Reprinted: Chinese Expert Consensus on Multidisciplinary Diagnosis and Treatment of Malignant Pleural Effusion Associated with Ovarian Cancer (2026 Edition)

Authors: Gynecologic Oncology Group, Obstetrics and Gynecology Physicians Branch, Chinese Medical Association; Gynecologic Oncology Group, Minimally Invasive Medicine Professional Committee, Chinese Medical Association

This article was published in the Chinese Journal of Practical Gynecology and Obstetrics, 2026, 42(3):306–318.

DOI: 10.19538/j.fk2026030110

[Citation] Gynecologic Oncology Group, Obstetrics and Gynecology Physicians Branch, Chinese Medical Association; Gynecologic Oncology Group, Minimally Invasive Medicine Professional Committee, Chinese Medical Association. Chinese Expert Consensus on Multidisciplinary Diagnosis and Treatment of Malignant Pleural Effusion Associated with Ovarian Cancer (2026 Edition) [J]. Chinese Journal of Practical Gynecology and Obstetrics, 2026, 42(3): 306–318.

Authors: Gynecologic Oncology Group, Obstetrics and Gynecology Physicians Branch, Chinese Medical Association; Gynecologic Oncology Group, Minimally Invasive Medicine Professional Committee, Chinese Medical Association

Funding Sources: National Key R&D Program of the 14th Five-Year Plan (2025YFC2708300); Key Projects of the Clinical Medicine Discipline Development Fund, School of Medicine, University of Electronic Science and Technology of China (YXYLCJJ202403006, YXYLCJJ202403008)

1. Background of Consensus Formation and Methodology

Malignant pleural effusion (MPE) refers to pleural fluid accumulation resulting from primary malignant tumors of the pleura or from metastases of malignancies originating elsewhere that spread to the pleura. Epithelial ovarian cancer (EOC), commonly referred to as ovarian cancer, exhibits marked heterogeneity, is prone to metastasis and recurrence, and remains the gynecologic malignancy with the highest mortality rate [1]. Ovarian cancer–associated MPE arises when ovarian cancer disseminates via the peritoneum, spreads through lymphatic or hematogenous routes to the pleura, or drains into the pleural cavity via diaphragmatic lymphatics (hereafter referred to as the pleural space), thereby increasing pleural capillary permeability or obstructing lymphatic drainage and leading to the formation of pleural effusion containing malignant tumor cells. As a typical manifestation of advanced-stage ovarian cancer with pleural metastasis, it is classified as FIGO stage IVa. According to the literature, the pleura is one of the most common extraperitoneal sites of metastasis in advanced ovarian cancer, with approximately 33% to 53% of patients at stage IV developing MPE [2–4]. Extensive MPE can cause significant dyspnea, limit cardiopulmonary function, and result in inadequate oxygen delivery, imposing a substantial pathophysiological burden and even affecting the tolerability and timing of antitumor therapies. MPE not only signifies progression of ovarian cancer to stage IVa but also portends more complex tumor biology, more challenging symptom management, and poorer prognosis [5]. In recent years, with continuous improvements in diagnostic and therapeutic approaches, overall outcomes for ovarian cancer have markedly improved; however, clinical practice still faces numerous challenges and uncertainties when managing advanced patients with MPE. To address these issues, the Gynecologic Oncology Group of the Obstetrics and Gynecology Physicians Branch of the Chinese Medical Association and the Gynecologic Oncology Group of the Minimally Invasive Medicine Professional Committee of the Chinese Medical Association convened multidisciplinary experts from gynecologic oncology, thoracic oncology, radiology, thoracic surgery, and pathology. By reviewing relevant literature—searching databases including PubMed, Embase, Cochrane, CNKI, and Wanfang, with English search terms such as “ovarian cancer,” “malignant pleural effusion,” “indwelling pleural catheter,” “thoracoscopy,” and “surgical management”—and drawing on clinical experience, they developed this consensus document through multiple rounds of deliberation. The recommendations presented in this consensus are grounded in evidence-based medicine and widely endorsed by expert clinical experience, aiming to further standardize and guide the clinical diagnosis, treatment, and comprehensive management of patients with ovarian cancer–related malignant pleural effusion, thereby improving their prognosis and quality of life.

The recommendation grades of this consensus and their corresponding meanings are shown in Table 1.

