Squamous Cell Carcinoma and Merkel Cell Carcinoma: Diagnostic and Therapeutic Management – Expert Opinion of the Polish Dermatological Society

Introduction

Squamous cell carcinoma (SCC) is the second most prevalent type of skin cancer after basal cell carcinoma (BCC). It is estimated that BCC and SCC collectively account for up to 99% of all non-melanoma skin cancers (NMSC), making them the most prevalent group of malignant tumors among the Caucasian population.
Cutaneous SCC grows slowly but has the potential to metastasize. If diagnosed late, it can cause significant tissue damage and lead to severe esthetic defects. SCC is significantly more likely to metastasize to regional lymph nodes and distant organs than BCC. The risk of metastasis is estimated at around 4% of all SCC cases, contributing to its greater malignancy and higher mortality rate compared to BCC.
Patients receiving immunosuppressive therapy are particularly vulnerable to developing SCC. Long-term immunosuppression – particularly following internal organ transplantation – increases the risk of developing SCC (60- to 150-fold) and other rare, aggressive skin cancers, such as basosquamous cell carcinoma and Merkel cell carcinoma (MCC), the incidence of which has recently been rising even among immunocompetent individuals.
The Polish Dermatological Society (PTD), based on the guidelines of the American Academy of Dermatology (AAD, 2018) [1], the current recommendations of the National Comprehensive Cancer Network (2.2024), data from the American Joint Committee on Cancer (AJCC, 2017) [2], and Polish multidisciplinary recommendations [3], has made an attempt to systematize diagnostic and therapeutic approaches for patients with suspected or confirmed SCC and MCC in Poland, with the goal of enhancing the quality of diagnosis and treatment.

Cutaneous squamous cell carcinoma (SCC)

Cutaneous SCC arises from the keratinizing cells of the epidermal spinous layer. Numerous population studies have revealed a significant ongoing rise in SCC incidence. Some data suggest that the incidence of SCC has been rising more rapidly than that of BCC in recent years, narrowing the gap between the two types of skin cancer [2]. Ultraviolet (UV) radiation is the most well-established environmental factor in SCC development. The frequency of sunburns, chronic UV exposure, and cumulative solar radiation dose are known to be strongly correlated with the development of cutaneous squamous cell carcinoma. SCC is more common in individuals with a fair skin phototype, typically over the age of 50, and primarily develops in areas affected by UV damage, actinic keratosis, leukoplakia, or in post-burn scars. The most common areas of cancer development are the skin of the face, particularly around the nose, auricles, and lower lip, as well as on the frontal-parietal region in bald men and the dorsum of the hands. However, SCC may also develop on or around mucous membranes. In addition to UV radiation, various carcinogenic factors increase the risk of SCC neoplasm, including arsenic, chewing tobacco, aromatic hydrocarbons, tar derivatives, HPV infections, chronic irritation, scarring, radiation-induced skin damage, and chronic skin inflammation associated with infectious diseases such as condyloma acuminata, granuloma inguinale, lymphogranuloma venereum, and chromoblastomycosis. The risk of developing SCC is also linked to chronic dermatoses such as lichen planus and lichen sclerosus of the mucous membranes, porokeratosis, cutaneous lupus erythematosus, dystrophic epidermolysis bullosa, and hidradenitis suppurativa. Consequently, individuals with these conditions require regular dermatological evaluations for monitoring and early detection of potential neoplastic changes [4].

