Sebaceous gland carcinoma (SGC) of the eyelid, including meibomian gland carcinoma, is a rare yet very aggressive tumor that has a high likelihood for local recurrence, regional metastasis to the lymph nodes, and systemic metastases if not properly treated [6]. Diagnosis early in the condition is always difficult because it mimics benign conditions, thus presenting late and at advanced disease stages at the time of evaluation [4]. Traditional management methods use mainly surgical resection with or without orbital exenteration, but procedures like these might not always be effective for cases involving extensive periocular or orbital disease. In such instances, multimodality treatment involving systemic chemotherapies and radiation therapy has proven a very promising option for optimizing local control and survival [5][2]. Neoadjuvant chemotherapy has also shown value in downsizing bulky tumors, facilitating organ-sparing surgery, and optimizing long-term results [3]; [8]. Recent reports also emphasize the enduring use of multimodality therapy in periocular SGC, oligomeric disease control and functional sparing [1]. In addition, lessons learned from related periocular cancers, like adenoid cystic carcinoma of the lacrimal gland, support the model that eye salvage and survival can be prolonged through multimodality therapies [7]. Overall, these results highlight increasing relevance for the combination of systemic therapy and radiotherapy and surgery for advanced meibomian gland carcinoma and merit further assessment of outcomes after treatment with multiple modalities.

Study Design and Setting It was a decade-long retrospective observational study carried out in a tertiary eye care center. The study strictly met the guidelines of the Declaration of Helsinki, and institutional ethics committee clearance was obtained. Medical records of histopathologically confirmed meibomian gland carcinoma patients treated multimodally were assessed. Patient Selection These enrolled patients were all primary or recurrent meibomian gland carcinoma cases that completed multimodal treatment, e.g., chemotherapy alongside surgery and/or radiotherapy. Patients with incomplete medical records, distant metastasis at presentation, or less than six-month follow-up were excluded. Clinical staging was provided according to the American Joint Committee on Cancer (AJCC) 8th edition classification Sen et al. 2023. Treatment Plan The treatment plan was individualized to the extent of tumor and operability. Patients with extensive primary disease or metastasis to regional lymph nodes received neoadjuvant chemotherapy, primarily in the form of platinum containing regimens, to achieve tumor shrinkage and best surgical outcome, according to protocols already in press Murthy et al. 2005; Kaliki et al. 2016; Verma et al. 2021. surgery encompassed wide local excision with margin control, eyelid reconstruction, or orbital exenteration as appropriate. Adjuvant radiotherapy was discussed in cases with positive margins from surgery, perineural tumor spread, or nodes. Outcome Measures Our main end points were local control of tumour, disease-free survival, and survival. We measured eye salvage rates, patterns of recurrence, and toxicity from treatment as secondary end points. We categorised tumour response to chemotherapy clinically as well as orbitally by imaging, grading partial or complete response according to RECIST criteria. Follow-Up Procedure They were thereafter observed every three months in the first two years, every six months in the next three years, and every year thereafter. Follow-up assessment involved systems review, ophthalmic evaluation, and imaging as appropriate. Recurrence was classified as local, regional, or distant, whereas survival end points were noted from diagnosis onwards until last follow-up or death.

Patient Demographics and Clinical Characteristics. 42 cases with histopathologically proven meibomian gland carcinoma were included in the study. Mean age of presentation was 58.6 years (34–79 years), with female dominance (64.3%). The majority of the tumors arose from the upper eyelid (71.4%), then from the lower eyelid (21.4%) and canthal area (7.2%). The classification as per the AJCC 8th edition was as follows: 17 cases (40.5%) with stage T2 disease, 15 (35.7%) with stage T3, and 10 (23.8%) with stage T4. Table 1 is given as follows to show the details of demographic and baseline clinical parameters. Table 1. Baseline Demographic and Clinical Characteristics of Patients Characteristic Value (n=42) Mean age (years) 58.6 (range 34–79) Gender (Male: Female) 15:27 Tumor site (Upper:Lower:Canthal) 30:9:3 AJCC Stage T2 17 (40.5%) AJCC Stage T3 15 (35.7%) AJCC Stage T4 10 (23.8%) Nodal involvement at baseline 9 (21.4%) Treatment Outcomes. 29 patients (69.0%) received chemotherapy as part of their treatment. Of these, 12 (41.4%) had complete response, 13 (44.8%) partial response, and 4 (13.8%) failed to show significant response. Surgery was done in 36 (85.7%) cases, involving 28 local excisions with reconstruction and 8 orbital exenterations. Adjuvant radiotherapy was given in 11 cases (26.2%), mainly in cases with nodal disease or positive surgical margins. Table 2 provides treatment modalities and rates of response. Table 2. Treatment Modalities and Response Outcomes Treatment Modality Number (%) Neoadjuvant chemotherapy (N=29) 29 (69.0%) – Complete response 12 (41.4%) – Partial response 13 (44.8%) – No response 4 (13.8%) Surgery performed 36 (85.7%) – Local excision & reconstruction 28 (66.7%) – Orbital exenteration 8 (19.0%) Adjuvant radiotherapy 11 (26.2%) Survival and Eye Salvage. At a median follow-up of 46 months (range, 12–108 months), overall survival rate was 78.6%, disease-free survival was 66.7%, and eye salvage was achieved in 34 cases (80.9%). Local recurrence occurred in 7 cases (16.7%), regional nodal recurrence in 4 cases (9.5%), and distant metastasis in 3 cases (7.1%). Overall survival based on Kaplan–Meier survival analysis was improved in the multimodality therapy group when compared to surgery alone.

