A Standardized Psychological Intervention Procedure for Ovarian Cancer Patients Based on the Lazarus Stress Coping Model

Ovarian cancer is among the most aggressive gynecological malignancies, frequently diagnosed at advanced stages because of subtle early symptoms and the absence of effective screening strategies¹. Standard treatment typically combines surgery with platinum-based chemotherapy², yet despite significant clinical advances, ovarian cancer remains the leading cause of death among gynecological cancers and ranks as the fifth most common cause of cancer-related mortality in women, with an increasing incidence observed in younger populations³. These epidemiological trends underscore the urgent need to improve not only survival outcomes but also the quality of life for affected patients.

Beyond its physical burden, ovarian cancer imposes profound psychological challenges. Treatment-related fatigue, weight loss, and physical deterioration often exacerbate anxiety, depressive symptoms, and emotional dysregulation⁴. Furthermore, repeated diagnostic procedures and continuous oncology follow-up can intensify psychological distress⁵. Consequently, psycho-oncology has become an essential dimension of comprehensive cancer care, focusing on structured support for the cognitive and emotional needs of patients.

Recent evidence also links psychosocial stress to both cancer onset and progression⁶. Dysregulation of neuroendocrine pathways and immune suppression are considered key mediators of this relationship⁷. In patients undergoing chemotherapy, these psychosocial stressors interact with physiological treatment stress, such as cytotoxic injury to rapidly dividing healthy cells in the nervous, gastrointestinal, and integumentary systems⁸, further compromising treatment adherence and potentially worsening clinical outcomes.

Despite growing recognition of these challenges, standardized psychological interventions remain scarce and inconsistently implemented in oncology practice. Existing approaches are often fragmented, lack reproducibility, and fail to systematically enhance coping capacity or emotional regulation. While alternative psychological frameworks, such as acceptance and commitment therapy (ACT) and mindfulness-based cognitive therapy (MBCT), have shown benefits in other oncology contexts, they remain underexplored in ovarian cancer care and lack standardized delivery formats.

To address these gaps, the present study develops and evaluates a standardized psychological intervention protocol grounded in the Lazarus stress coping model. The protocol integrates cognitive-behavioral strategies, emotional regulation training, and structured counseling modules into chemotherapy care, aiming to reduce anxiety and depression while improving coping capacity and emotional well-being. By combining validated psychometric tools with a multidisciplinary delivery framework, this study provides a reproducible, theory-driven intervention designed to meet the urgent need for integrated psychological support in oncology practice.

Objective of the research
This study aims to develop and evaluate a standardized psychological intervention protocol for ovarian cancer patients undergoing chemotherapy, grounded in the Lazarus stress coping model. The protocol integrates cognitive-behavioral strategies, emotional regulation training, and structured counseling modules into standard oncology care, with three primary objectives: enhancing coping skills, reducing anxiety and depression, and improving overall psychological well-being during chemotherapy. By combining validated psychometric tools with a multidisciplinary delivery framework, this study seeks to establish a theory-driven, reproducible model that embeds standardized psychological care into routine oncology practice.

Relevant articles
Research on the psychological needs and supportive care of ovarian cancer patients has expanded rapidly in recent years, yet several critical gaps remain. Bibliometric analyses indicate increasing interdisciplinarity but limited institutional and international collaboration, restricting integrated clinical strategies^9,10.

Qualitative studies report that up to 90% of ovarian cancer patients experience significant emotional stress based on interviews with patients, caregivers, and clinicians, yet small sample sizes and lack of quantitative validation limit generalizability. Similarly, a multicenter cross-sectional study found positive associations between psychological capital, coping competence, and emotional well-being among 223 ovarian cancer patients¹¹, but the absence of longitudinal data prevents causal inference.

Various supportive strategies have been explored, but most remain underdeveloped. Patient navigation (PN) programs benefit women at genetic risk¹², yet their long-term impact is rarely assessed. Studies on death-related anxiety demonstrate its predictive role in fear of cancer recurrence (FCR) and fear of progression (FOP)¹³, but they often rely on unidimensional measurement tools. Likewise, investigations into stress management, self-efficacy, and health control domains highlight the need for integrated care approaches¹⁴, yet face sample recruitment limitations.

