Systematic Review and Meta-Analysis Medicine ®

OPEN

Are spiritual interventions beneficial to patients

with cancer?
A meta-analysis of randomized controlled trials following PRISMA
∗
Lu Xing, MNa,b, Xiujing Guo, PhDa,b, Lu Bai, BNa,b, Jiahui Qian, MPHc, Jing Chen, MNa,b,

Abstract
Background: In addition to the physical burden, the quality of life and survival in patients with cancer may also be reduced because
of psychological distress, such as spiritual crisis, anxiety, and depression. Many studies have verified that spirituality could reduce
anxiety and depression and improve quality of life and adjustment to cancer. However, there is uncertainty regarding the effectiveness
of spiritual interventions in patients with cancer. The purpose of this meta-analysis is to use randomized controlled trials (RCTs) to
evaluate the effects of spiritual interventions on spiritual and psychological outcomes and quality of life in patients with cancer.
Methods: All RCTs using spiritual interventions relevant to the outcomes of patients with cancer were retrieved from the following
databases: Embase, PubMed, PsycINFO, Ovid, Springer Online Library, Wiley Online Library, Oxford Journals, the Cochrane
Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials. The reference lists of identified RCTs were
also screened. The Cochrane risk of bias tool was used to evaluate the quality of the studies, RevMan (5.3) was used to analyze the
data, and GRADE (3.6.1) was used to evaluate the evidence quality of the combined results.
Results: Ten RCTs involving 1239 patients were included. Spiritual interventions were compared with a control group receiving
usual care or other psychosocial interventions. The weighted average effect size across studies was 0.46 (P = .003, I2 = 78%) for
spiritual well-being, 0.19 (P = .005, I2 = 46%) for quality of life, 0.33 (P = .01, I2 = 50%) for depression, 0.58 (P = .03, I2 = 77%) for
anxiety, and 0.38 (P = .008, I2 = 0%) for hopelessness. In subgroup analysis according to the type of cancer, only the weighted
average effect size of spiritual well-being in patients with breast cancer had statistical significance (standardized mean difference
0.78, P = .01, I2 = 70%).
Conclusion: Spiritual interventions may improve spiritual well-being and quality of life, and reduce depression, anxiety, and
hopelessness for patients with cancer. However, due to the mixed study design and substantial heterogeneity, some evidence
remains weak. More rigorously designed research is needed.
Abbreviations: CI = confidence interval, RCT = randomized controlled trial, SMD = standardized mean difference.
Keywords: cancer, depression, meta-analysis, quality of life, spirituality

1. Introduction improved with advancements in medical sciences, the diagnosis of

cancer is still regarded as a tragic and life-threatening event.
Currently, cancer is highly prevalent in the world. It caused 13% of
Emotional problems may be caused by hearing “cancer,”
all deaths in 2015 and is the 2nd-leading cause of mortality after
informing relatives about the disease, planning for treatment
cardiovascular diseases.[1] Although the survival of cancer has
and surgery, and side effects of treating. Therefore, in addition to
the physical burden, patients with cancer may also be susceptible to
Editor: Massimo Tusconi.
suffering from deep psychological distress, such as spiritual crisis,
This work was funded by the Sichuan Provincial Health Department (130127),
depression, anxiety, phobia, and anger,[2–6] which in turn can lead
which provided financial support and supervised our job schedule.
to adverse outcomes.[7,8] So maintaining spiritual and psychologi-
The authors have no conflicts of interest to disclose.
a
cal well-being is an important issue for patients with cancer.
Department of Gynecology, West China Second University Hospital, Sichuan
Currently, an increasing number of patients with cancer tend to
University, b Key Laboratory of Birth Defects and Related Diseases of Women
and Children, Sichuan University, Ministry of Education, c West China School of seek complementary therapies to cure their disease and relieve their
Public Health, Sichuan University, Chengdu, Sichuan, China. discomfort, and spirituality has been described as the most
∗
Correspondence: Jing Chen, Department of Gynecology, West China Second commonly used complementary therapy by patients with cancer.[9]
University Hospital, Sichuan University, Key Laboratory of Birth Defects and Till now, because spirituality has been defined from various
Related Diseases of Women and Children, Sichuan University, Ministry of perspectives by different researchers, it does not have a consensus
Education, Chengdu, Sichuan 610041, China (e-mail: [email protected]).
definition.[10,11] A relatively comprehensive and accurate defini-
Copyright © 2018 the Author(s). Published by Wolters Kluwer Health, Inc. tion of spirituality is “the aspect of humanity that refers to the way
This is an open access article distributed under the terms of the Creative
Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-
individuals seek and express meaning and purpose, and the way
ND), where it is permissible to download and share the work provided it is they experience their connectedness to the moment, to self, to
properly cited. The work cannot be changed in any way or used commercially others, to nature and to the significance of the sacred.”[12]
without permission from the journal. Previous studies have reported the following: spirituality is a
Medicine (2018) 97:35(e11948) strong predictor and promoter of psychological health[13]; it can
Received: 13 May 2018 / Accepted: 27 July 2018 increase resistance against mental health crises following the
http://dx.doi.org/10.1097/MD.0000000000011948 diagnosis and treatment of cancer in patients[14]; and its effects on

