Cognitive function in patients undergoing robotic radical prostatectomy – 1 year follow up

Abstract

Postoperative neurocognitive disorders are clinically relevant, yet longitudinal data in patients undergoing radical prostatectomy are limited. This study aimed to evaluate longitudinal changes in cognitive function and identify factors associated with cognitive trajectories in patients undergoing robotic radical prostatectomy for prostate cancer. The study included 66 patients undergoing robotic radical prostatectomy for prostate cancer. Assessments were performed at baseline (at median 10 days before surgery), 6 months, and 12 months postoperatively. Evaluations included demographic and clinical data, cognitive performance (Neurotest), affective and depressive symptoms (HADS), and affective temperament (TEMPS-A). Global cognitive composite (GCC) scores changed significantly over time (baseline, 6, and 12 months after prostatectomy), while most individual domains remained stable. In the initial model, affective temperament was associated with cognitive change: depressive temperament showed a positive association (β = 0.37, p = 0.017), whereas anxious temperament showed a non-significant negative trend (β = −0.28, p = 0.061). In the adjusted model, baseline GCC was a strong independent predictor (β = −0.63, p < 0.001). Both depressive (β = 0.34, p = 0.009) and anxious temperament (β = −0.31, p = 0.013) remained significantly associated with cognitive trajectories, while physical activity and depressive symptoms (HADS-D) were not. Cognitive trajectories after robotic radical prostatectomy are dynamic may be related to psychological and clinical factors. These findings support longitudinal cognitive monitoring and highlight the potential value of incorporating psychological assessment into perioperative care to identify patients at risk of poorer cognitive outcomes.

Supplementary Information

The online version contains supplementary material available at 10.1007/s11701-026-03635-8.

Introduction

Cognitive function is essential for independent daily functioning, and its impairment—ranging from subtle deficits to overt dementia—has significant clinical consequences, including reduced treatment adherence, impaired social functioning, and increased mortality [1–3]. In oncology populations, cognitive dysfunction has been widely documented and may arise from both disease- and treatment-related factors [4, 5]. In prostate cancer, most research has focused on the cognitive effects of systemic therapies, particularly androgen deprivation therapy, which has been consistently associated with cognitive decline [6]. In contrast, relatively little is known about cognitive outcomes following surgical treatment alone [7].

Postoperative neurocognitive disorders, including postoperative delirium and delayed neurocognitive recovery, are common in surgical populations [8]. These entities are well established in the literature, with reported incidence rates ranging from 20% to 70% among surgical patients [8, 9]. The considerable variability in these estimates likely reflects heterogeneity in study populations, cognitive assessment methods, diagnostic criteria, and duration of follow-up. Evidence from non-oncological populations further indicates that postoperative cognitive decline is associated with adverse clinical outcomes, including prolonged hospital stay and an increased risk of mortality [10]. Emerging evidence suggests that cognitive trajectories after surgery are dynamic and may involve both early decline and subsequent recovery [11, 12]. This pattern has been well described in non-oncological populations across various surgical contexts, including cardiac, abdominal, thoracic, and orthopedic procedures [10, 13]. In such settings—for instance, following cholecystectomy or fibroid removal—patients are typically considered cured, and longer time intervals after surgery are associated with better cognitive performance [11].

In the general population, the passage of time is also inherently linked to cognitive decline. Advancing age remains one of the most robust risk factors for impaired cognitive function [14], and older age is associated with a higher burden of comorbidities that may further exacerbate cognitive deterioration. In oncology populations, this relationship is even more complex: surgery often represents only one component of multimodal treatment, and over time, patients may also experience disease progression or recurrence [15, 16].

Importantly, compared with other surgical disciplines, evidence regarding postoperative cognitive trajectories in oncological populations remains relatively limited [17].

