Laser Therapy in Basal Cell Carcinoma: Current Evidence, Literature Gaps and Future Perspectives

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This narrative review examines the role of laser‑based therapies as alternative or adjunctive treatments for basal cell carcinoma (BCC), particularly in low‑risk cases and cosmetically sensitive areas. By critically discussing ablative lasers, vascular lasers, and laser‑assisted photodynamic therapy, the manuscript addresses an important and evolving topic in dermatologic oncology. The comment that may improve the manuscript are as followed. Please address it .

1. The clinical rationale for exploring laser therapy as an alternative to surgery in selected BCC cases is well articulated and relevant. The distinction between low‑risk and high‑risk BCC should be more consistently emphasized throughout the review to avoid overgeneralization of findings.
2. The narrative structure is clear; however, inclusion of a brief methods section describing literature search and selection criteria would improve transparency.
3. The discussion of ablative lasers, particularly CO₂ lasers, is well balanced, though limitations related to tumor depth assessment should be more explicitly highlighted.
4. Clearance rates reported for superficial BCC should be interpreted cautiously in light of limited long‑term follow‑up data.
5. The section on vascular lasers is informative, but the paucity of robust long‑term outcomes should be more clearly underscored.
6. Laser‑assisted photodynamic therapy is presented as promising; however, clearer comparison with conventional PDT would strengthen this section.
7. Mechanisms of action are appropriately summarized, but a concise schematic or table could improve clarity for readers.
8. The emerging role of non‑invasive imaging for patient selection and response monitoring is a strength and deserves slightly expanded discussion.
9. Methodological heterogeneity across studies is correctly identified as a major limitation; examples of key sources of bias would be helpful.
10. The review would benefit from clearer guidance on clinical decision‑making, indicating which patients may realistically benefit from laser‑based approaches.
11. Overall, the manuscript provides a useful overview, but well‑designed comparative trials with standardized protocols are essential to define the definitive role of lasers in BCC management.
12. These are some recent literatures that may be review and included https://doi.org/10.1016/j.cclet.2023.108557, https://doi.org/10.2147/IJN.S466042
13. The tabular data need to cite in respective raw. 

 

Author Response

1) 

Importantly, non-surgical options are mainly appropriate for low-risk BCC, defined as superficial or lesions of small size (<10-15 mm), located in low-risk sites (trunk and limbs), with well-defined margins and without high-risk features (peritumoral, recurrent, or in immunosuppressed patients). High-risk BCC, including infiltrative, morpheiform subtypes, or located in H-zones of the face, require surgical approaches with histological control of the margins

2) 

The bibliographic search was conducted on PubMed and Google Scholar, focusing on randomized trials, prospective studies, and clinical investigations, concentrating on laser-based and combined strategies for basal cell carcinoma. The search included articles published up to December 2025 and aimed to provide an updated perspective on laser-based approaches for BCC management. Given the narrative nature of this review, no formal methodological scoring was applied.

3)

A key limitation of ablative laser therapy is the inability to assess tumor depth before treatment. Without histological margin control, incomplete ablation becomes more likely, especially in nodular BCCs or lesions with subclinical extension. As a result, clinical clearance may overestimate histological clearance, limiting the oncologic reliability of ablative approaches to superficially confined tumors.

4)

 It is important to emphasise that the reported clearance rates must be interpreted with caution, considering that most studies have limited follow-up (12-24 months), potentially insufficient to detect late relapses that may occur later than 3-5 years after treatment.

 

5)

However, not all studies support the efficacy of PDL in the treatment of basal cell carcinoma. Ballard et al. reported a persistence rate of 44.4% after a single treatment with PDL at 585 nm in a case series of BCC, concluding that this approach does not achieve the clearance rates achievable with standard therapeutic modalities and cannot be recommended as primary monotherapy. It is plausible that the unsatisfactory results observed are at least partly related to the use of a single session, which is insufficient to ensure adequate oncological control in the absence of histological confirmation[48]. Similarly, Chow et al. evaluated PDL at 595 nm using a double-pulse protocol in a randomised controlled trial, reporting lower cure rates than standard therapies and concluding that PDL, with the parameters adopted, cannot be recommended for the treatment of BCC [49]. In this context, the use of non-aggressive settings and limited protocols may have contributed to the negative outcomes. Overall, these data show a marked variability of results depending on the parameters and protocols used, underlining the importance of patient selection and caution when interpreting favourable results from uncontrolled studies. 