Clinical presentation

Clinically, SCC presents as an erythematous-exfoliative or erythematous-infiltrative lesion with well-defined borders and surface cornification, a nodule or mass containing central keratinized material, or an ulcerated nodule (fig. 1 A) [4]. On mucous membranes, SCC typically presents as an infiltrative, papillary, or ulcerated lesion with raised, irregular edges and a tendency for delayed healing. HPV-induced papillary SCC often arises from papillomatous exophytic lesions on mucous membranes (papillomatosis florida oris, condylomata acuminata, associated with HPV types 16 and 18) or on the soles of the feet (epithelioma cuniculatum, commonly linked to HPV types 6 and 11). Another example of HPV-related cutaneous oncogenesis is epidermodysplasia verruciformis (EV). Due to genetic background that predispose individuals to chronic and extensive skin infections with HPV types 5, 8, and 14, SCC develops in 30% to 50% of affected patients. The differential diagnosis of SCC includes common warts, genital warts, seborrheic keratosis, keratoacanthoma, basal cell carcinoma, actinic keratosis, amelanotic melanoma, cutaneous adnexal tumors (arising from hair follicles and sweat glands), atypical fibroxanthoma, and skin metastases.
SCC most commonly develops from actinic keratosis and on chronically sun-damaged skin. Histologically, it is characterized by the presence of atypical cells in the basal and suprabasal layers exhibiting dysplastic features. The nuclei vary in shape and appear compressed against one another, while in the upper spinous layer they gradually normalize and display signs of incomplete keratinization, such as parakeratosis or dyskeratosis (fig. 1 B). SCC associated with the transformation of keratinocytes across the full thickness of the epidermis, without breaching the basement membrane, is known as SCC in situ (keratinocytic intraepidermal neoplasia III). A classic example of SCC in situ is Bowen’s disease, associated with HPV-induced transformation of keratinocytes. When occurring on the glans penis, vulva, or vagina, SCC in situ is referred to as erythroplasia of Queyrat. The histological appearance of Bowen’s disease variant of SCC is highly distinctive, featuring large atypical keratinocytes with hyperchromatic nuclei and atypical mitoses (pagetoid cells), along with dyskeratosis and surface parakeratosis (fig. 1 C). Early invasion of SCC is characterized by atypical keratinocytes penetrating the dermis, forming oval nodules or epithelial tongues that, depending on the degree of differentiation, exhibit varying levels of keratinization. Highly differentiated SCC is characterized by the presence of cancer pearls, which are large foci of abnormal keratinized masses located in the lower regions of the tumor tissue (fig. 1 D). Less differentiated SCC invades the dermis with narrow tongues, surrounded by an inflammatory response, and shows minimal keratinization (figs. 1 E, F).
Undifferentiated forms of SCC, such as spindle cell, adenoid, and sarcomatoid SCC, lack keratinization features entirely. These variants pose challenges in histological diagnosis and tend to follow a more aggressive course [4].

Diagnostic procedure

Early diagnosis of SCC enables prompt excision of the lesion, lowering the risk of metastasis and reducing SCC-related mortality. Consequently, familiarity with the typical clinical and dermoscopic features of SCC, along with its common locations and characteristic progression, is crucial for accurate initial diagnosis.
Dermoscopy, like confocal microscopy, is a valuable tool for the initial diagnosis of SCC [5, 6]. Characteristic dermoscopic features help distinguish actinic keratosis, SCC in situ, and intraepidermal carcinoma (IEC), from invasive SCC. The dermoscopic features of IEC are characterized by dot-like vessels, homogeneous yellowish keratinous masses with scaling, and microerosions [5]. SCC in situ (Bowen’s disease) is characterized by white, structureless areas along with dot-like and/or glomerular vessels (figs. 2 A, B) [6]. In the pigmented variant of Bowen’s disease, which is often differentiated from melanocytic lesions, key diagnostic features visible on dermoscopy include the presence of brown or gray granules arranged in a linear pattern and/or glomerular vessels [7]. Invasive SCC shows the presence of white structureless masses (figs. 2 C, D), a central keratotic plug with ulceration (figs. 2 E, F), hairpin vessels and polymorphic vessels (figs. 2 D, F, H) [5, 6]. The above features are also present in images of keratoacanthoma (KA), except for the more frequent occurrence of irregular linear vessels in KA [5]. Dermoscopic features characteristic of high- or moderate-grade differentiated SCC include the presence of white structures: keratin masses, white circles, white haloes, and structureless white areas (fig. 2 D, F) [8]. In polarized light, white structures also include rosettes, which are less frequently observed in SCC than in actinic keratosis [9]. The central location of exfoliation or a keratotic plug significantly reduces the likelihood of low differentiation in SCC by a factor of 36 [8]. In poorly differentiated SCC, an erythematous base, erosions, and ulcers are more commonly observed [6]. Additionally, in this form of SCC, vessels often cover more than 50% of the tumor surface and are characterized by a small cross-sectional area [8].
The choice of an appropriate treatment method depends primarily on the cancer’s histological type, stage, and depth of infiltration, as well as the patient’s overall condition and the presence of concomitant diseases. In histologically challenging cases with atypical lesion morphology and cytology lacking features of dyskeratosis, immunohistochemical staining is performed to detect keratins AE1/AE3, CK5/6, and the expression of p63, p16, p53, and Ki-67 [4]. When deeper tissue invasion is suspected, it is advisable to expand the diagnostic workup with imaging examinations. Additionally, if lymph node involvement is suspected, a fine-needle aspiration biopsy should be performed, or the entire node should be excised for histopathological evaluation [1, 2].