2. Pathogenesis of malignant pleural effusion associated with ovarian cancer

2.1. Anatomical and Physiological Characteristics of the Thoracic Cavity Anatomically, the thoracic cavity is a potential space approximately 10–20 µm in width, situated between the parietal pleura and the visceral pleura [6]. The parietal pleura contains numerous microperforations (stomata), with diameters ranging from less than 1 µm to 40 µm; these serve as the primary pathways for pleural fluid, proteins, and cells to exit the thoracic cavity. The stomata are directly connected to lymphatic lacunae, which are rich in collagen fiber bundles and ultimately drain into the lymphatic network of the parietal pleura, following the rib course to the mediastinal lymph nodes [7]. The microvessels of the parietal pleura lie only about 10–12 µm beneath the pleural surface [6]; this anatomical feature enables the parietal pleura to play a pivotal role in the production and absorption of pleural fluid, while also facilitating the metastatic spread of tumor cells.

Under normal physiological conditions, the volume of fluid in each pleural cavity is approximately 0.1–0.3 mL per kilogram of body weight [8]. Pleural fluid is primarily produced by the parietal pleura, while its absorption occurs mainly via the lymphatic channels of the parietal pleura. The homeostasis of pleural fluid volume depends on a dynamic equilibrium among hydrostatic pressure, colloid osmotic pressure, and intrapleural pressure in both the systemic and pulmonary circulations [9]. When this balance is disrupted, such that pleural fluid production exceeds absorption, exudative or transudative pleural effusion may develop. In patients with ovarian cancer, the development of malignant pleural effusion (MPE) is predominantly associated with an exudative mechanism, characterized by a marked increase in pleural and microvascular permeability. The compensatory capacity of the parietal pleural lymphatic channels can reach up to 20 times the normal level [9]; however, in the context of malignancy, this compensatory mechanism is often impaired, leading to the formation of pleural effusion.

2.2. Pathogenesis of Malignant Pleural Effusion Associated with Ovarian Cancer The development of ovarian cancer–related malignant pleural effusion (MPE) involves complex pathophysiological mechanisms, primarily driven by the metastasis of tumor cells from the peritoneal and pelvic cavities to the thoracic cavity, disrupting the balance between pleural fluid production and absorption. This process may involve one or more of the following pathways [10–12]: (1) Ovarian cancer initially spreads extensively within the peritoneal and pelvic cavities. Tumor cells or tiny tumor emboli are absorbed via the lymphatic vessels abundant in the diaphragm along with ascites and transported through the lymphatic system to the pleura. The cardiophrenic lymph nodes (CPLN), located at the junction of the thoracic and abdominal lymphatic circulations, are among the most commonly involved sites when ovarian cancer cells migrate into the thoracic cavity through diaphragmatic lymphatics. CPLN enlargement can obstruct thoracic lymphatics and trigger inflammatory responses, thereby promoting the formation and recurrence of MPE. (2) Direct invasion of the diaphragm by tumor tissue. (3) Migration of ascitic fluid from the peritoneal to the pleural space through microscopic defects in the diaphragm. (4) In a small subset of cases, tumor cells may disseminate via the bloodstream to the lungs and/or pleura. Once in the thoracic cavity, these metastatic tumor cells interact with host cells—including mesothelial cells, endothelial cells, myeloid cells, and lymphocytes—stimulating the release of vasoactive mediators and permeability‑enhancing molecules. Together, these factors drive angiogenesis, increased vascular permeability, pleural inflammation, and lymphatic obstruction, ultimately leading to the development of MPE [13]. Such intricate cellular interactions can also induce local immune suppression, characterized by impaired cytotoxic functions of macrophages and lymphocytes, accompanied by the excessive production of pro‑inflammatory and tumor‑promoting mediators [14]. Studies have shown that pleural fluid, when cultured in vitro, promotes cancer cell proliferation, exhibiting clear growth‑promoting properties [15]. This suggests that MPE may not merely be a passive consequence of tumor burden but rather constitutes an active pro‑tumorigenic microenvironment. Consequently, therapeutic strategies for ovarian cancer–associated MPE should shift from symptom palliation toward early intervention and aggressive management of pleural effusions to improve patient outcomes.

Recommendation 1: Ovarian cancer–associated malignant pleural effusion arises when tumor cells metastasize from the pelvic and abdominal cavities to the thoracic cavity, disrupting fluid homeostasis through multiple mechanisms and establishing an immunosuppressive, pro‑tumorigenic microenvironment. In clinical practice, early intervention and aggressive management of malignant pleural effusion should be integral components of antitumor therapy, with the aim of alleviating symptoms such as dyspnea while potentially improving patients’ oncologic outcomes (recommendation grade: 2B).

