A Review of Neoadjuvant PD-1 Inhibitors in the Setting of Cutaneous Malignancies

J Clin Aesthet Dermatol. 2025;18(5):30–35.

by Ariel R. Darnall, DO, FAAD; David Baltazar, DO, FAAD; Dathan Hamann, MD, FAAD; Nathalie Zeitouni, MD, FAAD, FACMS; and Justin Moser, MD

Drs. Darnall, Hamann, and Moser are with the Department of Dermatology at Honorhealth in Scottsdale, Arizona. Drs. Baltazar and Zeitouni are with US Dermatology Partners in Dallas, Texas. Additionally, Dr. Hamann is with the Department of Internal Medicine at the University of Arizona College of Medicine in Phoenix, Arizona.

FUNDING: No funding was provided for this article.

DISCLOSURES: The authors declare no conflicts of interest relevant to the content of this article.

ABSTRACT: Considering the rapid pace of developments in the field of cancer immunotherapy, continuous updates on the topic are critical for the medical community. With incidences of cutaneous malignancies on the rise, it is more imperative than ever to utilize and understand current and future treatment modalities. Currently, the United States (US) Food and Drug Administration (FDA) approval for various immune checkpoint inhibitors (ICIs), particularly programmed cell death protein 1 (PD-1) inhibitors, in an adjuvant setting for various cutaneous malignancies is the mainstay in treatment of a number of cutaneous malignancies. Given the transformative potential of PD-1 inhibitors within the realm of immunotherapy, an understanding of the current state of research in this area is essential for dermatologists. This is important because in the cutaneous oncological world, neoadjuvant therapy is quickly demonstrating to show significant importance skin cancer treatment. Traditional neoadjuvant therapy involves a combination of chemotherapy, radiation, and/or targeted therapy, depending on the type and stage of malignancy. The main objective in these therapies has been to reduce tumor size for improved operability, manage systemic disease, and treat operable tumors prior to surgical intervention to obtain a more favorable long-term survivability. This review aims to provide a succinct analysis of both recent and current research of PD-1 inhibitors in the neoadjuvant setting of melanoma, squamous cell carcinoma, and merkel cell carcinoma.

Keywords: PD1, neoadjuvant, squamous cell carcinoma, melanoma, merkel cell carcinoma

Introduction

In recent years, detection and treatment of various malignancies has undergone profound growth and expansion. Remarkable strides have been taken in furthering our understanding of molecular mechanisms behind not only in uncontrolled tumor growth and evasion of T-cell destruction, but also in our abilities to manipulate the immune system to treat these cancers. Immunotherapy, treatment aimed to modify and alter the body’s immune system to target cancerous cells, has quickly become a mainstay in cancer treatment modalities. Immunologic agents specifically designed to amplify T-cell responses to cancerous cells have shown promising effectiveness in increasing overall survival in an array of various cancers.¹ This in turn has led to the the United States (US) Food and Drug Administration (FDA) approval of various immune checkpoint inhibitors (ICIs) in the treatment of numerous solid organ malignancies like lung or renal cancer, but also for melanoma and squamous cell carcinoma (SCC).² In particular, the advent of PD-1 inhibitors has been instrumental in reshaping the treatment paradigm for various malignancies, including skin cancer.³ Current approvals are noted traditionally to be in an adjuvant setting.² However, neoadjuvant therapy, or immunotherapy prior to tumor resection, has been gaining positive traction within the oncological world.

While neoadjuvant immunotherapy shares similar goals to traditional adjuvant therapy, the approach of immunotherapy represents a paradigm shift in treatment. Rather than targeting the cell cycle or damaging DNA, immunotherapy disrupts the mechanism in which malignant neoplasms avoid the immune system via PD-1/ cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibition. With this mechanism blocked, the immune system is activated, enabling it to detect and destroy malignant cells.^4,5

