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Melanoma in situ and invasive melanoma of the vulva: An analysis of the National Cancer Database

2020; Elsevier BV; Volume: 84; Issue: 6 Linguagem: Inglês

10.1016/j.jaad.2020.09.036

1097-6787

Sara Behbahani, Stefano Malerba, Christopher J. Warren, Miriam Keltz Pomeranz, Faramarz H. Samie,

Cancer Immunotherapy and Biomarkers

To the Editor: Vulvar melanoma (VM) accounts for 6% to 10% of vulvar malignancies.1Sanchez A. Rodríguez D. Allard C.B. et al.Primary genitourinary melanoma: epidemiology and disease-specific survival in a large population-based cohort.Urol Oncol. 2016; 34 (166.e7-166.e14)Crossref PubMed Scopus (36) Google Scholar Current knowledge comes from smaller retrospective studies.1Sanchez A. Rodríguez D. Allard C.B. et al.Primary genitourinary melanoma: epidemiology and disease-specific survival in a large population-based cohort.Urol Oncol. 2016; 34 (166.e7-166.e14)Crossref PubMed Scopus (36) Google Scholar,2Wohlmuth C. Wohlmuth-Wieser I. May T. Vicus D. Gien L.T. Laframboise S. Malignant melanoma of the vulva and vagina: a US population-based study of 1863 patients.Am J Clin Dermatol. 2020; 21: 285-295Crossref PubMed Scopus (25) Google Scholar This study investigated the demographics and survival of VM in situ (MIS) and invasive VM (IVM) using the National Cancer Database (NCDB). International Classification of Diseases for Oncology third edition histology codes for melanoma 8720 to 8774, combined with primary site codes for the vulva (C510-519), were used to identify patients with VM in NCDB between 2004 and 2016. The analysis included 394 patients with vulvar MIS and 1688 patients with IVM, with a median age at diagnosis of 63 and 66 years, respectively. The median Breslow thickness for IVM was 2.00 mm, and 56.8% of patients presented with ulceration. Regional lymph node metastasis was found in 22.8% of patients (Table I). The 5-year overall survival (OS) was 74.4% for vulvar MIS and 42.7% for IVM (Figs 1 and 2).Table IBaseline characteristics of invasive vulvar melanoma and vulvar melanoma in situDemographicsVulvar melanoma in situ (n = 394)Invasive vulvar melanoma (n = 1688)No.%P∗Bold values denote statistical significance (P < .05) on Pearson χ2 analysis or Fisher exact test.No.%P∗Bold values denote statistical significance (P < .05) on Pearson χ2 analysis or Fisher exact test.Age, y.0001.0001 <7027269.094556.0 ≥7012231.074344.0Race.0001.0001 White37093.9156092.4 Black71.8643.8 Other153.8452.7 Missing20.5191.1Primary site.0001.0001 Labia major4110.41438.5 Labia minor4110.41166.9 Clitoris112.8563.3 Overlapping lesion of vulva102.5553.3 Vulva NOS29173.9131878.1Surgical procedure.0001.0001 Local tumor excision15639.626615.8 Surgery NOS10.3251.5 Simple/partial surgical removal19349.068040.3 Total surgical removal328.128416.8 Radical surgery123.033619.9 None……975.7Breslow thickness, mm.0001 4……51330.4 Missing……1619.5Ulceration.0001 No ulceration present……60535.8 Ulceration present……95856.8 Missing……1257.4Facility type.0001 Community program14737.360435.8 Academic/research program15539.373143.3 Integrated network cancer program4711.922113.1 Missing4511.41327.8Charlson-Deyo Comorbidity Score.0001.0001 034286.8135980.5 1399.925214.9 ≥2133.3774.6Stage.0001 I……43225.6 II……55432.8 III……36821.8 IV……1317.8 Missing……20312.0Chemotherapy.0001.0001 No38196.7155191.9 Yes10.3824.9 Missing123553.3Radiotherapy.0001.0001 No38998.7150789.3 Yes10.31619.5 Missing41201.2Immunotherapy.0001.0001 No38798.2149288.4 Yes4118210.8 Missing30.8140.8Income Status.0001.0001 <$38,0004711.924214.3 $38,000-$47,999671739523.4 $48,000-$62,99911328.747628.2 ≥$63,00016742.456633.5 Missing……90.5Insurance status.0001.0001 Not insured92.3462.7 Private/managed care20852.871542.4 Government insurance (Medicaid, Medicare, other government)16742.489352.9Histology.0001.0001 Malignant melanoma NOS or other histologies37194.298058.1 Nodular melanoma……29117.2 Superficial spreading melanoma225.635621.1 Mucosal lentiginous melanoma10.3613.6Regional lymph node status.0001.0001 Negative……67840.2 Positive……38522.8 Not Examined……60435.8 Missing……211.2No., Number; NOS, not otherwise specified.