Factors associated with time to treatment for Merkel cell carcinoma
Authors: Raghav Tripathi, Jeremy S. Bordeaux, Rajiv I. Nijhawan
Journal: Journal of the American Academy of Dermatology (2020)

To the Editor: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer.1Hughes M.P. Hardee M.E. Cornelius L.A. Hutchins L.F. Becker J.C. Gao L. Merkel cell carcinoma: epidemiology, target, and therapy.Curr Dermatol Rep. 2014; 3: 46-53Crossref PubMed Google Scholar Although early treatment is critical for improving survival, little is known regarding factors associated with time from diagnosis to definitive surgical treatment (TTDS) for MCC.1Hughes M.P. Hardee M.E. Cornelius L.A. Hutchins L.F. Becker J.C. Gao L. Merkel cell carcinoma: epidemiology, target, and therapy.Curr Dermatol Rep. 2014; 3: 46-53Crossref PubMed Google Scholar Our primary objective was to investigate factors associated with delays in treatment for patients with MCC.In this retrospective review of the National Cancer Database from 2004 through 2015, patients with MCC were included, and patients with excisional biopsy as definitive treatment were excluded.2American College of SurgeonsNational cancer database.https://www.facs.org/quality-programs/cancer/ncdbGoogle Scholar Univariate analyses compared sociodemographic characteristics, stage/grade at diagnosis, primary site, and time to treatment by race. Multivariable logistic regression evaluated TTDS differences by sociodemographic characteristics/primary site. Multivariable linear regression determined the unique contribution (in days) of each sociodemographic/disease characteristic to TTDS. Analyses were performed in SAS 9.4 (SAS Institute), and P < .05 was considered significant.Of the 26,237 patients with MCC identified, 1766 (6.73%) were Black (Table I). More Black than non-Hispanic White (NHW) patients presented with later-stage, poorly differentiated/undifferentiated, anaplastic, and truncal MCC (P < .001). TTDS was greater for Black patients (58.9 days) than for NHW patients (46.3 days; P < .05). Time to radiation was 18.9 days longer for Black than NHW patients (P < .001), and time to chemotherapy did not differ by race (P = .1453). Black patients lived closer to the hospital (23.2 miles) than NHW patients (41.7 miles; P < .05). TTDS was longer for Black than NHW patients for stages I to III (P < .05), but not stage IV (P = .1319) MCC (Supplemental Table I; available via Mendeley at https://doi.org/10.17632/pv6dp9kn3g.1). Racial differences persisted for private insurance and Medicare (P < .01), but not for Medicaid (P = .8986) or uninsured patients (P = .7510).Table ISociodemographic characteristics of sample∗P < .001 for all chi-square and t tests except for time to chemotherapy (P = .1453).CharacteristicsWhiteBlackTotal number of patients24,4711766Age, y, n (%) <30649 (2.65)181 (10.25) 30-391105 (4.52)308 (17.44) 40-491763 (7.20)356 (20.16) 50-593043 (12.44)343 (19.42) 60-694811 (19.66)278 (15.74) 70-796551 (26.77)185 (10.48) 80+6549 (26.76)115 (6.51)Sex, n (%) Male14,718 (60.14)817 (46.26) Female9753 (39.86)949 (53.74)Stage at diagnosis, n (%) 0213 (0.87)7 (0.40) I6552 (26.77)211 (11.95) II2512 (10.27)139 (7.87) III3606 (14.74)79 (4.47) IV1015 (4.15)57 (3.23) Unknown/not applicable10,573 (43.21)1273 (72.08)Grade at diagnosis, n (%) Well differentiated984 (4.02)135 (7.64) Moderately differentiated807 (3.30)95 (5.38) Poorly differentiated2010 (8.21)87 (4.93) Undifferentiated/anaplastic807 (3.30)22 (1.25) Unknown/not applicable19,863 (81.17)1427 (80.80)Primary site, n (%) Lip310 (1.27)7 (0.40) Eyelid1047 (4.28)59 (3.34) External ear835 (3.41)35 (1.98) Other parts of face5029 (20.55)143 (8.10) Scalp and neck3226 (13.18)158 (8.95) Trunk4854 (19.84)717 (40.60) Upper limb and shoulder4574 (18.69)261 (14.78) Lower limb and hip3181 (13.00)327 (18.52) Overlapping lesion of skin97 (0.40)10 (0.57) Other1318 (5.39)49 (2.77)Time to treatment, d, mean (95% CI) Time to definitive surgery46.26 (45.65-46.88)58.86 (54.87-62.85) Time to chemotherapy72.15 (69.70-74.61)63.60 (54.91-72.29) Time to radiation92.49 (91.27-93.72)111.4 (102.3-120.5)Time to definitive surgery, d, n (%) 0-3012,217 (49.92)746 (42.24) 31-607905 (32.30)507 (28.71) 61-902558 (10.45)270 (15.29) More than 901791 (7.32)243 (13.76)Insurance, n (%) Not insured444 (1.81)151 (8.55) Private insurance8582 (35.07)846 (47.90) Medicaid620 (2.53)238 (13.48) Medicare14,053 (57.43)455 (25.76) Other government277 (1.13)34 (1.93) Unknown495 (2.02)42 (2.38)Median household income, n (%) <$38,0001894 (8.02)478 (28.10) $38,000-$47,9993715 (15.74)301 (17.70) $48,000-$62,9996524 (27.64)451 (26.51) $63,000+11,470 (48.60)471 (27.69)Distance from hospital, miles Mean (95% CI)41.71 (39.86-43.57)23.17 (18.52-27.82) <20, n (%)15,811 (64.97)1420 (80.73) 20-39, n (%)3803 (15.63)149 (8.47) 40-59, n (%)1593 (6.55)78 (4.43) >60, n (%)3129 (12.86)112 (6.37)Facility location New England1531 (6.774)42 (3.29) Middle Atlantic3911 (17.22)240 (18.79) South Atlantic4657 (20.50)402 (31.48) East North Central3968 (17.47)249 (19.50) East South Central1239 (5.45)93 (7.28) West North Central2026 (8.92)49 (3.84) West South Central1268 (5.58)113 (8.85) Mountain1231 (5.42)14 (1.10) Pacific2886 (12.70)75 (5.87)CI, Confidence interval.∗ P < .001 for all chi-square and t tests except for time to chemotherapy (P = .1453). Open table in a new tab After controlling for socioeconomic characteristics, stage, and primary site, Black race was associated with roughly twice the odds of having a TTDS of 61 to 90 (adjusted odds ratio [aOR], 1.97) or longer than 90 days (aOR, 2.11; P < .001) (Table II). Eyelid tumors were associated with increased odds of TTDS of 31 to 60 (aOR, 1.39), 61 to 90 (aOR, 2.12), and longer than 90 days (aOR, 1.47; P < .001). External ear tumors were associated with increased odds of TTDS of 31 to 60 (aOR, 1.40) and 61 to 90 days (aOR, 1.24), and primary site on other parts of the face (aOR, 1.28) and scalp/neck (aOR, 1.12) were associated with increased odds of TTDS of 31 to 60 days (P < .05). Black race, eyelid lesions, and Medicaid were uniquely associated with 11.1, 6.24, and 12.17 additional days from diagnosis to surgical treatment, respectively (P < .01) (Supplemental Table II; available via Mendeley at https://doi.org/10.17632/pv6dp9kn3g.1).Table IIMultivariable logistic regression for time to definitive surgery∗Reference time to definitive surgery: 0 to 30 days.CharacteristicsTime to definitive surgical treatment, d31-6061-90>90aOR (95% CI)PaOR (95% CI)PaOR (95% CI)PRace WhiteReference—Reference—Reference— Black1.15 (0.91-1.45).2451.97 (1.48-2.63)<.00012.11 (1.52-2.93)<.001Sex MaleReference—Reference—Reference— Female0.97 (0.89-1.05).4021.12 (0.99-1.26).0760.96 (0.82-1.13).627Age, y <30Reference—Reference—Reference— 