In recent years, targeted therapy has had an emerging role in the treatment of refractory tumors, such as advanced melanoma.60 For patients with metastatic or locally advanced BCC or SCC, targeted therapy against the Hedgehog pathway or epidermal growth factor receptor has been shown to be fairly efficacious in preventing disease progression.30,61 In a series of current studies, an overexpression of HER2 is observed in SC,23,62 thus suggesting the possibility of targeted therapy with monoclonal antibodies trastuzumab and cetuximab.61 Confirmation of frequent PI3K signaling pathway activation provides a strong rationale for the application of mammalian target of rapamycin inhibitors in targeted therapy of ocular SC.25
The management of metastasis
Up to 25% of SCs metastasize.17 For lymph node and distant metastases, combination treatments, including lymph node and neck dissection, radiation therapy, and systemic chemotherapy, should be considered.61,63,64
Two case reports on the management of recurrent, locally advanced, or metastatic SC of the eyelids showed neoadjuvant cisplatin and fluorouracil for 1 cycle in 1 case report and carboplatin and 5-fluorouracil for 3 cycles in the other with favorable responses and stable residual disease.63Neoadjuvant chemotherapy may enable local resection of advanced tumors, thus avoiding disfiguring procedures, such as exenteration.64,65
Orbital exenteration refers to a surgical procedure involving removal of the eyeball and intraorbital contents. This morbific surgery is usually reserved for SC that involves most of the conjunctiva and has invaded the orbit or for potentially life-threatening SC.66–68 Gerring et al67 demonstrated that orbital exenteration offered a 2-year mean disease-free survival of 39.2% among advanced SC cases.
In the past, ocular SC has led to cancer-specific mortality in ~18%–30% of patients.17,69 Fortunately, more attention has been paid to this tumor, and the mortality has decreased to 3%–7.3% due to comprehensive therapy.6,10,12,50
The indicators for prognosis have been disputed. On the basis of a retrospective study, the T category was significantly associated with lymph node metastasis and disease-specific survival, especially among patients with a T category of T3a or worse.27 Orbital involvement was once considered to be associated with worsened prognosis, while it has been challenged in a contemporary retrospective review of 1,394 cases of SC.1 Other histological markers of poor prognosis in previous reports include pagetoid spread, multicentric origin, tumor size >10 mm, tumor growth pattern,16 and invasion of vascular, lymphatic, and perineural structures. In addition, other poor prognostic indicators consist of delayed diagnosis (>6 months), involvement of both eyelids,27 and the presence of metastatic disease at the time of diagnosis.4 However, Takahashi et al16 found that the interval between the appearance of symptoms and referral to medical center did not significantly affect local recurrence or metastasis. Different patient characteristics may provide a possible explanation.
Compared to traditional isolated risk factors, the development of a new model for individualized prediction of tumor-related survival may pave the way for prognostic stratification.
Ocular SC is an uncommon, but aggressive malignancy with great potential to spread to regional lymph nodes and beyond. As its clinical presentation is nonspecific, definite diagnosis of this tumor relies on histopathologic confirmation, which can be challenging. Special efforts should be made to unveil the mechanism of ocular SC in order to provide evidence for targeted therapy. The existing literature related to the treatment of ocular SC primarily consists of small- to medium-sized case series and isolated case reports, impeding the possibility to reach a clinical consensus. As a result, surgical excision with a tumor-free margin continues to be the best choice for ocular SC that is discovered early. Adjuvant treatment options, including radiation therapy, cryotherapy, and topical therapy are adapted based on the extent of the tumor. Larger studies with longer follow-up periods are essential for clarifying the long-term effects of different treatment modalities. For the management of late-stage cases, multicenter clinical trials may be an appropriate solution to accrue adequate patient numbers. Patients with ocular SC require long-term follow-up with careful clinical examination for at least 5 years after radical antitumor therapy, regardless of tumor stage or anatomic location.
This work was supported by the Scientific Research Program of National Health and Family Planning Commission of China (201402014), the Science and Technology Commission of Shanghai (17DZ2260100) and the National Natural Science Foundation of China (Grant No 81500757).
RBJ and XQF are senior authors on this paper. YFX prepared the first draft of the manuscript; FL contributed to the design and writing of the manuscript. RBJ and XQF critically reviewed and revised the manuscript. All authors read and approved the final manuscript. All authors contributed toward data acquisition and analysis, drafting and critically revising the paper and agree to be accountable for all aspects of the work.
The authors report no conflicts of interest in this work.
Yangfan Xu,1,2,* Fang Li,1,2,* Renbing Jia,1,2 Xianqun Fan1,2
1Department of Ophthalmology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, People’s Republic of China
*These authors contributed equally to this work
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Source: OncoTargets and Therapy.
Originally published June 27, 2018.