 d, 47.4% vs 181-365 d, 47.6%), while survival for prostate cancer was least associated (eg, 5 y predicted mortality, high risk: TTI 61-120 d, 12.8% vs 181-365 d, 14.1%), followed by breast cancer (eg, 5 y predicted mortality, stage I: TTI 61-120 d, 11.0% vs. 181-365 d, 15.2%). A nonsignificant difference in treatment delays and worsened survival was observed for stage II lung cancer patients-who had the highest all-cause mortality for any TTI regardless of treatment timing. Conclusions and Relevance: In this cohort study, for all studied cancers there was evidence that shorter TTI was associated with lower mortality, suggesting an indirect association between treatment deferral and mortality that may not become evident for years. In contrast to current pandemic-related guidelines, these findings support more timely definitive treatment for intermediate-risk and high-risk prostate cancer.
Subject(s)
Antineoplastic Protocols , Breast Neoplasms , Colonic Neoplasms , Lung Neoplasms , Prostatic Neoplasms , Time-to-Treatment , Aged , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Breast Neoplasms/therapy , COVID-19/epidemiology , COVID-19/prevention & control , Cohort Studies , Colonic Neoplasms/mortality , Colonic Neoplasms/pathology , Colonic Neoplasms/therapy , Databases, Factual/statistics & numerical data , Female , Humans , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Lung Neoplasms/therapy , Male , Middle Aged , Mortality , Neoplasm Staging , Prognosis , Prostatic Neoplasms/mortality , Prostatic Neoplasms/pathology , Prostatic Neoplasms/therapy , Time-to-Treatment/standards , Time-to-Treatment/statistics & numerical data , United States/epidemiologyABSTRACT
BACKGROUND: During the COVID-19 pandemic, surgical delays have been common for patients with ductal carcinoma in situ (DCIS) and early-stage estrogen receptor-positive (ER+) breast cancer, often in favor of neoadjuvant endocrine therapy (NET). To understand possible ramifications of these delays, we examined the association between time to operation and pathologic staging and overall survival (OS). STUDY DESIGN: Patients with DCIS or ER+ cT1-2N0 breast cancer treated from 2010 through 2016 were identified in the National Cancer Database. Time to operation was recorded. Factors associated with pathologic upstaging were examined using logistic regression analyses. Cox proportional hazard models were used to analyze OS. Analyses were stratified by disease stage and initial treatment strategy. RESULTS: There were 378,839 patients identified. Among those undergoing primary surgical procedure, time to operation was within 120 days in > 98% in all groups. Among cT1-2N0 patients selected for NET, operations were performed within 120 days in 59.6% of cT1N0 and 30.9% of cT2N0 patients. Increased time to operation was associated with increased odds of pathologic upstaging in DCIS patients (ER+: 60 to 120 days: odds ratio 1.15; 95% CI, 1.08 to 1.22; more than 120 days: odds ratio 1.44; 95% CI, 1.24 to 1.68; ER-: 60 to 120 days: NS; more than 120 days: odds ratio 1.36; 95% CI, 1.01 to 1.82; 60 days or less: reference), but not in patients with invasive cancer, irrespective of initial treatment strategy. No difference in OS was seen by time to operation in DCIS or NET patients. CONCLUSIONS: Increased time to operation was associated with a small increase in pathologic upstaging in DCIS patients, but did not impact OS. In patients with cT1-2N0 disease, NET use did not impact stage or OS, supporting the safety of delay strategies in ER+ breast cancer patients during the pandemic.