Clinical staging

In 2017, the American Joint Committee on Cancer (AJCC) introduced an updated skin cancer staging classification based on the standard TNM system (T – tumor, N – node, M – metastasis), as shown in tables 1 and 2 [9]. In cases of locally advanced SCC, the NCCN-recommended method for assessing tumor recurrence risk [2] appears more appropriate. This approach considers both clinical and pathological parameters (table 3) to classify the lesion as either high or low risk for recurrence.

Treatment methods

The primary goal of treatment for patients diagnosed with SCC is the complete removal of neoplastic tissues while preserving optimal aesthetic appearance and function of the affected organ. The recommended therapeutic approach for suspected cutaneous SCC is shown in figure 3.

Surgical methods
Regardless of the risk assessment for potential recurrence, surgery remains the gold standard for treating cutaneous SCC, except for inoperable lesions. This approach results in complete recovery in most cases of SCC. Standard excision of SCC with a low risk of recurrence requires a 4–6 mm margin. However, if excision would result in significant cosmetic defects, a smaller margin may be used, provided cancer-free margins (R0) are achieved.
For lesions with a high or very high risk of recurrence, intraoperative assessment of surgical margins using Mohs micrographic surgery (MMS) is recommended whenever possible. In cases where this is not feasible, wider excision margins are recommended, but they must (ultimately) be free of cancer cells (R0).

Radiation therapy
Radiation therapy (RT) is the second most effective treatment for SCC after surgery. It is used when surgical intervention is either contraindicated or unfeasible. RT is also employed as an adjunctive therapy for patients who have undergone non-radical excision or cytoreductive surgery, particularly when the procedure was incomplete due to neoplastic infiltration of vital structures. Furthermore, it is indicated following lymphadenectomy for metastases to regional lymph nodes. Adjuvant RT may be considered for cSCC with extensive clinical or radiological perineural invasion (PNI), multifocal histological PNI, tumor diameter ≥ 6 cm, recurrent tumors, high risk of regional or distant metastases, close surgical margins when further resection is not feasible, and for desmoplastic or infiltrative tumors in chronically immunocompromised patients or those undergoing immunosuppressive therapy [2, 10].
For patients experiencing disease recurrence despite RT, repeating this treatment method is not recommended.

Cryosurgery
Cryosurgery is a generally safe treatment method that employs controlled destruction of involved tissues through the application of extremely low temperatures, typically ranging from –50 to –60°C. Studies on the effectiveness of this method have reported heterogeneous outcomes, likely due to variations in patient selection, surgical techniques, and operator expertise [2]. Although post-treatment wound healing typically results in minimal scarring, studies have shown that cryosurgery yields poorer cosmetic outcomes for SCC in situ compared to topical 5-FU [11, 12].

Topical therapies
In cases where surgical treatment is not feasible, alternative modalities should be considered, such as radiation therapy, topical treatments with imiquimod or 5-fluorouracil (5-FU), or photodynamic therapy with aminolevulinic acid (ALA) or methyl aminolevulinate (MAL). However, it should be noted that the cure rate with these options may be lower. Therefore, these therapies should be considered only for low-risk cancers in patients with small tumors who, for various reasons, are unable to undergo more invasive treatments [1, 2].

