22 October 2025: Review Articles
Non-Invasive Imaging in Post-Radiotherapy Monitoring of Non-Melanoma Skin Cancer
Piotr Sobolewski DOI: 10.12659/MSM.949669
Med Sci Monit 2025; 31:e949669
Abstract
ABSTRACT: Non-melanoma skin cancers, including basal cell carcinoma and squamous cell carcinoma, are the most common forms of skin cancer worldwide. Though less aggressive than melanoma, they cause significant morbidity if untreated. Radiotherapy is a common treatment alternative for patients for whom surgery is contraindicated, particularly the elderly or those with tumors in anatomically challenging locations. Effective post-radiotherapy monitoring assesses treatment response, recurrence, and complications. Traditional post-radiotherapy monitoring often involves clinical examination and, if needed, invasive biopsies. Recently, noninvasive imaging modalities, such as reflectance confocal microscopy and line-field confocal optical coherence tomography, have gained attention. These technologies provide high-resolution, in vivo skin visualization. Reflectance confocal microscopy and line-field confocal optical coherence tomography offer complementary imaging data, facilitating the identification of residual tumor cells, inflammatory changes, and radiotherapy-induced skin alterations. They are valuable for follow-up as they monitor skin without biopsy. Early studies suggest high sensitivity and specificity in detecting treatment response and complications. Reflectance confocal microscopy and line-field confocal optical coherence tomography represent promising noninvasive tools for post-radiotherapy assessment of non-melanoma skin cancers. They enhance diagnostic accuracy, reduce the need for biopsies, and may improve patient outcomes through earlier detection of recurrence or complications. Further studies are warranted to standardize imaging criteria and validate their routine clinical use.
Keywords: non-melanoma skin cancer, Radiotherapy, Reflectance Confocal Microscopy, Line-Field Confocal Optical Coherence Tomography, Humans, Skin Neoplasms, Tomography, Optical Coherence, Microscopy, Confocal, basal cell carcinoma, Carcinoma, Squamous Cell, Skin
Introduction
Skin cancer incidence is rising globally due to ultraviolet exposure, aging, and genetics [1,2]. The two most frequently diagnosed types of non-melanoma skin cancer are basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) [3]. While these cancers are generally less aggressive than melanoma, they still require prompt and effective treatment to prevent local tissue destruction, functional impairment, and, in rare cases, metastases. Non-melanoma skin cancer treatments include surgery, cryotherapy, photodynamic therapy, topical chemotherapy, and radiotherapy [4]. Among these, radiotherapy is a widely used approach, particularly for patients who are not ideal candidates for surgery due to factors such as advanced age, multiple lesions, wide size, or tumor location in cosmetically or functionally sensitive areas, such as the face, ears, or scalp [5].
Radiotherapy for skin cancer works by delivering targeted doses of ionizing radiation to malignant cells, effectively damaging their DNA and triggering cell death [6]. While this approach can be highly effective in eradicating cancerous lesions, it also affects the surrounding healthy tissue, leading to a range of acute and chronic skin changes. Acute effects include erythema, desquamation, ulceration, and radiation dermatitis, while long-term consequences can include fibrosis, telangiectasia, pigmentation changes, and even an increased risk of secondary malignancies [7,8]. Given these potential complications, radiotherapy-treated skin requires careful monitoring to ensure proper healing, detect signs of recurrent or residual disease, and manage any adverse effects of treatment.
Traditionally, post-radiotherapy skin assessment has relied on clinical evaluation, videodermoscopy, and histopathological analysis through invasive biopsies. While these methods are effective, they come with inherent limitations. Clinical assessment alone can lack the resolution needed to detect subtle microscopic changes, leading to delayed diagnoses or unnecessary biopsies. On the other hand, histopathological examination requires tissue sampling, which can be painful for the patient and can cause scarring or secondary infections [9]. Additionally, multiple biopsies can be needed over time to track disease progression or response to therapy, further increasing patient discomfort and healthcare costs.
In recent years, reflectance confocal microscopy (RCM) has emerged as a powerful non-invasive imaging modality that offers real-time, high-resolution visualization of skin structures at a cellular level [10]. This technique allows dermatologists and oncologists to assess radiotherapy-treated skin with unprecedented detail, facilitating early detection of residual or recurrent cancer while minimizing the need for invasive procedures.
As a complement to RCM, line-field confocal optical coherence tomography (LC-OCT) has recently gained attention as a novel imaging modality that combines the lateral resolution of confocal microscopy with the vertical sectioning capability of OCT. LC-OCT allows for more comprehensive assessment of dermal structures and enhances the ability to detect deeper residual or recurrent tumors.
Given the increasing role of RCM and LC-OCT in dermatologic oncology, there is a growing need to critically evaluate their clinical utility, particularly in the context of post-radiotherapy surveillance. This article aims to review the principles, applications, and comparative diagnostic performance of these noninvasive techniques and to propose their integration into clinical workflows for the effective monitoring of non-melanoma skin cancers following radiotherapy. To the best of our knowledge, this study is among the few that investigate the application of these advanced modalities in the post-radiotherapy assessment of skin cancer.
