Introduction
Psychiatric comorbidities are frequent in cancer care settings. In fact, patients with cancer are 2 to 3 times more likely to experience depression than the general population, with a prevalence that can reach 14% (Panjwani and Li Reference Panjwani and Li2021). Survivors are also at risk to suffer from anxiety disorders, with a reported prevalence estimated to 17% (Mitchell et al. Reference Mitchell, Ferguson and Gill2013). Such psychiatric comorbidities are associated with negative health outcomes, including decreased quality of life. Therefore, any innovation that could improve early identification of psychiatric disorders and improve access to treatment warrants consideration and empirical evaluation in cancer care.
In the past decades, biomarkers have been studied for research purposes and used as an innovation in various medical contexts. With the emergence of precision medicine and individualized therapy, the value of biomarkers has increased considerably. They have been linked to the etiology of many diseases across the life span (Furman et al. Reference Furman, Campisi and Verdin2019). In the mental health domain, inflammatory markers, such as cytokines and cortisol levels, have been used to study depression etiology and treatment response (Meshkat et al. Reference Meshkat, Ho and Cao2023), including for medically ill patients (Rosenblat et al. Reference Rosenblat, Kurdyak and Cosci2020). The hope is that biomarkers would eventually guide interventions and enhance treatment response in patients with mood disorders (Miller and Raison Reference Miller and Raison2016).
Based on these emerging data, it is interesting to reflect on biomarkers use in the field of psycho-oncology. Psychometric measures are already standard care in cancer care, and some biological markers such as thyroid-stimulating hormones are often monitored when ruling out hypothyroidism in a case of a depressive presentation. Some experts raised the question whether biomarkers would already be relevant in psycho-oncology practice as several appear promising (Chen et al. Reference Chen, Boreta and Braunstein2022; Eddington et al. Reference Eddington, McLeod and Trickey2021; Fertig and Hayes Reference Fertig and Hayes2001; Kim et al. Reference Kim, Kim and Suh2022; Koehler et al. Reference Koehler, Kessler and Stoffel2022; Lambert et al. Reference Lambert, Coumoundouros and Hulbert-Williams2020; Li et al. Reference Li, Kouzmina and McCusker2017, Reference Li, Soczynska and Kennedy2011; Mitchell et al. Reference Mitchell, Kim and Carver2021; O’Toole et al. Reference O’Toole, Bovbjerg and Renna2018; Patterson et al. Reference Patterson, Lu and Watson2022; Pedro et al. Reference Pedro, Monteiro-Reis and Carvalho-Maia2021; Petrova et al. Reference Petrova, Catena and Rodriguez-Barranco2021a, Reference Petrova, Redondo-Sanchez and Rodriguez-Barranco2021b; Rosenblat et al. Reference Rosenblat, Kurdyak and Cosci2020; Shi et al. Reference Shi, Misra and Li2020; Taylor et al. Reference Taylor, Scott and Steineck2021; Vistad et al. Reference Vistad, Skorstad and Demmelmaier2021; Warth et al. Reference Warth, Koehler and Brehmen2021; Wiley et al. Reference Wiley, Bei and Bower2017; Zhou et al. Reference Zhou, Li and Xiao2021). However, to our knowledge, no specific one has been currently validated in psycho-oncology practice. There is indeed a lack of recommendations regarding their use in everyday practice. The purpose of this article is to discuss existing data on biomarkers use in that field and argue whether they should now be utilized in every practice.
A difficult path from research to clinical practice
Simply defined, a biomarker is a characteristic that is measured as an indicator of normal biological processes or responses to an exposure or intervention (Garcia-Gutierrez et al. Reference Garcia-Gutierrez, Navarrete and Sala2020). Biomarkers may be identified at any moment occurring from the pathogenesis to the onset of clinical manifestations, diagnosis, treatment response, and recovery. Researchers and experts have distinguished several types of biomarkers based on their clinical application. A biomarker may meet multiple criteria for different uses or present specific features that enable its particular use (see Table 1 for examples).
Table 1. Potential uses of biomarkers in medical practice
In cancer care, the clinical use of both prognostic and predictive markers is growing. It ranges from screening, to assessing risk and prognosis, evaluating response to treatment, and detecting disease recurrence and progression (Lahoud et al. Reference Lahoud, O’Shea and El-Mouhayyar2021). It is well established that cancer itself is associated with increased levels inflammatory biomarkers, which can then influence illness trajectory. Tumor biology and cancer treatments have also been hypothesized to have some impact on neuronal mechanisms through which neuroimmune phenomenon could lead to changes in behavior (Santos and Pyter Reference Santos and Pyter2018).
Researchers in the field of neurosciences have also shown interest in biomarkers. Psychiatric disorders, for example, have been associated with some endocrine and inflammatory perturbations, notably via the cytokine system. Chronic inflammation is now considered to increase susceptibility to depression (Li et al. Reference Li, Soczynska and Kennedy2011), as well as many other medical conditions (Furman et al. Reference Furman, Campisi and Verdin2019). Higher plasma levels of cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α), have been correlated with more severe depressive symptoms (Hassamal Reference Hassamal2023). Emerging inflammatory biomarkers (including C-reactive protein, TNF-α, IL-6, COX-2) are now considered as potential treatment targets or prognostic predictors for depression phenotypes (Hassamal Reference Hassamal2023). Psychological distress and burnout have been linked to increased cortisol level in some specific populations (Cipriani et al. Reference Cipriani, Kerr and Longpre-Poirier2021; Knight et al. Reference Knight, Jiang and Rodriguez-Stanley2021; Marcil et al. Reference Marcil, Cyr and Marin2022). A recent study systematically reviewed randomized controlled trials on the effects of psychological interventions on pro-inflammatory biomarkers among a large adult population and concluded that such interventions contributed to reduce their levels (O’Toole et al. Reference O’Toole, Bovbjerg and Renna2018; Pedro et al. Reference Pedro, Monteiro-Reis and Carvalho-Maia2021).