This study indicates the effectiveness of multimodal treatment in favorably affecting patients with meibomian gland carcinoma, especially advanced disease. With a 78.6% overall survival and greater than 80% eye salvage rate, our results confirm the increasing sentiment that systemic chemotherapy integration with surgery and radiotherapy can significantly affect disease control and organ preservation. They are in accord with earlier reports showing that neoadjuvant chemotherapy makes downstaging and the globe-preserving surgery more feasible in periocular sebaceous gland carcinoma Kaliki et al. 2016; Verma et al. 2021. Previous series comparing outcomes with surgery alone have published increased rates of recurrence and metastasis, especially in those with widespread or intraepithelial disease. Chao et al. noted that intraepithelial invasion of the conjunctiva was highly correlated with worse survival and higher recurrence, highlighting the inadequacy of local excision only Chao et al. 2001. [10] Likewise, Lam et al. reported elevated recurrence and death in a long-term Chinese cohort treated largely with surgery, again highlighting the requirement for multimodal treatment [14]. In our series, the rate of recurrence was lower (16.7%), consistent with current evidence that multimodality therapy obtains lasting control Vempuluru et al. 2025. The prognostic value of AJCC staging in sebaceous gland carcinoma has been established. Esmaeli et al. showed that higher T category is associated with nodal metastasis and poorer survival Esmaeli et al. 2012and AlHammad et al. [9, 12] reaffirmed that the 8th edition AJCC system offers better prognostic stratification than the 7th edition AlHammad et al. 2021. Our findings support this, as patients with T4 disease had significantly worse disease-free survival than those with T2 or T3 disease. This is in keeping with findings in squamous carcinoma of the eyelid, where improvement in the AJCC 8th edition was likewise confirmed to provide effective outcome prediction Xu et al. 2019 [15]. Our findings also correlate with recent literature on multimodality treatment in other ocular adnexal cancers. Juratli et al. described promising results with neoadjuvant intra-arterial chemotherapy for lacrimal gland carcinoma with long-term control of otherwise inoperable tumors [11]. Likewise, data from systemic oncology corroborate the notion of organ-sparing multimodality therapy, as exemplified by fertility-preservation regimens in cervical cancer after neoadjuvant chemotherapy Zusterzeel et al. 2020 [13]. These analogies lend further support to the position of chemotherapy not merely as a palliative treatment but also as a unifying ingredient in curative-intent regimens. Collectively, our results lend support to the use of multimodality treatment in advanced meibomian gland carcinoma, especially in those at high risk of recurrence or in whom radical surgery would at least adversely affect function and cosmesis. Although our results are promising, larger multicentric prospective studies are needed to further establish survival benefits and better define treatment algorithms.

Multimodal therapy using neoadjuvant chemotherapy, surgery, and judicious application of radiotherapy has a substantial benefit in the treatment of advanced meibomian gland carcinoma, with acceptable survival and eye salvage rates and decreased recurrence versus surgery alone. Consistent with new evidence, our study underscores the value of synergistic multimodal therapy in optimizing both oncologic control and functional results. Larger cohort prospective studies are needed to establish standardized treatment protocols and maximize patient outcomes.

