A retrospective analysis of the impact of the COVID-19 pandemic on staging at presentation of patients with invasive melanoma.

To the Editor: We performed a single-institution retrospective analysis to evaluate the impact of the COVID-19 pandemic on staging at the presentation of patients with invasive melanoma at a large tertiary care center. A total of 246 patients were evaluated between March 11, 2020 (the declaration of the pandemic), and January 12, 2021, and 246 patients treated between March 1, 2019, and March 10, 2020, were then matched to form the prepandemic cohort. Categorical variables were compared using the 2-sided Fisher’s exact test. Continuous variables were compared using the 2-sided Wilcoxon rank sum test. The median progression-free survival and overall survival were estimated using the Kaplan-Meier method. P values were not adjusted for multiple comparisons because this was an exploratory study.

Patient characteristics are reported in Table I . In the postpandemic cohort, 200 (81.3%) patients presented with early-stage disease and 46 (18.7%) patients presented with metastatic disease, compared with 209 (85%) and 37 (15%) patients in the prepandemic cohort, respectively. In the postpandemic cohort, there was a significant decrease in the number of patients presenting with AJCC stage I disease (28.5% vs 40.7%, P = .006) and a significant increase in the number of patients presenting with stage III disease (30.5% vs 21.1%, P = .023). There was also an increase in the number of patients presenting with metastatic recurrence in the postpandemic cohort compared with the prepandemic cohort (7.7% vs 3.3%, P = .046). The median time to recurrence from the time of initial melanoma diagnosis was more than doubled in the postpandemic cohort (60.0 vs 25.5 months), although this did not reach statistical significance (P = .240). There was also a significant increase in the number of patients with brain metastases in the postpandemic cohort (6.5% vs 1.6%, P = .010) compared with the prepandemic cohort. An additional breakdown of the staging is presented in Table II .

Table I

Patient characteristics

Patient characteristics	Prepandemic patients (n = 246)	Postpandemic patients (n = 246)	P value
Median age at diagnosis, y	65 (IQR: 52-74, n = 246)	65 (IQR: 54-73, n = 246)	.8467
Sex			.5872
Male	130 (52.8%)	137 (55.7%)
Female	116 (47.2%)	109 (44.3%)
Race
White	244 (99.2%)	245 (99.6%)	.0000
Black	1 (0.4%)	1 (0.4%)
Other	1 (0.4%)	0 (0.0%)
ECOG performance status at diagnosis			.0606
0	215 (87.4%)	198 (80.8%)
1	25 (10.2%)	41 (16.7%)
2	6 (2.4%)	4 (1.6%)
3	0 (0.0%)	2 (0.8%)
Median time lesion present, mos	1 (IQR: 0-5, n = 241)	2 (IQR: 0-6, n = 225)	.3302
Median time from initial diagnosis, mos	25.5 (IQR: 13.5-78, n = 8)	60 (IQR: 14-114, n = 25)	.2395
Melanoma subtype
Superficial spreading	98 (49.7%)	90 (43.7%)
Nodular	54 (27.4%)	67 (32.5%)
Lentigo maligna	19 (9.6%)	9 (4.4%)
Acral	0	2 (1.0%)
Mucosal	0	1 (0.5%)
Other	26 (13.2%)	37 (18.0%)
Unknown	49 (19.9%)	40 (16.2%)
Presentation			.0929
Limited stage de novo	209 (85.0%)	200 (81.3%)	.3355
Metastatic de novo	29 (11.8%)	27 (11.0%)	.8872
Metastatic recurrence	8 (3.3%)	19 (7.7%)	.0459
Definitive surgical management	210 (86.1%)	203 (83.2%)	.4516
Adjuvant therapy			.0335
Immunotherapy	153 (72.5%)	121 (62.4%)
Targeted therapy	58 (27.5%)	73 (37.6%)
Systemic therapy			>.99
Immunotherapy	34 (89.5%)	39 (88.6%)
Targeted therapy	4 (10.5%)	5 (11.4%)

Bolded P-values correspond to statistically signficant differences between the pre- and post-pandemic cohorts.

ECOG, Eastern Cooperative Oncology Group; IQR, interquartile range.

Table II

Stage at diagnosis

Stage	Prepandemic patients (n = 246)	Postpandemic patients (n = 246)	P value
I	100 (40.7%)	70 (28.5%)	.0059
IA	45 (18.3%)	32 (13.0%)	.1361
IB	55 (22.4%)	38 (15.5%)	.0650
II	57 (23.2%)	55 (22.4%)	.9144
IIA	23 (9.4%)	21 (8.5%)	.8746
IIB	21 (8.5%)	18 (7.3%)	.7390
IIC	13 (5.3%)	16 (6.5%)	.7025
III	52 (21.1%)	75 (30.5%)	.0232
IIIA	13 (5.3%)	17 (6.9%)	.5726
IIIB	18 (7.3%)	25 (10.2%)	.3383
IIIC	20 (8.1%)	30 (12.2%)	.1789
IIID	1 (0.4%)	3 (1.2%)	.6235
IV	37 (15.0%)	46 (18.7%)	.3355
IV- M1a	6 (2.4%)	6 (2.4%)	>.99
IV - M1b	7 (2.8%)	5 (2.0%)	.7716
IV - M1c	21 (8.5%)	19 (7.7%)	.8692
IV - M1d	4 (1.6%)	16 (6.5%)	.0102

Bolded P-values correspond to statistically signficant differences between the pre- and post-pandemic cohorts.

