Proton beam radiotherapy for esophageal cancer: challenges and opportunities in the modern era

As the NRG GI006 and PROTECT trials seek to confirm results of the first randomized trial supporting the utility of proton beam therapy for esophageal cancer, several outstanding questions are discussed in this review. First, the applicability/extrapolation of the existing randomized trial is mentioned. This includes a potentially larger benefit of PBT at non-high-volume centers with less surgical expertise, along with the emerging use of active scanning PBT approaches that could further improve toxicity profiles. Patient selection for PBT is then discussed, including differential utility for patients based on the degree of baseline comorbidities, the extent/location of disease, and the surgical case volume at the treating institution. PBT in the setting of emerging techniques, such as minimally invasive esophagectomy, is also mentioned. Next, costs of PBT and insurance coverage hurdles are described, especially regarding pre-specified agreements between providers/institutions and payors, the need for cost-effectiveness analyses for PBT in this population, and effects of the new radiation oncology alternative payment model. Finally, immunotherapy has now become a standard option for esophageal cancer (resected or unresected/recurrent/metastatic cases). Therefore, in the context of immunotherapy for these patients, revisiting the role of radiation dose-escalation and elective nodal irradiation may be required.