Furthermore, integrating patient-reported outcomes (PROs) into ovarian cancer trials has been widely recommended¹⁵, but inconsistent implementation hampers systematic evaluation of psychological effects. Multimodal prehabilitation programs before cytoreductive surgery show promise in reducing postoperative complications¹⁶ and have demonstrated feasibility in small-scale pilot studies¹⁷; however, these interventions focus mainly on perioperative readiness and do not adequately address psychological well-being.

Collectively, these findings reveal a fragmented research landscape: while important insights exist, there remains a lack of standardized, reproducible psychological intervention protocols tailored specifically to ovarian cancer patients. This study addresses this critical gap by proposing a theory-driven, evidence-based framework that integrates validated coping strategies into oncology care.

This study was approved by the Ethics Committee of Baotou Central Hospital (Approval No.: 2025-YJS-076). Written informed consent was obtained from all participants before enrollment. All procedures were conducted in accordance with the Declaration of Helsinki and institutional guidelines for human research. The reagents and the equipment used are listed in the Table of Materials.

1. Study design and participants

1. Study overview
   A randomized controlled trial (RCT) was conducted to evaluate the effectiveness of a standardized psychological intervention protocol based on the Lazarus stress coping model among ovarian cancer patients receiving chemotherapy. Between March 2024 and September 2024, seventy eligible patients were recruited from the Department of Gynecologic Oncology, Baotou Central Hospital. Participants were randomly assigned in a 1:1 ratio to either the intervention group (n = 35), which received standard medical care combined with structured psychological support, or the control group (n = 35), which received standard medical care only.
2. Inclusion and exclusion criteria
   Inclusion criteria were histologically confirmed ovarian cancer, age between 25-45 years, scheduled for chemotherapy, and no prior psychiatric diagnosis. Exclusion criteria included cognitive impairment, severe psychiatric disorders, ongoing psychotropic medication, or refusal to participate.
3. Baseline data collection
   Baseline data were collected prior to intervention, including demographic and clinical characteristics such as age, body mass index (BMI), years of infertility, baseline follicle-stimulating hormone (FSH) levels, antral follicle count (AFC), and gonadotropin stimulation duration and dosage. Independent-sample t-tests confirmed no significant baseline differences between the groups (p > 0.05).

2. Intervention protocol

1. Intervention design
   The intervention was designed according to the Lazarus stress coping model, which emphasizes how individuals appraise stressful events and adopt coping strategies to regulate emotions. A multidisciplinary team consisting of psychologists, oncology nurses, and gynecologic oncologists delivered the intervention over eight consecutive weeks.
2. Session structure
   Each patient in the intervention group attended one 45 min session per week, conducted either individually or in a small group of three to five participants. All sessions took place in a quiet, private counseling room adjacent to the oncology ward to ensure comfort and confidentiality.
3. Intervention modules
   Each session comprised four integrated modules. In cognitive restructuring, patients were guided to identify maladaptive automatic thoughts related to diagnosis and treatment and to reframe them using adaptive interpretations. Standardized scripts adapted from Beck's Cognitive Therapy Manual (3^rd edition) were employed, and exercises lasted 10-15 min with guided reflection. Emotional regulation training combined progressive muscle relaxation, mindfulness-based breathing, and guided visualization, each delivered for about 10 min with scripted or audio guidance to ensure consistency. Coping skills education focused on distinguishing adaptive coping strategies, such as problem-focused approaches, from maladaptive strategies, such as avoidance. Patients rehearsed these skills through role-play scenarios and behavioral simulations tailored to chemotherapy-related stressors. Structured counseling sessions facilitated integration of the acquired skills, providing opportunities for guided group discussion, problem-solving exercises, and peer interaction for approximately 10-15 min.
4. Participant monitoring
   Participant well-being was closely monitored throughout the intervention. A clinical psychologist was present in every session to observe emotional responses. In cases of acute distress, immediate supportive counseling was provided, and when necessary, referral pathways to psychiatric services were activated. The complete intervention scripts, manuals, and validated psychometric scales are listed in the Table of Materials, including full names, publishers, version numbers, and catalog identifiers.

3. Outcome measures

The primary outcomes focused on changes in psychological distress, assessed at baseline and after the intervention using validated scales such as the Hospital Anxiety and Depression Scale (HADS), the Self-Rating Depression Scale (SDS), and the Self-Rating Anxiety Scale (SAS). Secondary outcomes included emotional regulation capacity, evaluated by clinician-rated coping ability scales, as well as reproductive indicators including the number of oocytes retrieved, the proportion of high-quality embryos, and both biochemical and clinical pregnancy rates.