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Xing et al. Medicine (2018) 97:35 Medicine

decreasing anxiety and depression, slowing the progression of (1997 to January 2018), Oxford Journals, the Cochrane
cancer, encouraging a healthier lifestyle, and improving quality of Database of Systematic Reviews, 2018, and the Cochrane
life and adjustment to cancer have also been confirmed.[15–19] In Central Register of Controlled Trials, 2018. The search terms
addition, 2 previous literatures suggested that nearly 85% to consisted of MeSH (medical subject headings) and the following
90% of the patients with cancer have reported they are spiritual keywords: (spirituality OR (spiritual intervention OR spiritual
and that spirituality is important in their lives.[20,21] In another care OR religiosity)) AND (neoplasms OR (tumor OR cancer OR
study, 78% of patients with cancer reported that spirituality was malignant neoplasms OR benign neoplasms)) AND (randomized
important to help them cope with their cancer experience.[22] controlled trial OR randomized). We also searched the reference
Therefore, spirituality is very important for the illness and in lists of original reports, case reports, guidelines, letters to the
healthcare practice. editor, reviews, and meta-analyses retrieved through electronic
However, the conclusions of the efficacy of spiritual searches for additional articles.
interventions on spiritual and psychological outcomes in patients
with cancer are inconsistent. In some studies, spiritual inter-
2.3. Data extraction and quality assessment
ventions demonstrated significant improvement in the psycho-
logical outcomes of patients with cancer,[23–25] but others have Titles and/or abstracts of studies retrieved using the above-
failed to find any improvement. For example, a study showed that mentioned search strategy and those from additional sources
in 85 patients with cancer, improving spirituality could not were screened independently by 2 review authors (XG and LB) to
statistically relief levels of depression and anxiety.[26] Koszycki identify studies that potentially met the inclusion criteria outlined
et al[27] also reported that spiritually based intervention had no above. For studies that potentially fulfilled the inclusion criteria,
impact on psychological adjustment improvement among we searched the full papers, which were assessed independently
patients with cancer. Therefore, the purpose of this meta-analysis by the same 2 authors. The same 2 authors also used a
is to use randomized controlled trials (RCTs) to evaluate the predesigned data collection form (Microsoft Office Excel 2013,
effects of spiritual interventions on the spiritual and psychologi- Microsoft, Redmond, WA) to extract all the data independently.
cal outcomes and quality of life of patients with cancer. The following information was collected: study design, study site,
participant inclusion and exclusion criteria, cancer type, sample
size (the 2 groups and the total size), mean and standard deviation
2. Methods
of the 2 groups, spiritual interventions (method, frequency,
All analyses were based on previously published studies. Thus, durations of each session, and total interventions), control
ethical approval and patient consent were not necessary. interventions, outcomes, and measures. Information used to
evaluate the risk of bias for each study was also collected,
including methods used to generate the randomization, allocation
2.1. Study selection
concealment, blinding, incomplete outcome data, and selective
All the studies were screened and selected by 2 independent reporting. The data were entered twice into Review Manager
review authors (LX and XG). The prespecified eligibility criteria (RevMan, Version 5.3, The Cochrane Collaboration, London).
were as follows—types of studies: RCTs that compared the effects We defined spiritual well-being and quality of life at post-
of spiritual interventions with a control group on patients with treatment as our primary outcomes (for any measure used). As
cancer; types of participants: patients aged above 18 and associated symptoms of spiritual distress in patients with cancer,
diagnosed with cancer; we accepted each individual trial’s degree of depression, anxiety, and hopelessness at post-treatment
exclusion criteria of participants; types of spiritual interventions: were combined as secondary outcomes. After extraction, all data
psychosocial or psychological interventions in which the primary were checked by another author (JC), and discrepancies were
or secondary aim is to enhance spirituality, that is, including at resolved by discussion. We sent letters to the authors of the
least one active spiritual component that aims to directly increase studies retrieved to clarify missing or unclear data.
spirituality or spiritual well-being; types of control groups: wait- The risk of bias assessment was conducted independently by 2
list control group, standard care, alternative intervention, and no authors (LX and JQ), and disagreements were discussed with a
treatment were included; types of outcome measures: spiritual third author (JC). The Cochrane risk of bias tool was used for the
well-being, quality of life, degree of depression, anxiety, and assessment of random sequence generation, allocation conceal-
hopelessness of interventional and control groups must be ment, blinding of participants and personnel, blinding of outcome
evaluated at post-treatment (for any measure used); sample size: assessment, incomplete outcome data, selective reporting, and
no requirement; type of journal: published in peer-reviewed other bias. Each domain was rated as low (unlikely to seriously
journals; and publication language: English only. If a duplicate alter the results), unclear, or high (seriously weakens confidence in
publication was identified, we used the most relevant publication. the results). The possibility of bias is minimal when all the criteria
We excluded retracted studies. After assessment, we resolved are met (grade A), and grade B has a medium possibility of bias
disagreements between the 2 authors through discussion with a occurring. If the criteria are not met at all, the possibility of bias is
third reviewer (JC). high and the grade is C. We acknowledge that it may be difficult to
achieve blinding of participants, therapists/investigators, and
outcome evaluators in trials using spiritual interventions.
2.2. Search method
We developed and conducted a comprehensive search of
2.4. Data synthesis and statistical analysis
published and unpublished RCTs using a wide range of scientific
medical and psychological databases, including Embase (1980 to Two review authors entered data separately (LB and JQ), and we
January 2018), PubMed (1966 to January 2018), PsycINFO conducted the meta-analysis using RevMan.
(1806 to January 2018), Ovid (1966 to January 2018), Springer For RCTs, heterogeneity was analyzed by conducting the chi-
Online Library (1997 to January 2018), Wiley Online Library squared test (P of .05 was used for statistical significance) and the