Radiotherapy
Radiotherapy, or radiation therapy, is a cornerstone in the treatment of various skin conditions, particularly skin cancers, which have seen an increased incidence in recent decades. As a noninvasive modality, radiotherapy offers both curative and palliative benefits, playing a significant role in the management of skin cancer, especially when surgical options are limited or impractical [11]. Skin cancers, notably BCC, SCC, and melanoma, are among the most common malignancies worldwide, with BCC and SCC being more prevalent and often treatable with radiotherapy.
Skin cancer arises when abnormal skin cells proliferate uncontrollably, often due to damage from ultraviolet radiation, although other factors, such as genetic predisposition and immunosuppression, can also contribute [12,13]. BCC, the most common type of skin cancer, generally manifests as slow-growing, locally invasive lesions on sun-exposed areas, like the face, neck, and hands [14]. In contrast, SCC, while also common, is more aggressive and can metastasize if not adequately treated [15].
Radiotherapy is considered a critical treatment modality, particularly for non-melanoma skin cancers, including both BCC and SCC. The primary mechanism of radiotherapy involves the use of high-energy X-rays or other forms of radiation to damage the DNA of cancer cells, leading to their death or preventing their division [16]. This makes radiotherapy highly effective in treating tumors localized in the skin, where surgical excision be can be challenging due to factors such as location (eg, near the eyes, nose, or ears), size, or patient comorbidities that can increase surgical risk [17].
One of the significant advantages of radiotherapy in treating skin cancer is its ability to target cancer cells precisely while minimizing damage to surrounding healthy tissue [18,19]. This is particularly beneficial for tumors in cosmetically sensitive areas, where surgical scarring can be undesirable or difficult to repair. In cases of BCC or SCC, radiotherapy may be used as an alternative to surgery, especially for tumors that are difficult to remove due to location, size, or patients’ lack of candidacy for surgery, due to age, frailty, or other health concerns. It is also an option when surgery has failed, or recurrence occurs after initial treatment. Radiotherapy can be used also in a neoadjuvant modality, in order to decrease the volume of the tumor. For SCC, radiotherapy can be used after surgical resection as an adjuvant therapy to reduce the risk of recurrence (particularly in high-risk cases in which margins may not be entirely clear) or as a neoadjuvant therapy before surgical treatment, or when lymph node involvement is suspected [20].
Another key benefit of radiotherapy is its role in treating superficial skin cancers. Superficial BCC, for example, can often be treated effectively with low-energy superficial radiation, which delivers radiation at a much shallower depth than deeper treatments [21]. This minimizes the exposure of deeper tissues and organs, ensuring a highly localized treatment.
Radiotherapy can also serve a critical palliative role in advanced skin cancers, especially in cases in which the cancer has spread or metastasized [11]. In such cases, the goal is not curative, but rather symptom relief, such as reducing pain, bleeding, and ulceration, or preventing further progression. Palliative radiotherapy is commonly used in patients with advanced SCC or melanoma, providing significant relief of symptoms and improving quality of life, especially in those who are not candidates for systemic treatments or extensive surgical interventions.
In terms of treatment planning and delivery, modern techniques have significantly improved the precision and effectiveness of radiotherapy for skin cancers. The advent of techniques such as intensity-modulated radiation therapy, image-guided radiation therapy, and brachytherapy has allowed for highly personalized and targeted treatment, reducing potential adverse effects while enhancing therapeutic outcomes [22]. Brachytherapy, which involves placing a radioactive source directly within or very near the tumor, is often used for superficial skin cancers, delivering a concentrated dose of radiation to the tumor site while limiting exposure to surrounding healthy tissue [23]. As demonstrated in recent investigations, including the work by Fionda et al, the use of modern image-guided planning systems in conjunction with intensity-modulated radiation therapy allows for tailored treatment protocols that can be adapted based on lesion depth, size, anatomical location, and surface curvature. Particularly for small, superficial lesions, contact interventional radiotherapy with intensity modulation provides dosimetric advantages by ensuring adequate target coverage with prescription dose while limiting the volume of tissue receiving high-dose exposure to within acceptable thresholds [24]. Furthermore, this technique can be implemented using standard applicators, such as Freiburg flaps or customized 3D-printed molds, which facilitate reproducible source placement and dose delivery even in anatomically complex regions [25,26].
Common adverse effects of radiotherapy for skin cancers include erythema (skin reddening), dry or moist desquamation (peeling of the skin), and mild discomfort or tenderness at the treatment site [27]. These adverse effects typically resolve after the completion of treatment. However, there is also the potential for longer-term effects, such as hyperpigmentation, telangiectasia (small, dilated blood vessels), or fibrosis (scarring or hardening of tissue) [28]. In rare cases, more severe complications, including secondary malignancies (ie, soft tissue sarcoma [29], non-melanoma skin cancer [30]) can arise years after treatment, although the risk is generally considered low when radiotherapy is administered appropriately and with care.
One of the challenges in using radiotherapy for skin cancers, particularly BCC and SCC, is ensuring that it is used appropriately within the broader context of patient management. For instance, while radiotherapy is highly effective for many patients, it is not the treatment of choice for every individual. Factors such as tumor type, location, and the patient’s age and overall health must be carefully considered. In some cases, radiotherapy is reserved for patients who are not surgical candidates or for those with tumors that are difficult to remove due to their location or size. Additionally, radiotherapy is not typically used as a first-line treatment for melanoma, as melanoma is more aggressive and often requires systemic therapies such as immunotherapy or targeted therapy in addition to surgery [31,32].
