Abstract
Cholangiocarcinoma (CCA) is an aggressive malignant tumor with extremely poor prognosis, and its global incidence is increasing, posing a growing public health burden. Behavioral factors, such as diet, alcohol consumption, smoking, physical activity, and psychological status, are closely associated with the development of CCA. This narrative review delves into the multidimensional burden of CCA, including psychological distress, symptom profiles, and socioeconomic impacts. It also summarizes evidence from related gastrointestinal cancers to explain the biological mechanisms through which lifestyle modifications may improve prognosis, including immunomodulation, inflammatory cascades, and metabolic reprogramming. Furthermore, we propose an integrated framework for behavioral medicine and hepatobiliary care, emphasizing the pivotal role of behavioral interventions in enhancing CCA prevention and clinical outcomes.
Keywords
1. Introduction
Cholangiocarcinoma (CCA) is an aggressive biliary tract malignancy with a poor prognosis, exhibiting a five-year survival rate below 20%. Its global incidence is relatively low, accounting for about 3% of gastrointestinal cancers, but has increased steadily in recent decades. 1 CCA also shows marked geographical variation. Southeast Asia carries one of the highest burdens worldwide. In Northeastern Thailand, the age-standardized incidence reaches 50–100 per 100,000 (especially in men), nearly 100-fold higher than the 1-2 per 100,000 reported in Western countries.2-4 South Korea also has a relatively high incidence of about 3.3 per 100,000, while the rate in China is approximately 2.49 per 100,000.5,6
These differences are largely driven by region-specific risk factors. In endemic areas, chronic liver fluke infection from consumption of raw or undercooked freshwater fish is a major contributor. 7 This exposure is classified as a Group 1 carcinogen by the International Agency for Research on Cancer, World Health Organization (WHO-IARC) and is the leading cause of CCA in parts of Asia. 8 Opisthorchis viverrini (OV) is a key risk factor in Southeast Asia9,10; related species, including Opisthorchis felineus in Siberia and Eastern Europe, as well as Clonorchis sinensis, which is endemic in China, Vietnam, and South Korea, are also associated with increased CCA risk. 11
Risk factors in Western populations differ substantially. In these settings, CCA is more often associated with chronic cholangitis and underlying hepatobiliary disease, particularly primary sclerosing cholangitis (PSC). 12 Other risk factors include chronic hepatitis B or C infection, cirrhosis, biliary cysts, and gallstones. 13 In addition, metabolic dysfunction has emerged as an important contributor. Obesity, metabolic syndrome, diabetes, and non-alcoholic fatty liver disease are increasingly linked to CCA development.1,13,14 These conditions are closely related to lifestyle factors including diet, physical activity, and stress, collectively creating a pro-inflammatory and carcinogenic hepatic microenvironment.
Given the limited number of studies directly examining behavioral medicine in CCA, this narrative review synthesizes evidence from hepatobiliary and gastrointestinal cancers to develop a conceptual framework for integrating behavioral interventions into CCA care. Rather than performing a formal systematic review, we conduct a narrative synthesis that bridges existing knowledge gaps and outlines directions for translational research. The objective of this review is to highlight how addressing the behavioral dimensions of CCA, from prevention through survivorship, may influence prognosis and quality of life. This review is guided by the Scale for the Assessment of Narrative Review Articles SANRA. 15
2. The Burden of CCA: A Biopsychosocial Perspective
Multidimensional Burden of CCA
Note. CBT, Cognitive-behavioral therapy; EORTC QLQ-C30, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30; HADS-A/D, Hospital Anxiety and Depression Scale-Anxiety/Depression subscale; QoL, Quality of Life.