∗ Bold values denote statistical significance (P < .05) on Pearson χ2 analysis or Fisher exact test. Open table in a new tab No., Number; NOS, not otherwise specified. When adjusting for confounders, independent predictors of worse OS in IVM were age (hazard ratio [HR], 1.02; 95% confidence interval [CI], 1.01-1.03), Charlson-Deyo Comorbidity Index score of 1 (HR, 1.31; 95% CI, 1.06-1.63), and Charlson-Deyo Comorbidity Index score of ≥2 (HR, 2.181; 95% CI, 1.58-3.02), nodular melanoma histology (HR, 1.23; 95% CI, 1.00-1.52), Breslow thickness >4 mm (HR, 1.37; 95% CI, 1.07-1.74), stage II (HR, 1.94; 95% CI, 1.42-2.66), stage III (HR, 2.21; 95% CI, 1.45-3.38), stage IV (HR, 5.81; 95% CI, 3.77-8.93), positive regional lymph nodes (HR, 1.92; 95% CI, 1.33-2.79), and regional lymph nodes not examined (HR, 1.64; 95% CI, 1.31-2.04). Private insurance (HR, 0.49; 95% CI, 0.29-0.84) and government insurance (HR, 0.47; 95% CI, 0.33-0.98) were also independently associated with improved OS in IVM (Table II).Table IIMultivariate Cox proportional hazards models of vulvar melanoma in situ and invasive vulvar melanomaVariableVulvar melanoma in situ∗Multivariate HRs are presented. Variables controlled for and included in the model for vulvar melanoma in situ were age, race, primary site, facility type, Charlson-Deyo Comorbidity Score, income status, insurance status, histology, surgical procedure. HRs presented are adjusted HRs for the aforementioned variables.,†The variables did not violate the proportionality assumption. The proportionality assumption for each variable included was evaluated graphically using log-negative-log survival curves and statistically using interactions with time.Invasive vulvar melanoma†The variables did not violate the proportionality assumption. The proportionality assumption for each variable included was evaluated graphically using log-negative-log survival curves and statistically using interactions with time.,‡Multivariate HRs are presented. Variables controlled for and included in the model for invasive vulvar melanoma were age, race, primary site, Breslow thickness, ulceration, facility type, Charlson-Deyo Comorbidity Score, stage, chemotherapy, radiotherapy, immunotherapy, income status, insurance status, histology, regional lymph node status, and surgical procedure. HRs presented are adjusted HRs for the aforementioned variables.HR (95% CI)P§Bold values denote significance (P < .05) on Cox proportional hazards multivariate model.HR (95% CI)P§Bold values denote significance (P < .05) on Cox proportional hazards multivariate model.Age1.094 (1.051-1.139).00011.019 (1.009-1.028).0001Race WhiteRefRefRefRef Black0.858 (0.001-9.818).9480.912 (0.582-1.429).686 Other0.742 (0.001-9.528).9200.602 (0.299-1.212).155Primary site Labia majorRefRefRefRef Labia minor0.991 (0.001-3.230).8331.044 (0.667-1.635).849 Clitoris1.408 (0.130-15.236).7781.447 (0.858-2.439).166 Overlapping lesion of vulva0.801 (0.0001-1.64).9401.090 (0.632-1.880).757 Vulva NOS1.899 (0.567-6.363).2981.131 (0.810-1.580).469Breslow thickness, mm 4……1.368 (1.074-1.743).011Ulceration No ulceration present……RefRef Ulceration present……1.184 (0.959-1.462).116Facility type Community programRefRefRefRef Academic/research program0.524 (0.253-1.085).0820.793 (0.657-0.957).016 Integrated network cancer program0.631 (0.252-1.580).3260.941 (0.736-1.202).626Charlson-Deyo Comorbidity Score 0RefRefRefRef 11.715 (0.752-3.909).1991.310 (1.055-1.626).015 ≥22.822 (0.811-9.812).1032.181 (1.576-3.019).0001Stage I……RefRef II……1.942 (1.419-2.658).0001 III……2.215 (1.452-3.380).0001 IV……5.805 (3.744-8.929).0001Chemotherapy No……RefRef Yes……0.967 (0.647-1.444).868Radiotherapy No……RefRef Yes……1.074 (0.830-1.390).585Immunotherapy No……RefRef Yes……1.057 (0.801-1.395).694Income status <$38,000RefRefRefRef $38,000-47,9990.464 (0.179-1.204).1141.182 (0.898-1.555).233 $48,000-$62,9990.394 (0.152-1.019).0551.005 (0.769-1.312).973 ≥$63,0000.416 (0.175-0.989).0470.977 (0.747-1.279).868Insurance status Not insuredRefRefRefRef Private/Managed Care9.710 (0.0001-40.190).9310.494 (0.290-0.840).009 Government Insurance (Medicaid, Medicare, Other Government)9.415 (0.0001-41.800).9810.569 (0.329-0.985).044Histology Malignant melanoma NOS or otherRefRefRefRef Nodular melanoma……1.234 (1.002-1.521).048 Superficial spreading melanoma1.207 (0.254-5.728).8130.951 (0.761-1.189).66 Mucosal lentiginous melanoma‖All cases analyzed were censored.……1.783 (0.903-3.519).096Regional lymph node status Negative……RefRef Positive……1.925 (1.330-2.786).001 Not examined……1.639 (1.314-2.045).0001Surgical procedure Local tumor excisionRefRef Surgery NOS33.467 (0.887-300.898).9851.654 (0.770-3.553).197 Simple/partial surgical removal0.965 (0.490-1.898).9171.059 (0.812-1.382).672 Total surgical removal0.443 (0.057-3.458).4381.161 (0.854-1.579).341 Radical surgery0.979 (0.212-4.517).9780.977 (0.728-1.312).879 None……2.490 (1.518-4.084).0001CI, Confidence interval; HR, hazard ratio; NOS, not otherwise specified; Ref, reference.