Overall, vascular lasers show clinical activity in selected low-risk BCCs, mainly superficial and very small nodular lesions. Evidence remains limited by short follow-up, heterogeneous endpoints, and scarce histological confirmation. Their role therefore remains experimental and not comparable to surgery for long-term oncologic control.

6)

Compared with conventional PDT, which achieves high clearance rates in superficial BCCs but suboptimal results in nodular lesions, laser-assisted PDT offers a relevant theoretical advantage. Partial ablation or microperforation may enhance photosensitizer penetration into deeper tumor layers, potentially extending efficacy to selected nodular BCCs. However, direct head-to-head comparisons in large, stratified cohorts remain limited. [50,51].

7)

We thank the reviewer for the suggestion. Given the narrative and clinically oriented nature of this review, we chose to integrate the mechanistic considerations directly into the relevant sections of the text rather than introducing an additional schematic figure. This approach was intended to maintain focus on clinical interpretation while avoiding oversimplification of mechanisms that remain context-dependent across different laser modalities.

8)

The integration of non-invasive imaging represents a fundamental methodological advance. Reflective confocal microscopy (RCM) and optical coherence tomography (OCT) allow in vivo visualisation of tumour structures before, during and after treatment, reducing the empiricism typical of destructive approaches. RCM, in particular, can identify clinically undetectable tumour margins and neoplastic remnants after laser ablation, guiding further treatment sessions in the same session or confirming clearance without the need for immediate biopsy. This image-guided approach could become the standard for extending the use of lasers into wider clinical settings.

9)

Methodological heterogeneity between studies represents a major barrier to the synthesis of evidence on laser therapy in basal cell carcinoma. Laser parameters vary substantially, even when the same devices are used, with differences in fluence, spot size, pulse duration, and cooling, limiting reproducibility and the definition of optimal settings. Treatment protocols are also heterogeneous, ranging from single-session approaches to multiple cycles with variable intervals, often without a clear rationale for session number or retreatment criteria, leaving treatment strategies largely empirical and center-dependent. Endpoints further contribute to variability, as some studies rely on clinical clearance while others require histological confirmation, frequently assessed at non-uniform time points. In this context, the available evidence was addressed through a critical, modality-specific discussion, underscoring the need for shared minimum criteria for technical reporting and more homogeneous outcome measures [56].

10)

From a clinical perspective, laser-based treatments should be considered only in carefully selected patients with low-risk BCCs, while high-risk tumors and lesions in critical anatomical sites should continue to be managed with surgery and histological margin control.

12) 

We thank the reviewer for suggesting these references. After reviewing both articles, we did not identify a direct overlap with the main focus of the present review, which is centered on laser-based therapies for basal cell carcinoma. However, we recognize their potential relevance in a broader phototherapy context and would be pleased to include them if the reviewer could indicate the section in which their integration would be most appropriate.

13) 

done 

Reviewer 2 Report

Comments and Suggestions for Authors

The peer-reviewed scientific paper makes a mixed impression. On the one hand, the authors have performed a very high-quality literature review on the relatively rare and relevant topic of laser destruction of basal cell carcinomas. The key technical and biomedical aspects are presented in sufficient detail. The list of issues requiring further study and standardization is also very well formulated. On the other hand, the review paper contains a number of obvious shortcomings:

I) The text of the reviewed paper lacks any images, diagrams, drawings, medical illustrations, etc. This clearly reduces its informative value of the paper under review. For example, malignant tumors typically include a necrotic core, a hypoxic region, and an oxygenated region. A thematic figure would enhance the review paper and highlight the importance of adaptive tuning of the key characteristics of the laser source used.