2.1 Clinical Challenges and Outcomes
The clinical course of CCA presents major challenges beyond tumor biology. Early symptoms are often subtle and non-specific, such as weight loss, abdominal discomfort, and fatigue. 23 As a result, most patients are diagnosed at an advanced and unresectable stage, which delays optimal treatment. 23 Even among the small proportion of patients who undergo liver transplantation, the two-year recurrence rate reaches 84%, reflecting the aggressive biology of this malignancy. 24
The anatomical location of CCA creates unique symptom burdens that profoundly impact quality of life. Biliary obstruction, present in up to 90% of patients, causes not only jaundice but also intractable pruritus that could be more distressing than pain.20,25 Cholangitis episodes requiring repeated hospitalizations, digestive dysfunction from biliary-pancreatic duct obstruction,21,22,25 and profound fatigue from liver dysfunction create a cascade of physical symptoms that erode functional capacity and independence.16,26
Although treatment options have improved, benefits remain limited to selected patients. Standard chemotherapy with gemcitabine and cisplatin, immune checkpoint inhibitors such as durvalumab, and targeted therapies for fibroblast growth factor receptor 2 (FGFR2) fusions or human epidermal growth factor receptor 2 (HER2) alterations have shown benefit in some populations. 27 However, many patients experience rapid progression, treatment intolerance, or lack actionable mutations. 27 And high financial burden may restrict access in resource-limited settings and worsen disparities in care, as well as psychological and social stress.28,29
2.2 Psychological Burden and Mental Health Impact
The psychological trauma of CCA diagnosis is profound and multifaceted.17,18 Unlike more common cancers where patients can find robust support communities and abundant information resources, CCA patients often experience profound isolation, a “rare cancer” within the already isolating experience of cancer. 30 The rapid trajectory from diagnosis to death, often measured in months, creates an existential crisis that standard oncology care is ill-equipped to address. 31 Moreover, the incidence of psychological disorders is relatively high in CCA populations. A study found that 54.8% of CCA patients met criteria for clinically significant psychological distress, with 54.3% experiencing depression and 35.6% anxiety disorders. 32 And these rates substantially exceed those in other gastrointestinal cancers. For instance, depression affects 38% to 45% of patients with pancreatic cancers,33,34 while anxiety and depression rates in gastric cancer patients are 33.8% and 25.0% respectively.35,36 In colorectal cancer, the rate are lower, at 20.9% for anxiety and 19.0% for depression.35-37 Notably, psychological distress could independently predict worse survival after controlling the disease stage and performance status, suggesting the mental health is not merely palliative but potentially life-extending. 38
2.3 Economic and Functional Consequences
Socioeconomic factors play a critical role in CCA outcomes. Lower income is associated with higher disease burden, including increased incidence of advanced-stage disease, reduced access to systemic treatment or personalized therapy, and poorer survival.28,29,39 Evidence from Western cohort studies shows similar patterns, with lower socioeconomic status linked to higher incidence, limited treatment access, and worse outcomes. 40
In addition, CCA disproportionately affects individuals in their prime working years, with median age at diagnosis of 68-72 years but substantial numbers diagnosed in their 40s and 50s. 41 The functional decline is precipitous, from full employment to disability within months, creating economic devastation for families already coping with emotional trauma. 42 In endemic regions of Southeast Asia, where CCA predominantly affects male agricultural workers, the loss of the primary breadwinner pushes entire families into poverty, creating an inter-generational cycle of hardship. 43
3. Behavioral Risk Factors in CCA Development
Behavioral Risk Factors for CCA: Mechanisms, Evidence and Interventions
Note. BECs, Biliary Epithelial Cells; DNA, Deoxyribonucleic Acid; HBV/HCV, Hepatitis B/C Virus; IR, Insulin Resistance; OS, Oxidative Stress.
