Fear of Cancer Recurrence and Death Anxiety: Unaddressed Concerns for Adult Neuro-oncology Patients

Abstract

Primary brain tumor (PBT) patients may experience existential distress; however, few studies have examined this issue. The objectives of this study were to (1) systematically review PBT representation in psycho-oncology literature regarding fear/anxiety related to progression, recurrence, and death and (2) preliminarily assess the prevalence of fear of dying in a sample of PBT patients. Systematic searching of three databases yielded 1555 articles for review. Of these, 327 studies met inclusion criteria (patient sample N = 132,951). Only eight studies (0.18% of the participants) included patients with a PBT diagnosis, potentially due to exclusion criteria such as cognitive impairment or specific treatment parameters which may prohibit PBT patient participation. Review of the results from the eight included studies revealed mixed methods and limited demographic analyses; existential distress was correlated with heightened depression and anxiety, and overall worsened quality of life. From the original data collection, approximately one-third of PBT patients endorsed fear of dying, which was positively related to depression severity. Taken together, results suggest that PBT patients are considerably underrepresented in existential psycho-oncology literature, despite preliminary findings suggesting prevalence of these concerns. Future research on existential distress in neuro-oncology is warranted.

Human beings are “forever shadowed by the knowledge that we will grow, blossom, and inevitably, diminish and die” (Yalom, 2008).

The fear of death is considered an innate survival instinct, often precipitated by death awareness (Abdel-Khalek & Tomás-Sábado, 2005). Researchers argue that in the absence of death awareness, individuals live life on autopilot with a false sense of certainty and no ownership of their lives (Heidegger, 1996; May & Yalom, 2005). But when someone’s life is questioned or threatened, the individual’s perspective shifts to awareness of both their active participation in living and the uncertainty of life. In this state, existential distress may be heightened (Heidegger, 1996; May & Yalom, 2005).

One well-supported hypothesis explaining this psychological phenomenon, Terror Management Theory (TMT), takes an extrinsic perspective on existential distress and posits that individuals possess an instinctive drive for self-preservation which is threatened when the idea of mortality is presented. In TMT, such death awareness produces existential anxiety which is managed with two defense mechanisms: cultural worldview validation and self-esteem enhancement (Burke, Martens, & Faucher, 2010; Mosher & Danoff-Burg, 2007). Another more recent theory, Posttraumatic Growth (PTG), utilizes an intrinsic perspective, a shift toward building meaningful and lasting resources, and satisfying essential human needs. PTG posits that facing ones mortality can lead to positive psychological change including a greater appreciation for life, changed sense of priority, more intimate relationships, a greater sense of strength, recognition of new possibilities for life, and spiritual development (Tedeschi & Calhoun, 1996).

When given a terminal diagnosis, such as advanced cancer, the awareness (or certainty) of mortality may provoke such fear by increasing the anticipation of death (Tomer & Eliason, 1996). With the advancement of life-prolonging medical treatments, patients now frequently experience an extended dying process with terminal symptoms (Adelbratt, Strang, & Srn, 2000). Subsequently, death and dying are often transferred from the comfort of home to a hospital setting where there is greater focus on the physical aspects of health rather than the psychosocial aspects of care, including existential distress (Adelbratt et al., 2000; Carver, Scheier, & Weintraub, 1989). This results in fewer resources allocated to address these issues, despite lengthy periods of time in which patients must face the reality of their finite existence.

A consistent finding in the oncology literature is that individuals with higher levels of existential well-being (e.g., less fears associated with death or disease recurrence) report better quality of life (QoL) and lower emotional distress (Brady, Peterman, Fitchett, Mo, & Cella, 1999; Edmondson, Park, Blank, Fenster, & Mills, 2008; Laubmeier, Zakowski, & Bair, 2004; Visser, Garssen, & Vingerhoets, 2010). However, the awareness of mortality can elicit a range of existential themes such as the threat of loss of control to oneself, existence, family, friends, and the chance to live a fulfilling life (Adelbratt et al., 2000). Neglecting existential issues is thought to contribute to depression, despair, anxiety, pain, and loneliness which may lead to isolation and loss of pleasure (Gonen et al., 2012a; Lehto, 2012; Salander, Bergenheim, & Henriksson, 2000; Strang, Strang, & Ternestedt, 2001). Paradoxically, it has been suggested that higher rates of fear surrounding death and dying can negatively affect health outcomes and thus life expectancy (Iverach, Menzies, & Menzies, 2014). Existential distress among those with cancer may not be limited to the fear of death and dying, but may also include fear of cancer recurrence (Herschbach & Dinkel, 2014; Koch et al., 2014). In some instances, anxiety about recurrence is medically warranted, given high rates of tumor return among certain types and stages of cancer (ACS, 2015). In other instances, this anxiety persists regardless of reassurance from physicians or test results that cancer is unlikely to recur or progress. In both cases, anxiety regarding disease recurrence can negatively impact QoL and psychological well-being (Simard, Savard, & Ivers, 2010). Thus, in this study, we refer to our investigation of existential distress as the fears associated with death, dying, and disease recurrence.