3. Clinical Features

3.1. Clinical Manifestations The clinical presentation of pleural effusion correlates with the volume of fluid: small effusions often remain asymptomatic or produce only subtle signs, whereas large effusions may cause marked palpitations and dyspnea, potentially progressing to respiratory failure. Pleural effusions associated with ovarian cancer exhibit the following characteristics: (1) Unilateral or bilateral moderate-to-large pleural effusions that expand rapidly; progressive dyspnea is the most common symptom and may even be the initial presenting complaint in patients with ovarian cancer [10]. (2) Often accompanied by cough and dull chest pain; fever is typically absent, and anti-inflammatory therapy proves ineffective. Asymptomatic cases are easily missed, leading to downstaging of the ovarian cancer diagnosis. Studies indicate that approximately 36% of stage IIIc patients may have pleural metastases [16]. (3) Frequently associated with massive ascites and/or a palpable pelvic mass; the clinical picture resembles that of gastrointestinal primary tumors with pleural effusions, necessitating careful differential diagnosis. (4) Can occur at any stage of the disease course and provides prognostic information regarding treatment response: persistent or newly developed pleural effusions during therapy suggest treatment resistance and are associated with a markedly shortened median survival [17]; conversely, reduction or resolution of pleural effusions indicates sensitivity to treatment. (5) A high rate of positive cytology—approximately 72%–83%—exceeding that observed in other types of tumor‑related pleural effusions [10, 18–19]. (6) Prone to concurrent hypoproteinemia, with generally poor overall condition. This is primarily attributable to the substantial protein loss resulting from the formation and ongoing exudation of malignant pleural (or peritoneal) effusions, abdominal distension due to massive ascites, and inadequate dietary intake of proteins and calories secondary to tumor‑related catabolism. (7) Exhibits a degree of refractoriness: in some patients, severe impairment of pleural function leads to continuous production of pleural effusions, making durable control difficult with conventional therapeutic approaches.

On physical examination, small pleural effusions may be asymptomatic, while some patients may exhibit pleural friction rub or hear pleural friction sounds. With moderate to large effusions, the affected hemithorax appears full; vocal fremitus is diminished on palpation, percussion reveals dullness, and breath sounds are diminished or absent, often accompanied by tracheal and mediastinal deviation toward the healthy side. Mediastinal lymph nodes are frequently enlarged.

3.2. Imaging Features The imaging manifestations of malignant pleural effusion (MPE) are influenced by the volume of the effusion, body position, and the presence of loculation or adhesions. In ovarian cancer–associated MPE, bilateral or unilateral (more commonly on the right side) moderate to large pleural effusions are typically observed, with mediastinal shift to the contralateral side and lung compression at the hilum, appearing as soft-tissue opacities. Some cases also exhibit diffuse or nodular pleural thickening and enlargement of the central pulmonary lymph nodes [20]. Most patients demonstrate clear signs of peritoneal and omental implantation metastases, including peritoneal and omental lesions, ascites, and primary or recurrent pelvic foci; in a subset, lymph node involvement and distant organ metastases may also be evident.

Recommendation 2: Malignant pleural effusion (MPE) is the initial or concurrent manifestation of distant metastasis in ovarian cancer, typically presenting as moderate to large, rapidly progressive unilateral or bilateral pleural effusions—more commonly on the right side—and often coexisting with ascites and pelvic–abdominal masses, reflecting a high tumor burden. The clinical presentation is predominantly characterized by progressive dyspnea, which fails to respond to anti-inflammatory therapy. Imaging studies frequently reveal pleural thickening and enlarged central lymph nodes, along with evidence of intra-abdominal metastases; cytologic examination has a relatively high positive rate, aiding both diagnosis and differential diagnosis. In clinical practice, when encountering newly developed, rapidly expanding pleural effusions—particularly in women with substantial ascites—ovarian cancer should be considered as a primary differential diagnosis. Even in asymptomatic patients, imaging evaluation is warranted to prevent misdiagnosis or missed diagnosis. For MPE, an immediate multidisciplinary team (MDT) assessment should be initiated to develop an individualized treatment strategy. MPE serves as a marker of treatment response and prognosis and should be monitored and evaluated dynamically (recommendation grade: 2A).

4. Clinical Evaluation of Malignant Pleural Effusion Associated with Ovarian Cancer

4.1. Patients with a history of ovarian cancer must have a confirmed diagnosis of ovarian cancer, established by pathological biopsy, and pleural effusion may occur at any stage of the disease. The gold standard for diagnosing ovarian cancer–associated malignant pleural effusion is the identification of malignant tumor cells of ovarian origin on cytological examination. In clinical practice, there are also cases in which malignant tumor cells are detected in pleural fluid samples and subsequently confirmed as ovarian cancer through immunocytochemical (ICC) staining.

