The effectiveness of dyadic interventions for health outcomes of prostate cancer patients and informal caregivers: a systematic review and meta-analysis

The inclusion criteria were as follows: (1) Study population: (a) patients with a confirmed diagnosis of prostate cancer and ≥ 18 years of age. (b) caregivers: informal caregivers; ≥18 years old. (2) Interventions: included interventions based on patients with prostate cancer and their informal caregivers. (3) Controls: any control group. (4) Outcome metrics: included health outcomes for prostate cancer patients and caregivers informally. (5) Study type: randomized controlled trial. (6) Language: Chinese or English were used in the published version of the study.

The exclusion criteria were as follows: (1) conference abstracts, reviews, theses, study protocols, and duplicate reports, and (2) studies that did not have relevant data.

The total sample size for the study comprised 17 [21] to 263 [22]pairs, and the patients’ and caregivers’ mean ages ranged from 51.7 to 77.0 years and 50.7 to 75.6 years, respectively. Two of the 19 studies did not report demographic information [21, 23]. In addition, of the relationships between patients and caregivers, 14 studies reported spousal or cohabiting relationships [21, 22, 24‐35], and 3 reported relationships limited to legal heterosexual couples [36‐38].

Nineteen studies involved twenty-two varied interventions. Nurses delivered the majority of interventions (n = 8) [22, 25, 26, 35‐39], and in three of these interventions the care providers also involved sports coaches, counsellors [39], doctors [36] or researchers, psychotherapists, and nurse practitioners [37]. The interventions in two studies required participants to complete the intervention on their own by logging on to a specific website provided by the researcher [33, 34].

The included studies described multiple modes of intervention delivery. In ten studies, interventions were delivered via conference or course [21‐24, 27, 29‐32, 39], with 2 studies also involving the provision of information materials, a holistic needs assessment, and a personalized self-management care plan [39] or reading of a brochure. In 6 studies [25, 26, 28, 35‐37], the intervention was delivered in the form of counselling, with 2 studies also involving the mailing of an information brochure or the delivery of a multimedia film [26] via an app or in conjunction with Pelvic Floor Muscle Training (PFMT) [28]; in the other studies (n = 3), the intervention was delivered by having participants log on to a specific website, such as TrueNTH [33], TEMPO [34] or ESCP [38], on their own.

All participants but 1 in the control group used Survivorship Care Plans (SCP) [38]. The remaining 18 studies used standard care or usual care.

Each study measured at least one outcome, including psychosocial health, sexual health, or an outcome related to dyadic relationships. For prostate cancer patients, the following ten outcomes were included in this study: psychosocial health (quality of life, neuropsychiatric symptoms, anxiety, depression, stress, self-efficacy), sexual health (sexual function, sexuality-related mental health), and dyadic relationships (relationship satisfaction, dyadic coping). For caregivers, the following nine outcomes were included: psychosocial health (quality of life, neuropsychiatric symptoms, anxiety, depression, stress, self-efficacy), sexual health (sexual function), and dyadic relationships (relationship satisfaction, dyadic coping). Other outcomes were not included in further analyses because they were reported in fewer than three studies.

For the meta-analysis of quality of life in prostate cancer patients, pooled data from 10 studies were used [21, 22, 24, 28, 29, 32, 34, 36, 38, 39]. These studies were heterogeneous (p < 0.00001, I² = 93%), and a subgroup analysis revealed that patients’ quality of life was not significantly affected by the duration of the intervention (< 3 months: SMD95% CI [95% CI] = 0.62 [-0.09;1.34], p = 0.09; ≥3 months: SMD95% CI [95% CI] =-0.15 [-0.56;0.25], p = 0.46) (Figure S1a-1) or the way it was delivered (offline: SMD95% CI [95% CI] = 0.08 [-0.17;0.33], p = 0.53; e-Health: SMD95% CI [95% CI] = 0.16 [-0.19;0.51], p = 0.37; mixed methods: SMD95% CI [95% CI] =-2.16[-4.63;0.32], p = 0.09) (Figure S1a-2).

For caregiver quality of life, 7 studies [21, 22, 24, 28, 32, 34, 38] reported that the intervention’s overall effect was not statistically significant (SMD [95% CI] = 0.11 [-0.08;0.30], p = 0.26) (Figure S2a).

The overall outcomes revealed that there was no meaningful change in the neuropsychiatric symptoms of patients (SMD95% CI [95% CI] = -0.09 [-0.44;0.25], p = 0.59) (Figure S1b) or caregivers (SMD95% CI [95% CI] = -0.86 [-2.23;0.50], p = 0.22) (Figure S2b). Furthermore, because all included studies had intervention durations of less than 3 months, subgroup analyses were not possible for both.

