Impact of Diagnostic Delays on Lung Cancer Survival Outcomes

A Population Study of the US SEER-Medicare Database

Perrin E. Romine, MD, MSc; Qin Sun, MPA; Catherine Fedorenko, MMSc; Li Li, MA, MPA; Mariel Tang, BA; Keith D. Eaton, MD, PhD; Bernardo H.L. Goulart, MD; Renato G. Martins, MD, MPH

Disclosures

J Oncol Pract. 2022;18(6):e877-e885. 

In This Article

Methods

Data Source and Study Cohort

The study leverages the National Cancer Institute SEER-Medicare database, which links SEER records of incidental cancer cases to Medicare health care claims.[12–14] The SEER records provide patient-level information on sociodemographic characteristics, tumor (eg, histologic type and stage), and OS.[15] Medicare claims provide longitudinal information on resource utilization, including diagnostic tests and procedures, surgery, radiation, chemotherapy, outpatient and emergency department visits, hospitalizations, skilled nurse facility, home health, hospice, and durable medical equipment.[14,16,17]

Eligible patients were age 67 years or older and had histologically confirmed NSCLC of any subtype (adenocarcinoma, squamous cell carcinoma, large cell carcinoma, or non—small-cell carcinoma not otherwise specified) diagnosed at any stage between January 1, 2011, and December 31, 2015. All patients had at least one computed tomography of the chest within 1 year before histologic diagnosis and were required to start stage-appropriate treatment within 6 months of diagnosis.

Since SEER defines the date of diagnosis on the basis of either clinical or histologic criteria, we applied the following algorithm to define date of histologic diagnosis: (1) we used International Classification of Diseases code (ICD)-9, ICD-10, and Healthcare Common Procedure Coding System codes to identify the procedures that commonly characterize diagnostic biopsies in NSCLC and extracted their respective dates; (2) we identified the closest biopsy procedure in time relative to the SEER diagnostic date; (3) if the date of the biopsy matched the date of SEER diagnosis, this date constituted the histologic confirmation date; (4) if the date of the biopsy differed from the SEER date of diagnosis (either before or after), the date in the biopsy claim served as proxy of the histologic confirmation date. For patients who underwent surgical resection upfront without previous biopsy, the date of surgery constituted the date of histologic confirmation. We excluded patients without continuous enrollment in Medicare parts A and B for 2 years before diagnosis and 6 months after diagnosis, those with prior or concurrent cancers (except nonmelanoma cutaneous cancers), those enrolled in Medicare as a result of end-stage renal disease or disability, and those who died within 2 months of diagnosis. This study was approved by the Institutional Review Board at the Fred Hutchinson Cancer Research Center.

Stage-appropriate Treatment

We defined stage-appropriate treatment within 180 days from the date of histologic confirmation of diagnosis as follows: Stage I patients underwent surgical resection (lobectomy, pneumonectomy, or segmentectomy) or stereotactic body radiotherapy. Stage II patients underwent surgical resection as defined above with or without adjuvant chemotherapy involving a platinum agent (carboplatin or cisplatin). Stage III treatment included surgical resection followed by platinum-based adjuvant chemotherapy, concurrent chemoradiation therapy also involving a platinum agent, or neoadjuvant platinum–based chemotherapy followed by surgical resection. Stage IV patients underwent systemic therapy characterized by the receipt of any form of oral (for those with Medicare Part D) or IV-based chemotherapy that received approval from the US Food and Drug Administration before or during the study observation period for use in first-line treatment of NSCLC and/or programmed cell death 1 or programmed cell death ligand-1 immune checkpoint inhibitors (immunotherapy). Neoadjuvant therapy was defined as chemotherapy regimens followed by surgery where the surgery date must fall within 3 months of the last chemotherapy billing claim. Adjuvant chemotherapy was defined as chemotherapy starting within 12 weeks of the time of surgery. Concurrent chemoradiotherapy required that at least one chemotherapy claim fell within the time of radiation therapy and/or started 2 weeks before radiation therapy start dates. We included all codes for external beam radiotherapy to ascertain the use of radiation therapy. For stage II and III patients who received sequential treatment modalities (eg, surgery followed by adjuvant chemotherapy), we considered the date of the first treatment modality in determining the date of treatment initiation.

Exposure and Outcome Measures

The exposure consisted of the time to diagnosis, defined as the interval in weeks between the last computed tomography of the chest and the date of histologic confirmation of diagnosis. We categorized patients into quartiles of time to confirmation (Q1 < Q2 < Q3 < Q4). To account for variations in the time from histologic confirmation of NSCLC to treatment initiation, we categorized patients as starting treatment ≤ 6 weeks or > 6 weeks from histologic confirmation. Our primary outcome was OS, defined as the time interval between the date of histologic confirmation of NSCLC to death of any cause. We censored patients who were alive at the last date of the observation period (December 31, 2017).

Statistical Analysis

We conducted descriptive analysis reporting medians with an interquartile range for continuous variables, and proportions and percentages for categorical variables.

We applied the Kaplan-Meier product limit method to estimate overall and used the log-rank test for unadjusted comparisons. We used a multivariate Cox proportional hazards regression model to estimate the effect of increasing quartiles of time intervals from suspicion to histologic confirmation of NSCLC on the risk of death from any cause for each stage of NSCLC, after adjustment for baseline confounding patient characteristics.

Sensitivity Analysis

To account for the use of oral therapies in advanced stage, we estimated the effects of increasing quartiles of diagnostic intervals on survival in a subset of patients who had Medicare part D coverage and stage IV NSCLC. To untangle associations of prolonged intervals from suspicion to diagnostic confirmation from prolonged time intervals from diagnosis to treatment initiation, we repeated all stage-specific analyses in a subset of patients who initiated oncologic therapy ≤ 6 weeks from the date of histologic confirmation of NSCLC.

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