4. Data analysis

All statistical analyses were performed using SPSS. Continuous variables were expressed as mean ± standard deviation (SD) or median (interquartile range, IQR) depending on distribution, and were compared using independent-sample t-tests. Categorical variables were analyzed using chi-square tests. Statistical significance was set at p < 0.05.

5. Start and end of procedure

The procedure began with obtaining informed consent, collecting baseline demographic and clinical data, and administering pre-intervention psychometric assessments. The intervention then proceeded with eight consecutive weeks of psychological sessions integrated into routine chemotherapy. The procedure concluded after the final post-intervention assessments were completed, all data were entered into SPSS, and participants were debriefed with information on available psychological support services.

Baseline demographic and clinical characteristics were comparable between the intervention and control groups (Table 1). There were no significant differences in age, body mass index, years of infertility, baseline follicle-stimulating hormone (FSH) levels, antral follicle count (AFC), gonadotropin stimulation time, or gonadotropin dosage (all p > 0.05). This indicates that the two groups were balanced prior to the intervention.

After the 8-week intervention, patients in the treatment group showed significant improvements in psychological outcomes (Table 2). Independent-sample t-tests revealed that the combined anxiety-depression score, measured using the Hospital Anxiety and Depression Scale (HADS), the Self-Rating Depression Scale (SDS), and the Self-Rating Anxiety Scale (SAS), decreased markedly from 11.77 ± 1.75 at baseline to 5.86 ± 1.78 post-intervention (p < 0.01). In contrast, no significant change was observed in the control group (11.14 ± 2.14 to 11.14 ± 2.14, p > 0.05). These reductions are consistent with the impact of the cognitive restructuring module, which enabled participants to reframe maladaptive thoughts, and with structured counseling sessions that provided opportunities for guided discussion and peer support.

Emotional regulation capacity, assessed through clinician-rated coping ability scales, also improved significantly in the intervention group compared with controls (Figure 1, p < 0.05). This improvement reflects the effectiveness of the relaxation and mindfulness-based exercises, including progressive muscle relaxation, mindfulness breathing, and guided visualization, which were incorporated into the protocol as emotional regulation training.

In terms of coping skills education, participants in the intervention group reported greater reliance on adaptive strategies and demonstrated higher coping ability scores after the program (p < 0.05). This finding highlights the value of psychoeducation and role-play exercises in helping patients acquire and rehearse positive coping strategies that can be applied to treatment-related stressors.

With respect to embryological indicators, the treatment group achieved a higher number of oocytes retrieved and a greater number of optimal embryos compared with the control group (Table 3). Specifically, the median number of oocytes obtained was 7 (IQR 5-11) in the treatment group versus 5 (IQR 3-8) in the control group (p = 0.04, Mann-Whitney U test). Similarly, the number of optimal embryos was higher in the treatment group (median 4, IQR 2-5) compared with controls (median 2, IQR 3, p = 0.03, Mann-Whitney U test). Although differences in the number of MII oocytes and fertilized embryos did not reach statistical significance, favorable trends were observed.

Pregnancy outcomes also reflected this pattern (Table 4). The clinical pregnancy rate was 48.57% in the treatment group compared with 28.57% in the control group, although the difference did not reach statistical significance (χ2 = 2.962, p = 0.227, chi-square test). Biochemical pregnancy rates were similar between groups (p > 0.05).

Taken together, the intervention group exhibited both significant psychological benefits and favorable trends in reproductive outcomes. These findings suggest that a standardized psychological intervention protocol may not only improve emotional well-being through modules such as cognitive restructuring, emotional regulation, coping skills education, and structured counseling but may also support treatment responsiveness and reproductive potential in ovarian cancer patients undergoing chemotherapy.

DATA AVAILABILITY:
The datasets generated and analyzed during the current study are publicly available in the Figshare repository at https://doi.org/10.6084/m9.figshare.30100714.v1 and are linked to this manuscript. 

Figure 1: Psychological and reproductive outcomes of ovarian cancer patients. (A) Changes in combined anxiety-depression scores before and after intervention in both groups. (B) Improvements in emotional regulation capacity following the standardized psychological intervention. Scale bar: 50 µm. (C) Comparison of high-quality embryo rates between intervention and control groups. Scale bar: 2 µm. (D) Clinical pregnancy rates for intervention and control groups. Error bars represent mean ± SD. Statistical analysis was performed using independent-sample t-tests and chi-square tests where appropriate. n = 35 per group. Significance level was set at p < 0.05. Please click here to view a larger version of this figure.