Along with the immune system being activated, there are multiple benefits that neoadjuvant PD-1 inhibitor therapy offers compared to traditional adjuvant therapy and traditional cancer therapy. The systemic immune response that is created against the tumor may enhance antigen presentation, effectively educating the immune system to recognize and target the tumor cells.⁴ Thus leveraging the adaptive immune response and creating memory T-cells, which can reduce the risk of metastasis, recurrence, and induce durable memory immune response which could potentially control the disease in the long term.^6,7 To accurately evaluate tumor responses to therapeutic agents, it is crucial to comprehend the methodologies employed in measuring such responses. These assessments are conducted through both gross and microscopic examination. A fundamental understanding of the principles underlying pathological remission is essential. Pathological remission can be categorized into four distinct types: pathological complete remission (pCR), major pathological response (MPR), partial pathological response (pPR), and pathological non-response (pNR). The criteria for these categories are established by the International Neoadjuvant Melanoma Consortium (INMC) guidelines.⁸ According to these guidelines, pCR is characterized by the absence of detectable residual tumor cells in resected tissues or following the completion of neoadjuvant therapy. MPR is defined as having less than 10 percent residual tumor post-neoadjuvant therapy. pPR is identified by the presence of less than 50 percent residual tumor, whereas pNR is indicated by more than 50 percent of the tumor remaining.

Furthermore, immunotherapy can provide an in vivo assessment of the tumor’s response to the treatment. If the tumor shrinks in response to the immunotherapy, it could offer important prognostic information and guide further treatment decisions. This knowledge is necessary to discuss the latest treatment options and make informed clinical decisions. Furthermore, an awareness of the most current research can stimulate further investigation, potentially prompting new studies within the dermatological community.

The purpose of this review is to help dermatologists not only stay updated but also actively contribute to the scientific discourse on neoadjuvant PD-1 inhibitor therapy, ultimately aiming for better patient outcomes in skin cancer treatment. In this review, we will aim to delineate and briefly describe current studies being performed with PD-1 inhibitors in a neoadjuvant setting in merkel cell carcinoma, melanoma, and squamous cell carcinoma.

Melanoma

With melanoma rates on the rise within the past few decades and melanoma being responsible for 80 percent of skin cancer related deaths, improving effective treatment modalities have become increasingly more important. While rates of melanoma have increased drastically, the mortality rate of melanoma has decreased by close to 30 percent due to the approval of various immunotherapies.⁹ Beginning in 2011, the human cytotoxic T-lymphocyte antigen 4 (CTLA-4)-blocking antibody medication, Ipilimumab, was approved for unresectable, late-stage melanoma.¹⁰ Ipilimumab quickly was further FDA-approved for metastatic melanoma in both adults and the pediatric population (12 years or older) after exhibiting improved survival in an adjuvant setting for metastatic melanoma with an overall favorable safety profile.¹⁰ Since then, numerous other immunotherapies have been approved including the novel ICIs known as PD-1 inhibitors.

Nivolumab was approved by the FDA shortly after Ipilimumab in December 2014 after exhibiting an increased overall response rate in addition to decreased toxicity in patients with unresectable metastatic melanoma after being treated with ipilimumab or a BRAF inhibitor (if positive for a BRAF mutation).¹¹ Subsequent trials over the next few years went on to illustrate improved progression-free survival (PFS) in addition to improved recurrence-free survival (RFS) in patients with advanced and/or metastatic melanoma in combination adjuvant therapy with ipilimumab.^12,13 This led to subsequent FDA-approval for the use of nivolumab in advanced melanomas that had already underwent surgical resection.¹³ Pembrolizumab was approved around the same time as nivolumab after various studies improved response rates in metastatic melanoma patients who previously tried and failed treatment with ipilimumab or a BRAF inhibitor.¹⁴

Approval for pembrolizumab in an adjuvant clinical setting soon grew to include untreated melanomas due to its superiority, when compared to conventional standard ipilimumab, in overall survival and PFS with the benefit of a more favorable, safer side effect profile than ipilimumab.¹⁴ Indications for pembrolizumab, like nivolumab, soon expanded to include refractory cases of melanoma in addition to completely resected melanomas with lymph node positivity.^15,16 These studies tested these immunotherapy agents in an adjuvant context. However, recent studies have shown that neoadjuvant therapy may bolster the effectiveness of these immunotherapies. This portion of the review is to accumulate and contextualize past, current, and prospective studies evaluating the efficacy of PD-1 inhibitors in an neoadjuvant setting of melanoma.