Previous studies have explored correlates of QoL in oncology populations (Aaronson et al., 1993; Ganz, 2002; Montazeri, Milroy, Hole, McEwen, & Gillis, 2001), but it is unclear how many of these have focused on primary brain tumor (PBT) patients. Like many cancer patients, PBT patients can experience negative consequences and maladaptive psychosocial functioning related to their diagnosis and treatment, such as depression, anxiety, anger, and dread (Gonen et al., 2012a). Unique to PBT patients are the additional cognitive and emotional consequences of brain tumor treatment, including the negative effects of radiotherapy and chemotherapy that necessarily cross the blood–brain barrier (van Vulpen, Kal, Taphoorn, & El-Sharouni, 2002). Disease progression can happen rapidly, with PBT patients fighting for their lives, trying to maintain their previous identities, and battling functional and cognitive deficits (Adelbratt et al., 2000). Noncurative treatment regimen and poor prognoses place the PBT population at increased risk for existential distress, including death anxiety and fear of recurrence. In both low- and high-grade patients, fear of recurrence may be prominent in the early stages of diagnosis and treatment, transforming into death anxiety when the disease progresses. For example, a diagnosis of low-grade brain tumor has a more favorable prognosis; however, in most cases, there remains the certainty of tumor recurrence or progression, leaving patients to guess as to when it may recur. For high-grade tumors, like glioblastoma multiforme, patients can be given a prognosis of 11–15 months (ACS, 2019b), again with certainty of recurrence but uncertainty of when. Therefore, it is important to investigate the prevalence of existential distress broadly, defined as both death anxiety and fear of recurrence.

While there is ample research demonstrating the numerous stressors that impact both the PBT patient and their family members (Budrukkar et al., 2009; Sterckx et al., 2013), the extent to which this population is troubled by existential distress is largely unknown. Fears surrounding cancer recurrence and death may amplify the negative health and functional consequences to an already burdensome brain tumor diagnosis (Adelbratt et al., 2000; Strang et al., 2001). Yet, with no systematic reviews on the prevalence of and treatment for existential distress in PBT patients, there is a limited understanding of the need for supportive services. Given the knowledge that psychosocial support is a necessary component of palliative care once a disease is deemed incurable, which is often the case in neuro-oncology, a review of this topic could inform screening and treatment in this population.

There have been no published reviews to date on the topic of existential distress in neuro-oncology. The purpose of the current study was twofold. The primary objective included a systematic review of the oncology literature in order to (1) provide an overview of oncology populations represented in investigations of existential distress, (2) determine the representation of PBT patients in these investigations, (3) provide an overview of the neuro-oncology specific findings including the identification of any existential themes, and (4) identify exclusion parameters and determine the rate at which PBT patients could have been excluded from these investigations. As a secondary objective, the prevalence of fear of dying was investigated in a small PBT sample and its relationship with symptoms of depression was explored. Examining existential distress in neuro-oncology may lead to a broader understanding of the concerns of PBT patients and more effective supportive care for them. Likewise, these findings may improve psychological functioning, positively affect health outcomes and therefore life expectancy, and enhance QoL.

Primary Investigation: Systematic Review of Existential Neuro-oncology Literature

Methods

Search Procedure and Review Parameters

In order to identify the extent to which PBT patients have been represented in the psycho-oncology literature regarding fear/anxiety related to progression, recurrence, and death, a literature search was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA; Liberati et al., 2009). Studies were identified through key-word searches relevant to the fields of psychology, nursing, and oncology. Three databases were systematically searched, PsycINFO, PubMed, and CINAHL. Search terms included (fear OR anxiety OR thanatophobia) AND (recurrence OR progression OR death OR dying OR palliative OR end of life) AND (cancer OR oncology OR tumor). In addition, reference lists from especially relevant texts (e.g., review papers) were checked to identify additional articles. There was no restriction to publication years. Article titles and abstracts were reviewed by four independent reviewers (AL, FA, RB, and SB) to evaluate whether they included an assessment of fear of cancer recurrence, fear of dying, death anxiety, or a related existential issue in a sample of oncology patients. If the abstract was ambiguous or unclear, articles were retrieved, and the full text reviewed.

The review was restricted to texts that met the following inclusion criteria: (a) use of quantitative methods, (b) sample limited to cancer patient population, (c) provided a breakdown of specific cancer diagnoses if mixed sample, and (d) assessed fear and/or anxiety specific to death and/or cancer recurrence (i.e., not generalized anxiety). Texts were excluded if they (a) were not in a cancer population, (b) were qualitative explorations, or (c) did not include a measure of cancer-specific fear or existential fear (e.g., death anxiety).

Data Extraction

Once an article was identified for inclusion, researchers extracted the sample breakdown of oncology patients represented in the overall sample. Sample breakdowns were recorded to investigate the percentage of PBT patients included. Exclusion criteria were also coded by four independent reviewers. Relevant exclusion criteria to neuro-oncology were divided into explicit exclusion (e.g., no PBT or CNS disease) and criteria that may have excluded PBT patients implicitly (e.g., no cognitive impairment, no ongoing treatment, no terminal disease, or requiring curative treatment). No reporting of exclusion criteria was also coded. The first three independent coders recorded queries and issues during the data extraction process for exclusion criteria. When a query was recorded, the last author consulted the publication under question to confirm relevant information and address the discrepancy. Queries related to coding exclusion criteria were present for 9.7% of the articles.