Imiquimod (5%) and 5-fluorouracil (0.5%)
Studies have demonstrated that imiquimod treatment for SCC in situ results in the resolution of 73% of lesions [2]. However, the therapy has been associated with adverse effects, including skin erythema, edema, exudate formation, scabbing, and pruritus [2]. In contrast, cure rates for topical 5-FU therapy are lower than those for imiquimod treatment, ranging from 27% to 93%, with comparable skin toxicity [2]. <br/>
Photodynamic therapy
Photodynamic therapy (PDT) is a two-stage treatment method used, among others, in the treatment of Bowen’s disease. It involves the topical application of a photosensitizer, either 5-aminolevulinic acid (ALA) in cream form or MAL in cream, gel, or patch form, to the affected tissues. After several hours of tissue penetration, the photosensitizer is activated by light with a wavelength of 610 nm.
The use of PDT for SCC in situ is linked to a higher recurrence rate, with sustained complete response rates estimated between 48% and 89% [2, 12, 13]. The significant discrepancy in reported data may be attributed to variations in PDT techniques. A review of the available literature indicates that MAL-PDT is more effective compared to 5-FU and cryosurgery [2, 12].

Systemic treatment
Evidence supporting the efficacy of systemic treatment with traditional cytostatics for advanced forms of SCC is limited. No phase III clinical trials have confirmed the effectiveness of cisplatin-based regimens, either as monotherapy or in combination with 5-FU, vindesine, or interferon. Further clinical trials with larger cohorts of patients with metastatic SCC are needed to validate the potential efficacy of both traditional cytostatic agents and EGFR inhibitors in the treatment of metastatic SCC [1, 2].
Cemiplimab has been used in the treatment of patients diagnosed with cSCC who are not candidates for surgery or radiotherapy [14]. Cemiplimab is a human IgG4 monoclonal antibody that binds to the programmed cell death receptor 1 (PD-1), inhibiting its binding with the PD-L1 and PD-L2 ligands. This phenomenon enhances the response of T cells by restoring their activity. This drug is the first to be accepted by both European (EADO – European Association of Dermato-Oncology; EDF – European Dermatology Forum; EOTC – European Organisation for Research and Treatment of Cancer) and American (NCCN) scientific societies, as well as by Polish scientific societies (PTOK – Polish Society of Clinical Oncology). The efficacy and safety of cemiplimab have been demonstrated in a phase 2 study involving 193 patients with lacSCC (locally advanced SCC) and mcSCC (metastatic SCC). Patients were divided into three groups. Group one consisted of patients with lacSCC receiving cemiplimab at a dose of 3 mg/kg body weight every 2 weeks. Group two included patients with mcSCC receiving the same dose. Group three comprised patients with mcSCC treated with cemiplimab at a dose of 350 mg, administered intravenously every 3 weeks. An analysis of the results from all patients in the trial published in 2020 showed an overall survival (OS) rate of 73.3% after 24 months. The detailed results of the objective response rate (ORR) for each group are presented in table 4. The most commonly reported adverse effects included diarrhea, fatigue, nausea, vomiting, and skin rashes.
Cemiplimab is available in Poland through the National Health Fund B.125 drug program for patients with metastatic or locally advanced cutaneous SCC, who are not eligible for surgical treatment or radical radiotherapy. The drug is administered as a 30-minute intravenous infusion at a fixed dose of 350 mg and does not require premedication prior to administration. Patients treated with cemiplimab may experience immune-related adverse events. As a result, they require close monitoring for these effects both during and after treatment. If treatment toxicity occurs, it is not recommended to reduce the dose. Instead, the administration of the drug should be delayed or discontinued entirely.
Currently, studies are ongoing to evaluate the efficacy of cemiplimab in adjuvant, neoadjuvant, and combined neoadjuvant-adjuvant treatments for patients with resectable or potentially resectable SCCs.

