Photodynamic therapy in esophageal cancer: trends, innovations, and future directions from a global perspective (1985–2024)

Abstract

Background

Esophageal cancer (EC) is a leading cause of cancer-related deaths worldwide. Photodynamic therapy (PDT) has emerged as a promising, minimally invasive treatment for EC due to its high selectivity. However, a comprehensive bibliometric analysis of PDT in EC is lacking. This study aims to assess research trends, key contributors, and emerging themes in PDT for EC from 1985 to 2024.

Methods

We performed a bibliometric analysis using data from the Web of Science Core Collection. VOSviewer, CiteSpace, and the R package ‘bibliometrix’ were employed to examine publication trends, collaboration networks, and primary research themes related to PDT in EC.

Results

The analysis included 581 publications by 2037 researchers from 593 institutions across 40 countries. The United States, China, and England were the top contributors, with significant input from the Mayo Clinic and Thompson Cancer Survival Center. Photodiagnosis and Photodynamic Therapy was the most prolific journal, while Gastrointestinal Endoscopy received the highest citations. Research areas covered various aspects of PDT in EC, including its combination with endoscopic treatments, use of photosensitizers, palliative care applications, biological mechanisms, and nanoparticle drug delivery advancements. Emerging themes highlighted the application of nanotechnology in drug delivery, integration of immunotherapy, and exploration of the tumor microenvironment.

Conclusion

This bibliometric study reveals a global expansion in PDT research for EC, emphasizing new directions such as nanotechnology-enhanced drug delivery, immunotherapy integration, and tumor microenvironment studies. These advancements are expected to improve PDT’s effectiveness, particularly in overcoming the limitations of current treatments for deeper and more advanced EC cases.

Supplementary Information

The online version contains supplementary material available at 10.1007/s12672-025-02643-8.

Introduction

Esophageal cancer (EC) is the seventh leading cause of cancer-related deaths globally, with increasing incidence and mortality rates posing a significant public health challenge [1]. In 2022, EC was responsible for approximately 445,000 deaths, accounting for 4.6% of all cancer-related fatalities. Due to its often asymptomatic nature in the early stages, EC is frequently diagnosed at an advanced stage, reducing treatment efficacy and survival rates [2]. While advancements in traditional treatments such as surgery, chemotherapy, and radiotherapy have been made, more effective and targeted therapies are urgently needed.

Photodynamic therapy (PDT) has emerged as a promising option due to its minimal invasiveness, high selectivity, ease of use, safety, and rapid recovery [3]. PDT uses photosensitizers to precisely target tumor cells while sparing healthy tissue [4]. It induces various types of cell death, including apoptosis, autophagy, and necrosis, leading to effective tumor eradication [5]. Clinically, PDT is widely used at all stages of EC, both as a primary and salvage therapy, administered through a flexible laser endoscopy system noted for its convenience and safety [3, 4].

Despite these advantages, PDT faces several challenges in clinical application. One major limitation is the limited tissue penetration of visible light, which reduces its effectiveness for deeper esophageal tumors. To address this, researchers are exploring alternative strategies such as higher-energy light sources (e.g., X-rays) and nanotechnology to enhance photosensitizer delivery and activation in deeper tissues [6, 7]. Additionally, patients undergoing PDT must take precautions against photosensitivity, which can lead to severe skin reactions upon sun exposure lasting several weeks [8]. Other side effects, including esophagitis, strictures, and swallowing difficulties, have also been reported [9]. In advanced EC cases, PDT is primarily employed for palliative purposes rather than with curative intent, focusing on alleviating symptoms such as dysphagia and improving quality of life when complete tumor eradication is not feasible [9].

