Neoadjuvant-Adjuvant or Adjuvant-Only Pembrolizumab in Advanced Melanoma.

BACKGROUND: Whether pembrolizumab given both before surgery (neoadjuvant therapy) and after surgery (adjuvant therapy), as compared with pembrolizumab given as adjuvant therapy alone, would increase event-free survival among patients with resectable stage III or IV melanoma is unknown. METHODS: In a phase 2 trial, we randomly assigned patients with clinically detectable, measurable stage IIIB to IVC melanoma that was amenable to surgical resection to three doses of neoadjuvant pembrolizumab, surgery, and 15 doses of adjuvant pembrolizumab (neoadjuvant-adjuvant group) or to surgery followed by pembrolizumab (200 mg intravenously every 3 weeks for a total of 18 doses) for approximately 1 year or until disease recurred or unacceptable toxic effects developed (adjuvant-only group). The primary end point was event-free survival in the intention-to-treat population. Events were defined as disease progression or toxic effects that precluded surgery; the inability to resect all gross disease; disease progression, surgical complications, or toxic effects of treatment that precluded the initiation of adjuvant therapy within 84 days after surgery; recurrence of melanoma after surgery; or death from any cause. Safety was also evaluated. RESULTS: At a median follow-up of 14.7 months, the neoadjuvant-adjuvant group (154 patients) had significantly longer event-free survival than the adjuvant-only group (159 patients) (P = 0.004 by the log-rank test). In a landmark analysis, event-free survival at 2 years was 72% (95% confidence interval [CI], 64 to 80) in the neoadjuvant-adjuvant group and 49% (95% CI, 41 to 59) in the adjuvant-only group. The percentage of patients with treatment-related adverse events of grades 3 or higher during therapy was 12% in the neoadjuvant-adjuvant group and 14% in the adjuvant-only group. CONCLUSIONS: Among patients with resectable stage III or IV melanoma, event-free survival was significantly longer among those who received pembrolizumab both before and after surgery than among those who received adjuvant pembrolizumab alone. No new toxic effects were identified. (Funded by the National Cancer Institute and Merck Sharp and Dohme; S1801 ClinicalTrials.gov number, NCT03698019.).

Neoadjuvant Cemiplimab for Stage II to IV Cutaneous Squamous-Cell Carcinoma.

BACKGROUND: In a pilot study involving patients with cutaneous squamous-cell carcinoma, a high percentage of patients had a pathological complete response with the use of two doses of neoadjuvant cemiplimab before surgery. Data from a phase 2 study are needed to confirm these findings. METHODS: We conducted a phase 2, confirmatory, multicenter, nonrandomized study to evaluate cemiplimab as neoadjuvant therapy in patients with resectable stage II, III, or IV (M0) cutaneous squamous-cell carcinoma. Patients received cemiplimab, administered at a dose of 350 mg every 3 weeks for up to four doses, before undergoing surgery with curative intent. The primary end point was a pathological complete response (the absence of viable tumor cells in the surgical specimen) on independent review at a central laboratory, with a null hypothesis that a pathological complete response would be observed in 25% of patients. Key secondary end points included a pathological major response (the presence of viable tumor cells that constitute ≤10% of the surgical specimen) on independent review, a pathological complete response and a pathological major response on investigator assessment at a local laboratory, an objective response on imaging, and adverse events. RESULTS: A total of 79 patients were enrolled and received neoadjuvant cemiplimab. On independent review, a pathological complete response was observed in 40 patients (51%; 95% confidence interval [CI], 39 to 62) and a pathological major response in 10 patients (13%; 95% CI, 6 to 22). These results were consistent with the pathological responses determined on investigator assessment. An objective response on imaging was observed in 54 patients (68%; 95% CI, 57 to 78). Adverse events of any grade that occurred during the study period, regardless of whether they were attributed to the study treatment, were observed in 69 patients (87%). Grade 3 or higher adverse events that occurred during the study period were observed in 14 patients (18%). CONCLUSIONS: Neoadjuvant therapy with cemiplimab was associated with a pathological complete response in a high percentage of patients with resectable cutaneous squamous-cell carcinoma. (Funded by Regeneron Pharmaceuticals and Sanofi; ClinicalTrials.gov number, NCT04154943.).

