Conjunctival Squamous Cell Carcinoma Outcomes Predicted by Orbital Exenteration, Nodal Metastases

Close up of the conjunctival squamous cell carcinoma.
The study also linked a history of organ transplantation and orbital exenteration.

Orbital exenteration and nodal metastasis are both associated with death due to disease, while a history of organ transplantation predicts orbital exenteration, according to research results published in Ophthalmic Plastic and Reconstructive Surgery. 

Many previous reports on ocular surface squamous neoplasia or conjunctival squamous cell carcinoma focus on local treatments for bulbar conjunctival disease; orbital invasion risks, orbital exenteration rates, and local recurrence risks have not been extensively reported on within the academic literature. 

Researchers conducted a retrospective study to evaluate the prognostic factors for orbital exenteration, local recurrence, nodal metastasis, and death in patients with conjunctival squamous cell carcinoma. Additionally, researchers sought to validate the prognostic value of the American Joint Committee on Cancer (AJCC) Eighth Edition TNM criteria for conjunctival SCC.

Clinical records from all consecutive patients treated between May 1999 and August 2018 for conjunctival squamous cell carcinoma were reviewed; sociodemographic data and clinical information like tumor location, clinical tumor size, eyelid, orbit, and structural involvement, presence and location of lymph node, and distant metastasis were collected. Data were also collected on treatments and outcomes of interest. Descriptive statistics were used to summarize these characteristics.

A total of 44 patients were included in the study (24 men; 84% White; median age, 64 years). Thirty-four patients (77%) presented with a primary lesion, while 10 presented with a recurrent lesion. Twenty-seven patients had left eye conjunctival squamous cell carcinoma, 24 patients had invasive conjunctival squamous cell carcinoma, and 20 presented with in situ disease. Median tumor thickness was 2 mm, and largest median tumor diameter was 14 mm. 

At presentation, 8, 9, and 7 patients had T2, T3, and T4 tumors, respectively; 18 had tumors that exclusively involved the bulbar conjunctiva. Thirty patients had excision, either with or without neoadjuvant or adjuvant therapy, 4 underwent chemotherapy alone, and 10 underwent orbital exenteration. 

One patient had nodal metastasis at presentation, while 3 additional developed nodal metastases during follow-up. Median time-to-nodal metastasis was 36.5 months. 

Two patients died due to disease by the conclusion of follow-up. 

No significant association was found between T category and noncutaneous malignancy history, history of organ transplant, or side of tumor. As T category increased, though, the proportion of patients who underwent orbital exenteration increased. Orbital exenteration was also significantly associated with organ transplant history. No association was seen between invasive squamous cell carcinoma and side of tumor. 

A statistically significant association between local-recurrence-free survival and a history of organ transplant was seen (hazard ratio [HR], 5.98; 95% CI, 1.12-32.02). However, local-recurrence-free survival was not associated significantly with a history of noncutaneous malignancy, T category at presentation, exclusive nonbulbar tumor location, nonbulbar tumor component, or tumor size. 

Only 3 patients had nodal metastasis during follow-up, making survival analysis not feasible. However, researchers studied the association between patient characteristics and nodal metastasis by the end of follow-up, where no statistically significant associations were seen between any characteristics and nodal metastases. 

Significant associations between orbital exenteration, N category at the end of follow-up, and death of disease occurrence were noted, although the results should be interpreted cautiously since only 2 patients died of disease. 

Researchers identified a statistically significant association between overall surgical and exclusive nonbulbar location of tumor.

Study limitations include those inherent to retrospective research, the small number of patients, and the disproportionate number of patients with locally advanced conjunctival squamous cell carcinoma with orbital and adnexal invasion. 

“We did not establish a significant correlation between T category at presentation, tumor size, or tumor location and risk of local recurrence,” the researchers explain. “In future modifications of the AJCC staging system, investigators should consider categorizing the T3 tumors differently and at least distinguishing minimal corneal involvement from involvement of the palpebral and tarsal conjunctiva and caruncle.” 


El-Hadad C, Rubin ML, Nagarajan P, et al. Prognostic factors for orbital exenteration, local recurrence, metastasis, and death from disease in conjunctival squamous cell carcinoma. Ophthalmic Plast Reconstr Surg. 2021;37(3):262-268. doi:10.1097/IOP.0000000000001798