3.1 Cultural Practices and Dietary Behaviors
The clearest example of behavioral influence on CCA risk comes from Southeast Asia, where the cultural practice of consuming pla ra and koi pla sustains the life cycle of carcinogenic liver flukes. 58 Pla ra is a fermented fish dish made from fish, rice, and garlic, while koi pla is a raw fish salad prepared with herbs and lime juice and consumed immediately. 59 Short-term fermentation does not reliably inactivate the metacestodes of OV, and the N-nitroso compounds and their precursors present in fermented fish and other pickled foods may also contribute to the CCA development.59,60 These dishes are not merely food but cultural identity, served at celebrations, offered to monks, and passed down through generations. 61
Raw, undercooked, lightly cured, or briefly fermented dishes could all lead to liver fluke infection; meanwhile, processed meat products, cured meats, and certain fish products may form or contain nitrosamines.55,62 These exposures promote chronic inflammation and bile duct injury, contributing to CCA development. 62 In contrast, diets rich in vegetables particularly cruciferous vegetables containing glucosinolates, reported greater protective effects (OR 0.61, 95% CI 0.50-0.75).63,64 While liver fluke–associated CCA represents a major burden in endemic regions, metabolic and lifestyle-related factors play a more prominent role in Western populations, reflecting regional differences in etiology.
3.2 Metabolic and Lifestyle Factors
The metabolic syndrome epidemic represents a modifiable behavioral risk factor for CCA with enormous public health implications. Obesity increases CCA risk by 49% (pooled RR 1.49, 95% CI: 1.32-1.70), operating through multiple mechanisms including chronic inflammation, altered bile acid metabolism, and adipokine dysregulation. 65 Type 2 diabetes, present in 20-30% of CCA patients in Western series, nearly doubles CCA risk (OR 1.59, 95% CI: 1.43-1.76) through hyperinsulinemia. 13
Physical inactivity further exacerbates metabolic risks and independently promoting carcinogenesis. Sedentary behavior, defined as <3 hours of moderate activity weekly, increases liver cancer risk by 25% through mechanisms including immune dysfunction, increased inflammation, and metabolic dysregulation. 66 The modern lifestyle, characterized by prolonged sitting, processed food consumption, and chronic stress, creates a perfect storm for CCA development in genetically susceptible individuals.
3.3 Environmental and Occupational Exposures
Occupational and environmental exposures, often reflecting behavioral choices about employment and residence, contribute significantly to CCA risk.
57
Workers in rubber and chemical industries have a 2-3 fold increased risk, likely due to exposure to nitrosamines and organic solvents.67,68 Agricultural workers exposed to pesticides, particularly in endemic regions where liver fluke infection provides a “first hit”, show elevated risk that may be synergistic rather than additive.69,70 Several studies have shown that agricultural workers, including farmhands, farmers, fishermen, and livestock farmers, have a higher risk of OV infection than workers in other occupations, with odds ratios ranging from 2.21 to 5.16. Given the causal relationship between OV and CCA, these occupational characteristics are likely to increase cancer risk.
71
These exposures often cluster in disadvantaged populations with limited occupational choices, highlighting the intersection between social determinants of health and behavioral risk factors in CCA development (Figure 1). Behavioral and environmental risk factors for CCA development
4. Lessons From Behavioral Oncology in Related Cancers
Evidence for Behavioral Interventions From Related Gastrointestinal Cancers
Note. CBT, Cognitive Behavioral Therapy; CCA, Cholangiocarcinoma; CRC, Colorectal Cancer; ONS, Oral Nutritional Supplements; RCT, Randomized Controlled Trial; GI, Gastrointestinal.
4.1 Smoking Cessation: Achieving Accessible Benefits
Tobacco cessation represents the most evidence-based behavioral intervention in oncology and has clear relevance to CCA. A meta-analysis of over 10,000 cancer patients showed that post-diagnosis smoking cessation reduces cancer-specific mortality by 34% (HR 0.66, 95% CI 0.57-0.76). 80 In surgical patients, cessation 4-8 weeks preoperatively reduces complications by 31% and shortens hospital stays by 2-3 days.81,82 In hepatobiliary cancers, continued smoking after diagnosis also accelerates disease progression through multiple mechanisms, including reduced chemotherapy efficacy, increased surgical complications, enhanced angiogenesis, and impaired immune surveillance.83,84 Despite this evidence, smoking cessation support remains sporadic in CCA care, representing a missed opportunity for a low-cost, high-impact intervention.