II) Issues related to the external and internal geometry of the boundaries of the area exposed to laser radiation were not considered. The authors correctly noted that energy absorption by water is one of the key biophysical aspects of laser radiation exposure on soft biological tissue. However, the directly related differences in hydration levels of different skin layers were not mentioned.

III) It was important to address issues related to laser dermatological surgery planning, for example, by using high-frequency ultrasound imaging of the region of ​​interest. Objective monitoring of heat propagation and basal cell carcinoma destruction, for example, by using a medical thermal imager was also necessary to mention.

In general, the peer-reviewed scientific paper is recommended for publication in the MDPI journal «Bioengineering» after Major Revision.

Author Response

 

1) We appreciate the suggestion. While we agree that visual elements would enhance the manuscript, this narrative review focuses on clinical evidence synthesis rather than biological mechanisms in depth. Adding detailed tumor microenvironment diagrams would require expanding the scope beyond laser therapy efficacy. However if also  editors will  ask for visual elements as foundamental, we will add them.

2) We thank the reviewer for this observation. While tissue hydration is indeed a relevant biophysical parameter, detailed discussion of water absorption coefficients and layer-specific hydration levels falls beyond the primary clinical focus of this review. We have briefly mentioned the role of water absorption in Section 2.1 when discussing CO2 and Er:YAG mechanisms. A more granular biophysical analysis would be better suited to a physics- or engineering-focused review.

3) High-frequency ultrasound and thermal imaging are emerging tools in dermatologic oncology. However, their application specifically to laser therapy planning for BCC is not yet established in the clinical literature. We have focused on non-invasive optical imaging (RCM, OCT) which has more robust evidence in this context. Ultrasound and thermal monitoring may be addressed in future reviews as the technology matures.

we add this sentence in the conclusions:

Emerging tools such as high-frequency ultrasound may assist pre-treatment planning by estimating tumor depth, while medical thermography could enable real-time monitoring of thermal diffusion during laser ablation. However, clinical evidence supporting these applications in laser-treated BCC remains preliminary.

 

Reviewer 3 Report

Comments and Suggestions for Authors

The article titled ‘Laser Therapy in Basal Cell Carcinoma: Current Evidence, Literature Gaps and Future Perspectives’ aims to review and critically evaluate the existing literature on the use of lasers in the treatment of basal cell carcinoma, with emphasis on the different laser types, their mechanisms of action, clinical results as well as limitations and may be an useful contribution to the journal; however, few changes should be taken into consideration, in the benefit of the reader:

Lines 60-62: manuscript states: ‘In such situations, cryotherapy, curettage and electrodessication, photodynamic therapy (PDT), and topical treatments represent established approaches and, in many cases, better supported by evidence than other physical modalities’- this should be rephrased as to make clearer what the other physical modalities refer to.

Methodology - although this manuscript is presented as a narrative review and therefore does not require a formal systematic methodology, a brief description of the literature selection aproach (e.g., databases consulted, time frame or key inclusion criteria) would improve transparency and strengthen the scientific rigor of the review. The modality the articles to be included in the review should be mentioned; the exact procedural methdolology should be listed. i.e. concise methodological statement is recommended, as to ensure transparency and minimise a potential selection bias.

In addition, the literature supporting the manuscript should be more comprehensively reviewed to ensure balanced representation of available evidence. E.g. There is a study from Ballard et al, Ballard CJ, Rivas MP, McLeod MP, Choudhary S, Elgart GW, Nouri K. that is not discussed. The pulsed dye laser for the treatment of basal cell carcinoma. Lasers Med Sci. 2011 Sep;26(5):641-4. doi: 10.1007/s10103-011-0952-8. Epub 2011 Jul 12. PMID: 21748324. As the reader cannot identify it in the references, the study states: ‘Although the PDL was able to clear over half of the BCCs in this study, there was an unacceptably high persistence rate of 44.4%. The PDL did not achieve the clearance rate that can be attained with current standard BCC treatment modalities. At this time, we do not recommend that a single treatment with the 585-nm PDL can be used as a primary therapy for BCC’. Caution should be therefore used in order to present all relevant studies in the field.