Nevertheless, ongoing research is actively addressing these challenges, making PDT an increasingly viable option for the treatment of EC. Strategies such as combining photosensitizers with nanoparticles and monoclonal antibodies, as well as integrating PDT with chemotherapy and immunotherapy, have shown promising potential to improve therapeutic outcomes. These advancements enhance tumor specificity and minimize collateral damage to surrounding healthy tissue, offering a more effective and targeted therapeutic approach [10, 11]. Clinical studies have shown that PDT has certain effectiveness in the treatment of EC, with an early complete remission rate reaching a certain proportion. However, some patients still face the risk of recurrence, and there are differences in tolerance to various therapeutic drugs. For example, one study demonstrated that PDT combined with endoscopic resection successfully treated a case of highly elevated squamous cell carcinoma of the esophagus that recurred after radical chemoradiotherapy, highlighting its potential value in cases of local recurrence [12]. Furthermore, PDT, as a palliative therapy, has been approved for the treatment of EC patients with obstructive symptoms, as it can rapidly relieve obstruction. However, it may be difficult to achieve complete ablation when used alone, leading to studies evaluating PDT in conjunction with a sequential dose-decreasing chemoradiotherapy regimen to explore more optimal treatment combinations [13]. Despite PDT’s potential in treating EC, some studies suggest that its effectiveness in patients with residual or recurrent EC after radical chemoradiotherapy remains limited. While esophagectomy is a potential curative treatment option, research on its efficacy is limited [14].

To improve the efficacy of PDT, Lin et al. designed fine nanoparticles to load photosensitizers (PSs) in order to improve their accumulation in tumors, which enhances the therapeutic effect of PDT [15]. Tsou et al. found that at a concentration of 200 μg/mL, dMSN-EuGd@Fucoidan nanoparticles resulted in a 47.7% survival rate in HCT116 cancer cells, and combination therapy (chemotherapy and PDT) exhibited superior anticancer effects compared to using PDT or chemotherapy alone. They successfully synthesized nanoparticles for combined chemotherapy and PDT [16]. Zhang et al. assessed the effect of sequential dose-decreasing chemoradiotherapy (CCRT) with PDT in the treatment of EC, showing that the combination of PDT and chemotherapy is being studied and applied to achieve better treatment outcomes [13]. Ren et al. explored chemotherapy and photodynamic therapy as a promising strategy to improve treatment efficacy. However, they also pointed out existing challenges, such as poor tumor targeting, insufficient microenvironment response, and unclear mechanisms, indicating that although there are challenges, the research on combination therapy is still ongoing and has certain potential [17].

Additionally, Yue et al. explored mesoporous hexagonal core–shell zinc porphyrin-silica nanoparticles (MPSNs), combining them with immunotherapy and phototherapy (such as PDT) to improve the effects of immunotherapy in cancer treatment. This suggests that the combined use of PDT and immunotherapy is under investigation and may enhance treatment efficacy [18]. A case report also mentioned that an EC patient developed immune-related adverse events (irAEs) after PDT treatment. Despite the adverse events, the patient showed significant tumor shrinkage, further demonstrating the potential and efficacy of PDT in the treatment of EC [19].

Despite these significant technological advances in PDT applications for EC treatment, there remains a notable gap in the literature regarding how research in this field has evolved over time. The absence of comprehensive bibliometric analyses hampers our understanding of research trends, collaborative patterns, and influential contributions. This study aims to fill that gap by analyzing PDT research in EC from 1985 to 2024, addressing the following key questions:

1. What are the major research trends and hotspots in PDT for EC?

2. Which institutions and researchers have made the most significant contributions?

3. How have collaborative networks evolved, and which journals and studies are most influential in this field?

4. What are the main research directions and bibliometric methodologies in PDT for EC?

5. What are the most promising future research directions to enhance the effectiveness of PDT in EC treatment?

This bibliometric analysis seeks to map the research landscape of PDT in EC, identify key contributors, and highlight emerging trends. As PDT becomes more widely applied, synthesizing existing findings will be crucial in guiding future research. Additionally, this analysis will support clinicians in developing evidence-based treatments, ultimately improving the effectiveness of EC therapy and enhancing patients’ quality of life.

Methods

This study employed a comprehensive bibliometric approach using multiple specialized tools to analyze the global research landscape of PDT in EC. The data collection process involved a systematic search of the Web of Science Core Collection from 1985 to 2024. The specific search terms, search process, inclusion and exclusion criteria, etc., can be found in Supplementary Table 1.