4.2. Imaging Studies

4.2.1. Radiographic Examination Chest radiography is economical and convenient, serving as a commonly used and important tool for diagnosing pleural effusion; it is typically performed in the upright, semi‑recumbent, or supine position. When the pleural effusion measures 300–500 mL, radiography may reveal only blunting of the costophrenic angle on the affected side. With volumes exceeding 500 mL, characteristic findings emerge: an arcuate superior margin extending laterally and superiorly, darkening of the affected hemithorax, and mediastinal shift toward the contralateral side. The sensitivity of radiographic diagnosis depends on the volume of fluid and the presence of loculation or adhesions; it cannot adequately assess pleural or pulmonary details, thus limiting its utility in the diagnosis of malignant pleural effusions (MPE).

4.2.2. Ultrasonic Examination: Thoracic ultrasound (TUS) not only enables accurate assessment of pleural effusion but also facilitates guided thoracentesis, dynamic monitoring of drainage efficacy, and evaluation of lung re-expansion. It is currently the most widely used and readily accessible diagnostic modality. When TUS reveals pleural effusion accompanied by pleural thickening exceeding 1 cm, pleural nodules, or diaphragmatic thickening greater than 7 mm, the likelihood of malignant pleural effusion (MPE) is significantly increased, necessitating further investigations to establish a definitive diagnosis [21].

Ultrasound examination is typically performed with the patient in a sitting position to facilitate a comprehensive assessment of pleural effusion depth, viscosity, septation, and morphological changes in the pleura and diaphragm, thereby providing robust support for developing individualized treatment plans. In clinical practice, ultrasound has become the standard imaging modality for guiding diagnostic thoracentesis; it not only enables precise selection of the puncture site and reduces the risk of complications but also allows for dynamic monitoring of drainage efficacy and lung reexpansion. With its advantages of being noninvasive, real-time, and readily repeatable, ultrasound has also emerged as an essential guidance tool for invasive pleural procedures—such as pleural biopsy—helping to minimize the risk of adverse events and playing an irreplaceable role throughout the entire diagnostic and therapeutic management of malignant pleural effusion (MPE).

4.2.3. Compared with ultrasound, chest CT is superior in differentiating small pleural effusions and in assessing potential metastases involving the pleura, mediastinal lymph nodes, lung parenchyma, diaphragm, and other structures. It can provide critical information for preoperative staging of ovarian cancer and should be included as part of the routine thoracic evaluation in patients with this disease.

4.2.4. PET–CT Examination PET–CT is not used as a routine screening tool; however, when the primary tumor site is occult and conventional imaging fails to identify the source of malignant pleural effusion (MPE), or when ovarian cancer with MPE is clinically suspected but repeated cytologic analyses of the pleural fluid remain negative, PET–CT can provide critical metabolic information. This helps differentiate the nature of the pleural effusion, localize the primary lesion, and precisely guide subsequent invasive biopsies, thereby offering unique clinical value. The main limitation of PET–CT in the diagnosis of MPE is the potential for false‑positive findings in cases of thoracic inflammation (infection) or following talc pleurodesis [22].

Recommendation 3: Imaging studies that detect, localize, and quantify pleural effusion constitute an essential initial step in the diagnostic workup of ovarian cancer–associated malignant pleural effusion. Chest ultrasound and CT each have distinct advantages and should be selected based on the clinical context. PET‑CT is not indicated for routine screening; it is reserved for challenging cases with an occult primary tumor or recurrently negative cytology of the pleural fluid, where differentiation between benign and malignant etiologies is required (recommendation grade: 2A).

4.3. Diagnostic Thoracentesis and Pleural Effusion Analysis When a pleural effusion is clinically suspected, the preferred approach is to perform thoracentesis to obtain pleural fluid for routine biochemical and cytological analysis, thereby characterizing the effusion and identifying its underlying cause [23]. Prior to the procedure, clear indications must be established, contraindications ruled out, and the patient provided with thorough informed consent. Ultrasound‑guided thoracentesis yields a higher success rate and fewer complications; therefore, it is recommended as the standard technique when resources permit. After obtaining an adequate volume of pleural fluid, the sample should be promptly sent for laboratory analysis.

4.3.1. Physicochemical Characteristics of Malignant Pleural Effusions Associated with Ovarian Cancer Routine and biochemical analyses of pleural effusions are used to differentiate exudates from transudates and to aid in the identification of malignant pleural effusions (MPE). MPE associated with ovarian cancer is typically an exudate, characterized by elevated protein levels, a normal or decreased pH and glucose concentration, and increased lactate dehydrogenase (LDH) activity. The effusion often appears hemorrhagic or serous; in a minority of cases, it may be chylous and tends to coagulate readily. In terms of cellular composition, the effusion background frequently contains abundant lymphocytes, mesothelial cells, and erythrocytes, along with tumor cells arranged in clusters or scattered throughout. Furthermore, the levels of carbohydrate antigen 125 (CA125) and human epididymis protein 4 (HE‑4) in the effusion are often markedly higher than those observed in pleural effusions caused by other etiologies—such as tuberculosis, heart failure, or other malignancies [10], whereas carcinoembryonic antigen (CEA) is only mildly elevated or within the normal range.