Another example missing from the review is Chow M, Eimpunth S, Hamman MS, Jiang SIB. Effectiveness of a 595-nm Pulsed Dye Laser for the Treatment of Basal Cell Carcinoma Using One Double-Stacked Pulse Session: A Randomized, Double-Blinded Controlled Trial. Dermatol Surg. 2021 May 1;47(5):630-633. doi: 10.1097/DSS.0000000000002689. PMID: 32852428, that states ‘the cure rate is lower than those of other treatments for BCC. Thus, PDL under the current settings cannot be recommended.’

Considering these and other relevant publications, the literature underpinning the manuscript should be more thoroughly and critically revised. Presenting both favourable and unfavourable evidence is essential to avoid selection bias and to provide a balanced and accurate overview of the current role of laser therapies in basal cell carcinoma. The literature that stands at the foundation of the manuscript should be more thoroughly revised.

Melanin also absorbs at vascular lasers wavelength, it is not clear from the mansucript to what extent this interferes with treatment outcomes, including aethetic outcomes. Discussing this would increase the value of the manuscript.

Grammar and punctuation must also be carefully checked within the entire article.

 

Author Response

1) The sentence has been rephrased for clarity.

In such situations, cryotherapy, curettage and electrodesiccation, photodynamic therapy (PDT), and topical treatments (e.g., imiquimod, 5-fluorouracil) represent established non-surgical approaches, often better supported by long-term evidence than emerging laser-based modalities.

2) this sentence has been added in the introduction.

The bibliographic search was conducted on PubMed and Google Scholar, focusing on randomized trials, prospective studies, and clinical investigations, concentrating on laser-based and combined strategies for basal cell carcinoma. The search included articles published up to December 2025 and aimed to provide an updated perspective on laser-based approaches for BCC management. Given the narrative nature of this review, no formal methodological scoring was applied.

3)  references has been added 

However, not all studies support the efficacy of PDL in the treatment of basal cell carcinoma. Ballard et al. reported a persistence rate of 44.4% after a single treatment with PDL at 585 nm in a case series of BCC, concluding that this approach does not achieve the clearance rates achievable with standard therapeutic modalities and cannot be recommended as primary monotherapy. It is plausible that the unsatisfactory results observed are at least partly related to the use of a single session, which is insufficient to ensure adequate oncological control in the absence of histological confirmation[48]. Similarly, Chow et al. evaluated PDL at 595 nm using a double-pulse protocol in a randomised controlled trial, reporting lower cure rates than standard therapies and concluding that PDL, with the parameters adopted, cannot be recommended for the treatment of BCC [49]. In this context, the use of non-aggressive settings and limited protocols may have contributed to the negative outcomes. Overall, these data show a marked variability of results depending on the parameters and protocols used, underlining the importance of patient selection and caution when interpreting favourable results from uncontrolled studies. 

Overall, vascular lasers show clinical activity in selected low-risk BCCs, mainly superficial and very small nodular lesions. Evidence remains limited by short follow-up, heterogeneous endpoints, and scarce histological confirmation. Their role therefore remains experimental and not comparable to surgery for long-term oncologic control.

4) Melanin also absorbs at vascular lasers wavelength, it is not clear from the mansucript to what extent this interferes with treatment outcomes, including aethetic outcomes.

 A clinically relevant aspect is the competing absorption of melanin at the wavelengths of vascular lasers (585-595 nm for PDL and 1064 nm for Nd:YAG). In darker phototypes (III-VI), the epidermal absorption of energy reduces the fluence available for the vascular target and increases the risk of adverse events, in particular post-inflammatory hyperpigmentation or hypopigmentation. This limits the applicability of vascular lasers in such patients and imposes a reduction in parameters, which may compromise efficacy [42,43]. 

 

 

Reviewer 4 Report

Comments and Suggestions for Authors

Thank you for the opportunity to review this manuscript. 