Each bibliometric tool was selected for its specific analytical strengths and applied systematically to address different aspects of the research landscape:

VOSviewer (version 1.6.18) was utilized for network visualization and analysis due to its robust capacity to handle large datasets and create interpretable maps [20, 21]. This tool was specifically applied to analyze:

1. Country and institutional collaboration networks, with node size representing publication volume and link thickness indicating collaboration strength

2. Co-authorship networks, with clustering based on collaborative frequency

3. Journal co-citation networks, revealing core knowledge sources in the field

4. Keyword co-occurrence networks, identifying thematic clusters and research hotspots

CiteSpace (version 6.1.R5) was employed to detect emerging trends and paradigm shifts in the research field [22]. We applied this tool to identify:

1. Keywords with citation bursts, with burst strength calculated using Kleinberg’s algorithm to detect rapid increases in citation frequency

2. Topic trends over time, with special attention to recent developments (2022–2024)

3. Institutional and author citation bursts, revealing influential contributors at different time periods

The ‘bibliometrix’ R package (version 4.1.1) [23, 24] was used to analyze:

1. Annual publication trends and growth patterns

2. Geographical distribution of research output

3. Thematic mapping of research areas based on density and centrality metrics

Statistical analysis of publication trends used a fourth-degree polynomial regression model to account for nonlinear growth patterns and forecast future publication volumes. Visual representations of results were optimized using Microsoft Office Excel 2021.

This multi-tool approach enabled comprehensive analysis of bibliometric indicators including publication counts, citation patterns, collaboration networks, and thematic developments, providing a holistic view of the evolution and current state of PDT research in EC.

Results

Annual publication trends

Figure 1A shows the annual publication volume of PDT in EC from 1985 to 2024. Research in this area has followed a varied trajectory—initial slow growth, followed by a rapid increase, reaching a peak, then declining, and recently showing signs of resurgence. Several factors contribute to this fluctuation, including technological limitations, the emergence of alternative therapies, shifts in research funding, and ongoing debates about PDT’s effectiveness.

Fig. 1.

Bibliometric analysis of photodynamic therapy in esophageal cancer applications. A Annual publication trends in research in this field. The red dotted trend curve fitted according to the number of publications (the ‘third order polynomial’ model of the number of publications). B Network diagram showing international cooperation among countries. C Geographical distribution of research contributions by region. D Map depicting the geographical locations of corresponding authors. E Network visualization of institutional collaborations

A forth-degree polynomial model was applied to account for the nonlinear growth in publications and to help forecast future trends. The model predicts that publication numbers in 2024, 2025, and 2026 will reach 88, 111, and 136, respectively, with an average annual growth rate of around 23.63%. This projected growth is likely fueled by technological advances and the growing interest in combination therapies, which have renewed attention on PDT research.

Geographical and institutional distribution

This analysis includes 581 documents, authored by 2,037 researchers from 593 institutions across 40 countries, published in 218 journals (Table S1). Figure 1B, C highlight global contributions, with the United States leading in publications (n = 187), followed by China (n = 77) and England (n = 66). Western institutions dominate the authorship network (Fig. 1D), showing strong collaboration among key institutions. However, when considering centrality—a measure of a country’s influence within the research collaboration network—the picture changes. Despite having fewer publications, China holds the highest centrality (0.40), indicating its pivotal role in connecting global research efforts. The United States follows with a centrality of 0.32, and England with 0.20, both playing important but lesser roles. The Mayo Clinic stands out with 30 publications and 1,051 citations, followed by Thompson Cancer Survival Center (17 publications, 2,012 citations), and Donghua University (16 publications, 114 citations), highlighting their leadership in this field (Fig. 1E, Table 1).

Table 1.

