Prognostication in eye cancer: the latest tumor, node, metastasis classification and beyond

Abstract

The tumour, node, metastasis (TNM) classification is a universal cancer staging system, which has been used for five decades. The current seventh edition became effective in 2010 and covers six ophthalmic sites: eyelids, conjunctiva, uvea, retina, orbit, and lacrimal gland; and five cancer types: carcinoma, sarcoma, melanoma, retinoblastoma, and lymphoma. The TNM categories are based on the anatomic extent of the primary tumour (T), regional lymph node metastases (N), and systemic metastases (M). The T categories of ophthalmic cancers are based on the size of the primary tumour and any invasion of periocular structures. The anatomic category is used to determine the TNM stage that correlates with survival. Such staging is currently implemented only for carcinoma of the eyelid and melanoma of the uvea. The classification of ciliary body and choroidal melanoma is the only one based on clinical evidence so far: a database of 7369 patients analysed by the European Ophthalmic Oncology Group. It spans a prognosis from 96% 5-year survival for stage I to 97% 5-year mortality for stage IV. The most accurate criterion for prognostication in uveal melanoma is, however, analysis of chromosomal alterations and gene expression. When such data are available, the TNM stage may be used for further stratification. Prognosis in retinoblastoma is frequently assigned by using an international classification, which predicts conservation of the eye and vision, and an international staging separate from the TNM system, which predicts survival. The TNM cancer staging manual is a useful tool for all ophthalmologists managing eye cancer. Keywords: conjunctival malignancies; eyelid malignancies; orbital malignances; retinoblastoma; uveal melanomaThe tumour, node, metastasis (TNM) classification is a cancer staging system, which has been in worldwide use across all medical specialties for five decades. 1 It emerged in 1968 when the International Union Against Cancer published the first edition of its classification based on the anatomic extent of the tumour after testing a set of draft classifications for 23 cancer sites. None of these sites related to the eye.Indeed, eye cancer is a latecomer in the TNM classification, appearing for the first time in the fourth and fifth editions. 2 The first ophthalmic section covered six sites and five cancer types-carcinoma and melanoma of the eyelid and conjunctiva, melanoma of the uvea, retinoblastoma, sarcoma of the orbit, and carcinoma of the lacrimal gland-but these classifications were untested and were rarely used outside cancer registries.The ophthalmic section was revised for the sixth edition of TNM in 2002. 3 This edition was based on the published literature, but the classifications were not tested against clinical data. The revision received publicity 4 but did not make a breakthrough. Meanwhile, data were collected of other cancers to improve staging. For the updated TNM classification of cutaneous melanoma, data from over 20 000

Conjunctival melanoma: survival analysis in twenty-two Mexican patients

“…Ophthalmic radiation may be used as a curative therapy, as adjuvant treatment following surgical excision, or as palliative therapy for advanced cases of eyelid and conjunctival tumors (18) . Some reports have mentioned that radiation therapy has not proved useful and generally results in the loss of the eye as a complication (17)(18)(19) . However, in our experience and in the experience of others (18)(19)(20) , the use of adjuvant therapy is being increased due the greater prevalence of limited (organ preservative) resections, with little, but useful, increase in survival and local control.…”

“…A recent review set a survival rate at 5 and 10 years of ~85% and 70%, respectively (17) . Overall mortality reported in different studies is ~25% (10) .…”

Expression of Angiogenic Factors in Invasive Retinoblastoma Tumors Is Associated With Increase in Tumor Cells Expressing Stem Cell Marker Sox2

“…Local spread of tumor cells into the neighboring tissues occurs through the invasion of the choroid or postlaminar invasion of the optic nerve. 36 Although relatively rare, retinoblastoma also metastasizes to distant sites via the lymphatic system, and several clinical factors have been identified that predict the likelihood of retinoblastoma recurrence and metastasis. For example, secondary neovascular glaucoma is highly predictive of optic nerve invasion.…”

The Significance of the Lymphocytes Infiltration and Endothelialdependent Angiogenesis in Choroidal Melanomas

“…Posterior uveal melanoma, together with metastatic carcinoma, is the most common primary intraocular malignant tumor in adults [1]. Standardized incidence rates of uveal melanoma in Europe (from 1983 to 1994) increased from south to north, from minimum of <2 per million in registries of Spain and southern Italy, up to >8 per million in Norway and Denmark [2].…”

“…Iris melanomas have the best and ciliary body melanomas have the worst prognosis. Tumor size and optic nerve infiltration are the best parameters used to predict the survival and metastatic potential of the tumor [1,3,8,10]. Histopathologically choroidal melanoma has a spectrum of cell types, ranging from thin and plump spindle cells to epithelioid cells (spindle-cell, mixedcell, and epithelioid-cell types) [5].…”