For the studies that explicitly reported on PBT patients, a more thorough data extraction was undertaken by four reviewers (AL, FA, RB, and SB). Coding was then checked by the first author (AL) to determine accuracy. Coding was determined to be accurate and no discrepancies were found between coders. In these studies, coders tracked study design, measure characteristics, and three domains of relevant results: (1) demographic correlates of existential measures, (2) psychological and health-related correlates of existential measures, and (3) psychosocial interventions utilized to improve existential outcomes.

Results

Following the removal of duplicate records and an initial screen of title/abstract for significance, 1555 full-text articles were reviewed and considered for inclusion. Three hundred twenty-seven articles met criteria. Of these, only eight articles included PBT patients and are presented here for full review (Cho & Park, 2017; Cutshall et al., 2015; Engelmann et al., 2016; Goffaux et al., 2009; Langeveld, Grootenhuis, Voûte, de Haan, & van den Bos, 2004; Muñoz et al., 2008; Tsai, Wu, Chiu, Hu, & Chen, 2005; Zebrack & Chesler, 2002). See Fig. 1 for the full PRISMA flow diagram and Table 1 for an overview of the eight included studies.

Fig. 1.

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)

Table 1.

Existential literature including PBT patients in study design

Study	Study design	Overall sample	PBT sample	Domain assessed	Measure(s) used	Findings	PBT-specific results
Cho & Park (2017)	Cross-sectional	N = 292 • 91.8% White; 7.2% “Other” race • Age = 33.3 ± 7.1; range 18–47 • 80.5% female Years since   dx = 3.8 ± 2.8; range 0–16	N = 16 (5.5% of overall sample)	Fear of recurrence	Assessment of Survivor Concerns: Cancer Worry Subscale	• 49.1% Reported moderate-to-high or high fear of cancer recurrence • Fear of recurrence related to poorer physical and psychological QoL • Association between fear of recurrence and psychological QoL was moderated by perceived growth	None assessed
Cutshall et al. (2015)	Cross-sectional	N = 260 • 96.0% White, 1% Asian, 1 % Latino • Age = 64.6 ± 12.7; range not reported • 74.0% female • Years since dx presented categorically	N = 6 (2.3% of sample)	Fear of recurrence	Single item	• 52.0% of the sample reported fear of cancer recurrence represented “somewhat or more” of a bother • Fear of recurrence was the most prevalent endorsed concern	None assessed
Engelmann et al. (2016)	Cross-sectional	N = 77 • German (no further race/ethnicity reported) • Age = 57.5 ± 12.4; range 28–86 • 52.0% female • Years since   dx = 4.7 ± 4.0; range 1–19	N = 22 (28.6% of over all sample)	Death anxiety; fear of progression	DADDS (German version) Fear of Progression Questionnaire	• DADDS score = 13.3 ± 8.5 • Specific items associated with the most distress were feeling of being a burden to others, running out of time, and not knowing what happens near the end of life • Associated with depression, anxiety, fear of progression, and reduced QoL	None assessed
Goflaux et al. (2009)	Cross-sectional	N = 105 • Canadian (no further race/ethnicity reported) • Age = 47.4 ± 14.5; range not reported • 43.8% female • Years since dx not reported	N = 85 (81% of overall sample) • HG: 53.3% • LG: 16.2% • Met: 19.0% • Other: 11.4%	Fear of death	SNAS: a 30-item QoL measure developed by the authors; “symptom severity/fear of death” is one of 7 subscales	• Symptom severity/fear of death subscale not significantly associated with KPS, or treatment history (surgery, radiation, chemotherapy) • Those who were on AC Vs reported greater symptom severity/fear of death (P = . 03)	Sample size did not allow for analyses based on tumor characteristics
Langeveld et al. (2004)	Cross-sectional	N = 400 • Netherlands (no further race/ethnicity reported) • Age = 24.0 ± 4.9; range not reported • 45.0% female • Years since dx not reported	N = 43 (10.8% of sample)	Death concern; fear of recurrence	Worry Questionnaire with three subscales: cancer-specific concerns, general health concerns, present and future concerns	• Survivors reported significantly less worry about dying than healthy controls • 54.0% Reported worry about a cancer relapse • 50.0% Reported worry about having another cancer	None assessed
Muñoz et al. (2008)	Cross-sectional/mixed methods	N = 20 • 50.0% White, 5% Black, 15% Asian, 30% Latinx • Age = 45.8 (SD not reported); range 22.9–70.6 • 55.0% Female • Years since dx = 2.9 (SD not reported); range 0.3–7.4	N = 20 (100% of sample) • GBM: 35.0% • AA: 20.0% • Oligo: 15.0% • Other: 30.0%	Death anxiety, worry about condition worsening, fear of cancer spreading	Quality of Life—Cancer Survivor and FACT-Br (single items from validated measures)	• Worry about condition worsening was among the most negative concerns on the FACT-Br • Fear of cancer recurrence was among the most negative concerns on the QOLCS	None assessed
Tsai et al. (2005)	Longitudinal	N = 224 • Taiwanese (no further race/ethnicity reported) • Age = 62.1 ± 15.5; range not reported • 42.4% Female • Years since dx not reported	N = 3 (1.3% of overall sample)	Fear of death	Patient’s fear of death (scale of 1–5) was reported by members of the care team upon admission, 1 week after admission, and 2 days prior to death	• Older pts (> 65 years) reported greater fear of death 2 days before death; no age difference at earlier timepoints • Fear of death decreased throughout inpatient stay in both age groups	None assessed
Zebrack & Chesler (2002)	Cross-sectional	N = 175 • Race/ethnicity not reported • Age = 21.8 ± 3.3; range 16–28 • 57.4% Female • Years since   dx = 13.3 ± 5.7; range 3–27	N = 19 (10.9% of overall sample)	Fear of recurrence	Quality of Life—Cancer Survivor	• Most negatively rated concern in the psychological subscale was fear of cancer recurrence	None assessed

