Anxiety and depression mediate the association between chemotherapy-induced peripheral neuropathy and fatigue: Results from the population-based PROFILES registry

Objective
Chemotherapy‐induced sensory peripheral neuropathy (CIPN) is common among colorectal cancer (CRC) survivors. The aim of this study was to examine whether CIPN is associated with both psychological distress (ie, anxiety and depression) and fatigue and whether the relationship between CIPN and fatigue can (partly) be explained by psychological distress.

Methods
All CRC survivors diagnosed between 2000 and 2009 as registered by the population‐based Netherlands Cancer Registry (Eindhoven region) were eligible for participation. Chemotherapy‐treated survivors completed questions on CIPN (EORTC QLQ‐CIPN20), psychological distress (HADS), and fatigue (FAS) on average 5.6 years after diagnosis. Simple and multiple mediation analyses were performed to examine anxiety and depression as possible mediators in the association between CIPN and fatigue.

Results
Survivors with high (ie, upper 30% of scores) CIPN (n = 172) reported more anxiety and depressive symptoms and more fatigue compared with those with low CIPN (n = 299). Furthermore, among survivors with high CIPN, those who were anxious, depressed, or both reported more fatigue compared with those without psychological distress. These differences were clinically relevant. Finally, mediation analyses showed that while CIPN was directly associated with fatigue, the relationship between CIPN and fatigue was also significantly mediated by both anxiety and depression.

Conclusions
CRC survivors with high CIPN report more fatigue, especially those who are also anxious and/or depressed. More research is needed on the direction of the relationship between CIPN, psychological distress, and fatigue. For now, the treatment of fatigue should also focus on addressing psychological distress, as treating fatigue alone might not be sufficient.