Clinical Stage of Retinoblastoma Based on Presenting Signs of 4578 Patients from 121 Countries

Abstract

Purpose: To investigate the associations between presenting signs and clinical stage of retinoblastoma at diagnosis in a global sample of patients with retinoblastoma.

Design: Cross-sectional analysis.

Participants: Treatment-naïve children who were diagnosed with retinoblastoma at 1 of 259 retinoblastoma referral centers across 121 countries during 2017 and 2019.

Methods: Presenting characteristics of patients who were diagnosed with retinoblastoma incidentally in 2017 and 2019 from 2 cross-sectional studies were analyzed. We examined the associations between presenting clinical sign (leukocoria, strabismus, orbital mass, orbital cellulitis, red eye, iris color change, and hyphema) and presenting stage of retinoblastoma.

Main outcome measures: Main outcome measures included frequency of clinical and pathologic stage per the American Joint Committee on Cancer Staging Manual, Eighth Edition; extraocular stage per the International Retinoblastoma Staging System (IRSS); and intraocular classification at presentation.

Results: A total of 4578 patients with retinoblastoma were included, 54.4% of whom were male, with a median age at presentation of 23.1 months. Patients with orbital mass and orbital cellulitis presented at later stages compared with those with leukocoria and strabismus. All signs, except for orbital mass, were seen more commonly in patients with curable disease (IRSS stages 0, I, and II): strabismus, 94.8%; leukocoria, 90.1%; iris changes, 89.7%; hyphema, 84.2%; red eye, 82.1%; orbital cellulitis, 66.7%; and orbital mass, 33.7%. Leukocoria was the most common presenting sign regardless of national income level, and the second most common sign was strabismus in high-income countries and orbital mass in low-income countries.

Conclusions: Any child with unexplained orbital cellulitis, persistent red eye, unexplained hyphema, orbital mass, or other changes in the iris or anterior chamber of the eye should undergo a dilated fundus examination to rule out retinoblastoma. Some patients with these signs can present with early stage and curable disease.

Financial disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Keywords: Cancer; Cancer staging; Retinoblastoma; TNM classification.