dx diagnosis, DADDS Death and Dying Distress Scale, QoL quality of life, HG high-grade tumor, LG low-grade tumor, Met metastasis, SNAS Sherbrooke Neuro-Oncology Assessment Scale, KPS Karnofsky Performance Status, ACV anticonvulsants, pts patients, SD standard deviation, GBM glioblastoma multiforme, AA anaplastic astrocytoma, Oligo oligodendroglioma, QOLCS Quality of Life—Cancer Survivor, FACT-Br Functional Assessment Cancer Therapy-Brain

Oncology Populations Represented in Investigations of Existential Distress

Across the 327 articles, 132,951 participants were represented. Death anxiety and/or fear of recurrence were most commonly assessed in breast (40.1%), colorectal (17.2%), prostate (12.2%), and gynecological cancers (7.2%). Less common cancer sites (< 7%) represented were gastrointestinal, genitourinary, head and neck, leukemia, lymphoma, melanoma, brain, and “other.” Articles including an “other” category provided a specific numeric breakdown of participants with more common types of cancer (e.g., breast), but also included a category of cancer types that were not further enumerated or described.

Representation of PBT in Investigations of Existential Distress

Individuals with a PBT diagnosis represented an extremely small proportion of the cancer populations assessed in this literature. Of the 327 articles, only eight included PBT patients and met criteria for full review. That is, out of the 132,951 total participants, only 0.18% were identified as PBT patients (n = 214). Within these 8 studies, PBT patients represented 13.8% (214 out of 1553; range 1.3–28.6%) of the total samples. Two studies (n = 125) focused exclusively on a brain tumor patients (Goffaux et al., 2009; Muñoz et al., 2008), though one (Goffaux et al., 2009) was not specific to PBT and included brain metastases (n = 20) in their sample. None of the studies with a mixed-diagnosis sample performed comparative analyses between cancer diagnoses in order to investigate within- or between-group differences with respect to death anxiety and/or fear of recurrence.

Neuro-oncology Specific Findings

Despite the limited representation of PBT in the reviewed literature, there were specific findings regarding topics assessed, methods used, and existential results identified.

Existential Topics Assessed in PBT Patients

All eight studies focused on existential distress. However, the domains in which they explicitly examined existential concerns varied. Fear of recurrence was examined in six of the eight studies (Cho & Park, 2017; Cutshall et al., 2015; Engelmann et al., 2016; Langeveld et al., 2004; Muñoz et al., 2008; Zebrack & Chesler, 2002) and death anxiety (i.e., fear of death or death concern) was examined in five (Engelmann et al., 2016; Goffaux et al., 2009; Langeveld et al., 2004; Muñoz et al., 2008; Tsai et al., 2005). Three of the eight studies examined both concepts (Engelmann et al., 2016; Langeveld et al., 2004; Muñoz et al., 2008).

Methods Used to Assess Existential Concerns Among Individuals with PBT

The methodological approach varied widely even within the small number of studies included for review. Measures ranged from single-item assessments (e.g., “How much does fear of recurrence bother you?”) to validated, multidimensional questionnaires (e.g., Functional Assessment Cancer Therapy—Brain and Death and Dying Distress Scale). The majority of studies used a cross-sectional approach, with only one study implementing a longitudinal design (Tsai et al., 2005), and another study combining cross-sectional data collection with qualitative analysis of interviews (Muñoz et al., 2008). None of the mixed cancer samples divided the oncology subgroups or were sufficiently powered to allow for within- or between-group comparisons.

Existential Results Among Individuals with PBT

Of the eight studies including PBT participants, three themes were identified: existential prevalence (Cho & Park, 2017; Cutshall et al., 2015; Engelmann et al., 2016; Langeveld et al., 2004), demographic correlates (Goffaux et al., 2009; Tsai et al., 2005), and association of existential concerns with QoL (Cho & Park, 2017; Engelmann et al., 2016; Muñoz et al., 2008; Zebrack & Chesler, 2002). Prevalence rates in fear of cancer recurrence were approximately 50%. Demographically, results suggested that fear decreased through hospital durations, yet older patients (> 65 years old) report increased fear in the days prior to death (Tsai et al., 2005). Those on anticonvulsants reported increased fear of death; however, there appeared to be no association between fear and Karnofsky Performance Status or history of surgery, radiation, or chemotherapy. Fear of cancer recurrence was the most negatively rated subscale when assessing QoL in multidimensional measures. Death anxiety and fear of cancer recurrence both appear to be related to heightened symptoms of depression and anxiety, and reduced overall QoL (Cho & Park, 2017; Engelmann et al., 2016; Muñoz et al., 2008). None of these eight studies investigated the effects of treatment approaches for existential concerns.