Top 10 countries and organization on the research of the application of photodynamic therapy in esophageal cancer

Rank	Country	Counts	Citations	Average Citation/publications	Centrality	Organization	Counts	Citations	Centrality
1	United States (North America)	187	8978	48.01	0.32	Mayo Clinic (United States)	30	1015	0.07
2	China (Asia)	77	1353	17.57	0.40	Thompson Cancer Survival Center (United States)	17	2012	0.00
3	England (Europe)	66	4243	64.29	0.20	Donghua University (China)	16	114	0.01
4	Japan (Asia)	53	1198	22.60	0.05	Massachusetts General Hospital (United States)	13	816	0.02
5	Germany (Europe)	43	2852	66.33	0.23	University College London (United Kingdom)	13	627	0.02
6	Netherlands (Europe)	28	1100	39.29	0.01	National Cancer Center Hospital East (Japan)	11	330	0.08
7	Switzerland (Europe)	22	835	37.95	0.01	Royal Hallamshire Hospital (United Kingdom)	11	232	0.08
8	Canada (North America)	19	1186	62.42	0.07	Shanghai Xianhui Pharmaceutical Co., Ltd. (China)	10	55	0.01
9	Australia (Oceania)	18	439	24.39	0.00	Harvard University (United States)	9	455	0.11
10	France (Europe)	17	551	32.41	0.00	Kyoto University (Japan)	9	332	0.03

These findings suggest that while the United States leads in output, China is emerging as a key player in international collaborations, signaling its growing influence in shaping future research directions. The collaborative strength among institutions, particularly between China and the United States, underscores the increasingly interconnected nature of global research. This trend highlights the importance of considering both publication volume and centrality when evaluating global research contributions.

Publication influence across journals and author collaboration networks

Figure 2A, B highlight the influence of key journals in PDT research for EC. Photodiagnosis and Photodynamic Therapy leads with the highest number of published articles (n = 39), emphasizing its central role in disseminating research in this field. Gastrointestinal Endoscopy stands out as the most cited journal in co-citation analysis, with 2,462 citations, marking its importance as a core source of knowledge (Table 2).

Fig. 2.

VOSviewer visualizations of networks in photodynamic therapy in esophageal cancer. A Network of journals publishing research on photodynamic therapy in esophageal cancer. B Network of co-cited journals in the field. C Visualization of author collaborations. D Network of co-cited authors. E Authors with the strongest citation bursts. F Institutions with the strongest citation bursts

Table 2.

Top 15 journals on the research of the application of photodynamic therapy in esophageal cancer

Rank	Journal	Counts	Citations	IFa	Qb	Co-cited journal	Co-citation	IFa	Qb
1	Photodiagnosis and Photodynamic Therapy	39	295	3.1	2	Gastrointestinal Endoscopy	2462	6.7	1
2	Gastrointestinal Endoscopy	33	2979	6.7	1	Gastroenterology	1353	25.7	1
3	Endoscopy	25	1157	11.5	1	American Journal of Gastroenterology	958	8.0	1
4	Lasers in Surgery and Medicine	25	810	2.2	2	Endoscopy	885	11.5	1
5	Current Opinion in Gastroenterology	17	75	2.6	2	Gut	830	23.0	1
6	Diseases of the Esophagus	17	202	2.3	3	Photochemistry and Photobiology	703	2.6	3
7	Journal of Photochemistry and Photobiology B-Biology	15	432	4.1	2	Cancer Research	477	12.5	1
8	Lasers in Medical Science	14	332	2.1	2	Journal of Photochemistry and Photobiology B-Biology	415	4.1	2
9	Annals of Thoracic Surgery	8	415	3.6	1	British Journal of Cancer	411	6.4	1
10	Gastroenterology	8	1213	25.7	1	Lasers in Surgery and Medicine	375	2.2	2
11	Scandinavian Journal of Gastroenterology	8	185	1.6	3	Annals of Thoracic Surgery	338	3.6	1
12	Alimentary Pharmacology & Therapeutics	7	275	6.6	1	New England Journal of Medicine	322	96.2	1
13	American Journal of Gastroenterology	7	511	8.0	1	British Journal of Surgery	321	8.6	1
14	Digestive Diseases and Sciences	7	227	2.5	2	Annals of Surgery	313	7.5	1
15	Photochemistry and Photobiology	7	272	2.6	3	Photodiagnosis and Photodynamic Therapy	274	3.1	2

^aThe impact factor of the journal are obtained from Journal Citation Reports 2023

^bThe quartile of the journal are obtained from Journal Citation Reports 2023

The author collaboration network analysis (Fig. 2C, D) reveals key contributors and their influence. Overholt, Bergein F, emerges as the most prolific and frequently co-cited author, with 21 publications, an H-index of 16, and 474 co-citations, demonstrating significant influence and integration of their work into broader scientific discussions (Table 3).