Five studies evaluated how an intervention affects patients’ anxiety [28, 31, 34, 36, 39]. However, the combined results (Figure S1c) demonstrated high heterogeneity (p < 0.00001, I² = 87%) and no intervention impact (SMD95% CI [95% CI] = -0.41 [-1.18;0.36], p = 0.30).

The impact of the intervention on caregivers’ anxiety was examined in five investigations [24, 28, 31, 34, 36]. The combined results (Figure S2c) revealed that the overall effect was statistically significant for anxiety (SMD95% CI [95% CI] = -0.35 [-0.65;-0.06], p = 0.02). Subgroup analyses revealed that intervention durations of less than three months (SMD95% CI [95% CI] = -0.50 [-0.87;-0.14], p = 0.007) (Figure S2c-1) and forms of intervention delivered through mixed methods (SMD95% CI [95% CI] = -0.51 [-0.92;-0.10], p = 0.01) (Figure S2c-2) were effective in reducing caregiver anxiety.

Six studies reported depression scores from prostate cancer patients [28, 30, 31, 34, 36, 39], and six studies reported depression scores from caregivers [24, 28, 30, 31, 34, 36]. Neither meta-analysis demonstrated an effect of the intervention on depression (patients: SMD95% CI [95% CI] = -0.21 [-0.68;0.26], p = 0.38; caregivers: SMD95% CI [95% CI] = -0.22 [-0.54;0.10], p = 0.18) (Figure S1d) (Figure S2d), and it is crucial to acknowledge that these studies had substantial heterogeneity (patients: p < 0.00001, I² = 84%; caregivers: p = 0.02, I² = 60%).

Among the included studies, only 3 investigated the impact of interventions on patient stress [27, 29, 30] (Figure S1e). The change in both groups of participants was not statistically significant (SMD95% CI [95% CI] = -0.02 [-0.21;0.16], p = 0.80). Only 2 studies investigated the effect of the intervention on caregiver stress [27, 30], and the results revealed no effect of the intervention (SMD95% CI [95% CI] = -0.17 [-0.39;0.05], p = 0.14) (Figure S2e).

Seven studies reported self-efficacy scores provided by prostate cancer patients [21, 22, 24, 28, 34, 38, 39] (Figure S1f). In contrast to the control group, the dyadic interventions failed to enhance patient self-efficacy in the intervention group (SMD95% CI [95% CI] = 0.04 [-0.15;0.23], p = 0.67) (Figure S1f).

Five studies reported self-efficacy ratings from caregivers [21, 22, 28, 34, 38] (Figure S2f), with low heterogeneity between studies (P = 0.20, I² = 33%); caregivers in the intervention group outperformed those in the control group with respect to improving self-efficacy, with a statistically significant difference (SMD95% CI [95% CI] = 0.22 [0.01; 0.43], p = 0.04) (Figure S2f). Notably, interventions that lasted less than three months were related to increased caregiver self-efficacy (SMD95% CI [95% CI] = 0.28 [0.03;0.52], p = 0.03) (Figure S2f-1).

The meta-analysis of sexual function in prostate cancer patients pooled data from 3 studies [25, 28, 33] and revealed no intervention effect (SMD95% CI [95% CI] = 0.06 [-0.17;0.30], p = 0.60) (Figure S1g).

However, the 2 RCTs [25, 33] that included sexual function as an outcome indicator had statistically significant effects only on caregivers (SMD95% CI [95% CI] = 0.29 [0.05;0.54], p = 0.02) (Figure S2g).

Only three of the included studies reported on sexuality-related mental health outcome indicators for patients [25, 28, 31] (Figure S1h). The intervention group’s total effect did not show any substantial benefit (SMD95% CI [95% CI] = -0.05 [-0.29;0.20], p = 0.71), and subgroup analyses could not be performed because the duration of the intervention was greater than 3 months in all three studies. No studies have reported on sexuality-related mental health outcomes for caregivers.

Four included studies, involving six different interventions [25, 28, 30, 37], assessed the impact of interventions on relationship satisfaction in patients (Figure S1i), and the heterogeneity test revealed substantial heterogeneity among the studies (P < 0.0001, I² = 82%). To explore the heterogeneity, a subgroup analysis by intervention was performed. The results indicated that an intervention in the form of offline delivery increased patients’ relationship satisfaction (offline: SMD95% CI [95% CI] = 1.14 [0.69; 1.59], p < 0.00001); however, neither the duration of the intervention (< 3 months: SMD95% CI [95% CI] = 0.36 [-0.32; 1.04], p = 0.30; ≥3 months: SMD95% CI [95% CI] =-0.21 [-0.47; 0.04], p = 0.10) (Figure S1i-1) nor the other two intervention forms had a significant effect on patient relationship satisfaction (e-Health: SMD95% CI [95% CI] =-0.19 [-0.46; 0.08], p = 0.16; mixed methods: SMD95% CI [95% CI] =-0.04 [-0.26; 0.19], p = 0.75) (Figure S1i-2).

