Long-Term Consequences of Anticancer Therapy-Treatment Complexity and Quality of Life as Determinants of Affective Disorder Phenotypes in Adolescent Cancer Survivors.
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Introduction: Advances in pediatric oncology have transformed cancer into a condition with chronic and long-term developmental consequences. While survival rates have improved significantly, the literature on psychosocial outcomes remains fragmented and inconsistent, with a notable lack of person-centered analyses that account for the heterogeneity of adaptive trajectories. Current evidence fails to explain why survivors with similar clinical profiles exhibit divergent psychological phenotypes, particularly regarding the late effects of multimodal treatments. The aim of this study was to identify heterogeneous psychosocial profiles among adolescent cancer survivors and to examine their associations with treatment complexity and quality of life. Materials and Methods: This cross-sectional study included 165 adolescents aged 12-18 years (mean age: 14.64 years) who were in clinical remission following oncological treatment. Standardized assessment tools were used: the Children's Depression Inventory 2 (CDI-2™) to measure depressive symptoms, the KIDSCREEN-10 index to assess health-related quality of life (HRQoL), and a scale evaluating satisfaction across 14 life domains. Adaptive profiles were identified using a Two-Stage Cluster Procedure, and risk factors were examined using multinomial logistic regression. Results: Four clusters were identified in the study population: a depressive-dysphoric profile, an anhedonic-withdrawn profile, a highly adaptive profile, and a mixed (struggling) profile. Treatment complexity was identified as a significant independent predictor of membership in the high-distress (depressive) cluster. While each additional therapeutic modality beyond standard chemotherapy was associated with a markedly increased risk (OR = 8.91; p < 0.001), the relatively wide confidence interval (95% CI: 3.27-24.31) suggests that the exact magnitude of this effect should be interpreted with caution. The high lower bound of the interval (3.27), however, strongly supports the directional association of cumulative iatrogenic burden with psychological adaptation. Subjective quality of life functioned as a protective factor against depressive symptoms (OR = 0.57); however, paradoxically, higher self-reported quality of life increased the likelihood of classification into the anhedonic group (OR = 1.81). This divergence between high self-reported HRQoL and social withdrawal potentially suggests a 'well-being paradox'. It is hypothesized that standard HRQoL instruments may primarily capture physical remission and relief from acute somatic symptoms, potentially masking underlying social-emotional deficits. This suggests that HRQoL scores in survivors should be interpreted with caution and complemented by specific affective screenings. Conclusions: The absence of a uniform pattern of psychological response to cancer among adolescent survivors supports the validity of a patient-centered approach. The burden associated with intensive multimodal treatment significantly increases the likelihood of full-syndrome depression during adolescence. Moreover, the identification of a cluster suggestive of anhedonic and socially withdrawn features highlights the limitations of standard screening tools focused solely on the detection of overt sadness. This heterogeneity underscores the need for personalized psycho-oncological care and the implementation of intensified monitoring for patients at high medical risk.