As with any cancer treatment, ongoing research and clinical trials continue to refine the use of radiotherapy in dermatology. Advances in radiation technology, treatment planning, and delivery methods are improving the precision of skin cancer treatment, reducing adverse effects, and enhancing overall outcomes. Personalized treatment approaches, based on genetic profiling and tumor behavior, are likely to shape the future of radiotherapy in dermatology, allowing for more tailored and effective treatment strategies.
Taking everything into consideration, radiotherapy remains an essential and versatile tool in the management of skin cancers, particularly for non-melanoma types like BCC and SCC. With its ability to provide curative treatment for localized tumors, palliation for advanced disease, and minimal disruption to surrounding healthy tissues, radiotherapy is a highly valuable option in the dermatologic oncologist’s armamentarium. However, despite the many advantages of radiotherapy, post-treatment surveillance presents unique challenges. Radiation-induced skin changes – such as fibrosis, telangiectasia, atrophy, pigmentary alterations, and persistent erythema – can mimic residual or recurrent tumor, complicating visual and clinical assessment. These changes often obscure anatomical landmarks and alter the appearance and texture of the treated area, making it difficult to distinguish between benign post-radiotherapy effects and malignant recurrence. Furthermore, standard clinical evaluation tools, including dermoscopy, can be limited in their ability to differentiate radiation-related tissue alterations from active disease. Histological assessment can also be inconclusive, as irradiated tissue often shows chronic inflammation, vascular changes, and cellular atypia that can resemble neoplastic processes. These diagnostic ambiguities underscore the need for more advanced imaging and assessment modalities to improve post-radiotherapy surveillance and guide appropriate management. As techniques evolve and the understanding of skin cancer biology deepens, radiotherapy will continue to play a critical role in improving the lives of patients with skin cancer, helping to provide them with the best possible outcomes while minimizing treatment-related morbidity.
Confocal Microscopy
There are 2 primary types of confocal microscopy used in dermatology: RCM and fluorescence confocal microscopy (FCM) [33]. RCM is a noninvasive, high-resolution imaging technique widely used in dermatology for the in vivo evaluation of skin at nearly histological detail. Using near-infrared laser light (typically 830 nm), RCM provides horizontal (en face) images of the epidermis and superficial dermis with lateral resolution around 0.5 to 1.0 μm and penetration depth of up to 250 to 300 μm [34]. RCM is the most commonly employed technique in clinical practice, using near-infrared laser light to detect variations in reflectivity between different cellular structures [35]. This approach allows for detailed visualization of keratinocytes, melanocytes, collagen fibers, and blood vessels, without the need for contrast agents [34,36].
In clinical applications, RCM has demonstrated high diagnostic accuracy, particularly for BCC. In a study including 1005 lesions – 740 of which were confirmed BCC – RCM used in conjunction with clinical and dermatoscopic evaluation achieved a sensitivity of 97.8% (95% CI, 96.5–98.8) and specificity of 86.8% (95% CI, 82.1–90.6). These values were significantly higher than with dermatoscopy alone, which showed a sensitivity of 93.2% (95% CI, 91.2–94.9) and a notably lower specificity of 51.7% (95% CI, 45.5–57.9). The positive predictive value of RCM was 95.4% (95% CI, 93.6–96.8) and the negative predictive value was 93.5% (95% CI, 89.7–96.2), highlighting the technique’s value in enhancing diagnostic confidence and reducing unnecessary biopsies [37].
In contrast, FCM relies on fluorescent dyes or endogenous fluorescence to enhance the contrast of specific molecular components within the skin [38]. While FCM offers additional molecular insights, it is less commonly used, owing to the requirement for exogenous staining agents.
In the context of radiotherapy-treated skin evaluation, RCM provides several advantages over traditional assessment methods. One of its most significant benefits is the ability to detect early signs of residual or recurrent disease. Malignant cells often exhibit characteristic features on confocal imaging, such as enlarged, irregularly shaped nuclei, loss of normal skin architecture, and increased vascularization [39]. By identifying these abnormalities in real-time, clinicians can make prompt decisions regarding the need for further intervention, potentially improving patient outcomes and reducing the risk of disease progression.
Beyond its role in cancer detection, RCM is valuable for monitoring radiation-induced skin changes. Following radiotherapy, the skin undergoes a complex healing process that involves inflammation, tissue remodeling, and fibrosis [40,41]. Confocal imaging enables clinicians to track these changes over time, providing insights into epidermal regeneration, collagen reorganization, and vascular alterations. This information can be used to guide post-treatment care, optimize wound healing strategies, and minimize long-term complications.
Another key advantage of RCM is its potential to reduce the number of unnecessary biopsies. In many cases, clinical suspicion of recurrent disease leads to biopsy procedures that ultimately reveal benign radiation-induced changes rather than malignancy. By providing high-resolution in vivo imaging, RCM can help differentiate between post-radiotherapy alterations and true neoplastic recurrence, thereby sparing patients from avoidable invasive procedures. This noninvasive approach not only improves patient comfort but also reduces healthcare costs associated with biopsy processing and histopathological analysis.