Current studies. While adjuvant therapy has proven to be effective in treating melanoma, more recent studies have gone on to illustrate how neoadjuvant therapy not only improves overall response rate (ORR), PFS, and RFS, but also appears to improve the overall pathologic response with higher rates of pCR.^17–20 Menzies et al¹⁹ collected data from six clinical trials evaluating the pathologic response to neoadjuvant immunotherapy and its effects on RFS and OS in patients with macroscopic Stage III resectable melanoma and found that neoadjuvant systemic therapy response was directly correlated with degree of pathological response. Furthermore, the more strongly correlated the pCR, the more RFS and OS were positively affected. This suggested that pathological response to neoadjuvant therapy may be instrumental in identifying clinical response rates in melanoma patients.

Blank et al²¹ reported similar results from the OpACIN trial (NCT02437279) that directly compared neoadjuvant combination therapy to adjuvant therapy in 20 patients with palpable Stage III melanoma. Patients were randomized and matched in each treatment arm to receive a combination of ipilimumab and nivolumab in a total of four courses (four treatments post operatively in the adjuvant group vs. two courses preoperative and two courses post operatively in the neoadjuvant group). The trial went on to show significant pathological response rates in the neoadjuvant group (n=7/9 [78%]) however significant adverse events were documented due to high toxicity rates. These findings, while impressive, highlighted the need to evaluate a regimen that reduced drug toxicity and adverse events while simultaneously preserving drug efficacy. Currently, a subsequent trial (OpACIN-neo, NCT02977052), is underway evaluating less intense treatment regimens with the goal of obtaining the same response rates to neoadjuvant therapy while attempting to mitigate drug toxicity and adverse events. Recently updated data in the OpACIN-neo trial has shown a correlation in the pathologic response rate to overall survival with immunotherapy in an neoadjuvant setting versus an adjuvant setting with pathologic response conferring a longer duration disease free outcome.^22,23 The PRADO study, a Phase II extension of the OpACIN-neo trial went on to treat 99 patients diagnosed with Stage IIIB–D nodal melanoma with the OpACIN-neo treatment regimen but expounded to include sampling of the largest metastatic lymph node (termed index lymph node) after neoadjuvant therapy.²⁴ 

Results indicated that 60 (61%) of the 99 patients experienced a MPR with 93 percent having RFS at two years and a metastasis-free survival rate of 98 percent at distant sites.²⁴

Published recently in March 2023, event-free survival (EFS) without additional toxic side effects with neoadjuvant therapy has been identified in a Phase II trial evaluating patients with resectable Stage IIIB to IVC melanoma with three doses of neoadjuvant pembrolizumab, surgery, and 15 doses of adjuvant pembrolizumab illustrating promising treatment regimens with more severe adverse events to be less than 15 percent in the neoadjuvant group.²⁵ This trial (SWOG S1801, NCT03698019) more importantly illustrated a substantial improvement in PFS at two years with an absolute difference of 23 percent for the neoadjuvant group (72%) versus the adjuvant group (49%) treated with pembrolizumab.²⁵

The promising outcomes shown in these neoadjuvant therapeutic studies with immune checkpoint inhibitors have in turn spurred other various trials investigating PD-1 inhibitor combination therapies with BRAF inhibitors to talimogene laherparepvec (T-VEC) to High Dose Interferon Alfa-2b to relatlimab in a neoadjuvant setting.^22,26–29 These studies have not only shown promising pathologic response rates and improved operability, but also a reduction in disease recurrence and progression free survival. ^22,26–29 The NIVEC trial (NCT04330430) currently underway by Rohaan et al²⁷ is a Phase II trial looking to evaluate the pCR rate in resectable Stage IIIB-IVM1a melanoma treated with a combination of systemic immunotherapy with nivolumab and T-VEC neoadjuvantly. Patients in this study are set to undergo treatment preoperatively with four courses of T-VEC and three courses of nivolumab with surgical intervention occurring nine weeks after neoadjuvant treatment. In addition to pCR rate, secondary goals of the trial include safety, event-free survival, and biomarker tracking related to overall disease burden and response.