Table 3.

Top 10 authors on the research of the application of photodynamic therapy in esophageal cancer

Rank	Author	Counts	H-index	Co-cited authors	Citations
1	Overholt, Bergein F	21	16	Overholt, Bergein F	474
2	Ell, Christian	17	13	Gossner, L	236
3	Panjehpour, Masoud	15	13	Dougherty, Thomas J	231
4	Gossner, L	16	12	Barr, Hugh	211
5	Monnier, Ph	15	12	Ackroyd, R	185
6	Yano, Tomonori	13	10	Sampliner, RE	175
7	Chen, Zhi-Long	13	6	McCaughan, JS	160
8	May, A	12	6	Sharma, Prateek	157
9	Wolfsen, H. C	12	10	Yano, Tomonori	137
10	Wang, Kenneth K	11	10	Wolfsen, H. C	133

Figure 2E, F highlight the strongest citation bursts for authors and institutions, identifying key contributors. Monnier, P., from University Hospital Lausanne, leads with a citation burst score of 5.25, followed by Wolfsen, H.C., also from University Hospital Lausanne, with a score of 4.77, indicating that their research has attracted significant attention.

Among institutions, Mayo Clinic stands out with the highest citation burst score of 6.46, sustained from 2001 to 2012, reflecting a decade of impactful research. Donghua University, with a burst score of 5.98, has maintained its influence over a longer period, from 2014 to 2024, showing a continuous and growing impact. In contrast, University Hospital Lausanne had a strong but shorter burst between 1995 and 2002, indicating an earlier period of intense research activity.

The timing and duration of these citation bursts provide insights into the evolving research landscape. Mayo Clinic’s strong performance in the early 2000 s highlights its pivotal role during that period, while Donghua University’s sustained citation burst positions it as an emerging leader in driving future research. The shorter, more focused burst from University Hospital Lausanne in the late 1990 s underscores how institutional influence can fluctuate over time based on key research contributions.

Keyword analysis, thematic development, and future research directions

The keyword analysis identifies evolving trends and key areas in PDT research for EC, grouped into five main clusters (Fig. 3A, Table 4). The red cluster focuses on combining PDT with endoscopic treatments, such as mucosal resection for Barrett’s esophagus, high-grade dysplasia, and early-stage EC, offering a non-invasive option. The green cluster highlights porphyrin-based photosensitizers that induce apoptosis in EC cells, enabling targeted therapy with minimal damage to surrounding tissues. The yellow cluster centers on using porfimer sodium and talaporfin sodium as photosensitizers in palliative treatments aimed at improving the quality of life. The purple cluster emphasizes 5-aminolevulinic acid (ALA), which produces protoporphyrin IX to destroy EC cells. Lastly, the blue cluster shows the growing role of nanoparticles as drug carriers in PDT, optimizing drug delivery and enhancing treatment efficacy and specificity. These clusters reflect both established and emerging strategies in PDT, spanning early interventions to advanced palliative care, and demonstrate ongoing advancements in the field.

Fig. 3.

A Cluster analysis of keywords, revealing key thematic areas of focus. B Keywords with the strongest citation bursts, highlighting emerging research trends. C Topic trends in the study of photodynamic therapy for esophageal cancer. D Thematic map: The horizontal axis represents mediating centrality, reflecting the theme’s importance to the field, while the vertical axis represents density, indicating the level of development of the theme. Quadrant 1 (top right) represents MOTOR themes, which are both highly relevant and well-developed. Quadrant 2 (top left) includes HIGHLY DEVELOPED but ISOLATED themes, well-developed but less central to the current field. Quadrant 3 (bottom left) contains EMERGING or DECLINING themes, which are underdeveloped and may either be gaining or losing significance. Quadrant 4 (bottom right) represents BASIC and TRANSVERSAL themes, which are foundational but not yet fully developed

Table 4.

