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.

Figure 1

Examples of TNM classification and staging of eye cancer with treatment and outcome. (a) Circumlimbal conjunctival intraepithelial neoplasm in an 84-year-old woman: Tis, topical fluorouracil, no recurrence at 8 years. (b) Perilimbal conjunctival squamous cell carcinoma 4.5 mm in diameter in a 75-year-old man: pT2N0M0, surgical excision, adjuvant topical fluorouracil, and no recurrence at 3 years. (c) Perifoveal choroidal melanoma 3.3 mm in thickness and 9.1 mm in largest diameter in a 50-year-old woman: T1aN0M0, ruthenium brachytherapy, and no recurrence at 7 years. (d) Choroidal and ciliary body melanoma 5.9 mm in thickness and 14.9 mm in diameter by histopathology with a 4-mm extraocular extension (inset) in a 54-year-old man: pT2dN0M0, stage IIIA, spindle cell type, enucleated recently, and postoperative adjuvant external beam radiotherapy. (e) Multiple hepatic metastases (arrowheads) from choroidal melanoma confirmed by needle biopsy in a 47-year-old woman, largest diameter of largest metastasis 16 mm: M1a and HUCH Working Formulation stage IVa, systemic chemotherapy, and survival 19 months. (f) Limbal conjunctival melanoma, 1.5 mm thick, in a 46-year-old man: pT1bN0M0, excision with adjuvant topical mitomysin, sentinel node biopsy not indicated, and no recurrence in 2 years. (g) Multifocal palpebral conjunctival melanoma, largest focus 3.5 mm thick, in a 60-year-old man: pT2cN0M0, resection, amniotic membrane reconstruction, sentinel node biopsy and adjuvant topical mitomycin, nodes negative, and no recurrence in 4 years. (h) Left eye of a 10-month-old girl with trilateral retinoblastoma, thickness 7.2 mm and largest diameter 16.5 mm, and no seeding: this eye T1bN0M0, group B in International Classification, managed with systemic chemotherapy and transpupillary thermotherapy, and no recurrence at 5 years.

Figure 2

(a) Size boundaries of T categories defined empirically by dividing data of 7369 patients with a chroidal and ciliary body melanoma of known largest tumour basal diameter and thickness into blocks representing 3 × 3 mm fractions and then combining blocks with similar survival. Numbers within blocks are T categories. (b) Kaplan–Meier survival curves displaying melanoma-related mortality for 5403 patients with known tumour size, ciliary body, and extraocular extension (stage I–IIIC), and for 224 patients with newly detected metastatic uveal melanoma (stage IV).