Marital Status and Stage at Diagnosis of Invasive Melanoma of the Skin James (Jay) L. Fisher, Ph.D. Comprehensive Cancer Center and James Cancer Hospital at The Ohio State University

Background Marriage provides a prognostic advantage to those with cancer, including invasive melanoma of the skin. May result from immunologic benefit of psycho-social support associated with marriage or from encouragement to follow through with diagnosis. Spouses may identify suspicious or changing nevi (moles) or nevi on areas of the body not easily or routinely viewed by one's self. Supported by anecdotal stories and by 1 recent study of marital status and stage at diagnosis of melanoma among older (ages 65+) individuals.

Goal To determine whether single, separated/divorced and widowed individuals are more likely to present with late stage melanoma, as compared to married individuals, and to determine whether associations are dependent on: –Sex; –Age at diagnosis; –Year of Diagnosis; –Histology; –Anatomic location.

Non-treatment Factors Related to Favorable Melanoma Prognosis Female sex Younger age at diagnosis White race Localized stage at diagnosis Histology of superficial spreading and lentigo, versus nodular and acral lentiginous Anatomic location of limb, compared to trunk Characteristics of lesion (e.g. lower levels of thickness)

5-Year Melanoma Survival Probability by Stage at Diagnosis, Source: SEER Cancer Statistics Review, , National Cancer Institute, 2008; Based on SEER 17 areas.

5-Year Melanoma Survival Probability by Marital Status, Source: SEER*Stat 6.4.3, 2008; Based on SEER 17 areas.

Methods: Data Source Surveillance, Epidemiology, and End Results (SEER) Program Database, 17 Regions, National Cancer Institute Data accessed using SEER*Stat (Released April 2008) Years of diagnosis: SEER Historic Stage A used for stage at diagnosis –in situ cases excluded from outset –Early stage characterized as localized stage –Late stage characterized as regional and distant stages combined Marital Status at Diagnosis was categorized as: –Married –Single/Never Married –Separated/Divorced –Widowed

Methods: Exclusions Age at Diagnosis – Younger than 25 years of age (n = 5,005) SEER Historic Stage A – Unknown (n = 8,728) Marital Status – Unknown (n = 32,256) 121,506 melanoma cases remained after exclusions

Methods: Design and Statistical Analyses Case-control Study –Cases defined as persons with late stage melanoma. –Controls defined as persons with early stage melanoma. Logistic Regression –Used to determine odds of specified marital status according to case status (case, control). –Odds ratios (ORs) estimate relative risks. –An OR > 1.0 means individuals with a specified marital status are more likely to be cases. –Hypotheses determined a priori. –Alpha set at 0.05 for 2-tailed hypothesis tests. Potential Confounder –Age at diagnosis (controlled by inclusion in a multivariate model).

Methods: Design and Statistical Analyses Potential Effect Modifiers –Sex –Age at diagnosis –Year of diagnosis –Histology –Anatomic location Effect modification assessed by stratification of regressions. Statistical analyses were conducted using SAS 9.1.

Marital Status at Diagnosis Stage at Diagnosis MarriedSingle/ Never Married Separated/ Divorced Widowed MaleEarly 78.2%12.0%5.2%4.6% Late 71.0%15.0%7.5%6.6% FemaleEarly 65.1%13.6%8.4%12.9% Late 52.0%12.6%10.2%25.2% Marital Status at Melanoma Diagnosis by Sex and Stage at Diagnosis

Crude and Age-adjusted ORs and 95%CIs Estimating Risk of Late Stage (versus Early Stage) Melanoma According to Marital Status by Sex MaleFemale Crude OR (95% CI) Age- Adjusted OR (95% CI) Crude OR (95% CI) Age- Adjusted OR (95% CI) Married 1.00 (ref.) Single/Never Married 1.34 ( ) 1.44 ( ) 1.12 ( ) 1.21 ( ) Separated/ Divorced 1.68 ( ) 1.71 ( ) 2.10 ( ) 1.91 ( ) Widowed 1.52 ( ) 1.32 ( ) 2.33 ( ) 1.41 ( )

Age-Adjusted ORs and 95%CIs Estimating Risk of Late Stage Melanoma According to Marital Status by Age of Diagnosis Among Males Males 25 to 3940 to 5455 to Married 1.00 (ref.) Single/Never Married 1.45 ( ) 1.60 ( ) 1.38 ( ) 1.22 ( ) Separated/ Divorced 2.94 ( ) 1.44 ( ) 2.00 ( ) 1.31 ( ) Widowed 1.24 ( ) 1.45 ( ) 1.40 ( ) 1.21 ( )

Age-Adjusted ORs and 95%CIs Estimating Risk of Late Stage Melanoma According to Marital Status by Age at Diagnosis Among Females Females 25 to 3940 to 5455 to Married 1.00 (ref.) Single/Never Married 1.10 ( ) 1.23 ( ) 1.22 ( ) 1.26 ( ) Separated/ Divorced 2.34 ( ) 2.87 ( ) 1.76 ( ) 1.24 ( ) Widowed 1.36 ( ) 1.27 ( ) 1.51 ( ) 1.36 ( )

Major Histologic Types of Melanoma Superficial Spreading Melanoma –Most common type, ~70%; Often found on legs and trunk; Good prognosis. Nodular melanoma –Second most common type, ~15-20%; Commonly occurs on trunk; Generally poor prognosis. Lentigo Melanoma –Usually least common, ~4-10%; Generally good prognosis. Acral Lentiginous Melanoma –Most common type among darkly-pigmented people, ~60%; only ~2- 8% of all melanomas; Prognosis between superficial spreading and nodular.