The issue becomes even more complex when considering postoperative cognitive outcomes after robot-assisted radical prostatectomy. In this setting, patients are exposed not only to the potential effects of general anesthesia, which are common across many oncological surgical procedures, but also to additional procedure-specific factors. Notably, during laparoscopic prostatectomy, patients are placed in a steep Trendelenburg position with the head tilted downward at approximately 30–40°, which necessitates the maintenance of capnoperitoneum. As demonstrated in recent studies, prolonged steep Trendelenburg positioning may significantly affect cerebral hemodynamics, including cerebral blood flow and intracranial pressure. Internal carotid artery flow has been shown to decrease after induction of anesthesia and remain reduced until it increases again upon return to the horizontal position. Similarly, cerebral perfusion pressure decreases and may remain lowered even after repositioning [18]. In addition, several other potential mechanisms may contribute to postoperative cognitive changes, including neuroinflammation, cytokine release, autophagy dysregulation, oxidative stress, and mitochondrial dysfunction, as well as impaired synaptic function. Together with blood–brain barrier disruption and altered cerebral perfusion, these processes may potentially contribute to cognitive dysfunction following prostatectomy [19–21]. Postoperative cognitive dysfunction may also be influenced by surgical stress–related changes and perioperative hormonal fluctuations, including alterations in androgen levels, which may contribute to postoperative cognitive outcomes [22–24].

Although postoperative cognitive impairment following surgical treatment of prostate cancer has been increasingly recognized [7, 25], the existing evidence is largely based on cross-sectional assessments. Consequently, the temporal dynamics of cognitive changes remain poorly understood. To our knowledge, longitudinal cognitive trajectories following radical prostatectomy remain insufficiently characterized. Therefore, the present study aimed to characterize longitudinal changes in cognitive function and identify factors associated with cognitive trajectories in patients undergoing robotic radical prostatectomy for prostate cancer.

Materials and methods

Study group

The initial study cohort comprised 100 Caucasian men who had undergone radical prostatectomy for prostate cancer. Patients were recruited from University Hospital No. 2 and the Urology Outpatient Clinic in Bydgoszcz, Poland. Due to substantial missing data at both baseline and follow-up assessments, the final analysis was restricted to 66 patients, who constituted the analytical cohort. Six patients underwent adjuvant therapy during the study period. In all cases, this consisted of adjuvant radiotherapy rather than salvage radiotherapy. Five patients received radiotherapy within the first six months after surgery, whereas one patient underwent treatment between 6 and 12 months postoperatively. The duration of radiotherapy was approximately 4–6 weeks, in accordance with standard treatment protocols. Importantly, none of the patients included in the analytical cohort received androgen deprivation therapy. Detailed characteristics of the study group are presented in Table 1.

Table 1.

Basic characteristics of the study cohort

Parameter	Total (n = 66)
Age (median, year)	67.5 (IQR 64–71)
BMI (kg/m2)	27.1 (IQR 24.5–29.4)
Diabetes (n, %)	8 (12.1%)
Hypertension (n, %)	38 (57.6%)
Myocardial infarction (n, %)	3 (4.5%)
Stroke (n, %)	1 (1.5%)
Education
Basic (n, %)	1 (1.5%)
Vocational (n, %)	14 (21.2%)
Secondary (n, %)	29 (43.9%)
Higher (n, %)	22 (33.3%)
Physical activity
None (n, %)	13 (19.7%)
<1x/week (n, %)	6 (9.1%)
2-3x/week (n, %)	17 (25.8%)
>3x/week (n, %)	30 (45.5%)
PSA at baseline (median)	6.735 ng/ml (IQR 5.2–9.6)
Hemoglobin at baseline (median)	14.05 g/dl (13.3–14.7)
Testosterone at baseline (median)	384 ng/dl (IQR 280–513)
Smoking (n, %)	15 (22.7%)
Grade Group
Group 1	13 (19.7%)
Group 2	26 (39.4%)
Group 3	15 (22.7%)
Group 4	6 (9.1%)
Group 5	6 (9.1%)
TNM classification
T2	59 (89.4%)
T3	7 (10.6%)
Time from baseline assessment to surgery, days (median)	10 (IQR 8–17)
Operative time, min (median)	187.5 (IQR 160–230)
Length of hospital stay, days (median)	3 (IQR 2–4)
Adjuvant treatment, n (%)	6 (9.1%)
Radiotherapy only, n (%)	6 (9.1%)
Androgen deprivation therapy, n (%)	0 (0.0%)
Persistent urinary incontinence at 12 months, n (%)	14 (21.2%)

IQR, interquartile ratio

Inclusion and exclusion criteria

Eligibility criteria included the ability to understand the study procedures, provision of written informed consent, histopathological confirmation of prostate adenocarcinoma, and treatment with robotic radical prostatectomy. All patients received general anesthesia with either propofol-sufentanil or sevoflurane-sufentanil for anesthesia maintenance. Exclusion criteria comprised cognitive impairment as well as severe psychiatric or significant somatic conditions.