Despite its many benefits, RCM is not without limitations. One of its primary drawbacks is its limited penetration depth, which restricts imaging to the superficial layers of the skin (typically up to 200–300 μ) [42]. While this is sufficient for evaluating many epidermal and superficial dermal structures, deeper lesions can be difficult to assess. Additionally, confocal imaging requires specialized training for accurate interpretation, as image artifacts and variations in reflectance can sometimes complicate diagnosis. Cost and accessibility are also potential barriers, as RCM devices are expensive and not widely available in all healthcare settings.
To overcome some of these limitations, ongoing research is exploring ways to enhance confocal microscopy’s capabilities. One promising avenue is the integration of artificial intelligence (AI) for automated image analysis and diagnosis [43]. Machine learning algorithms can be trained to recognize specific patterns associated with malignant or benign conditions, potentially reducing interobserver variability and improving diagnostic accuracy. Additionally, advancements in multiphoton microscopy and hybrid imaging techniques, such as the combination of RCM with OCT, may help extend imaging depth and provide a more comprehensive evaluation of radiotherapy-treated skin.
As RCM continues to evolve, its role in dermatology and oncology is likely to expand. In the coming years, an increased adoption of this technology for routine post-radiotherapy monitoring may be seen, as well as its integration into telemedicine platforms for remote consultations. By refining imaging techniques, improving accessibility, and incorporating AI-driven analysis, RCM has the potential to revolutionize skin cancer management and enhance patient care.
In summary, RCM represents a significant advancement in the noninvasive assessment of radiotherapy-treated skin in patients with skin cancer. Its ability to provide real-time, high-resolution imaging of cellular structures makes it an invaluable tool for detecting residual disease, monitoring radiation-induced changes, and guiding clinical decision-making. While challenges such as limited penetration depth and accessibility remain, ongoing research and technological innovations hold promise for further improving its utility. As the field continues to advance, RCM is poised to play an increasingly important role in optimizing post-radiotherapy skin care and improving long-term outcomes for patients with skin cancer.
Line-Field Confocal Optical Coherence Tomography
LC-OCT is an advanced, noninvasive imaging modality that combines the principles of confocal microscopy and OCT to achieve high-resolution, real-time visualization of skin microstructures at both the cellular and subcellular levels [44]. With an axial resolution of approximately 1.1 μm and lateral resolution of about 1.3 μm, LC-OCT enables vertical and horizontal scanning of the skin to depths up to 500 μm [45]. This technique has garnered increasing attention as a diagnostic and monitoring tool in dermatologic oncology, particularly in the evaluation of non-melanoma skin cancers, including BCC and SCC.
Recent studies have demonstrated the high diagnostic performance of LC-OCT in detecting these malignancies. When compared with dermoscopy, using histopathology as the gold standard, LC-OCT showed superior sensitivity, specificity, and diagnostic accuracy. The sensitivity, specificity, and diagnostic accuracy for LC-OCT were 0.99 (CI 0.971.00), 0.90 (CI 0.840.94), and 0.96 (CI 0.930.97), respectively, compared with 0.97 (CI 0.94–0.99), 0.43 (CI 0.36–0.51), and 0.77 (CI 0.72–0.81) for dermoscopy [46].
Following radiotherapy treatment for skin cancers, especially in patients for whom surgical excision is not feasible or desirable, LC-OCT offers a promising means of assessing therapeutic response, detecting residual or recurrent lesions, and monitoring post-treatment skin remodeling.
In the post-radiotherapy setting, LC-OCT facilitates the identification of specific morphological criteria associated with residual tumor activity. In BCC, these can include oval-shaped structures (with/without bright-colored centers), dark regions bordering the dermis (appearing as hyporeflective zones indicating the tumor’s lateral edge), black zones or cones protruding into the adjacent dermis, and interruptions in the epidermal layer [47]. In SCC, atypical keratinocytes, architectural disarray, and keratin-filled invaginations can be visualized [48]. Importantly, the ability of LC-OCT to perform en face and cross-sectional imaging allows for precise correlation with histological architecture, which enhances diagnostic accuracy. This method of skin examination, resembling transversal histological images, improves and accelerates the learning process.
The integration of LC-OCT into post-radiotherapy workflows provides several clinical benefits. First, it enables early detection of subclinical recurrences, potentially before they become apparent on the skin surface. Second, it reduces the need for repeated biopsies, which can be poorly tolerated in radiated, fragile skin. Third, it supports informed clinical decision-making by providing real-time visual feedback on lesion dynamics and treatment response.
Recent studies have demonstrated the feasibility and utility of LC-OCT in post-radiotherapy assessment, showing high concordance with histopathology in detecting residual tumor features [48]. As a result, LC-OCT is emerging as a valuable adjunctive tool in the multidisciplinary management of patients with skin cancer, particularly in complex cases in which clinical evaluation alone is insufficient. Additionally, by offering detailed structural information, LC-OCT may help assess cosmetic outcomes and skin regeneration following radiotherapy, which is of increasing interest given the potential for long-term aesthetic and functional sequelae.