Combination therapy with PD-1 inhibitors and newer therapeutic options like relatlimab, a human IgG4 LAG-3-blocking monoclonal antibody, have also recently been approved for metastatic melanoma by the FDA in March 2022 after combination therapy with PD-1 inhibitors and relatlimab in the RELATIVITY-047 trial (NCT03470922) illustrated superior response in progression free survival unresectable Stage III or Stage IV metastatic melanoma while maintaining a favorable side effect profile.³⁰ Lymphocyte-activation gene 3 (LAG-3) is an inhibitory molecule in T-cell activation thought to play a role in restricting T-cell function.³¹ By blocking this receptor, the restoration of T-cell functionality is thought to help promote effector T-cell activity and therefore re-exert their anti-tumor effects which in turn is proving to be a novel marker for T-cell depletion. Amaria et al²² (NCT02519322) are conducting a Phase II trial that is currently evaluating neoadjuvant therapy of relatlimab combined with PD-1 inhibitors (nivolumab alone or in combination with ipilimumab) in patients with resectable Stage IIIB–IV melanoma. Thus far, the data yielded is demonstrating a high pCR rate in addition to enhanced recurrence free survival at the 1- and 2-year marker. Conjointly, an abundance of data of current clinical trials is supportive of neoadjuvant therapy in not only efficacy, progression free survival, and overall treatment tolerability.

Squamous Cell Carcinoma

Cutaneous squamous cell carcinoma (cSCC) is a predominant skin cancer type, surpassed only by basal cell carcinoma in terms of global incidence.³² Originating from the aberrant proliferation of squamous cells, cSCC has the potential to be invasive, leading to considerable clinical complications and, in severe instances, death.³³ While surgical intervention remains the gold standard for early-stage cSCC, advanced forms, particularly those with nodal involvement or distant spread, necessitate more intricate therapeutic strategies.³⁴

The therapeutic domain of oncology has witnessed a paradigm shift in recent years with the introduction of immunotherapeutic agents. These agents, by modulating the immune system, offer a novel avenue to target and eliminate cancer cells, demonstrating efficacy in a spectrum of tumors like melanoma and lung carcinoma.³⁵ In this context, neoadjuvant immunotherapy, given prior to the main therapeutic intervention, has been explored for its potential to reduce tumor bulk, thereby optimizing the outcomes of subsequent surgical or radiological procedures.³⁶ Furthermore, neoadjuvant immunotherapy has demonstrated significant beneficial effects on survival in melanoma patients. Patel et al²⁵ demonstrated the two-year event-free survival rate was notably higher in the neoadjuvant–adjuvant group at 72 percent (95% confidence interval [CI], 64 to 80) compared to 49 percent (95% CI, 41 to 59) in the group that received only adjuvant therapy.

Current studies. Cutaneous squamous cell carcinoma ranks as the second most prevalent skin cancer, following basal cell carcinoma. The primary treatments for cSCC include Mohs micrographic surgery and excision, with the choice depending on factors such as location, size, depth of invasion, and pathological findings.³⁷ These methods are highly effective, showcasing low incidences of recurrence, metastasis, and disease-specific mortality.^38,39 Although these treatments are optimal for patients with localized disease, a minority (3–5%) will exhibit locally advanced stages, characterized by lymph node involvement.³⁸ Post-surgical procedures often incorporate adjuvant radiation as an additional treatment. However, even with this intensified approach, these patients face a 30 percent likelihood of disease recurrence and subsequent mortality.^38,40,41

In patients with a high risk of recurrence and mortality, neoadjuvant immunotherapy emerges as a pivotal treatment strategy.⁴² Cutaneous squamous cell carcinoma often exhibits a high tumor mutational burden, largely attributed to chronic ultraviolet (UV) light exposure.⁴³ This predisposition makes cSCC particularly amenable to neoadjuvant immunotherapy, as evidenced by the significant response rates reported by Migden et al.⁴⁴ In the Phase II trial, 78 patients with either locally advanced or metastatic disease received bi-weekly cemiplimab treatments. Depending on the reviewer, the objective response rate ranged from 44 percent (n=34/78) to 53 percent (n=41/78).⁴⁴ With the evolving landscape of cSCC treatment, enriched by neoadjuvant immunotherapy, the main goal is to give a review of the current ground-breaking literature.

Ferrarotto et al⁴² presented a Phase II trial which was published in 2021 involving 20 patients (13 with new disease and 7 with recurrent disease) with resectable Stage III–Stage IVA cSCC of the head and neck. After receiving two cycles of 350mg of cemiplimab every three weeks, patients underwent surgical resection. Radiographic assessments (CT or PET-CT) were conducted pre- and post-neoadjuvent cemiplimab treatment. Pathologic assessment was performed post surgically. The primary endpoints, Overall response rate (ORR), which is based on radiographic imaging before and after cemiplimab.