Overall, there was a significant increase in the median Breslow depth (2.0 vs 1.4 mm, P = .047) and mitotic rate of >1/mm2 (78.1% vs 66%, P = .008) in the postpandemic cohort. There were trends toward increased ulceration, lymphovascular invasion, perineural invasion, and microsatellite presence.

A total of 179 (73.7%) patients in the postpandemic cohort and 175 (71.1%) patients in the prepandemic cohort underwent sentinel lymph node (SLN) biopsy at the time of wide local excision. During the pandemic, most patients who were eligible for SLN biopsy by pathologic criteria underwent SLN biopsy, with SLN biopsy foregone in 4 patients. Sixty-six (38.2%) SLN biopsies were positive for melanoma involvement in the postpandemic cohort, compared with 51 (29.7%) biopsies in the prepandemic cohort.

For patients who received adjuvant therapy (194 in the postpandemic cohort and 211 in the prepandemic cohort), those in the postpandemic cohort were more likely to receive oral targeted therapy (73 [37.6%] patients vs 58 [27.5%] patients) than immunotherapy (121 [62.4%] patients, vs 153 [72.5%] patients, P = .034). There was no significant difference between the 2 groups in the type of systemic therapy administered in the metastatic setting. The median progression-free survival and overall survival were not reached in either group.

These findings suggest that patients had delays in coming to medical attention, likely resulting in more advanced disease. These data underscore the importance of early detection and oncology referral for patients with melanoma, even during the pandemic.

Conflicts of interest

Dr Davar reports research support from Merck, Bristol-Myers Squibb, Checkmate Pharmaceuticals, CellSight Technologies, MedPacto, and GlaxoSmithKline; is a consultant for Array BioPharma, Checkmate Pharmaceuticals, Incyte, Immunocore, Merck, and Shionogi; and is on the scientific advisory board of Vedanta Biosciences. Dr Luke reports stock and ownership interests in Actym Therapeutics, Alphamab, Arch Oncology, Kanaph Therapeutics, Mavu Pharmaceutical, Onc.AI, Pyxis, and Tempest Therapeutics; is a consultant for 7 Hills Pharma, AbbVie, Alphamab, Array BioPharma, Astellas Pharma, Bayer, Bristol-Myers Squibb, Checkmate Pharmaceuticals, Compugen, CStone Pharmaceuticals, Eisai, EMD Serono, Incyte, Janssen, Merck, Mersana, Nektar, Novartis, Partner Therapeutics, Reflexion Medical, Regeneron, Ribon Therapeutics, Rubius Therapeutics, Spring Bank, Synlogic, Tempest Therapeutics, Tesaro, TTC Oncology, Werewolf Therapeutics, Xencor, and Xilio Therapeutics; reports research funding from AbbVie, Agios, Array BioPharma, Astellas Pharma, Bristol-Myers Squibb, Checkmate Pharmaceuticals, Corvus Pharmaceuticals, EMD Serono, Immatics, Incyte, Kadmon, Macrogenics, Merck, Moderna Therapeutics, Nektar, Spring bank, Trishula Therapeutics, and Xencor; reports patents #15/612,657 (Cancer immunotherapy) and #PCT/US18/36052 (Microbiome biomarkers for anti-pd-1/pd-l1 responsiveness: diagnostic, prognostic and therapeutic uses thereof); and has received travel expenses from Array BioPharma, Bristol-Myers Squibb, EMD Serono, Janssen, Merck, Mersana, Novartis, Pyxis, Reflexion Medical, and Xilio Therapeutics. Dr Zarour reports research support from Bristol-Myers Squibb, Checkmate Pharmaceuticals, and GlaxoSmithKline and is a consultant for Bristol-Myers Squibb, Checkmate Pharmaceuticals, GlaxoSmithKline, and Vedanta Biosciences. Dr Kirkwood reports research support from Amgen, Bristol-Myers Squibb, Castle Biosciences, Checkmate Pharmaceuticals, Immunocore LLC, Iovance, and Novartis and is a consultant for Amgen, Bristol-Myers Squibb, Checkmate Pharmaceuticals, and Novartis. Dr Najjar reports research support from Merck, Pfizer, and Bristol-Myers Squibb; is a consultant for Array BioPharma; and is on the consulting/advisory board of Novartis. Drs Shaikh, Yang, Fortman, and Wang have no conflicts of interest to declare.