Defining High-risk Retinoblastoma

Abstract

High-risk histopathologic features of retinoblastoma are useful to assess the risk of systemic metastasis. In this era of globe salvage treatments for retinoblastoma, the definition of high-risk retinoblastoma is evolving.OBJECTIVE To evaluate variations in the definition of high-risk histopathologic features for metastasis of retinoblastoma in different ocular oncology practices around the world.DESIGN, SETTING, AND PARTICIPANTS An electronic web-based, nonvalidated 10-question survey was sent in December 2020 to 52 oncologists and pathologists treating retinoblastoma at referral retinoblastoma centers.INTERVENTION Anonymized survey about the definition of high-risk histopathologic features for metastasis of retinoblastoma. MAIN OUTCOMES AND MEASURESHigh-risk histopathologic features that determine further treatment with adjuvant systemic chemotherapy to prevent metastasis. RESULTS Among the 52 survey recipients, the results are based on the responses from 27 individuals (52%) from 24 different retinoblastoma practices across 16 countries in 6 continents. The following were considered to be high-risk features: postlaminar optic nerve infiltration ( 27[100%]), involvement of optic nerve transection (27 [100%]), extrascleral tissue infiltration (27 [100%]), massive (Ն3 mm) choroidal invasion (25 [93%]), microscopic scleral infiltration (23 [85%]), ciliary body infiltration (20 [74%]), trabecular meshwork invasion (18 [67%]), iris infiltration (17 [63%]), anterior chamber seeds (14 [52%]), laminar optic nerve infiltration (13 [48%]), combination of prelaminar and laminar optic nerve infiltration and minor choroidal invasion (11 [41%]), minor (<3 mm) choroidal invasion (5 [19%]), and prelaminar optic nerve infiltration (2 [7%]). The other histopathologic features considered high risk included Schlemm canal invasion (4 [15%]) and severe anaplasia (1 [4%]).Four respondents (15%) said that the presence of more than 1 high-risk feature, especially a combination of massive peripapillary choroidal invasion and postlaminar optic nerve infiltration, should be considered very high risk for metastasis. CONCLUSIONS AND RELEVANCEResponses to this nonvalidated survey conducted in 2020-2021 showed little uniformity in the definition of high-risk retinoblastoma. Postlaminar optic nerve infiltration, involvement of optic nerve transection, and extrascleral tumor extension were the only features uniformly considered as high risk for metastasis across all oncology practices. These findings suggest that the relevance about their value in the current scenario with advanced disease being treated conservatively needs further evaluation; there is also a need to arrive at consensus definitions and conduct prospective multicenter studies to understand their relevance.

Präoperativer Nachweis der lokalen Tumorausdehnung bei Patienten mit fortgeschrittenem Retinoblastom: prädiktiver Wert MR-tomografischer und klinischer Befunde

“…In the initial MRI assessment, it is particularly important to identify the high-risk factors (HRF) for metastasis and extraocular growth in order to provide adequate treatment 11 . There is a consensus that HRFs for metastatic disease include PLONI, extrascleral tumor manifestation, widespread choroidal infiltration, and tumor infiltration beyond the excision margin of an infiltrated optic nerve 3 . The increasing number of bulb-conserving therapeutic methods leads to a corresponding decrease in histopathological examinations, which means that the initial MRI examination becomes increasingly important 12 , 13 , 14 .…”

“…In Abhängigkeit von den erhobenen Parametern wird dann u. U. das operative Vorgehen angepasst, um eine Tumorinfiltration über den Absetzungsrand eines infiltrierten Sehnervs mit konsekutiver Prognoseverschlechterung zu vermeiden oder ggf. eine neoadjuvante Chemotherapie eingeleitet [3]. Die präoperative MRT-Untersuchung hat somit einen hohen Stellenwert bez.…”

“…Bei der initialen MRT-Beurteilung ist es insbesondere wichtig, die Hochrisikofaktoren (HRF) für eine Metastasierung und extraokuläres Wachstum zu erkennen, um eine adäquate Therapie einleiten zu können 11 . Es besteht Konsens, dass zu den HRF für eine metastasierende Erkrankung eine PLONI, eine extrasklerale Tumormanifestation, eine breitflächige Choroideainfiltration und eine Tumorinfiltration über den Absetzungsrand eines infiltrierten Sehnervs hinaus gehören 3 . Die steigende Anzahl der bulbuserhaltenden Therapiemethoden führt entsprechend zu einem Rückgang der histopathologischen Untersuchungen, sodass die initiale MRT-Untersuchung zunehmend wichtiger wird 12 , 13 , 14 .…”

Controversies in the Management of Choroidal Invasion in Retinoblastoma

“…Finally, another classification that is used is peripapillary massive choroidal invasion, which refers to massive choroidal invasion (as defined by IRSWG) that is near the optic nerve head. 9,10 Most data about the risk of extraocular relapse are from studies of patients with unilateral retinoblastoma who were treated with primary enucleation. With the growing use of IAC and intravitreous chemotherapy in cases of advanced retinoblastoma, fewer patients are primarily enucleated, and there is a need for information regarding the outcomes of patients who are secondarily enucleated after chemotherapy.…”

“…The criteria were not based in evidence but rather proposed to serve as the basis for studies that would validate the criteria. Finally, another classification that is used is peripapillary massive choroidal invasion, which refers to massive choroidal invasion (as defined by IRSWG) that is near the optic nerve head 9,10…”