Proton Beam Therapy in Cancer Treatment: Evaluation of Its Safety, Efficacy, Effectiveness, and Cost-Effectiveness vs Photon-Based Radiotherapy

OBJECTIVES: To evaluate the safety, clinical efficacy/effectiveness and cost-effectiveness of proton beam therapy (PT) compared to photon-based radiotherapy (RTx) in cancer treatment.

METHODS: We performed a systematic review of original studies. We followed the methodological standards of the Cochrane Collaboration, PRISMA and GRADE. Eligibility criteria were defined based on the PICO framework. Of note, we included randomized controlled trials (RCTs) and non-randomized comparative studies and excluded indications already approved for PT in Spain.

RESULTS: Safety and efficacy/effectiveness: 77 studies were included for analysis encompassing 16 cancer types; 1 in children (oral and pharyngeal cavity) and 15 in adults (oral and pharyngeal cavity; nasal cavity and paranasal sinuses; gliomas, glioblastomas and gliosarcomas; medulloblastoma; acoustic neuroma or vestibular Schwanoma; leptomeningeal metastasis; lung; esophageal; pancreatic; hepatocarcinoma; anal; prostate; testicular; breast; uterine).

Cost-effectiveness: 16 studies in 7 cancer types in adults were included for analysis (oral and pharyngeal cavity; nasal cavity and paranasal sinuses; lung; pancreatic; hepatocarcinoma; prostate; breast).

The ideal scenario where we could affirm with low or higher level of certainty that PT does not diminish efficacy/effectiveness while it maintains or diminishes acute or chronic severe adverse events did not occur in any of the studied indications. In 6 indications, however, there was evidence of enough certainty to suggest that PT might be equivalent of better than RTx. The results for cost-effectiveness varied according to cancer type and often depended on key characteristics of the patients.

CONCLUSIONS: The certainty of the evidence was in general very low, but there were some cancers where treatment with PT might be equivalent or better than that with RTx. A formal strategy oriented to selecting patients susceptible to benefit from PT, and the establishment of a registry to monitor the results of treatment with PT is desirable. Several ongoing RCTs and comparative observational studies were identified.