Top 20 keywords on research of the application of photodynamic therapy in esophageal cancer

Rank	Keywords	Counts	Rank	Keywords	Counts
1	Photodynamic Therapy	292	11	Esophageal Squamous Cell Carcinoma	25
2	Esophageal Cancer	137	12	Protoporphyrin IX	16
3	Barrett’s Esophagus	110	13	Porphyrin	14
4	Palliative Treatment	54	14	Talaporfin Sodium	13
5	Endoscopic Mucosal Resection	51	15	Nanoparticles	12
6	High-grade Dysplasia	49	16	Porfimer sodium	12
7	5-aminolevulinic Acid	42	17	Apoptosis	11
8	Cancer	32	18	Early Esophageal Cancer	10
9	Esophageal Adenocarcinoma	32	19	Ablation	9
10	Photosensitizer	30	20	Endoscopic Treatment	9

“Keywords with citation bursts” refer to terms that have seen a sudden rise in citations, indicating emerging trends or shifts in research focus. Figure 3B highlights the top 25 keywords with the strongest citation bursts, shown by red bars. Among them, “nanoparticles” had the highest burst score (n = 9.55), signaling its prominence in recent studies. From 2022 to 2024, terms like “trial,” “apoptosis,” “definitive chemoradiotherapy,” “delivery,” “porphyrin,” “nanoparticle,” “talaporfin sodium,” and “esophageal squamous cell carcinoma” have experienced the strongest citation bursts. This suggests a current research focus on evaluating PDT in clinical trials and on apoptosis as a key mechanism in EC cell death. The emergence of “definitive chemoradiotherapy” shows increased interest in combining PDT with traditional cancer treatments. Keywords like “delivery,” “porphyrin,” and “nanoparticle” further emphasize ongoing advancements in drug delivery technology, particularly involving photosensitizers like talaporfin sodium and nanoparticles to enhance treatment precision and efficacy.

Similarly, Fig. 3C highlights the most recent trends, with terms like “macrophage,” “hypoxia,” “salvage therapy,” “immunotherapy,” and “nanoparticle” gaining attention from 2022 to 2024. The inclusion of “macrophage” and “hypoxia” reflects a growing interest in understanding the tumor microenvironment and how it affects PDT efficacy. The rise of “salvage therapy” and “immunotherapy” suggests that PDT is being integrated into broader cancer treatment strategies, aiming to improve outcomes in advanced or recurrent EC cases. The continued prominence of talaporfin sodium and nanoparticles reinforces their role in enhancing PDT precision, particularly for targeting esophageal squamous cell carcinoma.

Additionally, the thematic map (Fig. 3D) illustrates the relevance and development of key themes in the field. The bottom right quadrant highlights essential but underdeveloped themes, revealing keywords that represent both established and emerging aspects of PDT research. For example, PDT remains central to treating esophageal cancer, especially in palliative care to alleviate symptoms like dysphagia [15]. This approach is particularly relevant for patients with esophageal squamous cell carcinoma, where PDT using porphyrin-based photosensitizers, such as talaporfin sodium, offers a less invasive alternative to traditional treatments. In early-stage EC, PDT combined with laser therapy has shown effectiveness, with potential applications in salvage treatment for recurrent cases [25, 26]. The map also underscores the growing interest in combination therapies, particularly the integration of PDT with immunotherapy [27]. This synergy aims to enhance therapeutic responses, providing a more comprehensive treatment approach for both early and advanced EC. These interconnected themes suggest a future where PDT is not only a standalone treatment but also a key component in combination therapies to improve patient outcomes across various stages of EC.

Discussion

To our knowledge, this is the first bibliometric analysis of PDT research within the context of EC. It offers a comprehensive view of global research trends, key collaborations, and emerging focus areas. By analyzing data from 1985 to 2024, we identified major research clusters, highlighted influential institutions and researchers, and mapped the evolution of PDT as a critical therapy for EC. This analysis provides not only a broad perspective on the development of PDT but also valuable insights to guide future research.