Study procedure

Clinical, demographic, and laboratory data were collected from medical records and patient interviews. Cognitive and psychological data were obtained using standardized questionnaires and the computerized Neurotest battery. Participants were assessed at baseline (preoperatively, at median 10 [IQR 8–17] days before surgery) and at 6- and 12-months follow-up visits. The study protocol was approved by the Bioethics Committee of the Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz (approval no. 476/2017), and all procedures were conducted in accordance with the Declaration of Helsinki.

Demographic and medical assessment

Demographic data included ethnicity, age, education level, smoking history and physical activity. Physical activity was assessed using a self-reported 4-point scale, in which participants indicated how frequently they engaged in activity leading to fatigue or shortness of breath (none; <1×/week; 2–3×/week; >3×/week). Medical assessment consisted of a clinical interview, medical history review, physical examination, and laboratory testing. Laboratory parameters included free and total testosterone levels and total prostate-specific antigen (PSA), measured using enzyme immunoassay. Body weight and height were measured, and body mass index (BMI) was calculated.

Clinical data included tumor stage according to the International Society of Urological Pathology (ISUP) Grade Group classification [26], comorbidities [27], disease course, details of the prostatectomy, operative time, length of hospital stay, postoperative complications after robotic radical prostatectomy, and the need for adjuvant therapy.

Psychological assessment

Psychological assessment included evaluation of anxiety and depressive symptoms using the Hospital Anxiety and Depression Scale (HADS) was done. For evaluation of affective temperament dimensions the Temperament Evaluation of Memphis, Pisa, Paris and San Diego Autoquestionnaire (TEMPS-A), and assessment of cognitive function using Neurotest neurocognitive battery was applied.

The Hospital Anxiety and Depression Scale (HADS) is a widely used and well-validated instrument for the screening of anxiety and depressive symptoms in patients with somatic conditions, both in inpatient and outpatient settings. The scale comprises 14 items, with 7 items measuring anxiety (HADS-A) and 7 assessing depressed symptoms (HADS-D). Respondents rate each item based on their experiences over the preceding week. Each item is scored on a 4-point Likert scale (0–3), with subscale scores calculated separately (for HADS-A and HADS-D). Higher scores indicate greater symptom severity for anxiety and depression, respectively [28].

The Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A) is a self-report instrument used to assess affective temperament profiles. The questionnaire consists of 110 statements to which respondents answer “yes” or “no,” depending on whether a given statement accurately describes them. Based on the responses, the distribution of affective temperament traits is determined. The instrument evaluates five dimensions of affective temperament: anxious, depressive, cyclothymic, hyperthymic, and irritable [29].

The computerized Neurotest battery was used for evaluation of different cognitive domains. The four individual tests comprising the battery are described in the following section.

Simple Reaction Time Test (SRT) is a basic measure for attention and reaction speed for single stimulus. The participants were instructed to press a designated button as quickly as possible when a green circle appears on the computer screen. The primary outcome measures are reaction time and the number of correct responses [30].

Go/No-Go Test (G/nG) – a more complex task used to assess inhibitory control, i.e., the ability to withhold a response to a stimulus. During the test, one of two stimuli is presented on the computer screen in a random sequence. The participants were asked to press a button when a green square appears (presented 75 times) and to refrain from responding when a blue square appears (presented 25 times). The primary outcome measures include reaction time as well as the number of correct and incorrect responses [31].

Verbal List-Learning Task (VL) – a test designed to assess verbal memory performance. The task consists of five trials. At the beginning of each trial, the examiner reads aloud a list of 10 words (the same list is used in each trial). The participant is then asked to recall as many words as possible from the presented list. The primary outcome measures include the number of correctly recalled words in each trial (VL1–VL5), as well as the number of intrusions (words recalled that were not on the list) and perseverations (words repeated multiple times within a single trial) [32].

Verbal List Delayed Task (VLDT) – this trial is designed to assess delayed memory. The participant is instructed to recall as many words as possible from the list presented in the previous task after a 20-minute delay, without the list being read again by the examiner. The primary outcome measures include the number of correctly recalled words, as well as any repetitions (perseverations) and intrusions [32].