Impact of the COVID-19 Pandemic on Characteristics of Cutaneous Tumors Treated by Mohs Micrographic Surgery.

The COVID-19 pandemic has impacted the practice of Mohs micrographic surgery (MMS). We sought to determine the characteristics of skin cancers treated by MMS during the pandemic compared with prepandemic controls. A retrospective chart review was conducted. Tumors included were all treated in accordance with best practice guidelines set forth by state- and national-level professional governing bodies. Bivariate and multivariate analyses were performed to compare outcome variables. Changes in tumor characteristics during the pandemic are of clinical significance, potentially affecting extent of reconstructive surgery, cost, operating time, and future tumor characteristics.

Impact of COVID-19 Pandemic on Non-Melanoma Skin Cancer's Tumor Burden and Care: a Multi-Center Study Based in Northern Italy.

The brisk remodeling in healthcare delivery observed after the COVID-19 outbreak led us to evaluate how the pandemic affected non-melanoma skin cancer's (NMSC) care and tumor burden. To address this topic, we set up a retrospective real-life multi-center study based on the cities of Bergamo and Varese, whose provinces were the worst hit in Italy by the pandemic. We analyzed medical and pathological data from patients that underwent surgery in the two months preceding the outbreak in Italy and compared them to those who did in the corresponding bimester of the following year, reaching 214 patients and 274 lesions. We observed a considerable and significant increase in NMSC's diameter, as well as in the proportion of squamous cell carcinomas. Both the average waiting time to obtain an evaluation visit and the average time in the surgical waiting list was shorter after the COVID-19 outbreak: the reason is that we evaluated and operated near-exclusive patients affected by high-priority lesions, who benefited from "fast-track" referrals. Conversely, less-concerning lesions were, and still are, left on hold, until they will become advanced enough to be labeled as "urgent". Plastic surgery departments should evade as soon as possible from this downward spiral, in order to provide our patients with timely cancer care and to be able to treat all plastic surgery-requiring pathologies.

Advanced-Stage Melanoma at Presentation Following the Peak of the Pandemic: A COVID-19 Cancer Canary in a Coal Mine.

BACKGROUND: For melanoma patients, timely identification and tumor thickness are directly correlated with outcomes. COVID-19 impacted both patients' ability and desire to see physicians. We sought to identify whether the pandemic correlated with changes in melanoma thickness at presentation and subsequent treatment timeline. METHODS: Retrospective chart review was performed on patients who underwent surgery for melanoma in an academic center surgical oncology practice from May 2019 to September 2021. Patients were split into two cohorts: "pre-pandemic" from May 2019 to May 2020 and "pandemic," after May 2020, representing when these patients received their initial diagnostic biopsy. Demographic and melanoma-specific variables were recorded and analyzed. RESULTS: A total of 112 patients were identified: 51 patients from the "pre-pandemic" and 61 from the "pandemic" time period. The pandemic cohort more frequently presented with lesions greater than 1 mm thickness compared to pre-pandemic (68.8% v 49%, p = 0.033) and were found to have significantly more advanced T stage (p = 0.02) and overall stage disease (p = 0.022). Additionally, trends show that for pandemic patients more time passed from patient-reported lesion appearance/change to diagnostic biopsy (5.7 ± 2.0 v 7.1 ± 1.5 months, p = 0.581), but less time from biopsy to operation (42.9 ± 2.4 v 52.9 ± 5.0 days, p = 0.06). CONCLUSIONS: "Pandemic" patients presented with thicker melanoma lesions and more advanced-stage disease. These results may portend a dangerous trend toward later stage at presentation, for melanoma and other cancers with rapid growth patterns, that will emerge as the prolonged effects of the pandemic continue to impact patients' presentation for medical care.

Impact of the COVID Pandemic on Mohs Micrographic Surgery: A Nationwide Survey.