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I2 test. The higher the percentage was, the higher the level of 3.2. Study characteristics
heterogeneity.[28] If P > .10 and I2 < 50%, we considered the The participants in the 10 RCTs were all patients with cancer. Of
heterogeneity to be insufficient, and a fixed-effects model was these, 7[24,25,31–35] and 5[31–34,36] studies identified spiritual well-
used to pool data; if P < .10 and I2 > 50%, we considered the being and quality of life, respectively, as the main outcome. Of the
heterogeneity to be substantial, so we used a random-effects 10 studies, 6 adopted five types of spiritual interventions,
model to summarize the results. including meaning-centered psychotherapy,[31,32] mindfulness-
Continuous data were pooled as the standardized mean based intervention,[35] imagination,[33] meditation,[37] and pray-
difference (SMD) with a 95% confidence interval (CI). We used er;[34] the other 4[7,24,25,36] did not focus on a specific spiritual
forest plots and funnel plots. The funnel plots can indicate intervention method; rather, they included a specifically designed
possible publication bias, evidence of asymmetry, and other small integrated intervention called a spiritual care program or a
study effects.[29] In addition, GRADE (3.6.1, The GRADE spirituality-based intervention. No matter what spiritual inter-
Working Group) was adopted to rank the evidence quality. ventions were used, these methods had a large degree of overlap.
Because some included studies examined patients with all kinds All studies described their control methods. Among them, 2 trials
of cancer and some studies recruited patients with a specific kind used wait-list control,[33,35] 2 trials used other psychotherapy
of cancer, we used subgroup analysis to check whether spiritual methods,[31,32] and another trial used no treatment[36] as a
interventions are beneficial to patients with different kinds of control. Standard care was performed in the other 5 trials, which
cancer. Finally, we followed the PRISMA (Preferred Reporting was described as routine treatment and education[25] and usual
Items for Systematic Reviews and Meta-Analyses) guidelines to care[7,24,34,37] in the original studies. For the measures, 4
report our findings.[30] trials[25,31,32,35] used the FACIT-SWB (Functional Assessment
of Chronic Illness Therapy Spiritual Well-Being Scale) to assess
3. Results spiritual well-being, whereas Musarezaie et al[24] used the SWB
Questionnaire (the Palutzian and Ellison Spiritual Well-Being
3.1. Results of the search Questionnaire), Olver and Dutney[34] and Freeman et al[33]
We identified 1087 records and ultimately recruited 10 studies adopted the FACIT-Sp (the Functional Assessment of Chronic
(Fig. 1). All 10 studies were RCTs involving a total of 1239 Illness Therapy Spiritual Scale). For quality of life, the McGill
patients with cancer for quantitative synthesis, and all were Quality of Life Questionnaire and the Functional Assessment of
reviewed by an institutional ethics committee before implemen- Cancer Therapy were used in 2[31,32] and 3[33,34,36] trials,
tation. Among the 1239 patients, 624 and 615 patients were respectively. Regarding the types of spiritual interventions, there
allocated into the intervention and control groups, respectively, were various frequencies and durations of interventions. The
after randomization. characteristics of the recruited studies are presented in Table 1.

Figure 1. Study flow diagram. RCT = randomized controlled trial.