4.3.2. Cytological Examination of Pleural Effusion The goal of cytological examination is to determine whether malignant tumor cells are present in the pleural effusion and, if so, to ascertain whether these tumor cells originate from the female reproductive system—particularly the ovaries, fallopian tubes, or peritoneum. Common methods include cytological smear (CS), liquid-based cytology (LBC), and cell block (CB) analysis. The first two approaches rely solely on cellular morphological features to distinguish benign from malignant lesions; they struggle to effectively differentiate reactive mesothelial cells in the background [24] and fail to meet the requirements for subsequent immunocytochemical staining and molecular testing, thus exhibiting limited diagnostic accuracy. In contrast, CB technology involves fixing the entire cell pellet obtained after centrifugation of the pleural effusion sample with methanol, embedding it in paraffin, and preparing a cell block that resembles a histologic specimen. This allows for long-term preservation and repeated sectioning, offering the following advantages: (1) Hematoxylin–eosin (HE) staining reveals higher cell density and clearer microscopic organization of cell clusters, thereby improving the detection rate of malignant pleural effusions [25]; (2) It can be used for immunocytochemistry, aiding in the identification of tumor cell types and their tissue of origin within malignant pleural effusions; (3) It enables the extraction of DNA or RNA for molecular pathology assays, such as BRCA mutation status and homologous recombination deficiency (HRD) assessment, thereby guiding targeted therapies. Therefore, after initial evaluation by CS or LBC, routine preparation of a pleural effusion cell block is recommended. When morphological findings suggest atypical cells, suspiciously malignant cells, or confirmed malignant cells, immunocytochemical analysis is advised to facilitate further diagnosis and differential diagnosis [23]. Furthermore, to enhance the detection rate and diagnostic accuracy of malignant pleural effusions, it is recommended to submit as large a volume of pleural fluid as possible—ideally 50–100 mL—and, when necessary, to repeat the submission [26].

4.4. Closed‑needle pleural biopsy: When cytology of pleural effusion remains repeatedly negative but clinical suspicion of malignancy is high, and imaging suggests pleural thickening or nodules, a pleural tissue biopsy may be considered to establish a definitive diagnosis. Blind‑guided pleural biopsy has poor localization accuracy and a high risk of complications; therefore, ultrasound‑ or CT‑guided closed‑needle pleural biopsy is recommended, with a diagnostic sensitivity for malignant pleural effusion ranging from approximately 70% to 94% [27].

4.5. Thoracoscopy allows for a comprehensive examination of the pleural cavity, enabling assessment of lesion morphology, extent of involvement, and adjacent organ involvement, while also facilitating multiple biopsies under direct visualization. Medical thoracoscopy (MT) and video-assisted thoracic surgery (VATS) serve both diagnostic and therapeutic purposes. MT demonstrates a sensitivity of 92.6%–97% and a specificity of 99%–100% for malignant pleural effusions, comparable to VATS [28]. For patients in whom the etiology remains unclear despite thoracoscopic biopsy, close follow-up is recommended to rule out malignancy.

The conventional approach of relying on imaging studies combined with pleural fluid cytology has a high rate of missed diagnoses for pleural metastases in ovarian cancer, leading to inaccurate staging. Several studies have demonstrated that, in advanced ovarian cancer patients with moderate-to-large pleural effusions, preoperative video-assisted thoracoscopic surgery (VATS) can provide a comprehensive assessment of the pleural surface and detect occult lesions [29–31]. According to retrospective analyses, VATS identified pleural lesions in 69% (29/42) of patients, with 62% (18/29) of these lesions measuring >1 cm in diameter. Furthermore, 36% (4/11) of patients who had previously tested cytologically negative were found to have abnormalities on VATS, resulting in an upstaging to stage IVA. Based on VATS findings, 43% of patients had their initial treatment strategy revised [30], suggesting that VATS plays a valuable role in refining the initial management decisions for advanced ovarian cancer patients with moderate-to-large pleural effusions.

