Clinical Review

Treatment Delay in Melanoma: A Risk Factor Analysis of an Impending Crisis

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References

Results

The final study population included 104,118 patients, most of whom were male (56.4%), white (96.6%), and aged 50 to 74 years (54.4%). Most patients were privately insured (52.6%), had no CD comorbidities (87.5%), and lived in metropolitan cities (80.4%)(Table 3). A large majority (95,473 [91.7%]) of patients received surgery as the first means of treatment, with a smaller portion (863 [0.8%]) having unspecified systemic therapy first. The remaining cases were first treated with chemotherapy (1738 [1.7%]), immunotherapy (382 [0.4%]), or radiation (490 [0.5%]), and the rest did not specify treatment sequence. The tumors were most commonly located on the extremities (40.7%), were stage I (41.2%), and had a Breslow depth of less than 1 mm (41.6%).

Treatment delay averaged 31.55 days, with a median of 27 days. Overall mean MTD increased significantly from 29.74 days in 2004 to 32.55 days in 2015 (2-tailed t test; P<.001)(Figure). A total of 78,957 cases (75.8%) received treatment within 45 days, whereas 2467 cases (2.5%) were postponed past 90 days. On bivariate analysis, age, sex, race, insurance status, Hispanic ethnicity, median annual income of residential zip code, percentage of the population of the patient’s residential zip code with high school degrees, CD score, and academic treatment facility held significant associations with mMTD and sMTD (P<.05)(Table 3). Analyzing bivariate associations with pertinent tumor characteristics—primary site, stage, and Breslow depth—also held significant associations with mMTD and sMTD (P<.001)(Table 4).

Overall trend of melanoma treatment delay (2004-2015).

On multivariate analysis, controlling for the variables significant on bivariate analysis, multiple factors showed independent associations with MTD (Table 2). Patients aged 50 to 74 years were more likely to have mMTD (reference: <50 years; P=.029; OR=1.072). Patients 75 years and older showed greater rates of mMTD (reference: <50 years; P<.001; OR=1.278) and sMTD (P<.001; OR=1.590). Women had more mMTD (P=.013; OR=1.052). Nonwhite patients had greater rates of both mMTD (reference: white; P<.001; OR=1.405) and sMTD (P<.001; OR=1.674). Hispanic patients also had greater mMTD (reference: non-Hispanic: P<.001; OR=1.809) and sMTD (P<.001; OR=2.749). Compared to patients with private insurance, those with Medicare were more likely to have mMTD (P=.046; OR=1.054). Patients with no insurance or Medicaid/other government insurance showed more mMTD (no insurance: P<.001, OR=1.642; Medicaid/other: P<.001, OR=1.668) and sMTD (no insurance: P<.001, OR=2.582; Medicaid/other: P<.001, OR=2.336).

With respect to the median annual income of the patient’s residential zip code, patients residing in areas with a median income of $48,000 to $62,999 were less likely to have an sMTD (reference: <$38,000; P=.038; OR=0.829). Compared with patients residing in zip codes where a high percentage of the population had high school degrees, areas with higher nongraduate rates had greater overall rates of MTD (P<.001). Patients with more CD comorbidities also held an association with mMTD (CD1 with reference: CD0; P=.011; OR=1.080)(CD2 with reference: CD0; P<.001; OR=1.364) and sMTD (CD2 with reference: CD0; P<.001; OR=1.877). Academic facilities had greater rates of mMTD (reference: nonacademic facilities; P<.001; OR=1.578) and sMTD (P<.001; OR=1.366). In reference to head/neck primaries, primary sites on the trunk and extremities showed fewer mMTD (trunk: P<.001, OR=0.620; extremities: P<.001, OR=0.641) and sMTD (trunk: P<.001, OR=0.540; extremities: P<.001, OR=0.632). Compared with in situ disease, stage I melanomas were less likely to have treatment delay (mMTD: P<.001, OR=0.902; sMTD: P<.001, OR=0.690), whereas stages II (mMTD: P<.001, OR=1.130), III (mMTD: P<.001, OR=1.196; sMTD: P=.023, OR=1.204), and IV (mMTD: P<.001, OR=1.690; sMTD: P<.001, OR=2.240) were more highly associated with treatments delays.