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 Table 1
Characteristics of the included studies.
Sample Intervention
Intervention Control Study Duration Duration
Study Inclusion criteria Exclusion criteria group, n group, n design Study site Intervention group Frequency of once of total Control group Outcomes Measures
Breitbart et al[31] Stage III or IV solid tumor cancers or Significant cognitive impairment, psy- 40 37 RCT Outpatient clinics at IMCP: individual 1/wk 1h 7 wk TM: therapeutic mas- Spiritual well-being SWB
non-Hodgkin lymphoma; being ambu- chosis, Karnofsky performance scores Memorial Sloan-Ket- meaning-centered sage Quality of life MQOL
latory; age >18 years; speaking Eng- below 50; other physical limitations tering Cancer Center psychotherapy Depression HADS
lish that precluded participation Anxiety HADS
Hopelessness BHS
Breitbart et al[32] Stage IV cancer (or stage III cancer if Significant cognitive impairment or 67 58 RCT Outpatient clinics at MCGP: meaning-cen- 1/wk — 8 wk SGP: supportive psy- Spiritual well-being SWB
diagnosed with poor-prognosis dis- psychotic symptoms; physical limita- Memorial Sloan-Ket- tered group psy- chotherapy Quality of life MQOL
ease); English speaking; age >18 tions that impeded completion of inter- tering Cancer Center chotherapy Depression BDI
Xing et al. Medicine (2018) 97:35

years; ambulatory vention Anxiety HADS

Hopelessness HAI
Cole et al[37] Diagnosed with unresectable meta- Not physically able to attend the 13 19 RCT University of Pitts- SpM: spiritually 5/4 1h 16 wk UUC: usual care con- Quality of life MQOL
static melanoma intervention sessions; cognitive impair- burgh Melanoma, focused meditation trol Depression CES-D
ment; were hospitalized for treatments Center, Pittsburgh, PA
Freeman et al[33] Diagnosis of breast cancer; age ≥ 18; — 48 47 RCT Anchorage, AK; Seat- Imagery-based beha- 1/wk 4h 5 wk WL: waitlist control Spiritual well-being FACIT-Sp-Ex
with no major psychiatric illness; visual tle, WA vioral intervention Quality of life FACT-B
and hearing capable; able to read;
write and speak English; demonstrate
an orientation to person, place, and
time
Jafari et al[25] Age > 18 years; breast cancer With concomitant chronic disease and 34 31 RCT Breast Cancer Spiritual therapy inter- 1/wk 2–3 h 6 wk Standard management Spiritual well-being FACIT-Sp12
diagnosis within the last 12 months; a major depression disorder; absent in 2 Research Center, St. vention and treatment and Quality of life EORTCQLQ-C30
treatment recommendation of radiation consecutive sessions S. Al-Shohada Hospi- routine educational
therapy of at least 2 wk tal program
Moeini et al[7] Definitely diagnosed with leukemia by Unaware of disease; had mental retar- 32 32 RCT Intensive care unit of Spiritual care pro- 1/d 4h 3d Given treatment and Anxiety DASS-42
a hematologist; consented to partici- dation, blindness, deafness, or active Sayed-Al-Shohada gram: supportive pre- routine care
pate; Shiite, native Iranian, and Per- mental diseases; undergoing che- Hospital sence and support for
sian speaker motherapy, radiotherapy, or surgery; religious rituals
unwillingness to continue the study;

4
cannot participate or transfer patients
to another hospital
Musarezaie et al[24] A definite diagnosis of leukemia by a Unaware of their disease; mental 32 32 RCT Isfahan Oncology Spirituality-based 1/d 4h 3d Given treatment and Spiritual SWB
hematologist; undergoing chemother- retardation, blindness, deafness, or Health Center intervention: suppor- routine care well-being Questionnaire
apy, radiotherapy, or surgery; consent active mental diseases; unwillingness tive presence and
to participate; Shiite; age ≥ 18 years; to continue the study; cannot partici- support for religious
native Iranians and Persian speaking pate or transfer patients to another rituals
hospital
Olver et al[34] A cancer diagnosis; age ≥ 18; the — 324 322 RCT Royal Adelaide Hospi- Intercessory prayer — — — Usual treatments Spiritual well-being FACIT-Sp
ability to read English and give con- tal Cancer Centre, Quality of life FACT-G
sent; a prognosis of over 6 months for South Australia
survival; no participation in other stu-
dies
Rausch et al[36] Underwent initial surgical treatment; With significant cognitive impairment 4 5 RCT Specialty clinics of Spiritual growth group 1/wk 150 min 10 wk No-treatment and Quality of life FACT-B
about to begin adjuvant chemotherapy or psychiatric impairment Massey Cancer Cen- standard health care Depression CES-D
for stage I or II breast cancer; age ≥ ter
21; read and speak English; physically
capable of participating; providing
informed consent
Zernicke et al[35] Age ≥ 18; speak and read English; Concurrent self-reported diagnosis by 30 32 RCT Tom Baker Cancer MBCR: mindfulness- 1/wk 2h 8 wk Treatment-as-usual Spiritual FACIT-Sp
could complete questionnaires; diagno- medical professional of psychosis, Centre in Calgary, based cancer recov- wait-list control well-being
sis of any type/stage of cancer; bipolar disorder, substance abuse, or Alberta, Canada ery
completed primary cancer treatment suicidality (however, self-reported diag-
within the last 3 years; exhibited at nosis of a depressive, anxiety, or
least moderate distress as established adjustment disorder did not prevent
by Distress Thermometer score of 4 or enrollment); previous participation in
greater (out of 10); no access to an F2F MBSR
F2F MBCR program; access to high-
speed Internet; resident of Alberta