Visual Working Memory Test (VWMT) - this task is designed to assess visuospatial working memory. The performance of this test required the ability to keep information in short term memory and manipulate them. At the beginning of the test, seven playing cards (from a standard deck) are presented sequentially on the computer screen in different locations. Each card is displayed for two seconds and then covered again. In the subsequent phase, the cards are presented again one by one, and the participant is required to indicate the location on the screen where each card was originally shown. The primary outcome measure is the number of correctly identified locations [33].

Statistical analysis

Continuous variables were tested for normality using the Shapiro–Wilk test and are presented as mean ± standard deviation (SD) or median with interquartile range (IQR), depending on data distribution. Categorical variables are expressed as frequencies and percentages. Between-group comparisons were performed using Student’s t-test or one-way analysis of variance (ANOVA) for normally distributed continuous variables, and the Mann–Whitney U test or Kruskal–Wallis test for non-normally distributed continuous variables, depending on the number of groups. Categorical variables were compared using the χ² test or Fisher’s exact test, as appropriate.

Cognitive test results were standardized using z-scores calculated relative to the baseline distribution of the analytical cohort. For each cognitive variable, the baseline mean and standard deviation were used as the reference values at all time points. For measures in which higher values indicated better performance, z-scores were calculated as: z = (individual score − baseline mean) / baseline SD. For measures in which higher values indicated worse performance, such as reaction time, scores were multiplied by − 1 after standardization so that higher z-scores consistently reflected better cognitive performance.

The global cognitive composite (GCC) score was calculated separately for each participant and time point as the arithmetic mean of six equally weighted standardized cognitive components: simple reaction time, verbal memory total learning, verbal memory learning gain, delayed verbal memory, visual working memory, and Go/No-Go reaction time. Reaction-time-based measures were inverted before inclusion in the composite. No differential weighting was applied across components. GCC was calculated only when all component cognitive measures required for the composite were available; participants with incomplete follow-up cognitive data were excluded from the longitudinal analytical cohort.

To identify factors associated with changes in global cognitive performance, multivariable linear regression analysis was performed with 12-month change in GCC as the dependent variable. Candidate variables were selected based on theoretical relevance, prior evidence, and preliminary correlation analyses. Overall, 14 candidate variables were considered: baseline GCC, demographic variables (age and education), lifestyle factors (smoking status and physical activity), clinical variables (adjuvant treatment, duration of surgery, and duration of hospitalization), depressive symptoms (HADS-D), and affective temperament dimensions assessed with TEMPS-A. Variables considered clinically or methodologically important, particularly baseline GCC and age, were retained irrespective of statistical significance. Other candidate variables were considered for inclusion in the final model if they showed an association with cognitive change in preliminary analyses at p < 0.10. Given the modest sample size and the risk of model overfitting, the final multivariable model was restricted to variables with clinical relevance and/or preliminary associations with cognitive change. The final model included baseline GCC, age, duration of hospitalization, adjuvant treatment, depressive temperament, and anxious temperament.

Regression analyses were performed using a complete-case approach. Because age data were unavailable for two participants, the final multivariable regression model included 64 patients. Multicollinearity was assessed using tolerance and variance inflation factor (VIF) values. Model fit was evaluated using R², adjusted R², and the overall F-test. Regression coefficients are presented as standardized β coefficients with 95% confidence intervals and p-values.

To address the potential mathematical coupling between baseline GCC and change scores, a sensitivity analysis was performed using 12-month GCC as the dependent variable, adjusted for baseline GCC and the same covariates included in the primary change-score model. In addition, to assess whether the exclusion of two participants with missing age data affected the results, a sensitivity analysis excluding age from the model was performed in the full analytical cohort of 66 patients. Given the modest sample size, all regression analyses were considered exploratory. A p-value < 0.05 was considered statistically significant. Statistical analyses were performed using STATISTICA version 13.3 and Microsoft Excel 2021.

Results

A significant change in global cognitive composite (GCC) scores over time was observed between baseline, 6 months, and 12 months (Friedman test: χ²(2) = 7.92, p = 0.019; Fig. 1). Post-hoc analysis using the Wilcoxon signed-rank test revealed a significant improvement in GCC between baseline and 12 months (Z = 3.70, p < 0.001). The baseline-to-12-month change corresponded to a Wilcoxon effect size of r = 0.46. Differences between baseline and 6 months (Z = 1.78, p = 0.075) and between 6 and 12 months (Z = 1.25, p = 0.21) were not statistically significant.

