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

Discussion

Leveraging the US SEER-Medicare data set, this study demonstrates that the median time from first radiographic suspicion of lung cancer to diagnosis in our study population was 20 days. This compares favorably with previous studies evaluating time to diagnosis and time to treatment in lung cancer.[4,11,18,19] Similarly, this study demonstrated shorter time to diagnosis in patients with more advanced-stage disease, a trend previously shown in time to treatment studies in NSCLC.[20] Interestingly, the median time to diagnosis for patients with stage IV disease was 7 days, which was shorter than we anticipated. This finding suggests that recent efforts to increase efficiency in the diagnostic workup may be shortening the time to diagnosis of lung cancer, particularly for stage IV disease.

Contrary to our initial hypothesis, longer time to diagnosis was in fact associated with improved survival outcomes, driven by patients with stage IV NSCLC. This association held when evaluating patients with only part D Medicare, ensuring that access to oral directed therapy was not affecting our results. Given previous work demonstrating an association between time to treatment and survival outcomes in NSCLC, a second sensitivity analysis was performed including only those patients with treatment initiation within 6 weeks of diagnosis with similar results.[5–9,21] Although our results do not support the use of time to diagnosis as a quality metric, we are not postulating that prolonged diagnostic workup of NSCLC improves OS. More likely, biases inherent to registry-claims database studies confounded the analysis of the association of time to diagnosis with OS. Specifically, SEER-Medicare does not include variables that accurately reflect tumor biologic behavior. We postulate that health care professionals appropriately react to patients presenting with clinical, radiographic, and laboratory characteristics suggestive of aggressive disease by expediting the diagnostic workup. Alternatively, longer time to diagnosis may be a proxy for a more thorough workup, including broad genomic profiling in stage IV NSCLC. We are unable to verify the latter explanation as our analysis did not capture details related to the procedures performed as part of the diagnostic workup. Further research may require the use of clinically enriched electronic health record–derived databases to tease out the elements of diagnostic workup that contribute to time to treatment initiation and survival.

To address the possible inherent bias of individual tumor biology, we used a conditional landmark analysis approach. The landmark method, first described in 1983, attempts to address immortal time bias, or the bias favoring the group treated or exposed in survival analyses, when the exposure or treatment may occur at a time point after study entry.[22] By excluding patients deceased within 6 months of diagnosis, we aimed to re-evaluate our model in patients with inherently less aggressive tumor biology. In our conditional landmark analysis, the association of shorter time to diagnosis with inferior survival was no longer significant, suggesting that immortal time bias partially accounted for our results.

Finally, it is worth noting that this study included more stage I than stage IV patients, contrary to known epidemiologic NSCLC stage trends.[23] This likely reflects our exclusion of stage IV patients who did not receive palliative systemic therapy. It is possible that this exclusion affected the results of our study by including patients with a more favorable underlying disease. Similarly, this study is inherently limited by the years of patient inclusion. Given the rapid pace of treatment advances since 2015, particularly within the field of immunotherapy, it is likely that we excluded advanced-stage patients for not receiving palliative therapy who may be considered candidates for newer treatments, affecting the generalizability of our results to a more contemporary patient population.

In conclusion, this study demonstrates that time to diagnosis of NSCLC in appropriately treated patients is inversely associated with survival outcomes in this US SEER-Medicare database population. This association was lost when patients deceased within 6 months of diagnosis were excluded, suggesting that time to diagnosis reflects underlying tumor behavior, although further prospective work is needed to evaluate this. Although limited by its retrospective nature, this study does not support the use of time to diagnosis as a quality metric, but may indicate that the oncology workforce is appropriately expediting the workup for patients presenting with more aggressive disease behavior.

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