The overall response rate was 30 percent (n=6/20) while there were two patients who had evidence of progression. Upon pathologic assessment of surgical specimens, 55 percent (n=11/20) of the patients demonstrated a pCR. An additional 20 percent (n=4/20) demonstrated an MPR. 

One-year survival metrics were promising: 95 percent for disease-specific survival, 89.5 percent for disease-free survival, and 95 percent for overall survival. At median follow-up of 22.6 months, there were three recurrences. Each of these recurrences did not achieve objective response on imaging, pCR, or MPR. Notably, all patients were scheduled to receive adjuvant radiation at baseline. However, 60 percent of patients did not receive adjuvant radiation, 11 were not recommended due to pathological response and one declined. None of these patients experienced a recurrence. 

In total, there were seven patients (35%) that had treatment related adverse events, with pruritus followed by maculopapular rash being the most common Grade 1 events. The most serious being diarrhea (Grade 3), but none were fatal and all were resolved.

Gross et al⁴⁵ presented a Phase II, multicenter, single-group, non-randomized clinical trial which consisted of 79 patients with resectable Stage III–Stage IVA cSCC of the head and neck. Furthermore, patients had a stage of M0 and patients with Stage II disease had a primary tumor of at least 3cm in diameter. The study was broken up into two parts; neoadjuvant therapy prior to surgery followed by an optional adjuvant cemiplimab therapy, adjuvant radiation, or observation dependent on investigator discretion. 

During the neoadjuvant period, patients received a 350mg of of cemiplimab every three weeks for up to four doses over a 12-week period. During the 12-week period, patients received imaging (CT, MRI, photography) at baseline, Week 6, and Week 12. After the neoadjuvant period, patients were to proceed with surgery within a 15-day window. The primary endpoint was cPR and secondary endpoints were considered MPR, objective response based on imaging, and any adverse events. 

The median age of patients in the study was 73 years old and the predominant tumor site was the head and neck (72 patients, 91%). Median duration of follow-up (time of first dose to data cut-off) was 9.7 months. Sixty-two patients (78%) received all four doses during the neoadjuvant period. There were 17 patients who did not receive all four doses of neoadjuvant cemiplimab. The most common reason was disease progression, which occurred in 11 patients. Overall, nine patients (11%) did not undergo surgery in the protocol-specified and did not have pathology for review.

Forty patients (51%) achieved a pCR with an additional 10 patients (13%) achieving MPR. On imaging assessments after the neoadjuvant phase, there was an objective response rate on imaging in 54 patients (68%). Five patients had a complete response, 49 had a partial response, 16 had stable disease, and eight had progressive disease; one patient had no imaging-based evaluation. Of the 70 patients who proceeded to surgery, five had a complete response, 44 had a partial response, and 16 had stable disease on imaging. All five with a complete response on imaging also achieved a pCR. Of the 44 patients showing a partial response on imaging, 30 (68%) had a pCR, eight (18%) had a MPR and six (14%) had neither a cPR or MPR. Among the 16 patients with stable disease on imaging, five (31%) achieved a cPR, while two (12%) had a MPR.

Adverse events occurred in 69 patients (87%). Adverse events that were treatment related by the investigators occurred in 57 patients (72%) with the most common being fatigue (28%), maculopapular rash (14%), and diarrhea (11%). Four deaths occurred during the study, one which is the only event to be treatment related which was an exacerbation of congestive heart failure in a 93-year-old patient.

Both studies underscore the transformative potential of neoadjuvant immunotherapy for advanced cSCC. Over 60 percent of patients in each trial achieved either a complete or major pathological response. This not only paves the way for less invasive surgeries, minimizing cosmetic and functional impairments, but also reduces the need for adjuvant radiation, thereby decreasing morbidity. Furthermore, neoadjuvant cemiplimab showcased enduring clinical benefits, with 95 percent of patients remaining disease-free at one year.⁴² While Gross et al⁴⁵ reported a higher incidence of adverse events, the treatment was generally well-tolerated. Collectively, these findings herald a paradigm shift in cSCC treatment, promising profound implications for patient care.