This manuscript provides a timely narrative review on laser-based approaches for basal cell carcinoma (BCC), with a clinically logical structure (ablative lasers, vascular lasers, laser-assisted PDT, and imaging tools). The discussion appropriately emphasizes that surgery remains the standard of care and that laser approaches are mainly relevant for selected, low-risk scenarios. The inclusion of summary tables (especially the “gaps/standards” table) is useful and actionable for future research directions

Major limitations: The review is explicitly narrative, but it lacks minimal methodological transparency (databases searched, date limits, keywords, and inclusion/exclusion logic). This reduces reproducibility and increases the risk of selective citation. In addition, there is no structured risk-of-bias/quality appraisal of included studies, which is important given the heterogeneity in endpoints (clinical vs histologic clearance), lesion risk profiles, and follow-up durations. Finally, Table 1 may inadvertently imply comparability of clearance rates across modalities; stronger caveats in the table legend and/or stratification by endpoint and follow-up would prevent overinterpretation

Recommendation: Minor-to-moderate revision. Add a brief “literature identification” methods paragraph, provide a simple study-quality framework (even narrative tiers), and strengthen table caveats/stratification to align conclusions more tightly with heterogeneous evidence.

Author Response

 Add a brief “literature identification”

The bibliographic search was conducted on PubMed and Google Scholar, focusing on randomized trials, prospective studies, and clinical investigations, concentrating on laser-based and combined strategies for basal cell carcinoma. The search included articles published up to December 2025 and aimed to provide an updated perspective on laser-based approaches for BCC management. Given the narrative nature of this review, no formal methodological scoring was applied.

 

Methodological Heterogeneity and conclusion has been rephrased

Methodological heterogeneity between studies represents a major barrier to the synthesis of evidence on laser therapy in basal cell carcinoma. Laser parameters vary substantially, even when the same devices are used, with differences in fluence, spot size, pulse duration, and cooling, limiting reproducibility and the definition of optimal settings. Treatment protocols are also heterogeneous, ranging from single-session approaches to multiple cycles with variable intervals, often without a clear rationale for session number or retreatment criteria, leaving treatment strategies largely empirical and center-dependent. Endpoints further contribute to variability, as some studies rely on clinical clearance while others require histological confirmation, frequently assessed at non-uniform time points. In this context, the available evidence was addressed through a critical, modality-specific discussion, underscoring the need for shared minimum criteria for technical reporting and more homogeneous outcome measures.

 

conclusion

Based on the gaps that have emerged, future perspectives should shift from heterogeneous case series to more focused and comparable studies. There is a need for RCTs designed on well-defined populations, prioritising superficial or small nodular BCCs, smaller than 1-1.5 cm, located in low-risk areas, comparing laser therapy with standard surgery and adopting uniform parameters and outcomes.  From a clinical perspective, laser-based treatments should be considered only in carefully selected patients with low-risk BCCs, while high-risk tumors and lesions in critical anatomical sites should continue to be managed with surgery and histological margin control.

 Non-invasive imaging, in particular LC-OCT and RCM, is expected to play a central role in patient selection, early monitoring and follow-up, reducing the risk of incomplete clearance that today limits the credibility of destructive approaches [23,58].

A still little explored area concerns combination therapies, which appear to be among the most promising strategies in the context of laser therapy [59,60]. Not only laser combined with topical drugs or laser-assisted PDT, but also combinations between different sources, such as CO2 and PDL, with or without PDT or topical treatments, many of which have not yet been systematically evaluated. Identifying which combinations provide the best balance between clearance, tolerability and aesthetic outcome is a key step before extending clinical indications.

Emerging tools such as high-frequency ultrasound may assist pre-treatment planning by estimating tumor depth, while medical thermography could enable real-time monitoring of thermal diffusion during laser ablation. However, clinical evidence supporting these applications in laser-treated BCC remains preliminary [63].

In conclusion, laser therapy in BCC is an evolving field, with concrete advantages in terms of minimal invasiveness and cosmetic outcome, but still limited by methodological heterogeneity, incomplete stratification and short follow-up. With standardised protocols, objective controls, and a focus on non-aggressive tumours in low-risk sites, it could find a more defined clinical space within the current guidelines, also helping to reduce the surgical burden of operating theatres without compromising oncological safety [6,7].

