Date Published: March 1, 2019
Publisher: Public Library of Science
Author(s): Alok A. Khorana, Katherine Tullio, Paul Elson, Nathan A. Pennell, Stephen R. Grobmyer, Matthew F. Kalady, Daniel Raymond, Jame Abraham, Eric A. Klein, R. Matthew Walsh, Emily E. Monteleone, Wei Wei, Brian Hobbs, Brian J. Bolwell, Aamir Ahmad.
Delays in time to treatment initiation (TTI) for new cancer diagnoses cause patient distress and may adversely affect outcomes. We investigated trends in TTI for common solid tumors treated with curative intent, determinants of increased TTI and association with overall survival.
We utilized prospective data from the National Cancer Database for newly diagnosed United States patients with early-stage breast, prostate, lung, colorectal, renal and pancreas cancers from 2004–13. TTI was defined as days from diagnosis to first treatment (surgery, systemic or radiation therapy). Negative binomial regression and Cox proportional hazard models were used for analysis. The study population of 3,672,561 patients included breast (N = 1,368,024), prostate (N = 944,246), colorectal (N = 662,094), non-small cell lung (N = 363,863), renal (N = 262,915) and pancreas (N = 71,419) cancers. Median TTI increased from 21 to 29 days (P<0.001). Aside from year of diagnosis, determinants of increased TTI included care at academic center, race, education, prior history of cancer, transfer of facility, comorbidities and age. Increased TTI was associated with worsened survival for stages I and II breast, lung, renal and pancreas cancers, and stage I colorectal cancers, with hazard ratios ranging from 1.005 (95% confidence intervals [CI] 1.002–1.008) to 1.030 (95% CI 1.025–1.035) per week of increased TTI. TTI has lengthened significantly and is associated with absolute increased risk of mortality ranging from 1.2–3.2% per week in curative settings such as early-stage breast, lung, renal and pancreas cancers. Studies of interventions to ease navigation and reduce barriers are warranted to diminish potential harm to patients.
Delays in time to treatment initiation (TTI) for new cancer diagnoses are commonly known to cause patient anxiety and distress [1, 2, 3, 4]. Physicians often reassure patients that current wait times to initiate therapy will not impact long-term outcomes, but the evidence is conflicting. Studies in breast, head and neck, gynecologic, and lung cancer suggest that increased time to treatment initiation (TTI) is associated with worsened survival [5, 6, 7, 8, 9, 10]. Other studies, however, suggest no association of increased TTI on survival [10, 11, 12, 13, 14].
The study cohort was obtained in de-identified form from the NCDB, a hospital-based, prospectively collected nationwide oncology outcomes database . The NCDB collects data annually from tumor registries of Commission on Cancer-accredited programs, comprising approximately 70% of all new US invasive cancer diagnoses. Data collection is standardized based on the Facility Oncology Registry Data Standards (FORDS). For this study, patients diagnosed between 2004–2013 with stages I-III breast, stages I-III colorectal, stages I-III prostate, stages I-II non-small cell lung cancer, stages I-III renal cancers and stages I-II pancreas cancers were identified (S1 Fig). This research was approved (exempted) by the Institutional Review Board of the Taussig Cancer Institute, Cleveland Clinic. We chose the four most common solid tumors amongst men and women; in addition, we included renal and pancreas cancers as less common solid tumors representative of cancers with excellent and poor cure rates, respectively. Patients were excluded if no treatment was given, first treatment occurred > 180 days after diagnosis, interval could not be determined, uncommon histology or uncommon presentations, such as male breast cancer.
We conducted a comprehensive analysis of TTI across a variety of common solid tumors and found a substantial worsening of TTI over recent years. Increased TTI was associated with increased risk of mortality ranging from 1.2–3.2% per week in early-stage breast, lung, renal and pancreas cancers.