Exclusion Parameters

In order to fully examine the possible reasons for the relative paucity of PBT patients included in the literature, we also reviewed the inclusion/exclusion criteria of the above-referenced 327 articles in order to assess whether individuals with PBT could have been excluded from participation, and why (Table 2). The above findings may be complicated by poor reporting methods, papers frequently included an “other cancer diagnosis” category in their sample break-down without providing additional information regarding the types of cancer that could be included. Based on the relevant exclusion criteria of CNS disease, cognitive impairment and specified treatment characteristics (e.g., off treatment or curative treatment), we determined that at least 245 of 319 studies (76.8%) could have either directly or indirectly excluded those with a diagnosis of PBT from participation.

Table 2.

Study 1 exclusion parameters

Exclusion criteria	Count (out of 319)	Percentage (out of 319)	Notes	Could exclude PBT
Not reported	67	21	Issue of poor reporting and heterogeneity of sample	X
Cognitive impairment	47	15	Often not defined	X
Metastatic disease	52	16	Any metastases
Brain metastases	5	2	Explicit exclusion of brain metastases
CNS disease/primary brain tumor	4	1	Explicit exclusion of PBTs	X
Off treatment	81	25	Not currently being treated	X
Curative treatment	13	4	Intent of treatment is to cure	X
No recurrent or terminal disease	63	20	Often poorly defined	X
Other	46	14	For example, ongoing or synchronous disease	X
Not explicitly stated	74	23	Inclusion criteria specified, but nothing specific to the categories above	X

Categories are not exclusive of one another. Studies could be coded for several exclusion criteria. The number 319 includes the total number of studies that were included in the review

Secondary Investigation: Preliminary Investigation of Fear of Dying in PBT Patients

Methods

Design and Participants

In order to determine a preliminary prevalence of fear of dying and its relationship with symptoms of depression in a small PBT sample, a cross-sectional analysis of data obtained during the course of patient care at an urban National Cancer Institute-designated Hospital Cancer Center was examined. Patients were recruited following neuropsychological evaluations, which are standard-of-care for all brain tumor patients at this cancer center. Ethical approval was granted from the Institutional Review Board and written informed consent was obtained for all study patients. Inclusion criteria were as follows: (1) confirmed PBT diagnosis via histopathology; (2) a minimum of 2 weeks post-surgical resection or biopsy (if applicable); and (3) English speaking. Patients were included if they were able to provide informed consent as indicated by the ability to understand their choice to participate in or decline participation, express understanding of risks/benefits, as well as ability to understand the questions on the survey provided. One hundred and two patients (age range 19–81 years) with PBT (grades I–IV) were included.

Measures

Beck Anxiety Inventory (BAI; Beck & Steer, 1993)

The BAI is a 21-item self-report inventory of anxiety symptoms in adults with high internal consistency (Cronbach’s α = .92) and test–retest reliability, r(81) = .75 (Beck, Epstein, Brown, & Steer, 1988). Each symptom is rated on a 4-point scale ranging from 0 to 3: 0 (not at all), 1 (mildly, It did not bother me much), 2 (moderately, It was very unpleasant, but I could stand it), and 3 (severely, I could barely stand it). To assess fear of dying, a single-item question from the BAI was used. This single item (Question #16) asked respondents to rate “Fear of Dying” on the same 4-point scale as described above. For the purposes of the present study, if patients endorsed a 1 through 3 (i.e., mild, moderate, or severe Fear of Dying) on this single item, they were considered to endorse fear of dying.

Beck Depression Inventory: Second Edition (BDI-II; Beck, Steer, & Brown, 1996)

The BDI-II is a 21-item self-report inventory that evaluates the severity of depressive symptoms in adolescents and adults with good internal consistency (α = .92 in clinical sample, α = .93 in nonclinical sample) and high test–retest reliability (r = .93) (Beck et al., 1996). Each symptom is rated on an item-specific 4-point scale ranging from 0 to 3, with total scores ranging from 0 to 63. The score for the 21 items is based on the patients’ responses in regard to each symptom over the past 2 weeks, which is then summed to yield a single score to determine the depression severity. The following guidelines have been proposed to interpret the scores: 0–13 = minimal depression, 14–19 = mild depression, 20–28 = moderate depression, and 29–36 = severe depression.

Statistical Analysis

Data analyses were conducted using SPSS 24. Demographic (age, gender, and ethnicity) and medical variables (tumor classification, tumor grade, and treatment) were analyzed for sample description. Frequencies were run to determine fear of dying prevalence in PBT. χ², Independent samples t tests, and analyses of variance were used to compare sample demographics (age, gender, tumor grade) and fear of dying endorsement. Independent samples t tests were also used to compare levels of depression between fear of dying endorsement. Correlations were used to determine the relationship between fear of dying severity and depressive symptomology.