Fig. 1.

Changes in global cognitive composite z-score over time

While global cognitive performance improved over time, this effect was not reflected across most individual domains (Table 2). A significant change was observed only for inhibitory control (p = 0.04), with post-hoc analyses indicating that this improvement was primarily driven by higher scores at 12 months compared to earlier timepoints. Other domains did not show statistically significant changes.

Table 2.

Changes in cognitive domain scores over time

Domain (cognitive test)	Baseline (median, IQR)	6 months (median, IQR)	12 months (median, IQR)	p-value
Global cognitive composite	0.04 (-0.39 to 0.24)	0.29 (-0.18 to 0.61)	0.39 (0.06 to 0.57)	0.019
Reaction time (attention)	0.25 (-0.71 to 0.72)	0.23 (-0.23 to 0.68)	0.36 (-0.20 to 0.68)	0.95
Verbal memory - total learning	-0.06 (-0.58 to 0.63)	0.29 (-0.06 to 1.15)	0.98 (-0.23 to 1.50)	0.11
Verbal memory- learning gain	0.22 (-0.41 to 0.84)	0.22 (-0.41 to 0.22)	-0.41 (1.03 to 0.22)	0.18
Delayed verbal memory	-0.04 (-0.48 to 0.85)	0.40 (-0.48 to 1.29)	0.40 (-0.04 to 0.85)	0.76
Visual working memory	-0.24 (-0.78 to 0.83)	0.29 (-0.24 to 1.37)	0.83 (0.29 to 1.37)	0.15
Inhibitory control	0.14 (-0.71 to 0.99)	0.14 (-0.71 to 0.99)	0.43 (-0.43 to 0.99)	0.04

To identify factors associated with changes in global cognitive performance, a multivariable linear regression model was constructed, with the change in global cognitive composite score at 12 months as the dependent variable. The final model included baseline GCC, age, duration of hospitalization, adjuvant treatment, depressive temperament, and anxious temperament. The model was based on 64 complete cases, as age data were unavailable for two participants.

The final multivariable regression model explained 55.4% of the variance in 12-month change in GCC, with an adjusted R² of 0.507 (F(6,57) = 11.81, p < 0.001). No relevant multicollinearity was observed; tolerance values ranged from 0.50 to 0.98 and VIF values from 1.02 to 1.99. Baseline GCC was the strongest factor associated with change in GCC (β = −0.63, 95% CI: −0.83 to − 0.43, p < 0.001; Table 3). Depressive temperament was positively associated with cognitive change (β = 0.34, p = 0.009), whereas anxious temperament was associated with a reduced magnitude of improvement (β = −0.31, p = 0.013). Duration of hospitalization, age, and adjuvant treatment were not significantly associated with cognitive change. Model assumptions were verified by inspection of residuals and formal testing, with no major violations observed.

Table 3.

Factors associated with changes in global cognitive performance

Parameter	Standardized β coefficient	95% CI	p-value
Baseline GCC	−0.63	−0.83 to − 0.43	< 0.001
Depressive temperament	0.34	0.09 to 0.59	0.009
Anxious temperament	−0.31	−0.56 to − 0.07	0.013
Duration of hospitalization (days)	0.00	−0.20 to 0.21	0.97
Adjuvant treatment (yes vs. no)	0.07	−0.11 to 0.25	0.42
Age	0.07	−0.12 to 0.25	0.47

β, standardized regression coefficient; CI, confidence interval. Physical activity was categorized with the highest level (>3 times/week) as the reference group. The regression model was based on complete cases; two participants were excluded due to missing age data

To assess whether the exclusion of two participants with missing age data affected the results, we performed a sensitivity analysis excluding age from the model and including all 66 patients. The results remained comparable: depressive temperament (β = 0.34, 95% CI: 0.11 to 0.58, p = 0.005), anxious temperament (β = −0.30, 95% CI: −0.54 to − 0.07, p = 0.013), and baseline GCC (β = −0.61, 95% CI: −0.80 to − 0.43, p < 0.001) remained significantly associated with cognitive change.

To address the potential mathematical coupling between baseline GCC and change scores, we performed a sensitivity analysis using 12-month GCC as the dependent variable, adjusted for baseline GCC and the same clinical and psychological covariates (Supplementary Table 1). In this model, depressive temperament remained positively associated with 12-month GCC (β = 0.44, p = 0.009), whereas anxious temperament remained negatively associated with 12-month GCC (β = −0.41, p = 0.013). Baseline GCC was also positively associated with 12-month GCC (β = 0.40, p = 0.004). Age, duration of hospitalization, and adjuvant treatment were not significantly associated with 12-month GCC.