1. Vempuluru VS, Luthra A, Reddy Palkonda VA, Kaliki S. Multimodal treatment with Neoadjuvant chemotherapy for eyelid and periocular sebaceous gland carcinoma: Long-term outcomes. Am J Ophthalmol Case Rep. 2025;38:102272. Published 2025 Feb 5. doi:10.1016/j.ajoc.2025.102272 2. Kaliki S, Ayyar A, Nair AG, Mishra DK, Reddy VA, Naik MN. Neoadjuvant Systemic Chemotherapy in the Management of Extensive Eyelid Sebaceous Gland Carcinoma: A study of 10 Cases. Ophthalmic Plast Reconstr Surg. 2016;32(1):35-39. doi:10.1097/IOP.0000000000000398 3. Verma S, Kumar N, Meel R, et al. Neoadjuvant Systemic Chemotherapy in Sebaceous Gland Carcinoma of the Eyelid: A Retrospective Study. Ocul Oncol Pathol. 2021;7(4):251-256. doi:10.1159/000515857 4. Sen S, Bhardwaj M, Jayaraj P, et al. Eyelid sebaceous gland carcinoma, validation of AJCC 8th edition T staging- a retrospective study from North India. Acta Ophthalmol. 2023;101(1):49-56. doi:10.1111/aos.15204 5. Murthy R, Honavar SG, Burman S, Vemuganti GK, Naik MN, Reddy VA. Neoadjuvant chemotherapy in the management of sebaceous gland carcinoma of the eyelid with regional lymph node metastasis. Ophthalmic Plast Reconstr Surg. 2005;21(4):307-309. doi:10.1097/01.iop.0000169426.57497.24 6. Sa HS, Rubin ML, Xu S, et al. Prognostic factors for local recurrence, metastasis and survival for sebaceous carcinoma of the eyelid: observations in 100 patients. Br J Ophthalmol. 2019;103(7):980-984. doi:10.1136/bjophthalmol-2018-312635 7. Manjandavida FP, Honavar SG, Murthy R, et al. Does Multimodal Treatment Improve Eye and Life Salvage in Adenoid Cystic Carcinoma of the Lacrimal Gland?. Ophthalmic Plast Reconstr Surg. 2022;38(4):348-354. doi:10.1097/IOP.0000000000002108 8. Kumar N, Meel R, Bakhshi S, et al. Neoadjuvant Chemotherapy in Non-Metastatic Eyelid Sebaceous Gland Carcinoma: A Report in 10 Cases. Ocul Oncol Pathol. 2024;10(3):123-130. doi:10.1159/000538295 9. Esmaeli B, Nasser QJ, Cruz H, Fellman M, Warneke CL, Ivan D. American Joint Committee on Cancer T category for eyelid sebaceous carcinoma correlates with nodal metastasis and survival. Ophthalmology. 2012;119(5):1078-1082. doi:10.1016/j.ophtha.2011.11.006 10. Chao AN, Shields CL, Krema H, Shields JA. Outcome of patients with periocular sebaceous gland carcinoma with and without conjunctival intraepithelial invasion. Ophthalmology. 2001;108(10):1877-1883. doi:10.1016/s0161-6420(01)00719-9 11. Juratli L, Kim J, Juntipwong S, et al. Long-Term Outcomes of Neoadjuvant Intraarterial Chemotherapy for Locally Invasive Lacrimal Gland Carcinoma ex Pleomorphic Adenoma. Ophthalmic Plast Reconstr Surg. 2025;41(4):432-438. doi:10.1097/IOP.0000000000002881 12. AlHammad F, Edward DP, Alkatan HM, et al. Eyelid sebaceous gland carcinoma: An assessment of the T classification of the American Joint Committee of Cancer TNM staging system 8th versus 7th edition. Eur J Ophthalmol. 2021;31(4):2055-2063. doi:10.1177/1120672120936488 13. Zusterzeel PLM, Aarts JWM, Pol FJM, Ottevanger PB, van Ham MAPC. Neoadjuvant Chemotherapy Followed by Vaginal Radical Trachelectomy as Fertility-Preserving Treatment for Patients with FIGO 2018 Stage 1B2 Cervical Cancer. Oncologist. 2020;25(7):e1051-e1059. doi:10.1634/theoncologist.2020-0063 14. Lam SC, Li EYM, Yuen HKL. 14-year case series of eyelid sebaceous gland carcinoma in Chinese patients and review of management. Br J Ophthalmol. 2018;102(12):1723-1727. doi:10.1136/bjophthalmol-2017-311533 15. Xu S, Sagiv O, Rubin ML, et al. Validation Study of the AJCC Cancer Staging Manual, Eighth Edition, Staging System for Eyelid and Periocular Squamous Cell Carcinoma. JAMA Ophthalmol. 2019;137(5):