Recommendation 4: When clinical suspicion of ovarian cancer with malignant pleural effusion (MPE) is present, diagnostic thoracentesis under ultrasound guidance should be performed as the first choice, and an adequate volume of pleural fluid should be promptly submitted for routine analysis and cytologic examination. The exudative characteristics of the fluid, together with markedly elevated levels of CA125 and HE-4, provide useful diagnostic differentiating features. It is recommended to routinely prepare cell paraffin blocks for hematoxylin–eosin staining, immunocytochemistry (ICC), and molecular pathology testing. When morphological assessment fails to determine the nature of the lesion, ICC should be performed to identify the cell type and tissue origin. Examination of cell‑rich pleural fluid pellets by ICC is a standard, recommended approach for confirming MPE. For patients with repeatedly negative cytology results but strong clinical suspicion of MPE, if imaging reveals pleural abnormalities, ultrasound‑ or CT‑guided pleural biopsy may be considered. Thoracoscopy allows for a comprehensive evaluation of intrathoracic lesions and can help optimize initial treatment decisions in advanced ovarian cancer patients with moderate to large pleural effusions; however, it is not currently recommended as a routine diagnostic procedure and should be used cautiously based on specific clinical indications (recommendation grade: 2A).

5. Diagnosis and Differential Diagnosis

5.1. The gold standard for diagnosing malignant pleural effusion of ovarian cancer origin is the identification of pathological evidence of ovarian cancer in the patient’s pleural fluid or pleural biopsy specimen, supplemented by a comprehensive assessment that integrates the patient’s medical history, clinical presentation, serum tumor markers, and imaging findings to arrive at an accurate diagnosis. In clinical practice, the diagnostic approach varies depending on whether the patient has already been diagnosed with ovarian cancer: (1) For patients with a confirmed diagnosis of ovarian cancer, the key to diagnosis lies in establishing the homology of the pleural effusion—once the effusion is identified as a malignant pleural effusion (MPE), immunocytochemical (ICC) analysis must be performed to confirm that its immunophenotype matches that of the primary ovarian tumor; concurrently, imaging studies should be used to rule out other primary malignancies. (2) For patients without a prior diagnosis of ovarian cancer, the diagnostic strategy should be guided by clinical manifestations, employing cytological examination of the pleural fluid and systematic ICC testing to trace the source of the MPE, while integrating imaging modalities (such as abdominal–pelvic CT/MRI and whole-body PET-CT) and tumor marker assessments to identify the primary ovarian tumor and any metastatic lesions.

5.2. Differential Diagnosis The underlying causes of most pleural effusions can be identified through routine analysis and cytological examination of the fluid. In patients with ovarian cancer, malignant pleural effusion (MPE) is often accompanied by a large amount of ascites. However, when both ascites and pleural effusion coexist, it is important to differentiate this from the following conditions: (1) Malignant tumors originating elsewhere, such as peritoneal or pleural metastases: Gastric cancer, colorectal cancer, breast cancer, and others frequently cause both MPE and malignant ascites [18]. A preliminary differential diagnosis can be made based on clinical manifestations of the primary tumor—such as gastrointestinal symptoms or breast masses—and further evaluation may include physical examination and imaging studies to identify potential primary sites. Definitive diagnosis relies on pathological analysis of the effusion or biopsy tissue; immunocytochemistry (ICC) or immunohistochemistry (IHC) is crucial for determining the tissue origin. (2) Liver cirrhosis: Portal hypertension secondary to liver cirrhosis is the most common cause of transudative pleural and abdominal effusions. This condition can usually be distinguished by a history of chronic liver disease, characteristic signs (e.g., spider angiomas, splenomegaly), abnormal liver function tests, and imaging findings revealing changes in liver morphology. (3) Tuberculous polyserositis: More commonly seen in immunocompromised individuals, it typically presents with systemic symptoms such as fever and night sweats, along with signs of pleural and abdominal effusion. Pleural fluid is an exudate predominantly composed of lymphocytes, with markedly elevated adenosine deaminase (ADA) levels. When tuberculous polyserositis is associated with cystic ovarian lesions and significantly elevated CA125, it may be misdiagnosed as ovarian cancer [32]. The gold standard for diagnosing tuberculous involvement is the identification of caseating granulomas in pleural or ascitic fluid, or isolation of Mycobacterium tuberculosis. (4) Meigs syndrome (MS) and pseudo‑Meigs syndrome (PMS): These are relatively rare clinical entities, each characterized by the triad of pelvic mass, ascites, and pleural effusion. Following complete resection of the pelvic tumor, both pleural and abdominal effusions typically resolve rapidly. The key distinction lies in the histological type of the tumor [33–34]. MS specifically refers to benign solid ovarian tumors—primarily fibromas—accompanied by pleural and abdominal effusions [33]. Compared with advanced ovarian cancer, patients with MS generally exhibit milder systemic wasting and better overall condition; their effusions are predominantly transudates with negative cytology results. Ovarian tumors are usually unilateral, well‑circumscribed, and have smooth surfaces without evidence of metastasis. Serum CA125 levels are normal or only slightly elevated. Cases with markedly elevated CA125 (>2000 kU/L) are prone to misdiagnosis as ovarian cancer [35]. Postoperative histopathological examination after surgical removal of the ovarian tumor is a critical differentiating factor: resolution of both pleural and abdominal effusions confirms MS, though definitive diagnosis still requires postoperative pathology. The concept of PMS was later expanded by Meigs himself to describe cases with clinical presentations similar to MS but involving different types of ovarian tumors [34]. In addition to benign pelvic neoplasms (such as mature teratomas or uterine leiomyomas), gastric cancer [36], colorectal cancer [37], breast cancer [38], and even certain primary malignant ovarian tumors [39] can also give rise to PMS. In these patients, pleural effusions are more commonly located on the right side and tend to be exudative, often accompanied by clear evidence of peritoneal metastasis. Serum CA125 levels may be significantly elevated, leading to diagnostic overlap with ovarian cancer complicated by pleural and abdominal effusions; therefore, pathologic confirmation is essential for differentiation. (5) Other non‑neoplastic conditions: Heart failure—particularly right‑sided heart failure—constrictive pericarditis, endometriosis, and ovarian hyperstimulation syndrome can all present with concurrent pleural and abdominal effusions. Such conditions can usually be differentiated through a combination of medical history, clinical presentation, imaging, and pathological findings. Differential diagnosis can be a complex, multi‑step process involving multiple methodologies; in some cases, the diagnostic journey is intricate and requires the collaborative input of multidisciplinary experts.