Follow-up after completed cancer treatment

There is currently no clear consensus regarding the optimal frequency and total duration of follow-up for patients diagnosed with cutaneous SCC. Patients with lesions at high risk of recurrence require ongoing, long-term monitoring following oncological treatment. The frequency of monitoring should be determined by the risk of potential recurrence. The first 2 years following treatment are critical, necessitating regular dermatological follow-ups, including dermoscopic examinations.
Any suspicion of recurrence or a new lesion should be confirmed through histopathological examination. In patients with regionally advanced disease, monitoring through imaging studies is also recommended. Additionally, patients should be trained to perform regular self-examinations of the skin at least once a month. Those diagnosed with regional SCC should also be instructed on how to examine their lymph nodes.
Recommended follow-up strategies for patients with a history of SCC and on chronic immunosuppression are presented in table 5.

Merkel cell carcinoma (MCC)

MCC is a rare skin cancer characterized by an aggressive clinical course and a high propensity for local recurrences and metastases to regional lymph nodes and distant organs [15, 16].
Although the incidence of MCC remains relatively low, estimated at 0.25–0.32 cases per 100,000 population annually, a steady and gradual increase in its occurrence has been observed over the past few decades. MCC typically develops in individuals over the age of 50, with an average onset age of 75 [17]. The incidence rises sharply with advancing age [18]. MCC is significantly more prevalent in white individuals and twice as common in men as in women. The most common sites for MCC lesions are the head and neck (approximately 48% of cases, particularly the face), followed by the extremities (around 35% of cases), and less frequently the trunk (less than 10% of cases) [15].

Risk factors

Although the exact etiology of MCC remains unclear, recent years have seen significant progress in understanding its etiopathogenesis. Three key factors are thought to contribute to the development of MCC:
1) polyomavirus infection (Merkel cell polyomavirus – MCPyV), detected in up to 80% of MCC cases, depending on the population;
2) exposure to ultraviolet (UV) radiation;
3) immunosuppression and conditions associated with impaired immunity, including the use of immunosuppressive drugs following organ transplantation, HIV infection, chronic lymphocytic leukemia, or a history of previous malignancies.
Polyomavirus-induced MCC is linked to a lower frequency of somatic mutations in the genome of MCPyV-transformed cells. MCC induced by the carcinogenic effects of UV is associated with numerous DNA mutations in MCC cells, leading to accelerated tumor progression [19]. Information derived from immunohistochemical staining for the presence of MCPyV in tumor tissue can provide valuable insights into the initial prognosis, influencing both disease monitoring and the urgency of treatment. In all MCC variants, dysfunction of the retinoblastoma gene responsible for regulating the cell cycle results in uncontrolled proliferation and loss of cell cycle arrest in the G1 phase [19, 20]. Nearly 50% of Merkel cell tumors exhibit trisomy of chromosome 6.
Genetic studies of MCC cells, murine models, and virological research are providing new insights into the histogenesis of Merkel cell carcinoma. Notably, Merkel cell carcinoma does not originate from Merkel cells [21]. MCPyV-transformed MCC cells most likely originate from dermal fibroblasts, though they may also derive from hair follicle epithelial cells. In contrast, MCPyV-negative tumors are thought to arise from UV-transformed pluripotent epidermal stem cells with retinoblastoma gene inactivation [21, 22]. This explains the need for histological differentiation of MCC from carcinomas and sarcomas. The histogenetic complexity of MCC likely contributes to the aggressive nature of this tumor. Improved understanding of the cytogenetics of MCC may lead to the development of preventive measures and targeted therapies in the future.

Clinical presentation

The clinical presentation of MCC is often non-specific. The most common clinical features of MCC include a cherry-red color, shiny surface, well-defined borders, and nodular appearance of the lesion [23]. MCC typically presents as a rapidly growing (within weeks or months), red-purple tumor with a firm consistency or as a hard skin infiltrate with a smooth surface. The lesion is typically painless and not associated with any other symptoms. The diagnosis of MCC is most often confirmed through histopathological examination. The primary clinical features of MCC are often summarized by the acronym AEIOU:
A – Asymptomatic – without symptoms;
E – Expanding rapidly – growing rapidly, for less than 3 months;
I – Immune suppressed – occurring in immunocompromised patients;
O – Older than 50 – in patients over 50 years of age;
U – UV-exposed fair skin – on fair skin intensely exposed to UV radiation.
In 89% of patients with primary MCC, at least three of the five mentioned characteristics are present [24].