Age-Adjusted ORs and 95%CIs Estimating Risk of Late Stage Melanoma According to Marital Status by Histology Among Males 1. Superficial Spreading 2. Acral Lentiginous Males SS 1 NodularLentigoAL 2 Married1.00 (ref.) Single/Never Married 1.38 ( ) 1.51 ( ) 1.12 ( ) 1.53 ( ) Separated/ Divorced 1.60 ( ) 0.67 ( ) 0.79 ( ) 0.79 ( ) Widowed 1.12 ( ) 0.98 ( ) 0.78 ( ) 1.31 ( )

Age-Adjusted ORs and 95%CIs Estimating Risk of Late Stage Melanoma According to Marital Status by Histology Among Females 1. Superficial Spreading 2. Acral Lentiginous Females SS 1 NodularLentigoAL 2 Married1.00 (ref.) Single/Never Married 1.13 ( ) 1.34 ( ) 0.67 ( ) 0.72 ( ) Separated/ Divorced 1.08 ( ) 1.30 ( ) 2.06 ( ) 6.64 ( ) Widowed 1.53 ( ) 1.31 ( ) 1.22 ( ) 0.78 ( )

Anatomic Location Individuals with melanomas located on areas of the body not easily or routinely viewed by one’s self may benefit more as the result of early spousal recognition. Ideal comparison would be easily visible areas of the body versus areas not easily visible (e.g. posterior versus anterior areas). However, this information is not available. These groupings of anatomic locations were used: –face/head/scalp/neck –trunk –upper limb/shoulder –lower limb/hip

Age-Adjusted ORs and 95%CIs Estimating Risk of Late Stage Melanoma According to Marital Status by Anatomic Location Among Males Males Face/Head/ Scalp/Neck TrunkUpper Limb/ Shoulder Lower Limb/ Hip Married1.00 (ref.) Single/Never Married 1.37 ( ) 1.63 ( ) 1.29 ( ) 1.50 ( ) Separated/ Divorced 1.75 ( ) 1.68 ( ) 2.30 ( ) 1.51 ( ) Widowed1.31 ( ) 1.41 ( ) 1.31 ( ) 1.20 ( )

Age-Adjusted ORs and 95%CIs Estimating Risk of Late Stage Melanoma According to Marital Status by Anatomic Location Among Females Females Face/Head/ Scalp/Neck TrunkUpper Limb/ Shoulder Lower Limb/ Hip Married1.00 (ref.) Single/Never Married 1.37 ( ) 1.29 ( ) 1.31 ( ) 1.20 ( ) Separated/ Divorced 1.75 ( ) 2.41 ( ) 2.04 ( ) 2.24 ( ) Widowed1.31 ( ) 1.51 ( ) 1.45 ( ) 1.47 ( )

Summary of Findings Marriage affords the advantage of diagnosis at an earlier stage. Associations between late stage melanoma and single marital status were stronger among males; associations with separated/divorced and widowed were stronger among females. No clear increasing/decreasing trend in late stage melanoma with age for any non-married marital status. For males, being single was associated with late stage superficial spreading and nodular melanoma; for females, being both single and widowed were associated with late stage nodular melanoma. No anatomic location for which associations with late stage melanoma were strongest/weakest for each non-married marital status.

Alternative Explanations Pertaining to Melanoma Prognosis According to Marital Status Alternative explanations pertaining to melanoma prognosis according to marital status: –Higher income and health insurance among the married; –Psychological stress among the non-married; –Reduced immunologic response to melanoma among the widowed; –Lower quality care among older widows.

Limitations Inability to examine late stage melanoma among monogamously coupled, yet unmarried, individuals No knowledge of length of marital status at time of diagnosis High proportion of unknown marital status (~20%) Possible uncontrolled confounding (or explanation) by factors associated with marriage (e.g. socioeconomic factors, physical appearance, personality characteristics)

The Point Because melanoma incidence is rapidly increasing and because localized melanoma has a very favorable prognosis, it is important to identify groups at greater risk of late stage melanoma. Marriage affords a melanoma survival benefit due, at least in part, to earlier stage at diagnosis. Unmarried individuals should be targeted in skin screening programs and educational efforts to improve early detection of melanoma.

Co-authors Holly L. Engelhardt, M.S. –Cancer Epidemiologist, Ohio Cancer Incidence Surveillance System, Ohio Department of Health Julie A. Stephens, M.S. –Senior Consulting Research Statistician, Center for Biostatistics, The Ohio State University Robert W. Indian, M.S. –Chief, Chronic Disease and Behavioral Epidemiology Section, Ohio Department of Health Electra D. Paskett, Ph.D. –Marion N. Rowley Professor of Cancer Research, Division of Epidemiology, College of Public Health; Associate Director of Population Sciences and Program Co-Leader, Cancer Control Program, Comprehensive Cancer Center, The Ohio State University

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