4.2 Prehabilitation: Preparing for the Marathon of Cancer Treatment
Prehabilitation, which aims to optimize physical and psychological fitness before cancer treatment, has improved perioperative care in hepatobiliary surgery. 85 The PREHEP trial randomized 60 sarcopenia patients with major liver resection to standard care versus a 6-week multi-modal prehabilitation program. The intervention reduced overall complication from 50% to 13% (p=0.004), shortened functional recovery time from 6-18 to 6-10 days, and decreased 90-day mortality from 3.3% to 0%. 86 For CCA patients, who often present with sarcopenia and malnutrition, prehabilitation may be particularly beneficial. Studies in hepatopancreatobiliary cancers shown improvements in nutritional status, reduced frailty, and better psychological readiness for surgery. 87 The 4-6 week period during biliary drainage and staging also provides an opportunity for implement prehabilitation, turning waiting time into preparation time. 88
4.3 Exercise During Treatment: Moving Through Cancer
Physical activity during cancer treatment is now considered safe and beneficial in many settings. 89 In pancreatic cancer, which shares clinical features with CCA, structured exercise program improve treatment tolerance and quality of life. 90 Exercise interventions also reduce cancer-related fatigue (with fatigue score improvements ranging from 2.5 to 9 points) and improve mental health, with a low incidence of exercise-related adverse events.91,92 In CCA, where baseline inflammation is common, exercise-induced anti-inflammatory effects may offer additional benefits. 93
4.4 Psychosocial Interventions: Healing the Mind to Help the Body
Psychosocial interventions influence cancer outcomes beyond symptom relief. A meta-analysis of 15 randomized trials showed that these interventions reduce depression (SMD -0.65) and anxiety (SMD-0.24), and may improve immune function and survival.94,95 Spiegel et al. reported that group psychotherapy doubled survival time in metastatic breast cancer (36.6 vs 18.9 months). 96 In hepatobiliary cancers, emerging evidence supports similar benefits. A randomized trial of 136 HCC patients showed that a structured psycho-oncology program reduced depression (16.2% vs 32.4%) and improved median survival (37.0 vs 32.0 months; p=0.026). 97 The survival benefit remained after adjustment for disease stage and treatment, suggesting a biological effects rather than confounding. 98
5. Mechanistic Pathways: From Behavior to Biology
The biological mechanisms linking behavioral factors to cancer outcomes are increasingly well-defined, providing a strong scientific rationale for behavioral interventions in CCA. These pathways, including immune, inflammatory, metabolic, and epigenetic, interact in complex networks that behavioral modifications can beneficially modulate
99
(Figure 2). Mechanistic pathways linking behavioral interventions to CCA outcomes
5.1 Immune Modulation
The immune system serves as a critical mediator between behavior and cancer progression. Chronic stress, through sustained activation of the hypothalamic-pituitary-adrenal axis and sympathetic nervous system, suppresses anti-tumor immunity. 99 Chronically stressed individuals show a 40-50% reduced natural killer (NK) cell activity, decreased CD8+ T cell proliferation.100,101 In CCA, where tumor-infiltrating lymphocytes are strong predictors of survival, stress-induced immune suppression may accelerate disease progression. 102 Conversely, behavioral interventions could restore immune competence through multiple mechanisms. Acute exercise can substantially increase NK-cell circulation and enhance their cytotoxic activity.53,54 Stress management interventions help normalize cortisol rhythms and reduce immunosuppressive effects of chronic glucocorticoid exposure. 103
5.2 Inflammatory Cascades