Results

Demographics

The sample was predominantly White (87%), male (53%), and diagnosed with glioblastoma multiforme (42%), followed by oligodendroglioma (22%) and astrocytoma (20%). Approximately 79% of patients underwent initial resection of tumor, 48% underwent radiation treatment, and 46% were subjected to at least one cycle of chemotherapy at the time of evaluation. Table 3 provides full demographics of the patient sample.

Table 3.

Demographics of primary brain tumor patients

Demographic	Frequency	Mean/percent
Age	N = 102	50.1 yrs (range 19–81 yrs)
Gender
Male	54	52.9%
Female	48	47.0%
Race
White	89	87.3%
African American	12	11.8%
Other	1	0.9%
Tumor type
Infiltrative meningioma	6	5.9%
Astrocytoma	20	19.6%
Oligodendroglioma	22	21.6%
Glioblastoma multiforme	43	42.2%
CNS lymphoma	4	4.0%
Other	l	6.7%
Tumor grade
Low	35	34.3%
High	67	65.7%
Therapy
Resection	81	79.4%
Radiation	49	48.0%
Chemotherapy	47	46.1%

CNS central nervous system, yrs years

Prevalence and Relation with Emotional Distress

Of the 102 participants, 31.4% (n = 32) endorsed a fear of dying on the BAI (see Fig. 2). Fear of dying endorsement was comparable between age, gender, and tumor grade (p > .05). Of the 32 who endorsed fear, 37.5% (n = 12) selected mild severity (It did not bother me much), 43.8% (n = 14) selected moderate severity (It was very unpleasant, but I could stand it), and 18.8% selected severe severity (I could barely stand it; see Fig. 2). Overall, this PBT sample reported mild depression on the BDI-II (M = 13.85, SD = 9.27; range 1–48) with 57.8% (n = 59) endorsing minimal, 18.6% (n = 19) mild, and 23.5% (n = 24) moderate to severe symptoms. There was a significant difference in depression scores (BDI-II) for those who endorsed fear (M = 16.7; SD = 11.1) when compared to those who did not (M = 12.6; SD = 8.1); t(100) = 2.10, p = .04 (see Fig. 3). There was also a positive correlation between fear of dying severity and overall depression (BDI-II; r = 0.33, p < 0.001) with fear of dying severity being significantly related to the following depressive symptoms on the BDI-II (in order of relation strength): loss of interest (r = .466, p < .001), changes in appetite (r = .338, p < .001), self-dislike (r = .331, p < .001), self-criticalness (r = .306, p < .01), pessimism (r = .301, p < .01), guilt (r = .291, p < .01), suicidal thoughts or wishes (r = .268, p < .01), loss of pleasure (r = .224, p < .05), and sadness (r = .213, p < .05).

Fig. 2.

Fear of dying prevalence and severity in primary brain tumor sample

Fig. 3.

Level of depression by fear of dying endorsement group. Note BDI-II Beck Depression Inventory-Second Edition

Discussion

The purpose of our primary objective was to identify the frequency of PBT patients’ inclusion in the psycho-oncology literature on existential distress, defined as fear or death, dying, or disease recurrence. Results were dismal, with only 0.18% of the participants identified as PBT patients. These results demonstrate that in current psycho-oncology literature, PBT patients are largely missing. This conclusion is exacerbated by the relatively large combined sample size from the 327 reviewed studies (N = 132,951). Death anxiety and fear of recurrence were most often assessed in breast (40.1%), colorectal (17.2%), prostate (12.2%), and gynecological cancers (7.2%). According to the American Cancer Society (2019a), these populations were estimated to be among the most commonly diagnosed cancer types (breast = 15.4%, colorectal = 5.85%, prostate = 9.9% and gynecological = 6.2%). However, despite brain tumors being less common (1.4%) than other cancers, the representation of cancer types in existential investigations has been skewed. According to our review, breast, colorectal, and prostate patients were overrepresented, while studies only captured 11% of the proportionate PBT population (0.18% of studied cancer population compared to 1.4% of diagnosed cancer types). If as a field we were trying to ensure corresponding distribution in the psycho-oncology existential literature, we are falling short.

Importantly, the rate of death is much greater in brain cancer. For example, the 5-year relative survival rate of breast cancer diagnosed at any Surveillance, Epidemiology, and End Results stage is 91%, colorectal is 65%, prostate is 99%, and gynecological is 69–83%, while the 5-year relative survival rate of brain cancer is 35% (ACS, 2019a) (e.g., glioblastoma multiforme ranges from 5 to 19%, anaplastic astrocytoma from 14 to 54%, and oligodendroglioma from 46 to 70%) (ACS, 2019c). PBT diagnoses are noncurative, suggesting this population is at an increased risk for existential distress (Tomer & Eliason, 1996). However, according to our results, most researchers (up to 76.8%) focused on other oncology populations or applied exclusion criteria, which may have unintentionally/unknowingly, eliminated PBT patients from participation. This included ruling out participants with cognitive impairment and/or specific treatment parameters (e.g., off treatment for specified time period/curative treatment). The exclusion of this population leaves neuro-oncology healthcare providers unaware of the prevalence of existential distress in their patients, with little to no guidance regarding the screening, monitoring, and treatment of this distress when it does manifest. While certainly some of the current literature can be used to guide research in PBT patients, the distinctiveness of the disease, treatments, and its cognitive/functional effects warrant specialized attention and investigation.

