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 (HRF). Multicentric international collaborative retrospective case series. One thousand three hundred and sixty-two patients with retinoblastoma from 16 centers and 11 countries. Primary enucleation; adjuvant therapy in patients with HRF. High-risk retinoblastoma defined as one 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)] vs. Children's Oncology Group (COG) classification schemes, the positive predictive value (PPV) of Group D eyes for HRF was 42.0% vs. 35.1% vs. 43.2% respectively and those for group E eyes were 58.5% vs. 59.0% vs. 59.5% respectively. Comparing Group D vs. Group E eyes, there was higher mean number of HRF (SD, 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%. Agreement between ICRB Philadelphia vs ICRB LA, ICRB LA vs COG and ICRB Philadelphia vs 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. All intraocular retinoblastoma classification schemes predict HRF and MFS equally. Group E includes a wide spectrum equivalent to 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.
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