Finally, LC-OCT represents a significant advancement in the noninvasive evaluation of skin cancers after radiotherapy. Its high resolution, real-time imaging capabilities, and capacity to
differentiate between neoplastic and post-treatment changes make it a powerful tool for improving patient care. Continued research and integration into clinical protocols will further define its role in enhancing diagnostic confidence, minimizing unnecessary procedures, and optimizing long-term outcomes in patients treated with radiotherapy for skin malignancies (Figure 1).
Discussion
This article highlights the pivotal role of advanced imaging modalities, particularly RCM and LC-OCT, in the noninvasive evaluation of radiotherapy-treated skin in patients with non-melanoma skin cancers. As skin cancer incidence continues to rise globally, especially among aging populations [49], the demand for precise, patient-friendly diagnostic tools grows increasingly urgent. Radiotherapy remains a cornerstone of treatment for patients unsuitable for surgery because of anatomical constraints, comorbidities, or cosmetic concerns [17,50]. However, while effective, radiotherapy introduces a spectrum of cutaneous adverse effects that necessitate vigilant post-treatment monitoring.
Traditional radiotherapy-treated skin assessments, such as clinical examinations and biopsies, have limitations in detecting early recurrences or distinguishing radiation effects from cancer regrowth.
RCM and LC-OCT provide real-time, high-resolution imaging of skin structures. These modalities have demonstrated utility not only in identifying residual tumor characteristics but also in documenting the dynamic reparative processes following radiotherapy, such as fibrosis, angiogenesis, and tissue remodeling [51,52].
A comparative evaluation of RCM and LC-OCT reveals both modalities as highly valuable noninvasive diagnostic tools for the post-radiotherapy surveillance of non-melanoma skin cancers, particularly BCC and SCC.
Importantly, the roles of RCM and LC-OCT in clinical workflows should be understood as complementary rather than mutually exclusive. RCM may be particularly useful as an initial modality for superficial assessment and short-term follow-up, whereas LC-OCT may offer greater diagnostic utility in ambiguous cases requiring vertical tissue analysis or evaluation of deeper structures. The integration of both techniques can provide a more comprehensive assessment, especially when used sequentially in cases in which diagnosis remains uncertain. This synergy may significantly enhance diagnostic accuracy while reducing unnecessary biopsies and improving patient comfort.
RCM has shown particular promise in visualizing cellular morphology and detecting hallmark features of malignancy, such as pleomorphism, disordered architecture, and abnormal vascularization [53]. However, its limited optical penetration depth (approximately 250–300 μm) can restrict its utility in evaluating deeper dermal structures, a limitation particularly relevant in cases of infiltrative or recurrent tumors after radiotherapy.
In contrast, LC-OCT has emerged as a technologically advanced alternative, combining the lateral resolution characteristic of confocal microscopy with the axial sectioning depth of OCT. LC-OCT’s ability to generate en face and cross-sectional images allows for a quasi-histological evaluation of epidermal and dermal compartments, offering superior visualization of tumor margins, architectural disarray, and invasion patterns [54]. The vertical imaging capability, in particular, provides additional diagnostic confidence in distinguishing post-radiation fibrosis, inflammatory changes, and true neoplastic persistence, which are often difficult to differentiate clinically or with RCM alone.
While LC-OCT appears to outperform RCM marginally in terms of overall diagnostic accuracy, it is important to consider practical aspects such as device availability, image acquisition time, cost-effectiveness, and the level of expertise required for accurate interpretation. RCM, particularly when using a wide probe, offers increased precision by enabling accurate correlation between dermoscopic features and cellular-level details, making it a highly practical choice for routine surveillance, especially in superficial or cosmetically sensitive areas, where real-time imaging is essential. Its key advantage over LC-OCT lies in the superior and more precise resolution it provides, which is particularly valuable in the differential diagnosis of pigmented lesions and melanoma. Conversely, LC-OCT is particularly advantageous for cases requiring deeper tissue assessment or when histopathologic correlation is critical. In conclusion, using these advanced imaging techniques may offer the most comprehensive approach to the post-radiotherapy management of patients with non-melanoma skin cancer, optimizing diagnostic precision while minimizing the need for unnecessary invasive biopsies. A detailed comparison of the technical features of RCM and LC-OCT is presented in Table 1. Furthermore, although preliminary studies have shown strong concordance with histopathology [55–58], larger, longitudinal studies are needed to validate their sensitivity and specificity in detecting post-radiotherapy recurrence across diverse patient populations and tumor subtypes.
Despite these advantages, the broader implementation of RCM and LC-OCT faces several barriers. High initial acquisition costs, limited access in non-academic or peripheral centers, and the necessity of specialized training for device operation and image interpretation remain significant obstacles. Moreover, the current lack of standardized diagnostic algorithms and insufficient reimbursement frameworks further restricts widespread adoption in routine clinical practice.
In response to these challenges, there is growing interest in the integration of AI and machine learning technologies into confocal imaging workflows. Preliminary studies suggest that AI-driven algorithms can support the automated identification of malignancy-associated features, reduce interobserver variability, and enhance diagnostic efficiency, particularly in high-volume clinical settings. These tools can also contribute to reducing the expertise barrier and facilitating broader use of RCM and LC-OCT by less-experienced clinicians [43]. Early applications suggest that AI could enhance diagnostic accuracy, standardize image interpretation, and streamline clinical workflows, making confocal-based technologies more accessible and user-friendly. Additionally, the development of hybrid devices combining RCM with other imaging modalities, such as multiphoton microscopy or full-field OCT, could overcome current depth limitations and further broaden clinical applications [61].