Discussion

In this longitudinal study of patients undergoing radical prostatectomy, we observed a delayed improvement in global cognitive performance, with significant changes emerging only at 12 months (Table 2). Although statistically significant, the magnitude of improvement was modest, suggesting a subtle but measurable recovery. Importantly, this pattern indicates that postoperative cognitive trajectories in this population may not follow a simple decline–recovery model, but instead involve delayed and potentially nonlinear changes over time. Notably, the absence of significant differences between baseline and 6 months, as well as between 6 and 12 months, further supports a delayed trajectory.

These observations are consistent with emerging data from broader surgical populations, indicating that postoperative cognitive outcomes are heterogeneous [11, 34]. While some patients exhibit early or persistent impairment, others demonstrate recovery over longer follow-up periods. In this context, our results extend previous findings by suggesting that delayed improvement may represent a relevant and underrecognized trajectory in oncological populations. However, interpretation remains complex, as cancer-related factors—including systemic effects of malignancy and comorbidities—may independently contribute to cognitive dysfunction [17].

Interestingly, despite the observed improvement in global cognitive performance, no significant longitudinal changes were detected across individual cognitive domains (Table 2). This discrepancy may reflect the greater sensitivity of composite measures to subtle, multidimensional changes that are not captured at the level of single tests. Alternatively, it may indicate that recovery occurs in a diffuse rather than domain-specific manner. This contrasts with some prior studies reporting domain-specific changes, particularly in executive and visuospatial functions [11, 35], and highlights the need for further research using standardized and comparable cognitive batteries.

An interesting finding of the present study is the association between psychological factors and cognitive trajectories. Preliminary analyses suggested that affective temperament may influence cognitive change, with depressive and anxious traits showing opposite associations. These associations remained significant after adjustment for baseline cognitive performance, supporting the notion that baseline psychological characteristics may contribute to shaping postoperative cognitive trajectories. This aligns with emerging evidence emphasizing the role of psychological vulnerability in postoperative neurocognitive outcomes [9], while also highlighting the need for further investigation into specific temperament profiles.

Contrary to several previous reports [6, 7], adjuvant treatment was not significantly associated with changes in cognitive performance in our cohort. This finding should be interpreted with caution, as it is likely influenced by selection bias. Patients receiving adjuvant therapy represented a small and potentially non-representative subgroup, while the overall cohort consisted predominantly of individuals treated with radical prostatectomy with curative intent and no initial indication for adjuvant therapy.

Baseline global cognitive performance was strongly associated with change in GCC between baseline and 12 months. Patients with lower baseline scores demonstrated greater improvement over time, which may reflect, at least in part, gradual recovery of cognitive performance during postoperative follow-up period. This finding underscores the importance of accounting for baseline cognitive status in longitudinal analyses and may partially explain inconsistencies across previous studies. This interpretation is consistent with previous findings showing that delayed neurocognitive recovery in the early postoperative period may be associated with greater subjective cognitive difficulties at 12 months, particularly in domains such as memory, attention, action, and perception [36]. However, this finding should be interpreted cautiously. Because change scores are mathematically dependent on baseline values, the association between baseline GCC and subsequent change may also partly reflect regression to the mean and mathematical coupling inherent to change-score analyses. Therefore, lower baseline GCC should not be interpreted as direct evidence of greater postoperative cognitive recovery. To address this issue, we performed a sensitivity analysis using 12-month GCC as the dependent variable, adjusted for baseline GCC and the same clinical and psychological covariates. In this model, the associations with depressive and anxious temperament remained consistent with the primary change-score model, supporting the robustness of these exploratory findings.

Physical activity was not associated with cognitive change, however, the relationship may be complex and context-dependent. The absence of a clear dose–response pattern suggests the presence of confounding factors, such as baseline health status or functional reserve. This is consistent with the heterogeneous and inconclusive evidence in prostate cancer populations [37], where exercise may exert context-dependent effects, particularly in patients receiving systemic therapies [38, 39]. Although a trend was observed in the initial model, depressive symptoms were not significantly associated with cognitive trajectories after full adjustment. While prior studies have demonstrated cross-sectional associations between depression and cognitive function in prostate cancer patients [40, 41], our findings do not support a longitudinal relationship in this cohort. This suggests that affective symptoms may co-occur with cognitive impairment but may not independently influence its evolution over time.