Table 1: Baseline comparison of demographic and clinical characteristics between intervention and control groups. Data are expressed as mean ± SD unless otherwise indicated. No significant differences were found between groups across baseline parameters (p > 0.05). Statistical analysis was conducted using independent-sample t-tests and chi-square tests. Please click here to download this Table.

Table 2: Comparison of anxiety and depression scores between intervention and control groups before and after intervention. Data are expressed as mean ± SD. Psychological distress was assessed using validated instruments, including the Hospital Anxiety and Depression Scale (HADS), Self-Rating Depression Scale (SDS), and Self-Rating Anxiety Scale (SAS). Statistical analysis was performed using independent-sample t-tests. Significance threshold was set at p < 0.05. Please click here to download this Table.

Table 3: Comparison of embryological outcomes between intervention and control groups. Variables include the number of retrieved oocytes, proportion of high-quality embryos, and fertilization rates. Data are expressed as median (P25, P75). Statistical comparisons were made using independent-sample t-tests. Please click here to download this Table.

Table 4: Comparison of pregnancy outcomes between intervention and control groups. Pregnancy outcomes include biochemical pregnancy rates and clinical pregnancy rates. Data are expressed as mean ± SD. Statistical analysis was conducted using chi-square tests. Significance threshold was set at p < 0.05. Please click here to download this Table.

This study developed and evaluated a standardized psychological intervention protocol for ovarian cancer patients grounded in the Lazarus stress coping model, integrating cognitive-behavioral strategies, emotional regulation training, coping-skills education, and structured counseling into oncology care. Prior studies investigating psychological interventions for ovarian cancer have been constrained by methodological limitations, including small sample sizes that reduce generalizability, a lack of longitudinal assessment of sustained effects, and limited incorporation of patient-reported outcomes into standard practice^1,2. In addition, existing studies frequently rely on one-dimensional psychological measures and exhibit limited institutional collaboration, which contributes to fragmented evidence and inconsistent translation into clinical care⁵.

By employing a validated and structured intervention, this study addresses these gaps and enhances reproducibility in clinical practice. Unlike previous investigations that often used brief counseling or unstructured psychoeducation, the present protocol systematically integrates multimodal cognitive-behavioral components with structured counseling, enabling comprehensive evaluation of both emotional well-being and treatment-related outcomes. The Lazarus stress coping model was specifically selected because it captures both cognitive appraisal and adaptive coping strategies, offering a broader and more operational framework compared to alternative models. For example, acceptance and commitment therapy (ACT) emphasizes psychological flexibility, and mindfulness-based cognitive therapy (MBCT) emphasizes present-moment awareness. Both have shown benefits in oncology contexts, but they are generally applied in individualized interventions and lack the standardization required for integration into routine cancer care⁷. In contrast, the Lazarus-based framework provides a scalable and reproducible structure that can be readily implemented within multidisciplinary oncology workflows.

The observed psychological improvements and favorable trends in reproductive outcomes suggest that reducing psychological stress may influence not only emotional well-being but also biological processes relevant to treatment responsiveness. These findings are consistent with emerging evidence linking stress reduction during cancer therapy with improved physiological outcomes, including reproductive health. By incorporating validated psychometric measures, patient-reported outcomes, and a structured delivery framework, this study contributes to advancing supportive oncology care and provides a foundation for future multicenter applications^11,16.

In conclusion, this study developed and evaluated a standardized psychological intervention protocol based on the Lazarus stress coping model for ovarian cancer patients undergoing chemotherapy. The protocol demonstrated significant improvements in psychological well-being and coping capacity, while also showing promising, though non-significant, trends in reproductive outcomes.

These findings underscore the feasibility, scalability, and reproducibility of embedding structured psychological interventions into oncology practice. Several limitations must nevertheless be acknowledged. The relatively small sample size, single-center design, and short intervention duration restrict the generalizability of the results, and the long-term effects remain unexplored. Future research should employ larger multicenter randomized trials with extended follow-up periods to confirm sustained outcomes. Furthermore, digital modalities such as tele-counseling and mobile health applications may expand accessibility, personalization, and scalability, particularly for patients in resource-limited settings. Integrating these innovations with standardized protocols could further strengthen the role of psychological care within modern oncology practice.