Reply to the Letter to the Editor: “Usefulness of texture features of apparent diffusion coefficient maps in predicting chemoradiotherapy response in muscle-invasive bladder cancer”

by Soichiro Yoshida, Koichiro Kimura, Yasuhisa Fujii (s-yoshida.uro@tmd.ac.jp, kmrdrnm@gmail.com, y-fujii.uro@tmd.ac.jp)

Usefulness of texture features of apparent diffusion coefficient maps in predicting chemoradiotherapy response in muscle-invasive bladder cancer

Dear Editor-in-Chief,

We thank Dr. Hatakenaka for his comments on our article [1], who has raised important points regarding the mechanism underlying the association between chemoradiotherapy (CRT) sensitivity and apparent diffusion coefficient (ADC) values. Generally, ADC value and histological grade are negatively correlated, and cancers with low ADC values are known to be high-grade [2, 3]. However, cancers with lower ADC values are reportedly more sensitive to CRT, as demonstrated in our previous report on bladder cancer [4, 5]. Although the mechanism is unclear, this finding is highly important from a clinical perspective because it provides an opportunity to identify bladder cancers for which CRT may improve functional and oncologic prognoses.

Dr. Hatakenaka proposed that the mechanism for this seemingly paradoxical finding is a bystander effect, wherein signals released by CRT in tumors with high cell density and low ADC values exert a therapeutic effect on the neighboring cells [6, 7]. We believe that the mechanism may be that ADC value and CRT sensitivity are each associated with tumor proliferation. While bladder cancers with high Ki-67 labeling index (LI), which are used as a marker of cell proliferation, have poor prognoses after radical cystectomy, we confirmed that high Ki-67 LI predicts favorable CRT response and survival in muscle-invasive bladder cancer patients treated with CRT-based bladder-sparing protocols [8]. Other studies have also identified a relationship between high Ki-67 LI and favorable CRT responses in squamous cell carcinoma of the head and neck and of the cervix [9, 10]. Tumor ADC values are negatively correlated with Ki-67 LI, indicating that tumors with lower ADC values have higher cell proliferative potential [2-4]. Thus, bladder cancers with lower ADC values are more likely to respond to CRT. Further studies are needed to clarify the relationship between the ADC value and the bystander effect on CRT sensitivity.