30-390.82 (0.41-1.64).3060.28 (0.12-0.65).0910.56 (0.22-1.47).808 40-490.98 (0.52-1.85).8640.44 (0.22-0.88).7890.64 (0.27-1.53).217 50-591.01 (0.54-1.86).5590.39 (0.20-0.76).4410.56 (0.24-1.30).665 60-690.96 (0.52-1.78).9920.38 (0.20-0.74).2350.55 (0.19-1.02).074 70-791.03 (0.56-1.92).3030.36 (0.18-0.70).0870.41 (0.18-0.95).020 80+0.95 (0.51-1.77).8860.36 (0.19-0.71).0990.33 (0.14-0.77)<.0001Median income <$38,000Reference—Reference—Reference— $38,000-47,9990.91 (0.78-1.07).0091.28 (0.99-1.65).3631.00 (0.74-1.37).856 $48,000-62,9991.09 (0.94-1.27).0351.29 (1.02-1.65).1951.02 (0.77-1.36).977 $63,000+1.07 (0.93-1.24).1011.27 (1.01-1.61).2631.05 (0.80-1.38).610Insurance Not insuredReference—Reference—Reference— Private0.92 (0.64-1.32).2060.73 (0.41-1.29).1961.27 (0.73-2.21).879 Medicaid1.43 (1.06-1.92).0671.31 (0.85-2.02).1872.00 (1.29-3.11).014 Medicare0.97 (0.87-1.08).0240.98 (0.83-1.17).7731.02 (0.82-1.27).112 Other government1.42 (0.98-2.06).1361.05 (0.57-1.95).8871.33 (0.66-2.67).784 Unknown1.09 (0.82-1.46).8471.08 (0.69-1.68).7420.99 (0.56-1.74).375Stage IReference—Reference—Reference— II0.86 (0.77-0.95)<.00011.04 (0.89-1.21).9451.41 (1.16-1.70)<.0001 III0.89 (0.81-0.98)<.00010.81 (0.69-0.94)<.00011.04 (0.85-1.26).919 IV0.35 (0.29-0.43)<.00010.51 (0.39-0.68)<.00010.81 (0.59-1.12).033Primary site Lip1.25 (0.93-1.68).0590.78 (0.47-1.30).6300.84 (0.46-1.53).720 Eyelid1.39 (1.09-1.78).00012.12 (1.57-2.87)<.00011.47 (0.99-2.19)<.0001 External ear1.40 (1.13-1.74)<.00011.24 (0.90-1.71).0140.81 (0.53-1.24).716 Other parts of face1.28 (1.13-1.46)<.00010.96 (0.79-1.16).2630.83 (0.66-1.05).380 Scalp and neck1.12 (0.96-1.31).0371.19 (0.95-1.48).0020.98 (0.75-1.28).028 TrunkReference—Reference—Reference— Upper limb/shoulder1.18 (1.03-1.35).00010.77 (0.63-0.94).1710.60 (0.47-0.7).031 Lower limb/hip1.07 (0.93-1.24).1130.82 (0.66-1.02).5090.62 (0.47-0.81).089 Overlapping lesion1.35 (0.69-2.66).2751.44 (0.57-3.62).2351.98 (0.78-5.05).024 Other0.12 (0.09-0.17)<.00010.12 (0.07-0.21)<.00010.11 (0.06-0.20)<.0001aOR, Adjusted odds ratio.∗ Reference time to definitive surgery: 0 to 30 days. Open table in a new tab Black patients experience delays in TTDS for MCC that persist for stages I to III MCC and for private insurance/Medicare, despite living closer to the hospital than NHW patients. Medicaid and primary facial MCC are also associated with substantial surgical delays. The 5-year survival of MCC is 64% for local disease, 39% for regional nodal disease, and 18% for metastatic disease.1Hughes M.P. Hardee M.E. Cornelius L.A. Hutchins L.F. Becker J.C. Gao L. Merkel cell carcinoma: epidemiology, target, and therapy.Curr Dermatol Rep. 2014; 3: 46-53Crossref PubMed Google Scholar Although we were unable to evaluate the association of TTDS with long-term survival, increased TTDS is associated with worse outcomes for melanoma, breast, and head/neck cancers.3Conic R.Z. Cabrera C.I. Khorana A.A. Gastman B.R. Determination of the impact of melanoma surgical timing on survival using the National Cancer Database.J Am Acad Dermatol. 2018; 78: 40-46Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar Increased TTDS in Black patients with MCC may affect racial disparities in MCC outcomes, although time to adjuvant radiation therapy does not affect MCC outcomes.4Yusuf M.B. Gaskins J. Wall W. Tennant P. Bumpous J. Dunlap N. Immune status and the efficacy of radiotherapy on overall survival for patients with localized Merkel cell carcinoma: an analysis of the National Cancer Database.J Med Imaging Radiat Oncol. 