Does Pre-Enucleation Chemotherapy Lead to Increased Risk of Metastasis in Advanced Retinoblastoma?

Abstract

TO THE EDITOR: We read the article by Zhao et al with interest. The authors have addressed an important question in an era where chemotherapy has become the mainstay of treatment in advanced retinoblastoma. The ocular salvage rates by chemotherapy in advanced retinoblastoma, International Intraocular Retinoblastoma Classification group D and E eyes, range between 37% and 47%. The concern about masking of high-risk histopathologic factors is apt especially with the advent of super-selective chemotherapy in retinoblastoma. We understand the limitations posed by a retrospective study. However, we would like to bring to the fore a few issues of concern. First is the lack of a protocol-based treatment in the series presented. The authors have acknowledged that the “pre-enucleation chemotherapy regimen was given at doses lower than therapeutic doses previously published.” The postenucleation treatment regimen in several patients was not based on pTNM risk and therefore inadequate adjuvant therapy was administered. We believe that this deficit in treatment may have affected disease-specific survival as an outcome in this study. Second, we beg to differ with the authors in their comment that primary enucleation would have prevented the spread of retinoblastoma in the four patients who developed metastasis. We suspect that extraocular disease may have been present in these patients at presentation. Despite the authors’ claim that extraocular retinoblastoma was excluded by imaging studies, the possibility of microscopic invasion remains. Even if primary enucleation had been done, the histopathologic risk stage would have remained at pT4b, necessitating aggressive adjuvant therapy. It might be agreed though, that had the patients undergone primary enucleation, time would have been gained in identifying the high risk factors earlier. Third, the shorter follow-up seen in the pre-enucleation chemotherapy group is implied by the authors to result from a lower risk perception leading to decreased surveillance. We feel however, that other unknown factors may have been responsible for the shorter follow-up in this group. The rationale behind chemoreduction is to downstage the tumor. Despite the deaths described in the article in the pre-enucleation chemotherapy group, a large majority (93%) of children did not develop metastasis. Of the four children who went on to die of metastasis, downstaging was noted only in one child while the rest showed a high pTNM stage after enucleation.