Moving forward, a multidisciplinary approach that combines radiotherapy with high-resolution imaging and personalized follow-up protocols may yield the most effective outcomes. RCM and LC-OCT should be viewed not merely as diagnostic tools, but as integral components of a larger strategy aimed at reducing morbidity, improving cosmetic results, and optimizing quality of life for patients with skin cancer. These technologies also hold promise for integration into teledermatology platforms, enabling remote follow-up and reducing the burden of frequent in-person visits for patients with mobility or access challenges.
Potentially, the use of these imaging techniques as a control examination during and after radiotherapy can influence the process of planning and dosing during irradiation of skin cancers, which enables the even more tailored form of this therapy.
Taking everything into consideration, RCM and LC-OCT represent transformative advancements in the post-radiotherapy evaluation of skin cancer. Their ability to noninvasively differentiate between benign post-treatment changes and residual malignancy offers the potential to reduce unnecessary biopsies, facilitate earlier intervention, and personalize post-treatment care. As technology advances and clinical experience grows, these imaging modalities are likely to become essential tools in the modern dermatologic oncologist’s arsenal.
Conclusions
In conclusion, non-melanoma skin cancer remains a major public health issue, and radiotherapy is an effective treatment option. Non-invasive imaging techniques, such as RCM and LC-OCT, show promising potential for post-treatment monitoring due to their high resolution and real-time capabilities. However, larger, standardized studies are needed to confirm their clinical utility and to guide their integration into routine dermatologic and oncologic care.
References
1. D’Orazio J, Jarrett S, Amaro-Ortiz A, Scott T, UV radiation and the skin: Int J Mol Sci, 2013; 14(6); 12222-48
2. Gordon R, Skin cancer: An overview of epidemiology and risk factors: Semin Oncol Nurs, 2013; 29(3); 160-69
3. Ciążyńska M, Kamińska-Winciorek G, Lange D, Author correction: The incidence and clinical analysis of non melanoma skin cancer: Sci Rep, 2021; 11(1); 15705 [Erratum for: Sci Rep. 2021;11(1):4337]
4. Kauvar AN, Cronin T, Roenigk RAmerican Society for Dermatologic Surgery, Consensus for nonmelanoma skin cancer treatment: Basal cell carcinoma, including a cost analysis of treatment methods: Dermatol Surg, 2015; 41(5); 550-71
5. Garbutcheon-Singh KB, Veness MJ, The role of radiotherapy in the management of non-melanoma skin cancer: Australas J Dermatol, 2019; 60(4); 265-72
6. Locke J, Karimpour S, Young G, Radiotherapy for epithelial skin cancer: Int J Radiat Oncol Biol Phys, 2001; 51(3); 748-55
7. Naylor W, Mallett J, Management of acute radiotherapy induced skin reactions: A literature review: Eur J Oncol Nurs, 2001; 5(4); 221-33
8. Glover D, Harmer V, Radiotherapy-induced skin reactions: Assessment and management: Br J Nurs, 2014; 23(4); S28-35
9. Elston DM, Stratman EJ, Miller SJ, Skin biopsy: Biopsy issues in specific diseases: J Am Acad Dermatol, 2016; 74(1); 1-16 [Erratum in: J Am Acad Dermatol. 2016;75(4):854]
10. Malvehy J, Pellacani G, Dermoscopy, confocal microscopy and other non-invasive tools for the diagnosis of non-melanoma skin cancers and other skin conditions: Acta Derm Venereol, 2017; 22-30
11. Vuong W, Lin J, Wei RL, Palliative radiotherapy for skin malignancies: Ann Palliat Med, 2017; 6(2); 165-72
12. Hasan N, Nadaf A, Imran M, Skin cancer: Understanding the journey of transformation from conventional to advanced treatment approaches: Mol Cancer, 2023; 22(1); 168
13. Mancebo SE, Wang SQ, Skin cancer: Role of ultraviolet radiation in carcinogenesis: Rev Environ Health, 2014; 29(3); 265-73
14. Dika E, Scarfì F, Ferracin M, Basal cell carcinoma: A comprehensive review: Int J Mol Sci, 2020; 21(15); 5572
15. Stratigos A, Garbe C, Lebbe CEuropean Dermatology Forum (EDF); European Association of Dermato-Oncology (EADO); European Organization for Research and Treatment of Cancer (EORTC), Diagnosis and treatment of invasive squamous cell carcinoma of the skin: European consensus-based interdisciplinary guideline: Eur J Cancer, 2015; 51(14); 1989-2007
16. Baskar R, Lee KA, Yeo R, Yeoh KW, Cancer and radiation therapy: Current advances and future directions: Int J Med Sci, 2012; 9(3); 193-99
17. Pashazadeh A, Boese A, Friebe M, Radiation therapy techniques in the treatment of skin cancer: An overview of the current status and outlook: J Dermatolog Treat, 2019; 30(8); 831-39