Diagnostic procedure

Due to its highly variable clinical presentation, the diagnosis of MCC is rarely established before histopathological examination. While dermoscopic evaluation can be helpful, it is challenging because the dermoscopic features of MCC overlap with those of other pink nodules. Dermoscopic features of MCC described in the literature include irregular linear, arborescent, and polymorphic vessels, poorly focused, as well as milky-pink areas, white areas, structureless regions, and disruption of the lesion architecture, as assessed by the CASH algorithm (color, architecture, symmetry, homogeneity) [23, 25].
Rapid growth of the lesion, indicating the malignant nature of the tumor, is an indication for excisional biopsy. Histopathological examination with H&E staining reveals a tumor composed of small, round basophilic cells, exhibiting numerous mitoses and prominent cell apoptosis. An early unfavorable histological sign of MCC is the invasion of tumor cells into blood and lymphatic vessels. MCC is diagnosed using immunohistochemical staining for markers including cytokeratin-20 (CK-20), CD56, chromogranin A, synaptophysin, neuron-specific enolase (NSE), and neurofilament protein (NFP) [26, 27]. CK-20 is a particularly sensitive marker for MCC. Positive CK-20 staining is observed in 89–100% of Merkel cell carcinomas, displaying a perinuclear granular pattern [28]. MCC requires a histological differential diagnosis to distinguish it from basal cell carcinoma, metastatic small cell lung cancer, cutaneous lymphoma, melanoma, rhabdomyosarcoma, and Ewing’s sarcoma.
INSM1 (insulinoma-associated protein 1) is also recognized as a sensitive and specific marker for identifying neuroendocrine cells, including those of MCC, and is used to detect MCC in both skin lesions and lymph node metastases [19]. INSM1 produces precise nuclear staining but does not distinguish MCC from other neuroendocrine tumors that metastasize to the skin. MCC cells do not express the following markers: S100, TTF-1 (thyroid transcription factor), CD45, CK-5/6 and the characteristic protein of normal Merkel cells, i.e. methenkephalin.
Neuroendocrine lung cancers that metastasize to the skin are histologically similar to MCC but exhibit a different immunotype (CK-20 “-” CK-7 “+”, TTF1 “+”, and PAX5 “-”).
If MCC is diagnosed, it is advisable to perform imaging tests, such as X-ray, CT, or MRI, to assess the stage of the primary tumor according to individual clinical indications.

Clinical staging

The MCC staging system proposed by the AJCC is currently widely used and recommended by most institutions, including the NCCN. It follows the standard TNM criteria (table 6).

Prognosis

Although the clinical stage and presence of metastases are the strongest predictors of survival, the size of the primary lesion has also been shown to be a crucial factor influencing the prognosis of patients diagnosed with MCC. The 10-year overall survival rate for lesions 2 cm or smaller is 61%, whereas for tumors larger than 2 cm the survival rate drops to 39.6% [18, 24].
Beyond the clinical stage of Merkel cell carcinoma, the type of neoplastic transformation – whether driven by the McPyV virus or UV-induced carcinogenesis – also significantly impacts patient prognosis. The latter, associated with numerous mutations, including those in the retinoblastoma 1 gene, is generally linked to a poorer prognosis.