Systemic inflammation drives CCA progression through well-characterized mechanisms: nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation, signal transducer and activator of transcription 3 (STAT3) signaling, and production of tumor-promoting cytokines. 48 Obesity is known to increase circulating levels of inflammatory markers such as Interleukin (IL)-6 and C-reactive protein (CRP). Smoking activates the NOD-like receptor protein 3 (NLRP3) inflammasome, while alcohol triggers Kupffer cell activation and hepatic inflammation.44-46 Behavioral interventions can reduce inflammation through complementary pathways. Modest weight loss (5–10%) induced by diet has been associated with significant reductions in circulating IL-6 and CRP levels.104,105 Exercise induces anti-inflammatory myokines including IL-10 and IL-6 while suppressing pro-inflammatory adipokines. 106 A single exercise session can reduce inflammatory markers for up to 48 hours, suggesting that regular activity may sustain an anti-inflammatory state. 107
5.3 Metabolic Reprogramming
Metabolic dysfunction contributes to a tumor-permissive environment in CCA. Hyperinsulinemia activates phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling, promoting cell proliferation and survival.49,50 Dyslipidemia provides substrates for membrane synthesis and signaling molecules. 51 Advanced glycation end-products from hyperglycemia trigger RAGE receptor activation and downstream inflammatory signaling. 52 Lifestyle interventions can reshape this metabolic environment. Caloric restriction and intermittent fasting reduce insulin-like growth factor 1 (IGF-1) levels by 25-30%, suppress mTOR signaling, and activate AMP-activated protein kinase (AMPK), thereby inhibiting tumor growth.108,109 Exercise improves insulin sensitivity by 25-40%, normalizes the IGF-1/IGFBP-3 ratio, and reduces circulating glucose and lipids.110,111
5.4 Epigenetic Modifications
Behavioral factors can induce epigenetic changes that affect cancer-related gene expression. Chronic stress alters DNA methylation patterns, particularly in genes involved in inflammation and DNA repair.112,113 Smoking induces hypermethylation of tumor suppressor genes including cyclin-dependent kinase inhibitor 2A (CDKN2A) and MutL homolog 1 (MLH1). 47 Diet influences one-carbon metabolism, thereby affecting DNA methylation and histone modifications.114,115 Remarkably, behavioral interventions may reverse these changes. Exercise induces beneficial changes in DNA methylation of genes involved in metabolism and inflammation within months. 116 Dietary rich in folate and B-vitamins can restore normal methylation patterns. 117 Stress management may alter gene expression through histone acetylation. 118 These epigenetic effects may explain the sustained benefits of behavioral interventions even after intervention cessation.
6. A Framework for Integrating Behavioral Medicine Into CCA Care
Translating behavioral medicine principles into CCA care requires systematic integration across the cancer continuum. We propose a framework addressing prevention, treatment, and survivorship/palliation, tailored to the unique challenges of CCA (Figure 3). Comprehensive framework for behavioral medicine integration in CCA care
6.1 Primary Prevention: Population-Level Interventions
In regions of Asia where liver flukes are endemic, culturally adapted behavioral interventions have shown substantial success. Primary prevention relies on controlling parasitic infections and preventing reinfection. Strategies include the “One Health” approach, sanitation improvements, Water, Sanitation, and Hygiene (WaSH) programs, and the establishment of open-defecation-free communities. 119 Thailand’s “Model Village” program, combining education, improved sanitation, and alternative food preparation methods, reduced O. viverrini prevalence from 14.1% to 0.9% over 8 years. 120 Key components include: 1) Comprehensive annual stool screening using one-step formalin ethyl-acetate concentration technique (FECT) with praziquantel treatment (40 mg/kg single dose) for infected individuals; 2) Intensive health education campaigns delivered by trained community health volunteers; 3) Biological control deploying domestic ducks to reduce Bithynia snail populations; 4) Environmental sanitation improvements including construction of public toilets with septic systems; 5) Veterinary interventions treating infected reservoir hosts (dogs and cats) with praziquantel; 6) Establishment of certified liver fluke-free fish production enterprises and a community learning center.