Of the eight articles identified which included PBT patients, only two were focused exclusively on neuro-oncology (Goffaux et al., 2009; Muñoz et al., 2008) and the rest examined mixed cancer samples with a limited amount of PBT patients (1.3–28.6%). None of the mixed cancer samples divided the oncology subgroups or were sufficiently powered to allow for within- or between-group comparisons. However, despite the existential oncology literature being dominated by other cancer types, we can derive from the small body of literature that includes PBT patients that death anxiety and fear of cancer recurrence appear to be related to heightened symptoms of both depression and anxiety, and reduced overall QoL (Cho & Park, 2017; Engelmann et al., 2016; Muñoz et al., 2008).

Prevalence rates in fear of cancer recurrence were approximately 50%, yet again these findings were not limited to PBT patients alone and are thus confounded by rates in other cancer groups given the pre-identified challenges of mixed-sample reporting. When overall QoL was assessed, fear of cancer recurrence was typically the most negatively rated subscale. Unfortunately, in addition to the challenges presented in mixed sampling, there is almost no longitudinal data available across disease or treatment trajectory as most research was cross-sectional by design. Furthermore, several studies used single-item and unvalidated measures of existential distress. In fact, only one (Engelmann et al., 2016) of the eight articles used a developed measure with established reliability and validity specific to existential distress (e.g., death and dying; DADDS). This is not due to a lack of validated scales; there are several published scales measuring aspects of existential distress including fear of cancer recurrence (Humphris, Watson, Sharpe, & Ozakinci, 2018), fear of cancer progression (Kwakkenbos et al., 2012), and death anxiety (Abdel-Khalek, 2011; Templer, 1970). The other seven either used a single question of fear/worry (n = 2; Cutshall et al., 2015; Tsai et al., 2005) or presented subscale results from a larger QoL index score (n = 5; Cho & Park, 2017; Goffaux et al., 2009; Langeveld et al., 2004; Muñoz et al., 2008; Zebrack & Chesler, 2002). With the lack of analysis of sample subgroups, conclusions regarding demographic and/or medical correlates with death anxiety or fear of cancer recurrence in the neuro-oncology population were difficult to examine.

As a secondary aim, we preliminarily investigated the prevalence of fear of dying in an adult PBT sample. Results determined approximately one-third of PBT patients endorsed a fear of dying. While this is less than other cancer populations in general (42%; Gonen et al., 2012b), these results are consistent with advanced cancer populations (32%; Neel, Lo, Rydall, Hales, & Rodin, 2015). These prevalence rates suggest that aside from the known physical and cognitive effects, a diagnosis of brain cancer has troubling psychosocial effects, including existential fears. Furthermore, our study identified a positive relationship between fear of dying and depressive symptoms (specifically loss of interest, changes in appetite, self-dislike, self-criticalness, pessimism, guilt, suicidal thoughts or wishes, loss of pleasure, and sadness), suggesting that this fear is also associated with and potentially contributes to additional symptoms of distress, such as depression. This aligns with the literature presented above (Engelmann et al., 2016) and supports increased efforts in understanding distress in PBT patients.

Depression is rapidly becoming one of the most pressing public health challenges in the world (Marcus, Taghi Yasamy, van Ommeren, Chisholm, & Saxena, 2012) and requires attention due to the adverse effects on psychological well-being and QoL (Grassi et al., 1996), association with noncompliance during medical treatment (Colleoni et al., 2000), relational distress in caregivers (Braun, Mikulincer, Rydall, Walsh, & Rodin, 2007), and increased health care utilization (Prieto et al., 2002). Depression is nearly six times more prevalent in PBT patients (40%; Pelletier, Verhoef, Khatri, & Hagen, 2002) than the general population (7%; American Psychiatric Association, 2013) and three times more prevalent than other oncology populations (13%; Linden, Vodermaier, MacKenzie, & Greig, 2012). Given the positive relationship between fear of dying and depression, understanding the risk factors for and effects of fear of dying and/or cancer recurrence in PBT patients has strong clinical relevance. Reducing this fear may lessen factors related to it, such as sadness, hopelessness, agitation, fatigue, and difficulty concentrating, all of which are symptoms of depression and should therefore be a consideration in PBT patient treatment. Unfortunately, emotional distress in these patients is often avoided, undetected, and untreated (Fallowfield, Ratcliffe, Jenkins, & Saul, 2001; Mitchell, Vaze, & Rao, 2009). Patients with advanced cancer are frequently not referred for psychosocial care, and of those referred, most do not receive specific or adequate treatment (Ellis et al., 2009). Quality existential support should include screening and monitoring existential distress, providing compassionate care by trained professionals, and prioritizing specialized psychological support across the continuum of care. Greater insight into the burdens of PBT diagnosis may help providers discuss these issues with their patients, thereby optimizing their prognosis and QoL.