These findings although preliminary, limited in potency or tested mostly on animal models, highlight opportunities for further research into mechanisms and potential interventions for psychiatric symptoms’ management among patients with cancer (Hassamal Reference Hassamal2023; Shi et al. Reference Shi, Misra and Li2020). Inflammatory biomarkers could therefore be compelling candidates as susceptibility and monitoring biomarkers in psycho-oncology practice. Some researchers and experts have in fact pointed out the relevance of investigating use of biomarkers in that field, especially for depression (Breitbart et al. Reference Breitbart, Rosenfeld and Tobias2014; Fertig and Hayes Reference Fertig and Hayes2001; Li et al. Reference Li, Kouzmina and McCusker2017, Reference Li, Soczynska and Kennedy2011; Menzies et al. Reference Menzies, Chochinov and Breitbart2005; Mitchell et al. Reference Mitchell, Ferguson and Gill2013).
Emerging biomarkers
There is growing evidence suggesting that cancer-related depression etiology might be linked to neuroinflammation (Ahmad et al. Reference Ahmad, Rizvi and Fatima2021). Recent data have indicated that such phenomenon may disrupt serotonin neurotransmission shedding new insight on a complex interplay between the immune system and the pathophysiology of depressive disorders (Troubat et al. Reference Troubat, Barone and Leman2021). For years, it has been hypothesized that inflammatory cytokine-associated depression could even represent a subtype of depression in that population (Panjwani and Li Reference Panjwani and Li2021). A study conducted found associations between cytokines and the somatic and psychological symptoms of depression, compared to controlled subjects (Li et al. Reference Li, Kouzmina and McCusker2017). A recently published systematic review and meta-analysis concluded that the association between inflammation and depression among patients with cancer was robust, with moderate-to-large effect sizes (McFarland et al. Reference McFarland, Doherty and Atkinson2022b). Another study reported that pro-inflammatory cytokines, such as TNF-α, have a good performance in predicting depression among patients with glioma (Li et al. Reference Li, Shi and Yang2022). McFarland and colleagues studied among 97 patients with metastatic cancer demonstrating that hypoalbuminemia may help establish the presence of anxiety or depression, and treatment refractoriness (McFarland et al. Reference McFarland, Applebaum and Bengtsen2022a). The effectiveness of mind and body therapies for addressing some biomarkers of stress and immune function in people with cancer have been documented, although this evidence is limited (Deleemans et al. Reference Deleemans, Mather and Spiropoulos2023). A cross-sectional analysis among 98 patients with metastatic lung cancer revealed that vitamin D deficiency was associated with depression (McFarland et al. Reference McFarland, Fernbach and Breitbart2022c).
Persistent challenges
Despite these emerging data, some limitations of the use of biomarkers in psycho-oncology must be acknowledged. First, association between biomarkers and comorbid psychiatric disorders in patients with cancer, including neurocognitive disorders and severe mental illnesses like psychosis or bipolar disorder, remains understudied beyond anxiety and depression. In fact, many psychological symptoms or psychiatric disorders other than depression can adversely affect patients with cancer. Even among patients’ caregivers, the inflammatory responses were associated with psychological distress (Kim et al. Reference Kim, Kim and Suh2022).
Sleep problems are highly prevalent among patients with cancer (Savard and Morin Reference Savard and Morin2001), and may persist into survivorship (Denlinger et al. Reference Denlinger, Ligibel and Are2014; Hall and Peppercorn Reference Hall and Peppercorn2020). Limited data recently raised the possibility that disruption of circadian activity rhythms and elevated cortisol awakening response among patients with breast cancer, may facilitate tumor promotion and progression (Cash et al. Reference Cash, Sephton and Chagpar2015), although such findings confirm correlations, not causality. Cancer-related cognitive impairment is another important problem found among cancer populations, which can have a major negative impact on a patient’s quality of life and be complex to analyze (Orszaghova et al. Reference Orszaghova, Mego and Chovanec2021). Identifying biomarkers for cancer-related cognitive impairment could be helpful for clinicians.
Despite this literature is growing fast, the use of biomarkers in clinical practice in the field of psycho-oncology is not yet recommended in clinical guidelines. Translating this new knowledge remains a challenge. Studies still struggle with significant methodological issues such as sample sizes, or existing data quality. It seems not yet clear if clinicians should now use biomarkers in their practice despite these gaps and lack of experts’ consensus. Their contribution within decision-making processes in everyday practice needs to pursue further investigation.
Conclusion
Biomarkers are being increasingly used in both mental health and cancer care research. However, little is known about the relevance of biomarkers in everyday psycho-oncology practice. Future studies should enhance understanding of the link between inflammation markers and psychiatric disorders in this population. Systematic reviews on that topic, including randomized controlled trials, could assist clinicians in enlightening this debate. Such data could help identify scalable and reliable biomarkers for the development of more effective treatments, including cancer-specific pharmacological or psychological treatments. In the realm of psycho-oncology, biomarkers hence offer potential interest to clinicians seeking to incorporate more biological parameters into their decision-making process, aligning with the principles of precision medicine. High-quality evidence is vital for improving clinical practices and delivering data-driven care that mostly benefits patients. Whether biomarkers have yet the potential to assist clinicians in making more informed treatment decisions, leading to wiser choices and potentially safeguarding patients from futile interventions, remains unanswered.
Funding
This research received no specific grant from any funding agency, commercial or not-for-profit sectors.
Competing interests
The authors declare none.