Two additional large-scale initiatives further demonstrate effective implementation. The “Lawa Model”, developed by Banchob Sripa and colleagues, applies a long-term, community-based, and interdisciplinary approach grounded in One Health principles. 121 The Cholangiocarcinoma Screening and Care Program (CASCAP), led by Narong Khuntikeo and colleagues, provides large-scale screening for high-risk populations combined with downstream clinical management. 122 CASCAP is particularly notable as a comprehensive model linking early detection with clinical care. Together, these initiatives illustrate how culturally tailored, system-level interventions can reduce CCA burden.
In Western populations, prevention focuses more on metabolic risk factors. Population-level strategies, including workplace wellness programs, urban design that promotes physical activity, and policies that reduce consumption of ultra-processed food, may help lower CCA incidence. 49 Given the long latency between exposure and disease development, prevention efforts should target younger populations before irreversible damage occurs. 123
6.2 Clinical Implementation of Behavioral Interventions
For patients with CCA, behavioral interventions should be integrated into standard oncologic care. At diagnosis, patients should be evaluated for key behavioral factors and offered appropriate support. Interventions must also be adapted to local cultural and healthcare contexts to ensure feasibility and sustainability.
The CASCAP model provides an example of how integrated prevention, screening, and care can be implemented at scale, particularly in resource-limited settings. However, successful implementation requires flexible adaptation to differences in healthcare systems, cultural practices, and available resources. Key components of clinical implementation include: 1) Smoking and alcohol assessment: Early cessation support may improve treatment tolerance and reduce complications. 124 2) Nutritional support: Early dietitian involvement is essential, as many patients experience weight loss or malabsorption. 125 3) Physical activity as tolerated: Even low-intensity exercise or short prehabilitation programs (2–4 weeks) can improve functional outcomes. 126 4) Psychosocial care: Routine distress screening and early referral to psycho-oncology or palliative care services are critical. Interventions may include counseling, pharmacologic support, and social assistance. Patient navigation services can further improve adherence to complex care pathways.
Together, these components form an integrated care pathway alongside standard oncologic treatment. A multidisciplinary rehabilitation model, such as that reported by Temel et al., demonstrates how combining exercise, nutrition, psychological support can improve and mental health outcomes. 127 We propose that cancer centers incorporate similar multidisciplinary behavioral care models into CCA management and evaluate their impact in prospective studies.
7. Future Directions and Challenges
Priority Research Areas in Behavioral Medicine for CCA
Note. CCA, Cholangiocarcinoma; EORTC, European Organisation for Research and Treatment of Cancer; EQ-5D, EuroQol 5-Dimensions; FACIT-Sp, Functional Assessment of Chronic Illness Therapy - Spiritual Well-Being; HADS, Hospital Anxiety and Depression Scale; PHQ-9, Patient Health Questionnaire-9; QLQ-C30, Quality of Life Questionnaire Core 30; QoL, Quality of Life; RCT, Randomized Controlled Trial; SAS, Self-rating Anxiety Scale; SDS, Self-rating Depression Scale; WHO QOL-BREF-THAI, World Health Organization Quality of Life Brief Version - Thai.
7.1 Prospective Intervention Trials
The absence of randomized trials examining behavioral interventions specifically in CCA represents the field’s most glaring gap. Priority trials should include135,136: 1) Prehabilitation in resectable CCA: Randomized trial of multimodal prehabilitation versus standard care, powered for postoperative complications and disease-free survival; 2) Exercise during chemotherapy: Feasibility and efficacy of supervised exercise in advanced CCA patients receiving Gemcitabine chemotherapy; 3) Integrated psychosocial support: Effectiveness of structured psycho-oncology programs on psychological morbidity, treatment adherence, and survival; 4) Digital health interventions: Mobile health applications for symptom monitoring, exercise coaching, and psychological support in CCA.