Limitations and Future Directions

The current study has several limitations. First, we did not critically evaluate the methodological quality of the studies included for review. While general information was systematically extracted from these studies, a rigorous evaluation of their study design, analyses, and contributes was beyond the scope of this paper and could be a potential area for future research. Furthermore, recent reviews of fear of cancer recurrence (e.g., in breast cancer patients; Koch, Jansen, Brenner, & Arndt, 2013) have evaluated study quality. With only eight studies including PBT patients, little could be gained from further study evaluation. More research is needed to evaluate trends, design, and draw conclusions. Though we searched three databases and references of relevant papers, it is possible that existing studies failed to use the same key words as described here and were thus overlooked or missed when compiling studies for this review. Further, the small sample size of studies including samples with PBT participants limits our ability to draw thematic conclusions or conduct a meta-analysis based on extant literature.

Secondly, during our preliminary investigation of fear of dying in PBT patients, fear of dying was measured using a single-item question on a measure designed to assess symptoms of anxiety generally, not specific to death anxiety. While there is evidence that single-item measures can be valid and reliably used to assess a single construct (Elo, Leppänen, & Jahkola, 2003; Robins, Hendin, & Trzesniewski, 2001), more comprehensive assessment of fear of dying may be indicated given the potentially complex nature of fear of dying (e.g., fear of dying process, being forgotten, after-life). However, despite other measures assessing fear of dying as a multidimensional construct (Death Distress Scale; Abdel-Khalek, 2011), it has also been measured as a distinct single construct (Death Anxiety Scale; Templer, 1970; Death and Dying Distress Scale; Lo et al., 2011). In fact, Lo and colleague’s Death and Dying Distress Scale found a positive correlation between fear of dying and depression similar to the relationships observed in the current study. As also mentioned in the current literature review, future research should use validated measures of anxiety specific to death and dying to better understand the construct in PBT patients. Additionally, qualitative research, such as focus groups with PBT patients or case studies of patients’ in therapy focused around end-of-life issues, would complement quantitative methods by elucidating additional themes for further investigation. Nonetheless, the targeted approach to measuring this construct in the present study serves as a foundation for future work using more robust measures. A larger sample size would also be beneficial to increase statistical power and generalizability of results. Future research should investigate the relationship between fear of dying and other factors such as disease prognosis, patient functional status, tumor characteristics (which have implications on prognosis), religiosity, and existential beliefs. Additionally, the exclusion of data beyond baseline examinations may prevent the development of a comprehensive picture of fear of dying in PBT patients over the course of their disease. Therefore, future studies should investigate fear of dying longitudinally in PBT patients to determine whether changes in fear of dying are related to changes in psychological distress or QoL and whether these markers are related to disease course. Despite these limitations, the present study represents a nascent and necessary step in our understanding of existential themes in PBT patients and can not only promote but also inform essential future investigations in this population.

Implications for Clinical Practice

Investigations of existential distress in PBT patients will only be as useful as their contribution to enhanced supportive services for this population. Understanding the existential fears and their correlates in neuro-oncology should inform screening and psychotherapeutic treatment. Based on the limited number of PBT patients in research on existential distress, it is possible this reflects a similar limitation within clinical settings. Therefore, several recommendations can be made based on this preliminary research to advance not only the science but the available services within neuro-oncology. First, screening of existential distress, to include death anxiety and fears of recurrence, should be included at relevant intervals throughout diagnosis and treatment in PBT patients. However, similar to the recommendations for mental health screening in primary care (Siu et al., 2016), this should only be done when appropriate services exist for in-house treatment or referrals. Thus, second, an effort to involve more psychologists and mental health professionals in the neuro-oncology treatment team is vital to providing adequate treatment of the whole patient. Third, based on the scarcity of psycho-oncology research in PBT patients and the general stigma of existential distress, it is recommended that interdisciplinary members of the treatment team receive brief, introductory training in psychotherapy for death anxiety. For example, Managing Cancer and Living Meaningfully, a psychotherapy for advanced cancer patients and their caregivers, has been shown to be effective when delivered by providers from several disciplines (e.g., psychiatrists, psychologists, social workers, and nurses; Lo et al., 2016).

Conclusion

In sum, there is a dearth of literature exploring death anxiety and fear of cancer recurrence in PBT patients. Despite being an at-risk noncurative cancer population, PBT patients may potentially be excluded from studies via specific study design parameters—even in mixed-sample investigations where there is no focus on a specific cancer population. At present, without informative investigations, neuro-oncology professionals are left unaware of the existential distress in their patients, and ultimately left without evidence-based treatments to improve QoL. The present study sought to not only examine the current literature but also begin to fill the identified gap in PBT patient samples. Findings from our secondary original study propose that fear of dying is prevalent in PBT patients and associated with depressive symptomology, suggesting a need for attention and further research into existential issues among PBT patients. Increasing overall PBT survival calls for more existential support and palliative care, including both awareness and education to the psychological well-being of the patient and their QoL.