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

Melanoma is the most lethal skin cancer and is the second most common cancer in adolescents and young adults.¹ It is the fifth most common cancer in the United States based on incidence, which has steadily risen for the last 2 decades.^2,3 For melanoma management, delayed initial diagnosis has been associated with more advanced lesions at presentation and poorer outcomes.⁴ However, the prognostic implications of delaying melanoma management after diagnosis merits further scrutiny.

This study investigates the associations between melanoma treatment delay (MTD) and patient and tumor characteristics. Although most cases undergo surgical treatment first, more advanced stages may require initiating chemotherapy, radiation therapy, or immunotherapy. In addition, patients who are poor surgical candidates may opt for topical field therapy, such as imiquimod for superficial lesions, prior to more definitive treatment.⁵ In the Medicaid population, patients who are older than 85 years, married, and previously diagnosed with another melanoma and who also have an increased comorbidity burden have a higher likelihood of MTD.⁶ For nonmelanoma skin cancers, patient denial is the most common patient-specific factor accounting for treatment delay.⁷ For this study, our aim was to further evaluate the independent risk factors associated with MTD.

Methods

Case Selection
The National Cancer Database (NCDB) was queried for all cutaneous melanoma cases from 2004 to 2015 (N=525,271). The NCDB is an oncology database sourced from more than 1500 accredited cancer facilities in the United States and Puerto Rico. It receives cases from academic hospitals, Veterans Health Administration hospitals, and community centers.⁸ Annually, the database collects approximately 70% of cancer diagnoses and 48% of melanoma diagnoses in the United States.^9,10 Per institutional guidelines, this analysis was determined to be exempt from institutional review board approval due to the deidentified nature of the dataset.

The selection scheme is illustrated in Table 1. International Statistical Classification of Diseases and Related Health Problems histology codes 8720/3 through 8780/3 combined with the site and morphology primary codes C44.0 through C44.9 identified all patients with a diagnosis of cutaneous melanoma. Primary site was established with the histology codes in the following manner: C44.0 through C44.4 for head/neck primary, C44.5 for trunk primary, C44.6 through C44.7 for extremity primary, and C44.8 through C44.9 for not otherwise specified. Because the NCDB does not specify cause of death, any cases in which the melanoma diagnosis was not the patient’s primary (or first) cancer diagnosis were excluded because of potential ambiguity. Cases lacking histologic confirmation of the diagnosis after primary site biopsy or cases diagnosed from autopsy reports also were excluded. Reports missing staging data or undergoing palliative management were removed. In total, 104,118 cases met the inclusion criteria.

Variables of Interest
The NCDB database codes for a variable “Treatment Started, Days from Dx” are defined as the number of days between the date of diagnosis and the date on which treatment—surgery, radiation, systemic, or other therapy—of the patient began at any facility.¹¹ Treatment delays were classified as more than 45 days or more than 90 days. These thresholds were chosen based on previous studies citing a 45-day recommendation as the timeframe in which primary site excision of melanoma should occur for improved outcomes.^1,6,12 Additionally, the postponement cutoffs were aligned with prior studies on surgical delay in melanoma for the Medicaid population.⁶ Delays of 45 days were labeled as moderate MTD (mMTD), whereas postponements more than 90 days were designated as severe MTD (sMTD).

Patient and tumor characteristics were analyzed for associations with MTD (Table 2). Covariates included age, sex, race (white vs nonwhite), Hispanic ethnicity, insurance status (private; Medicare, Medicaid or other government insurance; and no insurance), median annual income of the patient’s residential zip code (based on 2008-2012 census data), percentage of the population of the patient’s residential zip code without a high school degree (based on 2008-2012 census data), Charlson-Deyo (CD) comorbidity score (a weighted score derived from the sum scores for comorbid conditions), geographic location (rural, urban, and metropolitan), and treatment facility (academic vs nonacademic). Tumor characteristics included primary site (head/neck, trunk, and extremities), stage, and Breslow depth of invasion. Tumor stage was determined using the American Joint Committee on Cancer 6th and 7th editions, depending on the patient’s year of diagnosis.