 

Reviewer 5 Report

Comments and Suggestions for Authors

1.The research methods of this manuscript need to be improved. It is recommended to add a study design flow chart stating the inclusion and exclusion criteria of references.

2.The clinical take home message is still a bit vague.   Manuscript recommend spelling out what counts as low risk BCC, and when laser should not be used。

3.Table 1 Adverse events and probabilities of the different laser treatments recommended for supplementation

Author Response

1) We thank the reviewer for this comment. As this manuscript is a narrative review, a systematic study design with predefined inclusion and exclusion criteria was not applied. Instead, we specified how the literature was identified, outlining the databases searched and the clinical rationale guiding article selection, in line with the aims of a narrative and clinically oriented review. The inherent limitations of this approach, including the absence of a structured flow chart, have been explicitly acknowledged in the Limitations section.

 The bibliographic search was conducted on PubMed and Google Scholar, focusing on randomized trials, prospective studies, and clinical investigations, concentrating on laser-based and combined strategies for basal cell carcinoma. The search included articles published up to December 2025 and aimed to provide an updated perspective on laser-based approaches for BCC management. Given the narrative nature of this review, no formal methodological scoring was applied.

 

This work has several limitations related to its narrative design. The selection of studies was guided by clinical relevance and the author's interpretation, rather than by predefined systematic criteria, with a potential risk of selection bias. Critical reflections and future perspectives thus reflect the judgement of the authors and the articles considered, rather than a formal quantitative synthesis. The absence of a meta-analysis limits the direct comparison between different laser modalities and with standard surgery, but is consistent with the aim of the work, which is oriented towards a critical and clinically applicable reading of the literature. These limitations were addressed through a critical discussion of study design, endpoints, and follow-up within the relevant sections of the manuscript.

 

2)conclusion has been rephrased 

Based on the gaps that have emerged, future perspectives should shift from heterogeneous case series to more focused and comparable studies. There is a need for RCTs designed on well-defined populations, prioritising superficial or small nodular BCCs, smaller than 1-1.5 cm, located in low-risk areas, comparing laser therapy with standard surgery and adopting uniform parameters and outcomes. It should be emphasized that laser therapy should be restricted to low-risk basal cell carcinomas, while high-risk tumors or lesions located in critical anatomical sites should continue to be managed with surgery and histological margin control.

 Non-invasive imaging, in particular LC-OCT and RCM, is expected to play a central role in patient selection, early monitoring and follow-up, reducing the risk of incomplete clearance that today limits the credibility of destructive approaches [23,58].

A still little explored area concerns combination therapies, which appear to be among the most promising strategies in the context of laser therapy [59,60]. Not only laser combined with topical drugs or laser-assisted PDT, but also combinations between different sources, such as CO2 and PDL, with or without PDT or topical treatments, many of which have not yet been systematically evaluated. Identifying which combinations provide the best balance between clearance, tolerability and aesthetic outcome is a key step before extending clinical indications.

Emerging tools such as high-frequency ultrasound may assist pre-treatment planning by estimating tumor depth, while medical thermography could enable real-time monitoring of thermal diffusion during laser ablation. However, clinical evidence supporting these applications in laser-treated BCC remains preliminary [63].

In conclusion, laser therapy in BCC is an evolving field, with concrete advantages in terms of minimal invasiveness and cosmetic outcome, but still limited by methodological heterogeneity, incomplete stratification and short follow-up. With standardised protocols, objective controls, and a focus on non-aggressive tumours in low-risk sites, it could find a more defined clinical space within the current guidelines, also helping to reduce the surgical burden of operating theatres without compromising oncological safety [6,7].

 

3)Adverse events added in table 1 

 

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

All comments address. Accepted. 

Reviewer 3 Report

Comments and Suggestions for Authors

The manuscript has been properly revised by the authors, taking into consideration all the suggested changes and aspects raised by previous version. Therefore, I recommend the manuscript for being published.