Quality of Life as a Mediator between Cancer Stage and Long-Term Mortality in Nasopharyngeal Cancer Patients Treated with Intensity-Modulated Radiotherapy

SIMPLE SUMMARY: Even after the implementation of intensity-modulated radiotherapy (IMRT), nasopharyngeal cancer (NPC) survivors may continue to exhibit several physical symptoms that negatively affect long-term quality of life (QoL). An NPC patient cohort study (n = 682) was conducted to examine the potential mediating effect of QoL (evaluated at multiple treatment-related time points) on the cancer stage–mortality association. Patients with advanced NPC exhibited low global health QoL and high QoL-HN35 symptom pre-IMRT, 3 months post-IMRT, and 2 years post-IMRT. Global health QoL and QoL-HN35 symptom scores 2 years after IMRT explained 49.4% and 39.4% of the excessive effect of advanced NPC on mortality risk. Our findings indicate that global health QoL and QoL-HN35 symptom 2 years after IMRT are key mediators of the relationship between advanced NPC and high mortality. These findings emphasize the significance of QoL-HN35 symptom and global health QoL-associated medical support and care for patients with NPC who received IMRT. ABSTRACT: Background: Quality of life (QoL) attained before, during, or after treatments is recognized as a vital factor associated with therapeutic benefits in cancer patients. This nasopharyngeal cancer (NPC) patient longitudinal study assessed the relationship among QoL, cancer stage, and long-term mortality in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT). Patients and Methods: The European Organization for Research and Treatment of Cancer (EORTC) core QoL questionnaire (QLQ-C30) and the head and neck cancer-specific QoL questionnaire module (QLQ-HN35) were employed to evaluate four-dimensional QoL outcomes at five time points: pre- (n = 682), during (around 40 Gy) (n = 675), 3 months (n = 640), 1 year (n = 578) and 2 years post-IMRT (n = 505), respectively, for 682 newly diagnosed NPC patients treated between 2003 and 2017 at a single institute. The median followed-up time was 7.5 years, ranging from 0.3 to 16.1 years. Generalized estimating equations, multivariable proportional hazards models, and Baron and Kenny’s method were used to assess the investigated effects. Results: Advanced AJCC stage (III–IV) patients revealed a 2.26-fold (95% CI—1.56 to 3.27) higher covariate-adjusted mortality risk than early-stage (I–II) patients. Compared with during IMRT, advanced-stage patients had a significantly low global health QoL and a significantly high QoL-HN35 symptom by a large magnitude at pre-, 3 months, and 2 years post-IMRT. QoL scales at pre-IMRT, 1 year, and 2 years post-IMRT were significantly associated with mortality. The effect changes of mortality risk explained by global health QoL, QoL-C30, and QoL-HN35 symptom were 5.8–9.8% at pre-IMRT but at 2 years post-IMRT were 39.4–49.4% by global health QoL and QoL-HN35 symptoms. Conclusions: We concluded advanced cancer stage correlates with a long-term high mortality in NPC patients treated with IMRT and the association is partially intermediated by QoL at pre-IMRT and 2 years post-IMRT. Therefore, QoL-HN35 symptom and global health QoL-dependent medical support and care should be focused and tailored at 2 years post-IMRT.