BDI = Beck Depression Inventory, BHS = the Beck Hopelessness Scale, CES-D = the Center for Epidemiological Studies-Depression scale, DASS-42 = 42-item depression, anxiety, and stress scale, EORTCQLQ-C30 = European Organization for Research and Treatment of Cancer
Quality of Life, FACIT-Sp = the Functional Assessment of Chronic Illness Therapy Spiritual Scale, FACIT-Sp12 = the Persian version of 12-item Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being questionnaire, FACIT-Sp-Ex = the Functional Assessment of Chronic
Illness Therapy Spiritual scale, FACT-B = the Functional Assessment of Cancer Therapy—Breast, FACT-G = the Functional Assessment of Cancer Therapy—General, HADS = Hospital Anxiety and Depression Scale, HAI = Hopelessness Assessment in Illness Questionnaire, MQOL =
McGill Quality of Life Questionnaire, RCT = randomized controlled trial, SWB Questionnaire = the Palutzian and Ellison Spiritual Well-Being Questionnaire, SWB = Functional Assessment of Chronic Illness Therapy Spiritual Well-Being Scale.
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Xing et al. Medicine (2018) 97:35 www.md-journal.com

Figure 2. Risk of bias graph: review authors’ judgments about each risk of bias item, presented as percentages across all included studies.

3.3. Risk of bias in the included studies

We used the Cochrane risk of bias tool to assess the risk of bias of
each study. We present them using a “risk of bias graph” (Fig. 2)
and a “risk of bias summary” (Fig. 3). For the 10 RCTs that we
included, only 1[7] was grade A, and the other studies were all
grade B. All studies were described as “randomized,” but 2 of the
studies did not report the randomization methods and procedures
in detail (20.0%). In addition, 5 of the studies did not describe the
allocation concealment in detail (50.0%), which may have
produced selection bias and prevented us from assessing the
influence of allocation concealment in the remaining studies.
Thus, the generalization of results may have been influenced.
Furthermore, because of the nature and method of the
implementation of spiritual interventions, it was difficult to
perform blinding, especially the blinding of participants and
personnel. Blinding of the participants and therapists/investi-
gators only occurred in 4 studies (40.0%), and 4 studies
conducted the blinding of outcome assessment (40.0%). This lack
of blinding may have induced performance bias in the original
articles. Except for the study by Jafari et al,[25] the other 9 studies
described the dropouts and the reasons for these dropouts, which
could help to prevent attrition bias to some extent, and all of them
used intent-to-treat analysis to analyze the data except for
Rausch.[36] All studies clearly reported all expected results to
avoid reporting bias except for Cole’s research.[37] Moreover, all
studies reported that there were no statistically significant
differences in age, sex, and other demographic data between
the intervention and control groups at baseline (P > .05). Finally,
the funnel plot for the primary outcomes “spiritual well-being”
and “quality of life” at post-treatment (Figs. 4 and 5) did not
appear to be totally asymmetrical, but because the number of
trials included was insufficient, the assessment of publication bias
may be inaccurate.

3.4. Efficacy of spiritual interventions

3.4.1. Spiritual well-being. Seven studies[24,25,31–35] involving
1134 patients (575 in the intervention group and 559 in the
control group) reported the effect of spiritual interventions on the
spiritual well-being of patients with cancer at post-treatment,
indicating a statistically significant difference between the effects
of the spiritual intervention and the control (SMD 0.46, 95% CI
0.16–0.76, P = .003; I2 = 78%, P = .0001) (Fig. 6). However, the
Figure 3. Risk of bias summary: review authors’ judgments about each risk of estimate was associated with a high level of uncertainty due to
bias item for each included study.
severe heterogeneity after a random-effects model was adopted.

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Figure 4. Funnel plot of comparison: spiritual intervention versus control

condition, outcome: spiritual well-being at post-treatment. SE = standard error, Figure 5. Funnel plot of comparison: spiritual intervention versus control
SMD = standardized mean difference. condition, outcome: quality of life at post-treatment. SE = standard error,
SMD = standardized mean difference.