Five studies investigated the effects of treatments on caregiver relationship satisfaction [25, 28‐30, 37] (Figure S2h). The combined results indicate heterogeneity among these studies (P = 0.003, I² = 70%), and none of the effects of the intervention effects were substantial (SMD95% CI [95% CI] = 0.21 [-0.07;0.49], p = 0.15).

Four studies reported dyadic coping by prostate cancer patients and caregivers [22, 27, 34, 38]; for patients, the findings revealed a statistically significant effect (SMD95% CI [95% CI] = 0.22 [0.01;0.42], p = 0.04) (Figure S1j); however, the intervention did not affect caregivers (SMD95% CI [95% CI] = 0.13 [-0.09;0.34], p = 0.25) (Figure S2i).

A meta-analysis of studies of prostate cancer patients and their informal caregivers revealed no significant effect of dyadic care interventions on health-related quality of life, and the results of this study are consistent with those of previous studies [12]. Many factors contribute to quality of life, including mental, physical, social, and cognitive functioning [40]. On the one hand, the lack of effect of an intervention may be explained by several factors. First, the quality of life of the subjects included in some of the studies had already been assessed in a manner similar to that of the normal population at baseline, so the effect of the intervention was limited [21, 22]. Second, the content of the intervention implemented in the intervention group was broadly similar to that implemented in the control group; e.g., in Song et al.’s study [38] the NCI website used in the control group was similar to that used in the experimental group with the PERC mobile health care app, which had similar information, online chat and support features. In addition, even when standard care was set as the intervention in the control group, some force majeure issues, such as social support and economic levels, had an impact on quality of life [41]. On the other hand, according to some of the intervention studies, several potentially effective intervention mechanisms exist. First, the interventions mostly involved the prior organization of a multidisciplinary team, starting from the existing patient and caregiver problems and explaining the disease and its care to improve their comprehension so that effective measures can be applied to solve the actual problems [42]. Second, intervention processes are often long and monotonous, and including the caregiver in the care plan allows the prostate cancer dyad to empathize with one another and support each other’s coping, improving adherence to the intervention and quality of life [42]. Third, the intervention builds a relaxing atmosphere through empathy, communication, assistance, and attention from health care professionals to patients and caregivers, showing concern and professionalism and improving the dyad’s mental health as well as both patients’ and caregivers’ quality of life. Therefore, future dyadic interventions should incorporate these points to increase the quality of life for men with prostate cancer and their caregivers.

Depression and anxiety are prevalent in men with prostate cancer and lead to a lower quality of life, decreased treatment adherence, and increased mortality. Their caregivers are often more distressed than the patients are, and exhibit rates of major depression. The prevalence of generalized anxiety disorders may be up to twice as high as that in the general population and may remain elevated long after treatment [43‐46]. In line with previous findings [13], the intervention had no significant effect on depression in prostate cancer patients or caregivers. In contrast, this study revealed that the dyadic intervention significantly improved anxiety in caregivers, whereas no effective improvement in patient anxiety was observed; this is not surprising because patients and caregivers have different support needs. As the primary providers of care activities, caregivers carry a variety of physical, psychological, and financial burdens and face social pressures as well, with subgroup analyses revealing that an intervention duration of < 3 months significantly reduces their anxiety. However, this intervention effect was not sustained, with previous research suggesting that caregivers have more distress than patients do but receive less support [47]. Furthermore, the intervention provided them with information and support that reduced their negative appraisals of caregiving, uncertainty, and feelings of hopelessness and helped them learn how to cope with stress and symptom management. However, because prostate cancer is a ‘relational cancer’, many of the symptoms and sequelae of the disease affect both patients and their carers. In addition, because conventional cancer care or services do not provide sufficient social and family support during subsequent long-term care, the effectiveness of the interventions also change over time. Mixed-method interventions allow caregivers to feel less anxious. Offline interventions, such as conferencing, face-to-face communication, and coaching, are able to foster a more sympathetic connection and identify caretakers’ deeper needs [48, 49]. E-health interventions, in the form of audiovisuals, which take advantage of the internet’s portability and expandability, are capable of laying down information barriers between doctors and patients. A mixed-methods intervention that incorporates both approaches provides for more tailored and comprehensive assistance. Overall, given the aforementioned factors, intervenors should select acceptable formats for delivery methods for informal caregivers based on their characteristics and the circumstances of the scenario. The impact of implementing therapies focused on improving anxiety and depression in patients and their informal caregivers requires further investigation.