Significance of the findings

The findings reveal key trends with important implications for both clinical practice and future research. The growing integration of combination therapies, the use of nanoparticles for improved drug delivery, and the increasing focus on immunotherapy suggest that PDT is evolving beyond a standalone treatment. Additionally, our analysis emphasizes PDT’s potential as a minimally invasive and highly selective option, especially in palliative care and early-stage EC. However, challenges such as limited light penetration and photosensitivity still need to be addressed.

Global impact, collaboration, and research landscape

This study underscores the expanding global contributions to PDT research in EC. While the United States continues to lead in publication volume, China has emerged as a key player in international collaborations, reflected by its highest centrality score, indicating strong global research connections. Institutions such as the Mayo Clinic and Donghua University have made sustained contributions, helping to advance PDT applications. Collaborative efforts, particularly between Western and Chinese institutions, are driving innovation in PDT. The analysis also highlights the increasingly interdisciplinary nature of research, where collaborations are shaping new therapeutic approaches, such as the integration of PDT with nanotechnology and immunotherapy. This positions PDT as an essential component of future EC treatment strategies.

Limitations and future directions

While this study provides a detailed analysis of current trends, it has some limitations. One key issue was using only the Web of Science Core Collection, as merging data from other databases like Scopus or PubMed posed challenges due to differences in file formats. These inconsistencies made it difficult to unify the datasets, which could have disrupted certain visual analyses. As a result, using multiple databases could have prevented us from conducting as thorough an analysis as using a single, unified dataset. Additionally, focusing only on English-language publications may have excluded relevant studies published in other languages. Future studies could benefit from incorporating multiple databases to capture a broader, more global research landscape.

Moreover, expanding the dataset to include more recent publications and utilizing advanced bibliometric tools would allow for a deeper exploration of emerging research dynamics. As PDT research in EC evolves rapidly, regularly updating bibliometric analyses will be crucial for tracking new developments and guiding future research directions.

Future prospects of PDT in EC

The outlook for PDT in EC is both broad and promising. Advances in nanoparticle technology are enhancing drug delivery, improving tumor targeting, and reducing systemic toxicity [28, 29]. The integration of immunotherapy and improvements in photosensitizer technology, such as porphyrin-based compounds and 5-aminolevulinic acid (ALA), are also increasing precision and safety [30]. Additionally, combination therapies involving PDT alongside chemotherapy, radiotherapy, and targeted therapies are gaining traction. These approaches leverage synergistic effects to improve treatment outcomes by attacking cancer from multiple angles [17, 31]. Another emerging area of focus is modifying the tumor microenvironment, particularly addressing hypoxia and macrophage activity, which can make tumors more susceptible to PDT [7, 32]. As personalized medicine becomes more prominent, therapies tailored to the genetic and molecular characteristics of individual tumors are likely to further enhance PDT’s efficacy. These innovations point to PDT becoming a key component in the future management of EC [30].

Clinical and public health implications

PDT offers significant clinical advantages in EC management across multiple patient populations and disease stages. For early-stage EC and high-grade dysplasia in Barrett’s esophagus, PDT provides organ-sparing treatment with potential for comparable oncological outcomes to surgery while potentially reducing treatment-related morbidity [14, 33–36]. Studies have shown promising response rates for high-grade dysplasia, offering potential for disease control while preserving esophageal function and quality of life [37, 38].

For advanced EC, PDT addresses critical symptoms, particularly dysphagia, which affects a substantial proportion of patients and significantly impacts nutritional status and quality of life. Clinical studies have demonstrated that PDT can achieve meaningful dysphagia relief in patients with obstructing tumors [13, 39]. This symptom control can reduce hospitalization time, decrease the need for feeding tubes or stents, and potentially allow earlier initiation of systemic therapies.

For recurrent EC after radiotherapy (a particularly challenging clinical scenario), PDT offers salvage treatment options in cases where few alternatives exist [14, 36]. This application is especially valuable given its potentially favorable toxicity profile compared to re-irradiation or systemic therapy in previously treated tissues.