∗ Multivariate HRs are presented. Variables controlled for and included in the model for vulvar melanoma in situ were age, race, primary site, facility type, Charlson-Deyo Comorbidity Score, income status, insurance status, histology, surgical procedure. HRs presented are adjusted HRs for the aforementioned variables.† The variables did not violate the proportionality assumption. The proportionality assumption for each variable included was evaluated graphically using log-negative-log survival curves and statistically using interactions with time.‡ Multivariate HRs are presented. Variables controlled for and included in the model for invasive vulvar melanoma were age, race, primary site, Breslow thickness, ulceration, facility type, Charlson-Deyo Comorbidity Score, stage, chemotherapy, radiotherapy, immunotherapy, income status, insurance status, histology, regional lymph node status, and surgical procedure. HRs presented are adjusted HRs for the aforementioned variables.§ Bold values denote significance (P < .05) on Cox proportional hazards multivariate model.‖ All cases analyzed were censored. Open table in a new tab CI, Confidence interval; HR, hazard ratio; NOS, not otherwise specified; Ref, reference. The 5-year OS for IVM (42.7%) is consistent with previous studies showing worse OS in IVM compared with cutaneous melanoma (52%-88% depending on the cutaneous melanoma subtype), even when accounting for stage.1Sanchez A. Rodríguez D. Allard C.B. et al.Primary genitourinary melanoma: epidemiology and disease-specific survival in a large population-based cohort.Urol Oncol. 2016; 34 (166.e7-166.e14)Crossref PubMed Scopus (36) Google Scholar, 2Wohlmuth C. Wohlmuth-Wieser I. May T. Vicus D. Gien L.T. Laframboise S. Malignant melanoma of the vulva and vagina: a US population-based study of 1863 patients.Am J Clin Dermatol. 2020; 21: 285-295Crossref PubMed Scopus (25) Google Scholar, 3Sundararajan S. Acharya U. Kumar A. Kanaan M. Cui H. Jeter J.M. Effect of histological subtype on overall survival in cutaneous melanoma: a Surveillance, Epidemiology, and End Result program (SEER) database review.J Clin Oncol. 2016; 34: e21051Crossref Google Scholar These results underscore the importance of vulvar screening as part of full-body skin examinations and educating patients in self-examination in anatomically sensitive areas. A survey of dermatologists showed that only 4% of dermatologists included the vulva as part of their full-body skin examinations.4Zikry J. Chapman L.W. Korta D.Z. Smith J. Genital melanoma: are we adequately screening our patients?.Dermatol Online J. 2017; 23 (13030/qt7zk476vn)PubMed Google Scholar Only 66% of dermatologists felt diagnosing VM was their role compared with 81% of gynecologists.4Zikry J. Chapman L.W. Korta D.Z. Smith J. Genital melanoma: are we adequately screening our patients?.Dermatol Online J. 2017; 23 (13030/qt7zk476vn)PubMed Google Scholar However, dermatologists play a key role in educating patients on features of VM and in bridging the gap with other specialties to ensure adequate screening. Insurance coverage in our study for patients with IVM was independently associated with improved OS. Similarly, in patients with vulvar MIS, annual income >$63,000 was independently associated with improved OS. Low socioeconomic status has been previously linked with advanced disease at presentation and poor prognosis of melanoma, particularly in the elderly, which is especially relevant in VM given the median age of diagnosis.5Reyes-Ortiz C.A. Goodwin J.S. Freeman J.L. Kuo Y.-F. Socioeconomic status and survival in older patients with melanoma.J Am Geriatr Soc. 2006; 54: 1758-1764Crossref PubMed Scopus (66) Google Scholar Retrospective, registry-based studies have several limitations. NCDB is a clinician-reported database that relies on accurate record keeping and reporting by contributing institutions. NCDB does not report disease-specific survival, which may overestimate the mortality risk from VM. Vulvar MIS and IVM show worse OS than cutaneous melanoma. Our results confirm that Breslow thickness, lymph node status, and stage are significant predictors of survival. Earlier diagnosis, better health care access, and treatment at academic facilities may help improve OS in patients with VM. Supplemental material is available via Mendeley at https://data.mendeley.com/datasets/s24y42424b/1.Fig 2Kaplan-Meier overall survival curves in invasive vulvar melanoma by ulceration, Breslow thickness, regional lymph node status, and stage.View Large Image Figure ViewerDownload Hi-res image Download (PPT)