Recommendation 5: The gold standard for diagnosing ovarian cancer–associated malignant pleural effusion (MPE) is the identification of pathological evidence of ovarian cancer in either the pleural fluid or pleural tissue, requiring three definitive criteria: confirmation of the presence or absence of pleural effusion, determination of whether the effusion is malignant, and establishment that the MPE originates from ovarian cancer. In clinical practice, any female patient with both pleural and peritoneal effusions must be evaluated to rule out ovarian cancer; particular attention should be paid to differentiating such cases from pleural and peritoneal metastases from gastric, colorectal, or breast cancers, as well as tuberculous involvement of the pleural cavity. Key diagnostic considerations include the patient’s medical history, clinical presentation, serum tumor markers, biochemical and cytological analysis of the pleural fluid, and imaging findings. Immunocytochemistry (ICC) or immunohistochemistry (IHC) can aid in definitive diagnosis, and multidisciplinary team (MDT) consultation is often necessary (recommendation grade: 2A).

6. Grading of Malignant Pleural Effusions Associated with Ovarian Cancer

Currently, neither domestically nor internationally has a dedicated grading system been established for ovarian cancer–associated malignant pleural effusion (MPE). Clinical assessment typically involves a comprehensive evaluation that integrates factors such as the characteristics of the pleural fluid, the volume of the effusion, the severity of symptoms, and treatment requirements—including whether thoracentesis or pleurodesis is indicated. Previous literature on pleural disease and malignant pleural effusion has generally relied on radiologic descriptions to stratify the extent of pleural effusion, rather than on precise volumetric measurements. Common radiologic stratification criteria include: small effusions confined to the costophrenic angle or the posterior costophrenic recess; moderate effusions occupying less than half of a hemithorax; and large effusions that occupy more than half of a hemithorax—particularly those exceeding two-thirds and accompanied by mediastinal shift. These radiologic descriptors have been widely adopted in thoracic imaging textbooks and in guidelines for managing malignant pleural effusion, and are regarded as highly reproducible and clinically practical. To promote standardization in clinical diagnosis and management, this consensus document, drawing on both the literature and clinical experience, has developed the Ovarian Cancer–Associated Malignant Pleural Effusion Grading System (OC‑MPE Grading System) as a reference framework for assessment (Table 2). This grading system incorporates the aforementioned clinical parameters and can serve as a basis for therapeutic decision‑making and prognostic evaluation.

Recommendation 6: To promote standardization in clinical diagnosis and treatment, it is recommended to adopt the Ovarian Cancer–Related Malignant Pleural Effusion Grading System (OC-MPE Grading) as a standardized assessment tool for guiding therapeutic decision-making and prognostic evaluation (recommendation grade: 2A).

7. Principles and Strategies of Treatment

7.1. Treatment Principles Compared with other malignant tumors, patients with ovarian cancer–associated malignant pleural effusion (MPE) have a relatively better prognosis and longer survival [17, 40]. The therapeutic goal should not be limited to transient symptom relief; rather, it should aim for long-term, stable control of the pleural effusion, thereby improving quality of life and prolonging survival. Prompt initiation of standard antitumor therapy is critical for controlling ovarian cancer progression and forms the cornerstone of MPE management. Accordingly, the overarching principle for treating ovarian cancer–related MPE is to prioritize antitumor therapy—specifically, treatment directed at the underlying ovarian cancer—while actively incorporating local interventions and supportive care. Treatment decisions must be individualized, requiring clinicians, guided by standardized diagnostic and therapeutic protocols for ovarian cancer, to conduct dynamic, comprehensive assessments of symptom severity, performance status, tumor burden, and response to therapy; multidisciplinary team (MDT) evaluation plays an essential role in this process [41]. (1) For patients in good general condition with mild dyspnea, antitumor therapy should be initiated as soon as a definitive diagnosis is established. (2) In contrast, patients with prominent symptoms and poor baseline status should receive aggressive local pleural interventions to alleviate symptoms and enhance their tolerance to systemic antitumor therapy.