Taken together, these findings highlight the dynamic and multifactorial nature of postoperative cognitive trajectories in prostate cancer patients. From a clinical perspective, they support the need for longitudinal cognitive monitoring beyond the early postoperative period. Furthermore, the observed associations with psychological factors suggest that incorporating mental health assessment into perioperative care may help identify patients at risk of less favorable cognitive outcomes.

Limitations

This study has several limitations that should be acknowledged. First, the relatively small sample size may limit the statistical power of the analyses and reduce the generalizability of the findings. Second, the absence of postoperative cognitive assessment in the immediate postoperative period (up to 1 month) precludes direct evaluation of the magnitude of postoperative cognitive decline and the incidence of delayed neurocognitive recovery. However, it is important to emphasize that the primary aim of the present study was not to quantify the acute cognitive deterioration attributable to surgery itself, but rather to characterize the longitudinal trajectory of cognitive function in the postoperative period. Accordingly, the observed changes should be interpreted as reflecting the dynamic evolution of cognitive performance over time, influenced by multiple perioperative and patient-related factors, rather than as a direct measure of surgery-induced cognitive decline. Moreover the absence of a non-surgical control group limits the ability to disentangle surgery-related effects from natural cognitive aging.

A further limitation is the substantial amount of missing data at both baseline and follow-up assessments, which reduced the final analytical cohort to 66 of the 100 enrolled patients. This may have resulted in a selected study population and introduced the potential for selection bias. Consequently, the generalizability of the findings may be limited, and the results should be interpreted with appropriate caution.

A further limitation is the inability to formally correct repeated cognitive assessments for practice effects. For the applied testing methodology and the study-specific GCC, validated test–retest norms, alternate forms, or practice-effect correction factors were not available. Since such correction would require longitudinal norms or a control group assessed with the same battery at comparable intervals, the observed improvement in GCC should be interpreted cautiously, particularly for memory-related components that may be more susceptible to repeated test exposure.

Because GCC was constructed as a study-specific standardized composite score, no established threshold for minimal clinically important change is available for this measure. Therefore, although the observed change in GCC was statistically significant, its clinical significance should be interpreted cautiously, particularly given the stability of most individual cognitive domains and the possibility of practice effects. In addition, the present study did not systematically assess functional independence, treatment adherence, or cognitive change in relation to patient-reported recovery outcomes; this should be addressed in future studies.

Another potentially valuable aspect that was not assessed in the present study is decision regret. The inclusion of a validated measure such as the Decision Regret Scale could provide additional insight into patients’ perceptions of their treatment choices and their potential relationship with cognitive trajectories. Patients’ attitudes toward and satisfaction with the treatment decision they made may influence psychological adjustment and, consequently, cognitive outcomes [42]. Therefore, incorporating decision regret into future studies could represent an informative extension of our findings.

Future studies should incorporate larger, well-characterized cohorts with preoperative baseline assessments, early postoperative cognitive evaluation, non-surgical control groups, and extended follow-up to more precisely delineate the trajectory, determinants, and clinical significance of cognitive changes in patients undergoing prostate cancer surgery.

Electronic Supplementary Material

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Author contributions

[AP]: conceptualization, methodology, data collection, writing – original draft preparation, [BB]: conceptualization, methodology, data collection, writing – critical revision of the manuscript, [JB]: data analysis, interpretation of results, writing – review and editing, [JBS]: data collection, revision of the manuscript, [JP]: data collection, revision of the manuscript, [PJ]: conceptualization, supervision, critical revision of the manuscript, [AB]: supervision, critical revision of the manuscript, [MB]: conceptualization, methodology, supervision, critical revision of the manuscript . All authors reviewed the manuscript.

Funding

The authors declare that no funding was received for this study.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Competing interests

The authors declare no competing interests.

Ethics approval

The study was conducted in accordance with the ethical standards of the institutional and/or national research committee and with the Declaration of Helsinki. Ethical approval was obtained from the Bioethics Committee of the Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz (approval no. 476/2017) prior to the commencement of the study.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Animal welfare

Not applicable, as this study did not involve animals.