Treatment methods

In patients with locoregional MCC (stages I and II – N0, M0), the main treatment objective is the surgical removal of the neoplastic tissue. If imaging does not detect metastases to regional lymph nodes, wide excision of the postoperative scar with a 1-2 cm margin is recommended. This may be followed by sentinel lymph node biopsy (SLNB) and, if high-risk features of the primary lesion are present, optional adjuvant radiotherapy [15].
Performing SLNB is crucial in the final staging of Merkel cell carcinoma, as approximately one-third of patients with early-stage MCC are found to have micrometastases in regional lymph nodes [29]. The presence of metastasis in regional lymph nodes (grade III, indicated by the N feature) is an indication for lymphadenectomy. Retrospective studies show that adjuvant local radiotherapy following complete excision of the lesion reduces the risk of locoregional recurrence and improves overall survival in patients who have undergone lymphadenectomy [30].
The presence of the M feature indicates advanced disease (stage IV). Treatment of metastatic MCC is inherently palliative. Although MCC is considered a chemosensitive tumor, there is no objective evidence confirming the impact of treatment with conventional cytostatic agents on overall survival. The majority of conventional therapies for MCC are based on multidrug regimens incorporating cisplatin, cyclophosphamide, doxorubicin, vincristine, or etoposide. However, regardless of the cytostatic drugs used, the duration of response is short, with most patients experiencing a relapse within 8 months [31]. Due to the aggressive clinical course and relatively short response to chemotherapy, studies have been initiated to determine the efficacy of modern checkpoint inhibitors – anti-PD-L1 (avelumab) and anti-PD-1 (pembrolizumab, nivolumab, retifanlimab) – in the treatment of patients diagnosed with MCC.
The first drug to demonstrate efficacy and safety in a prospective phase II study for the treatment of metastatic MCC was avelumab. The study included patients who had previously received systemic treatment (arm A) and patients who had not previously been treated for metastatic disease (arm B). After more than 10 months of follow-up, the objective response rate in group A was 31.8%, with 20 patients showing a partial response (23%) and 8 patients achieving a complete response (9%). Treatment-related adverse effects, primarily grade I and II, were observed in 70% of patients, with a toxicity profile consistent with the known tolerability of checkpoint inhibitors. The median overall survival in this group was 11.3 months, with a higher treatment response observed in patients who had received only one prior line of treatment [32].
Long-term results from arm B of the same study confirm the efficacy of avelumab in the first-line treatment of patients with advanced Merkel cell carcinoma. The initial promising study results presented in 2018 demonstrated relatively high survival rates, with 66% at 1 year and 23% at 5 years of follow-up. The mean overall survival (mOS) in this group was 49.9 months [33]. Further analyses have confirmed the long-term efficacy of avelumab [34–36].
The effectiveness of other anti-PD-L1 antibodies, such as pembrolizumab, nivolumab, and retifanlimab, in treating advanced forms of MCC has been confirmed in multiple clinical studies [37–41].
Current global guidelines recommend anti-PD-1 and anti-PD-L1 antibodies as the therapy of choice for treating advanced MC. Due to the aggressive nature of MCC, immunotherapy should be initiated as soon as possible in cases of unresectable or metastatic MCC. Classic cytostatic therapy is recommended for patients with this diagnosis only if they have contraindications to immunotherapy or have experienced relapse or progression during this treatment modality. Since September 1, 2018, an access program has been available in Poland, allowing patients with advanced MCC to receive avelumab therapy in both first-line and subsequent lines of treatment. This treatment may continue even after radiological progression, provided it is not accompanied by significant clinical deterioration of the patient’s condition.

Post-treatment follow-up

It is important to consistently monitor the skin, as patients are at an increased risk of developing other skin cancers, including melanoma. In high-risk patients, routine CT scanning should be considered to detect and quantitatively assess metastases, especially bone involvement. The detection of recurrence is associated with a poor prognosis [20].

Conclusions

The final decision regarding the suitability of a specific method for skin cancer treatment should be made by the physician in consultation with the patient, considering all relevant factors, including the patient’s overall health, concurrent conditions, lesion location, and, most importantly, the potential effectiveness and safety profile of the therapy. Comorbidities may influence the choice of a specific therapeutic option which – while it may have a lower long-term cure rate – is nonetheless the most suitable for preserving the patient’s quality of life in a given clinical situation. This study does not serve as an endorsement by the Polish Dermatological Society for any particular medicinal product, medical device, or manufacturer. The treatment methods outlined in this article are intended as general recommendations only.

Funding

No external funding.

Ethical approval

Not applicable.

Conflict of interest

The authors declare no conflict of interest.

References