From a public health perspective, PDT may offer cost-effectiveness benefits that could impact healthcare resource allocation [40, 41]. Its ambulatory application can reduce hospitalization requirements, which is particularly valuable in resource-constrained settings. As PDT technologies advance toward more targeted approaches using nanotechnology and immunomodulation, their potential impact on EC-related mortality could be substantial, particularly in regions with high EC incidence, where early detection and minimally invasive therapies are urgently needed [42–45].

Comparison with existing literature

Our bibliometric analysis reveals several key distinctions from previous literature reviews on PDT in EC. While earlier studies primarily emphasized PDT as a standalone therapy for early-stage EC and dysplasia [27], our findings indicate a strong shift toward integration within multimodal treatment approaches, particularly combining PDT with immunotherapy and nanotechnology.

Previous literature concentrated on photosensitivity and light penetration limitations as primary barriers to widespread PDT adoption [46], whereas our analysis identifies an emerging focus on tumor microenvironment modification—particularly addressing hypoxia and macrophage activity—as a key research direction for enhancing PDT efficacy.

The research landscape has also evolved geographically. While Western institutions historically dominated PDT research in EC, our analysis demonstrates the growing influence of Chinese institutions in shaping global research direction, as evidenced by their high centrality score in collaboration networks.

Regarding clinical applications, earlier literature primarily highlighted PDT’s palliative role for managing dysphagia, but our findings demonstrate expanding applications into salvage therapy, definitive treatment for early disease, and novel combination protocols that extend PDT’s utility across the disease spectrum.

In terms of delivery technology, previous studies focused predominantly on conventional photosensitizers, whereas our analysis reveals nanoparticle-based delivery systems as a significant research focus, indicating a paradigm shift in approaches to optimizing drug delivery and treatment precision.

This comparison demonstrates that while earlier literature established PDT’s foundational role in EC management, our analysis reveals an evolution toward more sophisticated, integrated, and technologically advanced applications. The field is moving from viewing PDT as a niche palliative option to positioning it as a component of comprehensive precision medicine approaches with broader therapeutic potential across the EC disease spectrum.

Conclusion

This comprehensive bibliometric analysis of PDT in EC reveals a field undergoing rapid evolution from specialized palliative therapy to integral component of multidisciplinary cancer management. Our findings demonstrate that while traditional PDT applications in early-stage and palliative EC remain foundational, three transformative trends are reshaping the landscape: (1) integration of nanotechnology-enhanced delivery systems, overcoming historical limitations of photosensitizer distribution and activation depth; (2) strategic combination with immunotherapy, leveraging PDT-induced immunogenic cell death to amplify systemic anti-tumor responses; and (3) targeted modification of the tumor microenvironment, particularly addressing hypoxia and macrophage polarization to enhance treatment efficacy. These directions represent a paradigm shift from PDT as standalone therapy to its role as a precision medicine tool within personalized treatment algorithms. As technological advances continue to address historical limitations of light penetration and photosensitivity, PDT is positioned to significantly impact EC management across the disease spectrum—from curative applications in early disease to vital symptom control in advanced cases. The expanding global research network, with increasing contributions from collaborative efforts between Western and Asian institutions, promises to accelerate these innovations toward clinical implementation.

Author contributions

Yao-Xuan Chen: Methodology, Data curation, Formal analysis, Conceptualization, Writing original draft, Writing—review & editing Feng Guo: Methodology, Data curation, Formal analysis, Conceptualization, Writing original draft, Writing—review & editing Hao-Han Rao: Methodology, Data curation, Formal analysis, Conceptualization, Writing original draft, Writing—review & editing Chong-Qi Fan: Methodology, Data curation, Formal analysis, Writing original draft, Writing—review & editing Chun-Jian Zuo: Methodology, Data curation, Formal analysis, Writing original draft, Writing—review & editing Peng-Yu Che: Methodology, Data curation, Formal analysis, Writing original draft, Writing—review & editing Cao Yu: Methodology, Data curation, Formal analysis, Conceptualization, Writing original draft, Writing—review & editing Huan-Wen Chen: Methodology, Data curation, Formal analysis, Conceptualization, Writing original draft, Writing—review & editing All authors contributed to manuscript revision, and read and approved the submitted version.

Funding

None.

Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication 

Not applicable. 

Competing interests

The authors declare no competing interests.