3.4.2. Subgroup analysis of spiritual well-being. Because the 3.4.5. Degree of anxiety. Three studies[7,31,32] involving 266
included studies recruited patients with different kinds of cancer, patients (139 in the intervention group and 127 in the control
including breast cancer,[25,33] leukemia,[24] and other kinds of group) reported the effect of spiritual interventions on cancer
cancer,[31,32,34,35] we used subgroup analysis to check whether patients’ degree of anxiety and showed a significant difference
spiritual interventions can improve spiritual well-being for between the intervention and the control groups (SMD 0.58,
different cancer patients. We found that there was a significant 95% CI 1.12 to 0.05, P = .03; I2 = 77%, P = .01) (Fig. 10).
difference between the 2 groups only in patients with breast However, the estimate was associated with a high level of
cancer (SMD 0.78, 95% CI 0.17–1.39, P = .01, I2 = 70%, uncertainty due to severe heterogeneity after a random-effects
P = .07), but not among patients with all types of cancer (SMD model was adopted.
0.24, 95% CI 0.02 to 1.39, P = .07, I2 = 57%, P = .07) or
leukemia (SMD 0.23, 95% CI 0.26 to 0.73, P = .35) (Fig. 7). 3.4.6. Degree of hopelessness. Two studies[31,32] involving
202 patients (107 in the intervention group and 95 in the
3.4.3. Quality of life. Five studies[31–34,36] involving 923 patients control group) reported the effect of spiritual interventions on
(466 in the intervention group and 457 in the control group) cancer patients’ degree of hopelessness and showed a
reported the effect of spiritual interventions on quality of life at statistically significant difference between the 2 groups (SMD
post-treatment in patients with cancer. As shown in Fig. 8, there 0.38, 95% CI 0.65 to 0.10, P = .008; I2 = 0%, P = .85)
was a statistically significant difference between the intervention (Fig. 11).
and the control groups (SMD 0.19, 95% CI 0.06–0.32, P = .005;
I2 = 46%, P = .12).
3.5. Quality of evidence
3.4.4. Degree of depression. Four studies[31,32,36,37] involving GRADE was used to evaluate the quality of evidence. As shown
242 patients (124 in the intervention group and 118 in the control in Table 2, the outcomes for spiritual well-being—leukemia
group) reported the effect of spiritual interventions on cancer were graded as high evidence; meanwhile, the evidence grades
patients’ degree of depression at post-treatment, indicating a for other spiritual well-being were moderate. The evidence
statistically significant difference between the spiritual interven- grades for degree of depression, anxiety, quality of life were
tion and the control groups (SMD 0.33, 95% CI 0.59 to low, and the evidence quality for degree of hopelessness was
0.08, P = .01; I2 = 50%, P = .11) (Fig. 9). very low.

Figure 6. Forest plot of comparison: spiritual intervention versus control condition, outcome: standardized mean difference for spiritual well-being at post-
treatment. CI = confidence interval, SD = standard deviation.

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Figure 7. Forest plot of comparison: spiritual intervention versus control condition, outcome: standardized mean difference for spiritual well-being at post-
treatment by subgroup analysis. CI = confidence interval, SD = standard deviation.

Figure 8. Forest plot of comparison: spiritual intervention versus control condition, outcome: standardized mean difference for quality of life at post-treatment. CI =
confidence interval, SD = standard deviation.

Figure 9. Forest plot of comparison: spiritual intervention versus control condition, outcome: standardized mean difference for degree of depression at post-
treatment. CI = confidence interval, SD = standard deviation.

Figure 10. Forest plot of comparison: spiritual intervention versus control condition, outcome: standardized mean difference for degree of anxiety at post-
treatment. CI = confidence interval, SD = standard deviation.

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Figure 11. Forest plot of comparison: spiritual intervention versus control condition, outcome: standardized mean difference for degree of hopelessness at post-
treatment. CI = confidence interval, SD = standard deviation.

4. Discussion meta-analysis.[38] However, the heterogeneity of spiritual well-

being was high after the random-effects model was adopted,
4.1. Summary of results
which may be due to several reasons. First, due to the quality of
This study, which synthesized data from RCTs, is an update of a spiritual intervention, the fact that 5 of the 7 included studies did
previous published meta-analysis verifying the effects of spiritual not blind the participants, personnel, and outcome assessors may
interventions on physical and psychological outcomes in patients induce performance bias and detection bias. Second, in the study
with cancer. This meta-analysis provides evidence for doctors of Jafari et al,[25] the outcome data were incomplete, which may
and nurses to potentially improve spiritual well-being and quality lead to some attrition bias. Third, components of the spiritual
of life, and to reduce degree of depression, anxiety, and interventions used in these 7 studies differed, such as the
hopelessness via spiritual interventions with these patients. In duration, methods, and control groups, which may lead to
addition to using spiritual well-being and quality of life as differences in the combination of results. For example, 2 studies
primary outcomes, we defined other psychological problems that used supportive psychotherapy[32] and therapeutic massage[31] as
cancer patients often have as secondary outcomes, including the control groups, which was different from the other 5 studies
degree of depression, anxiety, and hopelessness, which made our (usual care or wait-list control). Finally, the scales used in these
meta-analysis more comprehensive. However, due to the studies provide a subjective assessment of spiritual well-being,
methodological limitations of the included studies and the and all the studies allowed patients to complete the scale
subjectivity of the assessment scales used, we failed to obtain independently, which may have resulted in large differences.
much high-quality evidence in the present meta-analysis, as the And an interesting finding of our meta-analysis is that in the
majority of the accumulated evidence ranged from low to subgroup analysis, spiritual interventions were shown to improve
moderate quality. spiritual well-being only in patients with breast cancer. This
finding indicates that spiritual interventions can confer quick
benefits in the spiritual well-being of patients with breast cancer
4.2. Primary outcome
but not other kinds of cancer, and emphasizes the need for
With the extensive application of holistic nursing, mental health individualization when adopting spiritual interventions. In other
and quality of life have received increasing attention from nurses words, for patients with breast cancer, it may be appropriate to
and have become active research fields. Patients with cancer are adopt spiritual intervention methods to improve their spiritual
subject to spiritual distress and low quality of life, so it is well-being, but for patients with other kinds of cancer, these
extremely important to keep their spiritual well-being and quality methods are not as suitable, thus, other psychological inter-
of life satisfactory. ventions should be used to effectively improve their spiritual well-
Spiritual interventions are helpful for patients’ spiritual well- being.
being, based on the results from previous reports.[24,32] Our Regarding quality of life, the combined results also showed a
meta-analysis confirmed this conclusion and showed a statisti- statistically significant difference between the intervention and
cally significant difference between the spiritual intervention control groups at post-treatment, indicating that spiritual
group and the control group, indicating that spiritual inter- interventions might improve quality of life in patients with
ventions were able to improve the spiritual well-being of patients cancer. This finding is consistent with the results of Kruizinga
with cancer, which is in line with the findings of the previous et al[39] and de Bernardin Gonçalves et al.[40] In their reviews,

