Response assessment of bone metastatic disease: seeing the forest for the trees RECIST, PERCIST, iRECIST, and PCWG-2

Tumor response is often used as a surrogate marker for survival practically in all clinical trials. Therefore, robust and valid response criteria during the course of trials are fundamental for the assessment of response to therapy. This aspect, however, becomes particularly challenging when it comes to bone metastases. In the era of targeted therapies and immune-checkpoint inhibitors (ICI), response assessment by morphologic-based criteria cannot detect the real tumor response and, consequently, fail to demonstrate the actual clinical benefit. This review will focus on some of the most common morphologic and metabolic response criteria and their application for bone lesions, highlighting relative strengths and weaknesses as well as potential future methods in the era of target therapies and immunotherapy with ICI.