An Updated Systematic Review of Quantitative Studies Assessing Anxiety, Depression, Fear of Cancer Recurrence or Psychological Distress in Testicular Cancer Survivors

Figures & data

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Table 1 Characteristics of Included Studies and Study Quality

Study # Citation, Year	Research Location (# of Centres)	Study Design; Assessment Time Points Given as M (SD) [Range]*	Comparison Group	Number of TC Survivors (Response Rate)	TC Survivor Characteristics, Age in Years Given as M (SD) [Range]*	Tx Received	Relevant PROs Assessed (Measures)	Systematic Review Objective Addressed	Study Quality (Rating)
1, Bandak et al, 2018^Citation32	Denmark (1)	Cross-sectional study; 18y [IQR 12–24y] post Dx	NA	2260 (59%)	53y [46–61]	ORCH+SUR: n=1098 ORCH+CT: n=788 ORCH+RT: n=300 ORCH+>1 treatment: n=74	Anxiety and depression (HADS)	1	Good (92)
2, Kreiberg et al, 2020^Citation31	Denmark (1)	Cross-sectional; median 19y [IQR 12–24y] post Dx	Random sample of Danish citizens aged 16 or more without any cancer history (n=61,927)	2252 (53%)	Med 53y [IQR 46–61]	ORCH+SUR: n=1134 ORCH+CT: n=807 ORCH+RT: n=311	Stress (PSS)	1, 2	Good (92)
3, Skott et al, 2019^Citation34	Denmark (1)	Cross-sectional study; >10 years post Dx	NA	147 (93%)	At survey completion: Group A=43y, Group B=44y At Dx: Group A=33y, Group B=30y	ORCH only: A n=29, B n=15 CT: A n=33, B n=12 RT: A n=15, B n=8 RPLND: A n=28, B n=10 GCNIS: A n=3, B n=15 Other: A n=7, B n=10	Anxiety and depression (HADS)	1, 2	Good (82)
4, Adams et al, 2018^Citation30	Canada (2)	Prospective 2-armed, Phase 2, randomized controlled trial; baseline 8y on average post Tx; T1: within 48 hours prior to randomization, T2: immediately post-intervention (intervention group: within 4 days of intervention cessation; control group: after 12 weeks), T3: 3-month follow-up.	NA	63 (7%)	43.7y (10.8)	ORCH only: n=29 ORCH+CT: n=23 ORCH+RT: n=11	Depression (CES-D 10 item), Anxiety (SSAS-10), Stress (PSS)	1	Fair (75)
5, Manhães et al, 2019^Citation33	Brazil (1)	Cross-sectional; 6y (3y) post Tx	NA	29 (66%)	31.5y (10.4)	ORCH only: n=4 ORCH+CT: n=21 ORCH+RT: n=4	Distress (DT), anxiety and depression (HADS)	1, 3	Fair (78)
6, Van Leeuwen et al, 2017^Citation28	Europe** (UTD)	Cross-sectional; 11.9y (3.8y) post Tx	Prostate cancer patients (n=116)	126 (64%)	43.1y (8.8)	ORCH+CT: n=126	Cancer-related worry (QLQ-TC26 future perspective subscale)	1, 2	Fair (64)
7, Wang & Hoyt, 2020^Citation35	USA (1)	Cross sectional; 3y post Dx	NA	171 (NR)	25.2y (3.3)	ORCH: n=80 ORCH+CT: n=91	Depression (CES-D 20 item)	1, 3	Fair (67)
8, Whitford et al, 2019^Citation29	Australia and New Zealand (16)	Longitudinal; T1: ≤ 6 months post-ORCH/pre-CT, T2: 12–18 months post-baseline.	NA	102 (70%)	ORCH: 34.5yORCH+CT: 34.8y	ORCH only: n=41 ORCH+CT (Group A): n=61	Anxiety and depression (HADS)	1	Fair (71)

Notes: *Unless indicated otherwise. **Study recruited participants from the Netherlands, Italy, Norway, and the United Kingdom.

Abbreviations: TC, testicular cancer; M, mean; SD, standard deviation; Med, median; IQR, inter quartile range; Tx, treatment; Dx, diagnosis; PROs, patient reported outcomes; ORCH, orchidectomy; CT, chemotherapy; RT, radiotherapy; SUR, surveillance; HADS, Hospital Anxiety and Depression Scales (both HADS-D and HADS-A); PSS, Perceived Stress Scale; CES-D10, Centre for Epidemiologic Studies Depression Scale 10 item scale; CES-D20, Centre for Epidemiologic Studies Depression Scale 20 item scale; SSAS-10, Spielberger State Anxiety Scale 10-item inventory; QLQ-TC26, Quality of Life Questionnaire - Testicular Cancer-26; DT, Distress Thermometer; T1, assessment timepoint 1 (baseline); T2, assessment timepoint 2; T3, assessment timepoint 3; NR, not reported; UTD, unable to determine; RPLND, retroperitoneal lymph node dissection due to retroperitoneal residual disease after chemotherapy; GCNIS, germ-cell neoplasia-in-situ.