2020; 64: 435-443Crossref PubMed Scopus (5) Google Scholar,5Shinde A. Verma V. Jones B.L. et al.The effect of time to postoperative radiation therapy on survival in resected merkel cell carcinoma.Am J Clin Oncol. 2019; 42: 636-642Crossref PubMed Scopus (6) Google Scholar Regardless of the association of treatment delays with survival, racial discrepancies in time to treatment may affect quality of life and comorbidity burden and reflect systemic disparities in health care delivery/quality of care that should be addressed by dermatologists. Variability in TTDS by insurance and primary site underscores the importance of improving access to timely treatment for MCC, which may involve coordination of multiple specialties. Ultimately, better understanding the components underlying disparities in treatment delays is integral to developing interventions to improve MCC outcomes. To the Editor: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer.1Hughes M.P. Hardee M.E. Cornelius L.A. Hutchins L.F. Becker J.C. Gao L. Merkel cell carcinoma: epidemiology, target, and therapy.Curr Dermatol Rep. 2014; 3: 46-53Crossref PubMed Google Scholar Although early treatment is critical for improving survival, little is known regarding factors associated with time from diagnosis to definitive surgical treatment (TTDS) for MCC.1Hughes M.P. Hardee M.E. Cornelius L.A. Hutchins L.F. Becker J.C. Gao L. Merkel cell carcinoma: epidemiology, target, and therapy.Curr Dermatol Rep. 2014; 3: 46-53Crossref PubMed Google Scholar Our primary objective was to investigate factors associated with delays in treatment for patients with MCC. In this retrospective review of the National Cancer Database from 2004 through 2015, patients with MCC were included, and patients with excisional biopsy as definitive treatment were excluded.2American College of SurgeonsNational cancer database.https://www.facs.org/quality-programs/cancer/ncdbGoogle Scholar Univariate analyses compared sociodemographic characteristics, stage/grade at diagnosis, primary site, and time to treatment by race. Multivariable logistic regression evaluated TTDS differences by sociodemographic characteristics/primary site. Multivariable linear regression determined the unique contribution (in days) of each sociodemographic/disease characteristic to TTDS. Analyses were performed in SAS 9.4 (SAS Institute), and P < .05 was considered significant. Of the 26,237 patients with MCC identified, 1766 (6.73%) were Black (Table I). More Black than non-Hispanic White (NHW) patients presented with later-stage, poorly differentiated/undifferentiated, anaplastic, and truncal MCC (P < .001). TTDS was greater for Black patients (58.9 days) than for NHW patients (46.3 days; P < .05). Time to radiation was 18.9 days longer for Black than NHW patients (P < .001), and time to chemotherapy did not differ by race (P = .1453). Black patients lived closer to the hospital (23.2 miles) than NHW patients (41.7 miles; P < .05). TTDS was longer for Black than NHW patients for stages I to III (P < .05), but not stage IV (P = .1319) MCC (Supplemental Table I; available via Mendeley at https://doi.org/10.17632/pv6dp9kn3g.1). Racial differences persisted for private