Table 2
Quality of evidence of included studies.
Variables
Outcomes Risk of bias Inconsistency Indirectness Imprecision Publication bias Quality of evidence
Spiritual well-being Serious ( 1) No No No Undetected Moderate
Spiritual well-being—all cancer Serious ( 1) No No No Undetected Moderate
Spiritual well-being—breast cancer Serious ( 1) No No No Undetected Moderate
Spiritual well-being—leukemia No No No No Undetected High
Quality of life Serious ( 1) No No Serious ( 1) Undetected Low
Degree of depression No Serious ( 1) No Serious ( 1) Undetected Low
Degree of anxiety Serious ( 1) Serious ( 1) No No Undetected Low
Degree of hopelessness Serious ( 1) Serious ( 1) No Serious ( 1) Undetected Very low

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spiritual interventions had small to moderate benefits in terms of represents the short-term effect of spiritual interventions on
improving the quality of life of patients with cancer in hopelessness in patients with cancer, the long-term effect remains
comparison to the control group. unknown.

4.3. Second outcome 4.4. Comparison with other published reviews

Depression, anxiety, and hopelessness are common mental We retrieved previously published meta-analyses[39,40,45–47] that
problems in patients with cancer, and sometimes, they can cause studied the effects of spiritual interventions on physical and
severe outcomes.[7,8,41,42] Previous studies showed that the psychological outcomes in patients with cancer, other diseases or
prevalence of depression and anxiety in patients with cancer in healthy persons. On the one hand, some of these reviews were
varied from 9.4% to 66.1% and from 17.9% to 33.3%, published earlier, thus, they cannot represent the latest findings.
respectively.[43,44] It is thus important to reduce the symptoms of On the other hand, some of the original studies included in those
these forms of psychological distress. Determining whether meta-analyses were not RCTs, which might influence the quality
spiritual interventions can reduce cancer patients’ degree of of evidence. By comparison, all RCTs that met the inclusion
depression, anxiety, and hopelessness was another aim of this criteria were included in our review, and we only included RCTs
meta-analysis. to certify the evidence quality. Additionally, this meta-analysis is
Currently, antidepressants are still the main therapy for an update for previous reviews. We searched for and retrieved the
depression. The National Institute for Health and Clinical latest studies that previous reviews did not include to obtain more
Excellence recommends treatment for at least 6 months and even accurate findings. Third, we included not only spiritual well-
for at least 2 years if patients have a risk of relapse. Many patients being and quality of life but also degree of depression, anxiety,
cannot maintain drug therapy because of its chronicity and side and hopelessness as outcomes to discuss the effect of spiritual
effects, such as drowsiness, dry mouth, tachycardia, and interventions more comprehensively.
dependence. As a common complementary therapy, spiritual
interventions are easily accepted by patients without the side
4.5. Implications for nursing practice
effects of antidepressants. And in our meta-analysis, it is shown
that spiritual interventions could reduce the degree of depression In patients with cancer, spiritual interventions may improve
in patients with cancer, which is the same with that of the spiritual well-being and quality of life, and reduce the degree of
previous meta-analysis.[38] Therefore, spiritual interventions may depression, anxiety, and hopelessness within a short period of
be a good choice for patients with cancer to reduce their time. And in terms of spiritual well-being, it is especially effective
depression. However, we must interpret this result with caution for patients with breast cancer. Therefore, the current meta-
due to the relatively high heterogeneity. The reasons for the high analysis provides initial support for the practicability and
heterogeneity include the variety of interventions, subjectivity effectiveness of spiritual interventions to some extent due to
and the diversity of measurements used to assess depression. In the positive outcomes, and it emphasizes the importance of
addition, because of the nature of spiritual interventions, it is individualized interventions. However, due to the lack of follow-
difficult to blind participants and therapists, and few of the up in the original studies, the above results may merely represent
included studies described allocation concealment. For instance, the post-treatment effects of spiritual interventions, while the
Rausch[36] and Breitbart et al[32] were neither blinding long-term effects of these interventions remain unknown.
participants, therapists, or outcome assessors nor describing Moreover, there are various types of spiritual interventions,
the allocation concealment method. Moreover, Breitbart et al[31] and some interventions are difficult to implement because of their
obtained results that differed from those of the other included long duration or complex content. Thus, there were many
studies, which showed that spiritual interventions could not dropouts in the majority of the included studies, even though the
reduce degree of depression in patients with cancer. And due to authors had already chosen participants whose condition
the lack of follow-up in the original studies, we failed to evaluate allowed for their participation in the entire intervention phase.
the long-term effects of spiritual interventions on depression in To improve the adherence of patients receiving spiritual
patients with cancer, it still needs to be further discussed. interventions, nurses must adopt the best intervention in terms
The combined results revealed that spiritual interventions were of the characteristics of the patients and the culture of their
able to significantly reduce cancer patients’ degree of anxiety, society. In addition, more convenient and easier methods of
which is also consistent with the findings of another review.[38] spiritual interventions should be developed. For example, nurses
However, this result should be interpreted with caution. That can teach and guide patients through the Internet or an app in
may because the majority of the included studies did not use mobile phones, and they can develop more efficient formats to
blinding, studies used different measurements of anxiety, and the shorten the duration of interventions.
conclusions of included studies were different. Moeini et al[7]
drew positive conclusions that spiritual interventions were able to 4.6. Implications for future research
reduce cancer patients’ anxiety, while the other 2 studies[31,32]
concluded that spiritual interventions could not reduce anxiety. Because of the flaws in the original studies, such as low
All of the above could result in relatively high heterogeneity. methodological quality, differences among the interventions and
This meta-analysis also reported the ability of spiritual subjects, and the subjectivity of the questionnaires used, there was
interventions to reduce cancer patients’ hopelessness. Among relatively high heterogeneity among the studies and some bias.
the 2 included studies, Breitbart et al[32] drew the conclusion that Hence, we could not draw many conclusions based on high-
patients receiving spiritual interventions showed significantly quality evidence. The influences of spiritual interventions on
greater reductions in hopelessness compared with those in cancer patients’ spiritual well-being, quality of life, and other
control groups, and no significant difference were observed for psychological outcomes remain to be further investigated by
changes in hopelessness in the another studies.[31] But this only more rigorously designed studies. In this meta-analysis, we did