18. Zeng L, Gowda BHJ, Ahmed MG, Advancements in nanoparticle-based treatment approaches for skin cancer therapy: Mol Cancer, 2023; 22(1); 10
19. Chen HHW, Kuo MT, Improving radiotherapy in cancer treatment: Promises and challenges: Oncotarget, 2017; 8(37); 62742-58
20. Warren TA, Panizza B, Porceddu SV, Outcomes after surgery and postoperative radiotherapy for perineural spread of head and neck cutaneous squamous cell carcinoma: Head Neck, 2016; 38(6); 824-31
21. Van der Walt JG, Radiation field shaping through low temperature thermal-spray in radiotherapy: Thesis, 2009, Central University of Technology, Free State
22. Grégoire V, Guckenberger M, Haustermans K, Image guidance in radiation therapy for better cure of cancer: Mol Oncol, 2020; 14(7); 1470-91
23. Devlin PM, Holloway CL, Stewart AJ: Brachytherapy: Applications and techniques, 2016, New York Demos Medical Publishing House
24. Fionda B, Placidi E, Rosa E, Multilayer intensity modulated contact interventional radiotherapy (brachytherapy): Stretching the therapeutic window in skin cancer: J Contemp Brachytherapy, 2023; 15; 220-23
25. Poltorak M, Banatkiewicz P, Poltorak L, Individualized 3D printing for skin cancer brachytherapy: Development, implementation, clinical applications, and treatment assessment: J Contemp Brachytherapy, 2024; 16(3); 173-83
26. Poltorak M, Banatkiewicz P, Poltorak L, Brachytherapy and 3D printing for skin cancer: A review paper: J Contemp Brachytherapy, 2024; 16(2); 156-69
27. Gewandter JS, Walker J, Heckler CE, Characterization of skin reactions and pain reported by patients receiving radiation therapy for cancer at different sites: J Support Oncol, 2013; 11(4); 183-89
28. Cuperus E, Leguit R, Albregts M, Toonstra J, Post radiation skin tumors: basal cell carcinomas, squamous cell carcinomas and angiosarcomas. A review of this late effect of radiotherapy: Eur J Dermatol, 2013; 23(6); 749-57
29. Rubino C, Shamsaldin A, Lê MG, Radiation dose and risk of soft tissue and bone sarcoma after breast cancer treatment: Breast Cancer Res Treat, 2005; 89(3); 277-88
30. Friedman DL, Whitton J, Leisenring W, Subsequent neoplasms in 5-year survivors of childhood cancer: The Childhood Cancer Survivor Study: J Natl Cancer Inst, 2010; 102(14); 1083-95
31. Seth R, Agarwala SS, Messersmith H, Systemic therapy for melanoma: ASCO guideline update: J Clin Oncol, 2023; 41(30); 4794-20
32. Switzer B, Puzanov I, Skitzki JJ, Managing metastatic melanoma in 2022: A clinical review: JCO Oncol Pract, 2022; 18(5); 335-51
33. Jayamohanan R, Confocal microscopy-working principle and applications in dermatology: J Skin Sex Transm Dis, 2023; 5; 81-89
34. Nehal KS, Gareau D, Rajadhyaksha M, Skin imaging with reflectance confocal microscopy: Semin Cutan Med Surg, 2008; 27(1); 37-43
35. Lboukili I, Stamatas G, Descombes X, Automating reflectance confocal microscopy image analysis for dermatological research: A review: J Biomed Opt, 2022; 27(7); 070902
36. Scope A, Benvenuto-Andrade C, Agero AL, In vivo reflectance confocal microscopy imaging of melanocytic skin lesions: Consensus terminology glossary and illustrative images: J Am Acad Dermatol, 2007; 57(4); 644-58
37. Longo C, Guida S, Mirra M, Dermatoscopy and reflectance confocal microscopy for basal cell carcinoma diagnosis and diagnosis prediction score: A prospective and multicenter study on 1005 lesions: J Am Acad Dermatol, 2024; 90(5); 994-1001 [Erratum in: J Am Acad Dermatol. 2024;91(3):618]
38. Roberts MS, Dancik Y, Prow TW, Non-invasive imaging of skin physiology and percutaneous penetration using fluorescence spectral and lifetime imaging with multiphoton and confocal microscopy: Eur J Pharm Biopharm, 2011; 77(3); 469-88
39. Ahlgrimm-Siess V, Laimer M, Rabinovitz HS, Confocal microscopy in skin cancer: Curr Dermatol Rep, 2018; 7(2); 105-18
40. Yu Z, Xu C, Song B, Tissue fibrosis induced by radiotherapy: Current understanding of the molecular mechanisms, diagnosis and therapeutic advances: J Transl Med, 2023; 21(1); 708
41. Olascoaga A, Vilar-Compte D, Poitevin-Chacón A, Contreras-Ruiz J, Wound healing in radiated skin: pathophysiology and treatment options: Int Wound J, 2008; 5(2); 246-57
42. Calzavara-Pinton P, Longo C, Venturini M, Reflectance confocal microscopy for in vivo skin imaging: Photochem Photobiol, 2008; 84(6); 1421-30
43. Malciu AM, Lupu M, Voiculescu VM, Artificial intelligence-based approaches to reflectance confocal microscopy image analysis in dermatology: J Clin Med, 2022; 11(2); 429