BACKGROUND: At the onset of the COVID-19 pandemic, many Mohs micrographic surgeries (MMS) were delayed over concerns for propagating further infectious spread and scarcity of medical resources. OBJECTIVE: To assess the impact of the pandemic on MMS and the treatment of skin cancer Methods and Materials: An electronic survey was sent to fellowship trained Mohs surgeons to assess patient outcomes, practice viability, and physician sentiment related to performing MMS during the COVID-19 pandemic. RESULTS: Of the 303 respondents, 82% reported declines in case volume for at least 3 months, and average case difficulty increased for 69% of surgeons following these delays. Instances of local tumor spread following delays were seen by 69% of respondents, and 20% noted cases of regional or systemic metastasis. Only 8 cases of staff testing positive (and 7 cases of patients) were reported, and 97% of respondents felt comfortable performing MMS during the pandemic. Private practice surgeons more often viewed practice restriction recommendations negatively initially (42% vs 26% in academics, P=0.03) and in hindsight (63% vs 36% in academics, P<0.001). CONCLUSIONS: Mohs surgeon’s ability to minimize spread of COVID-19 during routine patient care, alongside potential risks of delaying treatment of skin cancers, should be considered in future recommendations for patient care. J Drugs Dermatol. 2022;21(5):545-547. doi:10.36849/JDD.6189.

Implementation of a telemedicine service to provide skin cancer care in a tertiary plastic surgery unit during COVID-19 - a comprehensive review.

BACKGROUND: In response to the COVID-19 pandemic, our tertiary skin cancer service had to adapt rapidly to reduce hospital footfall. Consequently, all clinic appointments for skin cancer patients were converted to telephone consultations. This study aims to provide a comprehensive review of this new service. METHODS: This study consisted of three domains: patient and staff experience, efficacy and productivity. Patient and staff experience was assessed through prospective surveys. Efficacy of telephone appointments was assessed through prospective review of clinic coding to evaluate outcomes including rate of conversion to face-to-face appointment. Markers of treatment pathway efficacy included time from referral to surgical listing and the incidence of benign lesions placed on skin cancer pathways. Productivity was evaluated through review of the cumulative number of completed and missed appointments over a 1-month period before and during the pandemic. RESULTS: All patients were satisfied with the telephone consultation and were preferred to previous experience of face-to-face appointments by 67%. Over 80% of responding clinicians felt telephone clinics should remain as a legacy of COVID-19. Time from referral to scheduling for surgery was significantly shorter for urgent lesions when listed through a teleclinic compared to face-to-face appointment. The telephone service allowed us to maintain 46% of the plastic surgery outpatient activity of May 2019 and missed appointments almost halved. CONCLUSION: Patients and clinicians have responded positively to the new service. This study highlights the merits of an ongoing telephone clinic service for select patients on resolution of the COVID-19 impact on health services.

The impact of treatment delay on skin cancer in COVID-19 era: a case-control study.

BACKGROUND: The outbreak of COVID-19 pandemic led to a 2-month lockdown in Europe. Elective surgeries, including skin cancer excisions, were postponed. The purpose of this prospective case-control study was to assess the impact of the treatment delay on patients with non-melanoma skin cancer (NMSC) or melanoma operated in the first post-lockdown period. METHODS: A comparative study of skin cancer operations performed in a 4-month period either in 2020 or in 2019 was conducted. All data were collected from a prospectively maintained clinic database and the pathological reports. Continuous variables were compared with t test or Mann-Whitney U test according to their distribution. Categorical variables were compared with Fisher exact test. Odds ratio (OR) with 95% confidence interval (95% CI) was used to assess the risk of excising high-risk NMSC in 2020 compared with 2019. RESULTS: Skin cancer excision was performed in 158 cases in 2020 compared to 125 cases in 2019 (26.4% increase). Significantly, more SCC were excised in 2020 (p = 0.024). No significant difference for several clinical parameters regarding BCC, SCC, and melanoma was identified. However, the reconstructive method applied, following NMSC excision, was significantly different, requiring frequently either skin grafting or a flap. CONCLUSION: These results indicate that skin cancer treatment delay, due to COVID-19 pandemic, is related to an increased incidence of SCC and more complicated methods of reconstruction. Considering the relapsing COVID-19 waves, significant skin cancer treatment delays should be avoided. TRIAL REGISTRATION: The study adhered to the STROBE statement for case-control studies.