Merkel Cell Carcinoma

Current studies. Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer, often associated with the Merkel cell polyomavirus. While relatively uncommon, treatment for primary and metastatic MCC is not well defined. Current data on neoadjuvant therapy for MCC is in its infancy with only one study highlighting its use. This clinical trial was conducted to explore the potential of neoadjuvant therapy using anti-PD-1 (nivolumab) in the treatment of resectable merkel cell carcinoma.⁴⁶

Checkmate 358 46 is a Phase I/II multicenter, open-label, multicohort clinical trial that assessed the safety and efficacy of administering neoadjuvant nivolumab to 39 patients with resectable Stage IIA–IIIB MCC with a primary tumor of 2cm, oligometastatic Stage IV, or locoregional recurrence with a tumor size 1cm. Patients involved in the trial received a regimen involved a 240mg intravenous dose of nivolumab on Days 1 and 15, followed by surgery on Day 29. 

The primary endpoints for the cohort were safety and tolerability which were measured by treatment-related adverse events (TRAEs). Exploratory endpoints included response rates (both pathologic and radiographic), RFS (time from surgery to date of recurrence or death), and overall survival (time from first nivolumab dose to date last known alive or death). 

In total, 39 patients were treated with a mean age of 68 years old, mean follow-up was 20.3 months. A majority 66.7 percent of patients had Stage III disease at enrollment. Thirty-six of 39 patients received both doses of the immunotherapy. Three of the patients experienced Grade 2–3 TRAEs which stopped them from receiving the 2nd dose. In total 18/39 patients experienced TRAEs, however only three patients experienced Grade 3–4 TRAEs. The most common TRAE were skin reactions with four patients.

Of the 36 patients who underwent surgery, nearly half (n=17, 47.2%) achieved pCR according to site review. A central pathology review of 26 patients found a similar proportion achieving pCR (n=12, 46.2%), with an additional four patients (15.4%) achieving an MPR. Radiographic evaluations were possible for 33 of the 36 patients, revealing that a vast majority (n=29, 87.9%) showed some degree of tumor reduction, and over half (n=18, 54.5%) exhibited a significant tumor reduction of 30 percent or more. 

The median RFS was not reached in all 36 patients who underwent surgery. One and two years postoperative, the RFS rates were 77.5 percent and 68.5 percent, respectively. The difference in RFS rates between patients achieving a pCR (by site review) versus those who did not at 12 and 24 months was 100 percent versus 59.6 percent and 88.9 percent versus 52.2 percent respectively. Further analysis comparing patients that achieved pCR/MPR to those without these responses demonstrated RFS rates at 12 and 24 months was 100 percent and 88.9 percent versus 50 percent at both time points. Furthermore, overall survival rates of patients who had a pCR or MPR at 12 and 24 months were 100 percent and 88.9 percent, respectively. 

Among 33 radiographically evaluable patients, comparing those with radiographic tumor reduction of 30 percent versus those with 30 percent or progression, RFS at 12 months was 100.0 percent versus 56.5 percent, and at 24 months was 90.9 percent versus 48.5 percent. The patients who demonstrated a 30 percent radiographic reduction in tumor response had an overall survival of 100 percent at 12 and 24 months.

Results indicate that neoadjuvant nivolumab was generally well-tolerated and led to radiographic tumor regressions and pathologic complete responses (pCRs) in about half of the participants. Moreover, those who responded positively to the treatment showcased a significantly enhanced recurrence-free survival rate.

The study suggests that preoperative neoadjuvant immunotherapy, with a macroscopic tumor present, has the potential to induce a lasting systemic antitumor immunity. This could be pivotal in preventing postsurgical relapse. However, a therapeutic approach may signify a notable advancement in treatment, meriting further investigation and validation in larger-scale studies.

Conclusion

The potential of neoadjuvant immunotherapy in various cutaneous malignancies is an area of active investigation. However, the available data is dispersed across diverse studies, each characterized by its unique design, patient cohorts, and endpoints. An integrated analysis of this data is imperative to delineate the true benefits, risks, and therapeutic positioning of neoadjuvant immunotherapy for cSCC, melanoma, and merkel cell carcinoma. This systematic review endeavors to aggregate and critically appraise the extant literature, offering a consolidated perspective to healthcare professionals, academicians, and patients, in addition to setting the stage for future inquiries. Furthermore, this gives dermatologists who diagnose patients with high-risk skin cancers, pertinent novel and upcoming knowledge to ensure patients receive the highest standard of care available.

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