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

Abstract

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 IPatient characteristicsPatient characteristicsPrepandemic patients (n = 246)Postpandemic patients (n = 246)P valueMedian age at diagnosis, y65 (IQR: 52-74, n = 246)65 (IQR: 54-73, n = 246).8467Sex.5872 Male130 (52.8%)137 (55.7%) Female116 (47.2%)109 (44.3%)Race White244 (99.2%)245 (99.6%).0000 Black1 (0.4%)1 (0.4%) Other1 (0.4%)0 (0.0%)ECOG performance status at diagnosis.0606 0215 (87.4%)198 (80.8%) 125 (10.2%)41 (16.7%) 26 (2.4%)4 (1.6%) 30 (0.0%)2 (0.8%)Median time lesion present, mos1 (IQR: 0-5, n = 241)2 (IQR: 0-6, n = 225).3302Median time from initial diagnosis, mos25.5 (IQR: 13.5-78, n = 8)60 (IQR: 14-114, n = 25).2395Melanoma subtype Superficial spreading98 (49.7%)90 (43.7%) Nodular54 (27.4%)67 (32.5%) Lentigo maligna19 (9.6%)9 (4.4%) Acral02 (1.0%) Mucosal01 (0.5%) Other26 (13.2%)37 (18.0%) Unknown49 (19.9%)40 (16.2%)Presentation.0929 Limited stage de novo209 (85.0%)200 (81.3%).3355 Metastatic de novo29 (11.8%)27 (11.0%).8872 Metastatic recurrence8 (3.3%)19 (7.7%).0459Definitive surgical management210 (86.1%)203 (83.2%).4516Adjuvant therapy.0335 Immunotherapy153 (72.5%)121 (62.4%) Targeted therapy58 (27.5%)73 (37.6%)Systemic therapy>.99 Immunotherapy34 (89.5%)39 (88.6%) Targeted therapy4 (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. Open table in a new tab Table IIStage at diagnosisStagePrepandemic patients (n = 246)Postpandemic patients (n = 246)P valueI100 (40.7%)70 (28.5%).0059 IA45 (18.3%)32 (13.0%).1361 IB55 (22.4%)38 (15.5%).0650II57 (23.2%)55 (22.4%).9144 IIA23 (9.4%)21 (8.5%).8746 IIB21 (8.5%)18 (7.3%).7390 IIC13 (5.3%)16 (6.5%).7025III52 (21.1%)75 (30.5%).0232 IIIA13 (5.3%)17 (6.9%).5726 IIIB18 (7.3%)25 (10.2%).3383 IIIC20 (8.1%)30 (12.2%).1789 IIID1 (0.4%)3 (1.2%).6235IV37 (15.0%)46 (18.7%).3355 IV- M1a6 (2.4%)6 (2.4%)>.99 IV - M1b7 (2.8%)5 (2.0%).7716 IV - M1c21 (8.5%)19 (7.7%).8692 IV - M1d4 (1.6%)16 (6.5%).0102Bolded P-values correspond to statistically signficant differences between the pre- and post-pandemic cohorts. Open table in a new tab 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. 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. Bolded P-values correspond to statistically signficant differences between the pre- and post-pandemic cohorts. ECOG, Eastern Cooperative Oncology Group; IQR, interquartile range. 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. 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.