Neuropsychiatric manifestations of prostate cancer and its treatment: Biological mechanisms and psycho-oncology perspectives

Table 1 Represents the summarization of the evidence of psychological and neurocognitive outcomes

Treatment modality	Psychological neuropsychiatric outcomes	Key findings	Quantitative estimates	Ref.
Active surveillance	Anxiety, depression	Most men show stable, low levels of psychological distress over time, although a minority experience clinically relevant symptom	Anxiety prevalence: Up to 23%-24%; depression prevalence: Approximately 12.5%	Watts et al[28], Alvisi et al[29], van den Bergh et al[30]
Radical prostatectomy	Mental distress, depression, anxiety	Persistent psychological distress may occur after surgery and is associated with urinary and sexual dysfunction and reduced quality of life	Approximately 8%-20% may require psychological support	Köhler et al[31], Ilie et al[32], Meissner et al[33], Mehnert et al[41]
Radiation therapy	Depression, anxiety	Psychological morbidity may be lower than with watchful waiting or ADT, although depression and anxiety remain clinically relevant	Not consistently reported across the cited studies	Ravi et al[34], Crump et al[35]
ADT	Depression, anxiety, cognitive impairment, reduced quality of life	ADT is associated with increased psychiatric and cognitive morbidity and reduced physical, social, and functional well-being	Depression: RR = 1.51; anxiety: HR = 2.08; cognitive impairment: RR = 1.45	Saini et al[36], Siebert et al[37], Galvão et al[38], Crump et al[39]
PCa- depression associated – healthcare burden	Depression-associated healthcare utilization	Comorbid depression is associated with substantially greater emergency care, hospitalization and mortality among men with PCa	ER visits: OR = 4.45; hospitalization: OR = 3.22; mortality: HR = 2.82	Jayadevappa et al[40]

Active surveillance and androgen deprivation therapy are the periods where anxiety and depression are most evident, though the majority of surveillance groups experience longitudinal stability while a delicate subgroup continues to suffer with persistent distress. Androgen deprivation therapy still stands as the strongest factor that predicts and leads to depression, anxiety, poor cognitive functioning and living with a low quality of life, the impact of which will be felt not only in the first year of treatment but also later on. Besides post-prostatectomy distress and radiation-related mood shifts that are considered additional factors contributing to the overall morbidity, the point about the necessity of integrative psycho-oncologic care is brought about more strongly. ADT: Androgen deprivation therapy; PCa: Prostate cancer; RR: Relative risk; HR: Hazard ratio; OR: Odds ratio; ER: Emergency room.

Table 2 Risk factors and predictors of psychological morbidity in prostate cancer

Risk factor	Psychological outcomes	Effect size/association	Statistical significance	Ref.
Divorced relationship status	Anxiety	Higher prevalence of clinically relevant anxiety among divorced men (56.3%) compared with the overall cohort (23.1%)	P = 0.011	Watts et al[28]
High-risk PCa	Depression, anxiety	Major depression: AHR = 1.82 (95%CI: 1.75-1.89); anxiety disorders: AHR = 1.96 (95%CI: 1.87-2.05)	P < 0.001	Crump et al[35], Crump et al[39]
ADT	Depression, anxiety, cognitive impairment	Depression: RR = 1.51; anxiety: AHR = 2.08 (95%CI: 1.93-2.25); cognitive impairment/dementia: RR = 1.45	Depression: P = 0.0002; anxiety: P < 0.001; cognitive impairment: P = 0.024	Siebert et al[37], Crump et al[39]
Younger age (per 10-year decrease)	Depression	OR = 1.38 (95%CI: 1.16-1.60)	P = 0.001	Fervaha et al[48]
Poor social support/absence of caregiver	Anxiety, depression	Absence of caregiver: OR = 5.02; emotional support: OR = 0.81; instrumental support: OR = 0.67	P < 0.05	Mehnert et al[41], Morris et al[49]
Moderate-to-severe urinary dysfunction	Mental distress	OR = 4.79 (95%CI: 1.04-22.03)	P < 0.05	Ilie et al[32]
Poor relationship satisfaction/sexual difficulties	Psychological distress	Lower relationship satisfaction associated with greater distress; OR = 0.14 (95%CI: 0.03-0.77)	P < 0.05	Köhler et al[31], Ilie et al[32]
Pre-existing depression or anxiety	Depression	OR = 3.64 (95%CI: 2.42-5.48)	P < 0.0001	Fervaha et al[48]
High-risk disease classification	Depression	OR = 1.49 (95%CI: 1.05-2.12)	P = 0.027	Fervaha et al[48]
Poor performance status (ECOG > 1)	Depression	OR = 5.01 (95%CI: 3.49-7.20)	P < 0.0001	Fervaha et al[48]
Cancer-related/treatment-related fatigue	Psychological burden, Reduced quality of life	Fatigue prevalence: 42% with ADT, 21% after radical prostatectomy, 40% after radiotherapy	Reported with 95%CIs	Luo et al[50]

It provides a brief summary of the demographic, clinical, treatment-related and psychosocial factors associated with depression, anxiety, mental distress, cognitive impairment, and poor quality of life. The strongest predictors were high-risk disease, androgen deprivation therapy, younger age, poor social support, urinary and relationship problems, pre-existing depression and anxiety, poor performance status and treatment-related fatigue. The literature reports varying levels of association from modest to strong (e.g., odds ratio up to 5.02, adjusted hazard ratio up to 2.08). ADT: Androgen deprivation therapy; PCa: Prostate cancer; aHR: Adjusted hazard ratio; RR: Relative risk; OR: Odds ratio; ECOG: Eastern Cooperative Oncology Group.