44. Dubois A, Levecq O, Azimani H, Line-field confocal optical coherence tomography for high-resolution noninvasive imaging of skin tumors: J Biomed Opt, 2018; 23(10); 1-9
45. Cappilli S, Paradisi A, Di Stefani A, Line-field confocal optical coherence tomography: A new skin imaging technique reproducing a “virtual biopsy” with evolving clinical applications in dermatology: Diagnostics (Basel), 2024; 14(16); 1821
46. Donelli C, Suppa M, Tognetti L, Line-field confocal optical coherence tomography for the diagnosis of skin carcinomas: Real-life data over three years: Curr Oncol, 2023; 30(10); 8853-64
47. Niculet E, Craescu M, Rebegea L, Basal cell carcinoma: Comprehensive clinical and histopathological aspects, novel imaging tools and therapeutic approaches (review): Exp Ther Med, 2022; 23(1); 60
48. Cinotti E, Tognetti L, Cartocci A, Line-field confocal optical coherence tomography for actinic keratosis and squamous cell carcinoma: A descriptive study: Clin Exp Dermatol, 2021; 46(8); 1530-41
49. Urban K, Mehrmal S, Uppal P, The global burden of skin cancer: A longitudinal analysis from the Global Burden of Disease Study, 1990–2017: JAAD Int, 2021; 2; 98-108
50. Yosefof E, Kurman N, Yaniv D, The role of radiation therapy in the treatment of non-melanoma skin cancer: Cancers (Basel), 2023; 15(9); 2408
51. Gandhi S, Chandna S, Radiation-induced inflammatory cascade and its reverberating crosstalks as potential cause of post-radiotherapy second malignancies: Cancer Metastasis Rev, 2017; 36(2); 375-93
52. Chargari C, Rassy E, Helissey C, Impact of radiation therapy on healthy tissues: Int Rev Cell Mol Biol, 2023; 376; 69-98
53. Guida S, Pellacani G, Ciardo S, Longo C, Reflectance confocal microscopy of aging skin and skin cancer: Dermatol Pract Concept, 2021; 11(3); e2021068
54. Latriglia F, Ogien J, Tavernier C, Line-field confocal optical coherence tomography (LC-OCT) for skin imaging in dermatology: Life (Basel), 2023; 13(12); 2268
55. Sollena P, Salvi M, Marraffa M, LC-OCT for early diagnosis and characterization of dermatologic adverse events to oncologic drugs and correlation to histopathology: Int J Dermatol, 2025; 64(4); 719-24
56. Ruini C, Schuh S, Gust C, In-vivo LC-OCT evaluation of the downward proliferation pattern of keratinocytes in actinic keratosis in comparison with histology: first impressions from a pilot study: Cancers (Basel), 2021; 13(12); 2856
57. Perino F, Suarez R, Perez-Anker J, Concordance of in vivo reflectance confocal microscopy and horizontal-sectioning histology in skin tumours: J Eur Acad Dermatol Venereol, 2024; 38; 124-35
58. Broggi G, Verzì AE, Caltabiano R, Correlation between in vivo reflectance confocal microscopy and horizontal histopathology in skin cancer: A review: Front Oncol, 2021; 11; 653140
59. Levine A, Markowitz O, Introduction to reflectance confocal microscopy and its use in clinical practice: JAAD Case Rep, 2018; 4(10); 1014-23
60. Ali A, Colombe L, Mélanie P, Comparison of facial skin ageing in healthy Asian and Caucasian females quantified by in vivo line-field confocal optical coherence tomography 3D imaging: Skin Res Technol, 2024; 30(9); e13643
61. Wang L, Fu R, Xu C, Xu M, Methods and applications of full-field optical coherence tomography: A review: J Biomed Opt, 2022; 27(5); 050901
In Press
Clinical Research
Institutional and Regional Variations in Access to Clinical Trials and Next-Generation Sequencing in Turkis...Med Sci Monit In Press; DOI: 10.12659/MSM.951027
Clinical Research
Low-Intensity Blood Flow-Restricted Multi-Joint Exercise Improves Muscle Function in Patients With Patellof...Med Sci Monit In Press; DOI: 10.12659/MSM.950516
Review article
Musculoskeletal Ultrasound and MRI in the Evaluation of Chemotherapy-Induced Peripheral Neuropathy: A ReviewMed Sci Monit In Press; DOI: 10.12659/MSM.951283
Clinical Research
Sensory Processing, Dissociation, and Affective Symptoms in Misophonia: A Cross-Sectional Study of 35 AdultsMed Sci Monit In Press; DOI: 10.12659/MSM.950938
Most Viewed Current Articles
17 Jan 2024 : Review article 10,187,196
Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron VariantDOI :10.12659/MSM.942799
Med Sci Monit 2024; 30:e942799
13 Nov 2021 : Clinical Research 3,708,487
Acceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology ...DOI :10.12659/MSM.932788
Med Sci Monit 2021; 27:e932788
14 Dec 2022 : Clinical Research 2,341,643
Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase LevelsDOI :10.12659/MSM.937990
Med Sci Monit 2022; 28:e937990
16 May 2023 : Clinical Research 706,524
Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...DOI :10.12659/MSM.940387
Med Sci Monit 2023; 29:e940387