Comment

The path to successful melanoma management involves 2 timeframes. One is time to diagnosis and the other is time to treatment. With 24.2% of patients receiving treatment later than 45 days after diagnosis, MTD is common and, according to our results, has increased on average from 2004 to 2015. This delay may be partially explained by a shortage of dermatologists, leading to longer wait times and follow-up.13,14 Melanoma treatment delay also varied based on insurance status. Unsurprisingly, those with private insurance showed the lowest rates of MTD. Those with no insurance, Medicare, or Medicaid/other government insurance likely faced greater socioeconomic barriers to health care, such as coverage issues.15 Transportation, low health literacy, and limited work schedule flexibility have been described as additional hurdles to health care that could contribute to this finding.16,17 Similarly, nonwhite patients, Hispanic patients, and those from zip codes with low high school graduation rates had more MTD. Although these findings may be explained by socioeconomic barriers and heightened distrust of the health care system, it also is important to consider physician accessibility.18,19

Considering the 2011 Affordable Care Act along with the 2014 Medicaid expansion, our study holds implications on the impact of these legislations on melanoma treatment. Studies have supported expected rises in Medicaid coverage.20,21 The overall uninsured rate in the United States declined from 16% in 2010 to 9.1% in 2015.22 In our study, the uninsured population showed the highest average MTD rates, though those with Medicaid also had significant MTD. Another treacherous hurdle for patients is the coordination of care among dermatologists, oncologists, general surgeons, plastic surgeons, and Mohs surgeons as a multidisciplinary team. Lott et al6 found that patients who received both biopsy and excision from a dermatologist had the shortest treatment delays, whereas those who had a dermatologist biopsy the site and a different surgeon—including Mohs surgeons—excise it experienced significantly greater MTDs (probablility of MTD >45 days was 31% [95% CI, 24%-37%]. This discordant care and referrals could explain the surprising finding that treatment at an academic facility was independently associated with more MTD, possibly due to the care transitions and referrals that disproportionately affect academic centers and multidisciplinary teams, as mentioned above, regarding the transition of care to other physicians (eg, plastic surgeon). A total of 70.1% of our cases treated at academic facilities reported a prior diagnosis at another facility. These results should not dissuade the pursuit of multidisciplinary treatment teams but should raise caution to untimely referrals.

Age, sex, and race were all associated with more MTD. Patients older than 50 years likely face more complex decisions regarding treatment burden, quality of life, and functional outcomes of more aggressive treatments. High rates of surgical refusal for a number of malignancies have been documented in the elderly population,23-25 which is of particular concern for the high surgery burden of head and neck melanomas,26 as further supported by the findings of more MTD for head and neck primaries. As with elderly patients, patients with higher comorbidity scores and more advanced tumors face similar family–patient care discussions to guide treatment. Additionally, women were more likely to experience MTD, which may be connected to a greater concern for cosmesis27 and necessitate more complex management options, such as Mohs micrographic surgery (a procedure that has gained some support for melanoma excision with the help of immunostaining).28

There are several limitations to this study. Accurate data rely on precise record keeping, reporting, and coding by the contributing institutions. The NCDB case diagnosis is derived from data entry without a centralized review process by experienced dermatopathologists. We could not assess the effects of tumor diameter, as these data were inadequately recorded within the dataset. The NCDB also does not provide details on specific immunotherapy or chemotherapy agents. The NCDB also is a facility-based data source, potentially biasing the melanoma data toward thicker advanced tumors more readily managed at such institutions. Lastly, it is impossible to distinguish between patient-related (ie, difficult decision-making) and health care–related (ie, health care accessibility) delays. Nonetheless, we maintain that minimizing MTD is important for survival outcomes and for limiting the progression of melanomas, regardless of the underlying rationale. We believe that our study expands on conclusions previously limited to a Medicare population.

Conclusion

According to the NCDB, mean MTD has increased significantly from 2004 to 2015. Our results suggest that MTD is relatively common in the United States, thereby increasing the risk for metastases. Higher MTD rates are independently associated with being older than 50 years, female, nonwhite, not privately insured, Hispanic, and treated at an academic facility; having a positive comorbidity history and stage II to IV tumors; and residing in a zip code with a low high school graduation rate. Stage I tumors, primaries not located on the head or neck, and residing in a zip code with a higher median income are associated with lower MTD rates. Policymakers, patients, and dermatologists should better recognize these risk factors to facilitate patient guidance and health equity.

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