7.2 Mechanistic Studies
Understanding how behavioral interventions impact CCA biology could optimize intervention design and identify responsive patient subgroups. Priority areas include: 1) Circulating biomarkers [e.g. circulating tumor DNA (ctDNA)] as early indicators of intervention response. Serial liquid biopsies should assess ctDNA clearance, mutant allele dynamics, resistance emergence, and cfDNA methylation, alongside CA19-9 and inflammatory or metabolic markers, to provide earlier and more sensitive signals of biologic response than imaging alone. 137 2) Tumor microenvironment changes with behavioral interventions using serial biopsies. Paired pre- and post-intervention biopsies, or pretreatment biopsy plus resection tissue, could evaluate immune infiltration, stromal remodeling, hypoxia, and spatial organization using multiplex and single-cell approaches, helping define how behavioral interventions reshape the desmoplastic and immunosuppressive CCA microenvironment. 138 3) Microbiome modulation by diet and exercise in CCA patients. Longitudinal profiling of stool, bile, and relevant microbial metabolites should be incorporated into diet and exercise studies to determine whether microbiome shifts correlate with bile acid metabolism, systemic inflammation, treatment tolerance, and tumor-related outcomes. 139 4) Epigenetic profiling to identify intervention-responsive signatures. DNA methylation, chromatin, and non-coding RNA analyses in tumor tissue and cfDNA may identify epigenetic states that predict or reflect response to behavioral interventions and support minimally invasive monitoring.140,141
7.3 Implementation Science
Even evidence-based interventions fail without effective implementation strategies. 142 Key implementation research priorities include143-145: 1) Adaptation of behavioral interventions for resource-limited settings in endemic regions; 2) Integration of behavioral specialists into hepatobiliary tumor boards and care pathways; 3) Cost-effectiveness analyses to support insurance coverage and policy changes; 4) Training programs for oncology providers in behavioral assessment and brief interventions.
7.4 Challenges and Opportunities
Despite increasing recognition of behavioral factors in CCA, implementation remains challenging. The rarity and rapid progression of the disease limit patient recruitment and long-term follow-up. 23 Cultural resistance to lifestyle change, particularly in endemic regions, may further reduce intervention uptake. 59 In addition, limited resources and lack of integration of behavioral specialists constrain delivery. 1 At the same time, new opportunities are emerging. Telemedicine and digital health platforms enable scalable delivery of behavioral interventions. 136 Integration of psycho-oncology and multidisciplinary care also provides a practical pathway for implementation.27,137,139 Overall, while challenges remain, these advances create opportunities to translate behavioral interventions into clinical practice. Identifying feasible, culturally appropriate, and resource-sensitive strategies will be essential for improving real-world outcomes.
8. Conclusion
CCA challenges us to think beyond the tumor. While ongoing advances in molecular and targeted therapies hold promise, the influence of behavioral factors on disease onset, progression, and patient well-being warrants greater attention. Behavioral medicine offers practical, evidence-based approaches, spanning prevention, perioperative care, and survivorship that complement biomedical innovation. Integrating behavioral interventions such as smoking cessation, exercise, nutrition, and psychosocial support may strengthen immunity, reduce inflammation, and enhance quality of life. Future research should consider implementing behavioral medicine clinical trials alongside novel therapeutics studies. Importantly, the contribution of behavioral risk factors varies across regions, highlighting the need for context-specific prevention and intervention strategies. Moving behavioral medicine from the periphery to a more integrated role in CCA care represents a natural and necessary evolution toward more holistic cancer management.
Footnotes
Ethical Considerations
This study does not require the approval of an ethics statement.
Author Contributions
(I) Leshui Wang, Yan Lu and Ye Qian: Validation, Visulazation, Writing - original draft, Writing - Review & Editing.
(II) Xiao Wang and Yihuan Xu: Validation.
(III) Xinggang Guo and Wei Dong: Conceptualization.
(IV) Hui Liu & Susu Luo: Conceptualization, Methodology, Validation, Funding acquisition, and Writing - review & editing.
Funding
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Natural Science Foundation of Shanghai Municipality (Grant No. 25ZR1402578), the Shanghai White Magnolia Talent Program (Pujiang Project, Category A; Grant No. 25PJA018), and the National Science and Technology Major Project for Noncommunicable Chronic Diseases (Grant No. 2023ZD0502000).
Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.