High-Risk Retinoblastoma Based on International Classification Systems

Abstract

Purpose

To determine the predictive value of International Intraocular Retinoblastoma Classification schemes and the American Joint Committee on Cancer (AJCC) classification for histopathological high-risk features (HRFs).

Design

Multicentric international collaborative retrospective case series.

Subjects

One thousand three hundred and sixty-two patients with retinoblastoma from 16 centers and 11 countries.

Intervention

Primary enucleation; adjuvant therapy in patients with HRF.

Main Outcome Measures

High-risk retinoblastoma defined as 1 or more HRF (anterior segment involvement, massive choroidal invasion, minor choroidal infiltration with prelaminar optic nerve invasion, retrolaminar or resected optic nerve cut end involvement, scleral or microscopic extrascleral infiltration); metastasis-free survival (MFS).

Results

Of the 1362 patients, 751 (55.1%) had HRF. According to the International Classification of Retinoblastoma (ICRB) (Philadelphia vs. Los Angeles [LA]) versus Children’s Oncology Group (COG) classification schemes, the positive predictive value (PPV) of group D eyes for HRF was 42.0% versus 35.1% versus 43.2%, respectively, and that for group E eyes was 58.5% versus 59.0% versus 59.5%, respectively. Comparing group D versus group E eyes, there was higher mean number of HRF (standard deviation, range) among group E eyes using the ICRB Philadelphia (0.7 [0.9, 0.0–6.0] vs. 1.3 [1.7, 0.0–9.0], P < 0.001), ICRB LA (0.6 [0.8, 0.0–6.0] vs. 1.3 [1.7, 0.0–9.0], P < 0.001) and COG (0.8 [1.2, 0.0–7.0] vs. 1.3 [1.6, 0.0–8.0], P < 0.001) classifications. The PPV for HRF was above 55% for AJCC clinical tumor (cT) group cT3a with increments through cT3e to 72.3%. An agreement between ICRB Philadelphia versus ICRB LA, ICRB LA versus COG, and ICRB Philadelphia versus COG was 0.9, 0.8, and 0.8, respectively (P < 0.001). Metastasis-free survival rates and overall survival rates were also comparable between all intraocular retinoblastoma classification schemes but better stratified within the AJCC scheme.

Conclusions

All intraocular retinoblastoma classification schemes predict HRF and MFS equally. Group E includes a wide spectrum equivalent to the AJCC group cT3. Uniform grouping with subcategorization of group E might improve risk stratification. We propose that everyone across the retinoblastoma world henceforth adopts the AJCC classification for all reporting and publishing.

Financial Disclosure(s)

The authors have no proprietary or commercial interest in any materials discussed in this article.