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not define pharmacotherapy as a control; thus, the relative effects spiritual interventions may improve spiritual well-being and
of drug therapies and spiritual interventions on cancer patients’ quality of life, and reduce degree of depression, anxiety, and
psychological outcomes need to be further investigated. In hopelessness for patients with cancer. The results have substantial
addition, only a few studies included long-term follow-ups in clinical significance because they are highly relevant to the daily
their investigations, so we could not evaluate the long-term effects work of doctors and nurses. However, because most of the scales
of spiritual interventions on the improvement of spiritual well- used to measure the outcomes had strong subjectivity, the
being and quality of life and on the treatment of depression, methodological quality of some of the included studies was not
anxiety, and hopelessness in patients with cancer. As we know, very high. We should thus interpret these results with caution,
improvements in spiritual and psychological health require a and more comprehensive research is needed.
relatively long period of time. Thus, additional studies are
recommended. In addition, we found that most of the original
studies that aimed to discuss the effect of spiritual interventions in Acknowledgments
cancer patients address patients with breast cancer only or all The authors appreciate the advice on statistical methods provided
types of cancer, while few related studies address patients with by Professor Guanjian Liu (a statistician from the West China
other kinds of cancer. In this meta-analysis, it was shown that the Hospital, Sichuan University).
effect of spiritual interventions may be different in patients with
different kinds of cancer. Therefore, in the future, it is
recommended that patients with other types of cancer are Author contributions
recruited as study participants to allow for this topic to be Data curation: Lu Xing, Xiujing Guo, Lu Bai, Jing Chen.
examined more thoroughly. Finally, researchers should design Formal analysis: Lu Xing, Lu Bai, Jiahui Qian, Jing Chen.
more theoretically based and reliable implementation methods Methodology: Lu Xing, Xiujing Guo, Lu Bai, Jiahui Qian, Jing
for spiritual interventions. Chen.
Resources: Jing Chen.
4.7. Strengths and limitations Software: Lu Bai, Jiahui Qian.
Supervision: Jing Chen.
This meta-analysis is an update of previous published reviews Writing – original draft: Lu Xing, Xiujing Guo, Jiahui Qian.
and meta-analyses. In this meta-analysis, the trials we included Writing – review & editing: Lu Xing, Jing Chen.
were all RCTs, which is different from previously published
reviews and improves the quality of evidence of our outcomes.
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