insurance and Medicare (P < .01), but not for Medicaid (P = .8986) or uninsured patients (P = .7510). CI, Confidence interval. After controlling for socioeconomic characteristics, stage, and primary site, Black race was associated with roughly twice the odds of having a TTDS of 61 to 90 (adjusted odds ratio [aOR], 1.97) or longer than 90 days (aOR, 2.11; P < .001) (Table II). Eyelid tumors were associated with increased odds of TTDS of 31 to 60 (aOR, 1.39), 61 to 90 (aOR, 2.12), and longer than 90 days (aOR, 1.47; P < .001). External ear tumors were associated with increased odds of TTDS of 31 to 60 (aOR, 1.40) and 61 to 90 days (aOR, 1.24), and primary site on other parts of the face (aOR, 1.28) and scalp/neck (aOR, 1.12) were associated with increased odds of TTDS of 31 to 60 days (P < .05). Black race, eyelid lesions, and Medicaid were uniquely associated with 11.1, 6.24, and 12.17 additional days from diagnosis to surgical treatment, respectively (P < .01) (Supplemental Table II; available via Mendeley at https://doi.org/10.17632/pv6dp9kn3g.1). aOR, Adjusted odds ratio. Black patients experience delays in TTDS for MCC that persist for stages I to III MCC and for private insurance/Medicare, despite living closer to the hospital than NHW patients. Medicaid and primary facial MCC are also associated with substantial surgical delays. The 5-year survival of MCC is 64% for local disease, 39% for regional nodal disease, and 18% for metastatic disease.1Hughes M.P. Hardee M.E. Cornelius L.A. Hutchins L.F. Becker J.C. Gao L. Merkel cell carcinoma: epidemiology, target, and therapy.Curr Dermatol Rep. 2014; 3: 46-53Crossref PubMed Google Scholar Although we were unable to evaluate the association of TTDS with long-term survival, increased TTDS is associated with worse outcomes for melanoma, breast, and head/neck cancers.3Conic R.Z. Cabrera C.I. Khorana A.A. Gastman B.R. Determination of the impact of melanoma surgical timing on survival using the National Cancer Database.J Am Acad Dermatol. 2018; 78: 40-46Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar Increased TTDS in Black patients with MCC may affect racial disparities in MCC outcomes, although time to adjuvant radiation therapy does not affect MCC outcomes.4Yusuf M.B. Gaskins J. Wall W. Tennant P. Bumpous J. Dunlap N. Immune status and the efficacy of radiotherapy on overall survival for patients with localized Merkel cell carcinoma: an analysis of the National Cancer Database.J Med Imaging Radiat Oncol. 2020; 64: 435-443Crossref PubMed Scopus (5) Google Scholar,5Shinde A. Verma V. Jones B.L. et al.The effect of time to postoperative radiation therapy on survival in resected merkel cell carcinoma.Am J Clin Oncol. 2019; 42: 636-642Crossref PubMed Scopus (6) Google Scholar Regardless of the association of treatment delays with survival, racial discrepancies in time to treatment may affect quality of life and comorbidity burden and reflect systemic disparities in health care delivery/quality of care that should be addressed by dermatologists. Variability in TTDS by insurance and primary site underscores the importance of improving access to timely treatment for MCC, which may involve coordination of multiple specialties. Ultimately, better understanding the components underlying disparities in treatment delays is integral to developing interventions to improve MCC outcomes.