Table 2 The Prevalence, Severity, and Correlates of Anxiety, Depression, Distress and Fear of Cancer Recurrence

Study #	Quality Rating	Citation, Year	Q1: Prevalence Questionnaire [Cut-Point], % (95% CI)*	Q1: Severity Questionnaire [Full Scale Range], Mean (SD, if provided)	Q1: Prevalence (P) and/or Severity (S) Relative to CG (of Non-TC Survivors)	Q2: Demographic, Disease and Treatment Correlates	Q3: Associations Between PROs
Anxiety
1	Good	Bandak et al, 2018^Citation32	HADS [≥7], 20%	NR	NA	NR	NR
3	Good	Skott et al, 2019^Citation34	HADS [>7], 21.08%	NR	NA	Non-sig: age	NR
4	Fair	Adams et al, 2018^Citation30	NR	SSAS-10 [20–80, unclear how they weighted the scores]: baseline exercise group: 18.6 (5.5), baseline control: 16.2 (4.7).	NA	NR	NR
5	Fair	Manhães et al, 2019^Citation33	HADS [≥8], 6.9%	HADS [0–21], 3.2 (3.8)	NA	NR	Sexual Confidence and Functioning (p = 0.04), Cognitive-Emotional Regulation (p = 0.001), and Specific Sexual Functioning (p = 0.04) were predictors of anxiety symptoms (R^2= 61%).
8	Fair	Whitford et al, 2019^Citation29	NA	HADS [0–21], Baseline Group A: 6.16 (4.08), baseline group B: 4.13 (3.69); FU Group A: 4.72 (3.36), FU Group B: 3.25 (3.69)	NA	Non sig: Treatment type (surgery alone vs surgery + chemo)	NR
Depression
1	Good	Bandak et al, 2018^Citation32	HADS [≥7], 7%	NR	NA	NR	NR
3	Good	Skott et al, 2019^34	HADS [>7], 4.7%	NR	NA	Non-sig: age	NR
4	Fair	Adams et al, 2018^Citation30	NR	CES-D10 [0–30]: baseline exercise group: 5.3 (4.7), baseline control: 4.5 (4.4)	NA	NR	NR
5	Fair	Manhães et al, 2019^Citation33	HADS [≥9], 6.9%	HADS [0–21], 1.8 (3.7)	No	NA	Sexual Confidence and Functioning was associated with symptoms of depression (p = 0.01). Cognitive-Emotional Regulation (p = 0.001) and Specific Sexual Functioning (P = 0.005) were predictors of symptoms of depression (R2N = 74%).
7	Fair	Wang & Hoyt, 2020^Citation35	NR	CES-D20 [0–60], 12.99 (12.08)	NA	NR	Depression was significantly and positively correlated with cancer-related masculine threat. Depression was significantly and negatively correlated with benefit finding
8	Fair	Whitford et al, 2019^Citation29	NR	HADS [0–21], Baseline Group A: 3.05 (3.66), baseline group B: 2.1 (2.21); FU Group A: 2.09 (2.55), FU Group B: 1.8 (2.72)	NA	Non sig: Treatment type (surgery alone vs surgery + chemo)	NR
Distress
2	Good	Kreiberg et al, 2020^Citation31	PSS [≥16], 25%	PSS [0–40], 11.5 (6.3)	Multivariate adjusted prevalence ratio to reference population 1.56 (95% CI 1.40–1.73, P<0.0001)’.	Age (higher P of stress in TCS until 70 years of age, it changes after this age and the CG becomes the most stressed). Significantly higher S than the general male population in multivariable adjusted analysis for all treatment groups, but no direct comparison between treatment groups. High distress associated with being single, unemployed, and poor self-rated fitness.	NR
4	Fair	Adams et al, 2018^Citation30	NA	PSS [0–40]: baseline exercise group: 19.7 (8.5), baseline control: 16.3 (9.1).	NA	NR	NR
5	Fair	Manhães et al, 2019^Citation33	DT [≥4], 41.4%	DT [0–10], 3.2 (2.8)	NA	Cognitive-Emotional Regulation predicted distress (p = 0.01; R^2 = 37%).	NR
Fear of Cancer Recurrence
6	Fair	Van Leeuwen et al, 2017^Citation28	NA	QLQ-TC26 future perspective subscale [0–100], 77 (24)	NR	Marital status: single men had worse FCR (future perspective sub-domain of the QLQ-TC-26)	NR

Note: *or proportions of patients with high levels of the outcome.

Abbreviations: TC, testicular cancer; Q1, research question 1; Q2, research question 2; Q3, research question 3; P, prevalence; S, severity; SD, standard deviation; CG, control group; FU, follow-up; PROs, patient-reported outcomes; FCR, fear of cancer recurrence; HADS, Hospital Anxiety and Depression Scale; PSS, Perceived Stress Scale; CES-D10, Centre for Epidemiologic Studies Depression Scale 10 item scale; CES-D20, Centre for Epidemiologic Studies Depression Scale 20 item scale; SSAS-10, Spielberger State Anxiety Scale 10-item inventory; QLQ-TC26, Quality of Life Questionnaire - Testicular Cancer-26; DT, Distress Thermometer; MOS-HDS, Medical Outcomes Study - Health Distress Scale; Sig, significant; NR, none reported; NA, not applicable.

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