Self-efficacy has a powerful influence on a person’s motivation, perseverance, and thought processes and plays an important role in deciding whether to take action, the amount of work to put in, and how often to persevere when faced with obstacles or failures [50]. However, meta-analyses have shown that dyadic interventions do not have a significant impact on self-efficacy in prostate cancer patients. First, the included studies originated in developed countries, where the study population was well educated and well adjusted, making it harder to achieve the desired intervention outcomes. Second, most studies did not include self-efficacy as a primary outcome and therefore did not design targeted intervention modules to improve it. Conversely, the dyadic intervention improved caregivers’ self-efficacy through mechanisms comparable to those that promote other psychosocial outcomes. Future research should focus on study participants who require support and help or add routine care to assess self-efficacy.

As a component of overall health, the World Health Organization defines sexual health as the state of physical, emotional, spiritual, and social well-being related to sexuality [51]. All aspects of sexual health are affected after prostate cancer treatment. Furthermore, most caregivers are postmenopausal women whose sexual function also requires assistance. Sexual dysfunction is one of the most prevalent sexual health issues, and it encompasses not only erectile dysfunction but also impaired arousal and orgasm, with far-reaching consequences for intimacy, communication, and fulfilment in relationships between patients and companions [52]. This meta-analysis revealed three research reports on the consequences of dyadic therapies for patients’ sexual function [25, 28, 33], two of which involved caregivers [25, 33]. The findings did not show an effect of dyadic interventions on the patients but did show an effect on the caregivers. The reasons for this may be include that patients’ distress with penile shortening and erectile and urinary dysfunction limits their desire to engage in sexual activity during recovery, irrespective of the primary type of treatment. Most of the study intervention durations and follow-up times may be premature; previous studies have shown that the mean recovery time for patients whose sexual function returned to baseline levels was 13.2 months [53] and that some patients were not able to regain firmer and more reliable erectile function until 2–4 years after surgery. Given that suppressing emotions and thoughts is not only a coping mechanism but also a means of maintaining relationship continuity, patients and their caregivers often choose to avoid discussing topics related to sexual issues [54]. Interventions related to sexual function have gradually shifted from the early patient-dominant, caregiver-supportive model to one in which both are equal participants in the intervention [55]. The interventions included in the study not only provided pharmacological and surgical treatment for erectile dysfunction but also involved comprehensive psychological and sexual counselling, which has helped them recognize the need for communication, mutual acceptance, and assistance in sexual rehabilitation after prostate cancer care, in turn helping improve sexual function. Due to the limited number of meta-analyses, more high-quality randomized controlled trials could be conducted in the future for prostate cancer patients and their caregivers. The reliability and validity of the intervention results still must be interpreted in conjunction with newly published studies and follow-up work.

Dyadic coping is a process in which both individuals and partners collaborate to maintain or reestablish the balance of mental health, physical health, and the dyadic relationship [56]. In this study, the results of the meta-analysis revealed that the intervention was effective in improving dyadic coping in patients. Communication and obtaining expert direction in interventions can help dyad members develop relationships and self-expression as well as understand each other’s genuine thoughts and emotions and provide encouragement and support. However, prostate cancer affects not only the individual but also the structure and hierarchy of the entire family. Some studies have reported a strong positive correlation between dyadic coping and relationship satisfaction [57], which is the most commonly studied dependent variable in dyadic intervention studies. Given that female caregivers receive less attention and appear to be at greater risk of reduced marital satisfaction than men, reduced marital satisfaction may be of greater concern to prostate cancer patient‒caregiver dyads [43]. Evidence among prostate cancer patients indicates that greater marital satisfaction is linked to patient health several years after treatment [58], as well as with a longer median survival time [59], and that there is a connection between physical health, mental health, and partner relationship satisfaction in couples who have faced prostate cancer. Although meta-analyses have shown that interventions do not have a significant effect on relationship satisfaction, the theory of spousal disclosed intimacy suggests that enhanced dyadic communication has a positive effect on spousal intimacy, as reflected in the results of Luo et al.‘s [37] intervention, which are consistent with the results of a previous intervention on enhancing couple communication to increase relationship satisfaction [60]. Furthermore, the statistically significant findings of this subgroup analysis should be interpreted with caution, because only one trial took the intervention offline. As a result, future dyadic interventions should include caregivers, incorporating communication interventions to help them navigate potential mutual benefits and conducting more studies of higher-quality to provide more conclusive evidence, such as determining appropriate intervention durations and providing enrichment support resources.