Recommendation 7: Ovarian cancer patients with malignant pleural effusion should receive individualized treatment in accordance with standardized ovarian cancer management guidelines. The primary principle is to prioritize standard ovarian cancer therapy, supplemented by active local treatments, and a multidisciplinary team (MDT) approach should be integrated throughout the patient’s entire diagnostic and therapeutic course (recommendation grade: 2A).

7.2. Treatment for ovarian cancer should be conducted in strict accordance with domestic and international guidelines on the diagnosis and management of ovarian cancer, ensuring standardized care. This consensus document primarily addresses key issues that require particular attention during the treatment of patients with ovarian cancer complicated by malignant pleural effusion (MPE).

7.2.1. Initial Treatment Decision For newly diagnosed ovarian cancer patients with malignant pleural effusion (MPE), the choice between primary debulking surgery (PDS) and neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) significantly impacts subsequent treatment strategies and outcomes. This decision should carefully balance both patient‑specific factors, such as overall health status, and tumor‑related considerations [42]. Whether R0 resection—no visible residual disease—is safely achievable is a critical determinant; currently, the Suidan score, Fagotti score, and Mayo criteria are commonly used to predict the likelihood of achieving R0 in advanced ovarian cancer. In patients with MPE, additional assessment of the potential impact of intrathoracic lesions is also required [43]. It must be emphasized that MPE is not an absolute contraindication to PDS; subjective judgments that surgery cannot achieve satisfactory cytoreduction or the mere desire to simplify the procedure should not serve as grounds for indiscriminate use of NACT. Past prospective randomized controlled trials and retrospective studies have documented cases of stage IV ovarian cancer patients who achieved satisfactory cytoreduction with PDS and subsequently experienced long-term survival benefits. One study employed a target trial simulation approach, leveraging medical databases to analyze 2,772 patients with stage IV ovarian cancer: 42.6% underwent PDS, while 57.4% received NACT–IDS, with baseline characteristics broadly comparable between the two groups [44]. Compared with the IDS group, the PDS group demonstrated a median progression-free survival (PFS) that was 4.0 months longer (19.7 vs. 15.7 months) and a median overall survival (OS) that was 7.5 months longer (63.1 vs. 55.6 months). Five-year PFS rates were improved by 4.5% (95% CI, 2.4%–6.9%), and seven-year OS rates increased by 10.1% (95% CI, 5.0%–14.7%). Survival benefits were particularly pronounced in subgroups with stage IVA disease, pleural metastases, and supra‑diaphragmatic lymph node involvement. Therefore, for newly diagnosed ovarian cancer patients with MPE, a multidisciplinary team (MDT) comprising gynecologic oncologists, gastrointestinal surgeons, hepatobiliary and pancreatic surgeons, thoracic surgeons, radiologists, medical oncologists, internists, anesthesiologists, and intensivists should thoroughly evaluate the patient’s performance status and the resectability of pelvic, abdominal, and thoracic lesions to develop an individualized treatment plan. When the MDT determines that R0 resection is highly feasible, PDS remains the preferred option; conversely, if the MDT judges that satisfactory cytoreduction is unlikely or the patient cannot tolerate surgery, NACT should be initiated first [45].

Recommendation 8: For patients with newly diagnosed ovarian cancer complicated by malignant pleural effusion (MPE), whether surgery can safely achieve R0 resection is a critical factor in determining the initial treatment strategy. MPE itself is not an absolute contraindication to primary debulking surgery (PDS); rather, a multidisciplinary team (MDT) should comprehensively assess the patient’s performance status and the resectability of the tumor burden. If the MDT estimates a high likelihood of achieving R0 resection, PDS should be prioritized; if satisfactory cytoreduction is deemed unlikely or the patient cannot tolerate surgery, neoadjuvant chemotherapy (NACT) is recommended (recommendation grade: Category 1).

7.2.2. Prior to initiating neoadjuvant chemotherapy (NACT), a definitive pathological diagnosis must be established. Tumor‑site biopsy or cytologic examination of pleural effusion combined with immunocytochemistry (ICC) is preferred to obtain a histopathological confirmation; it is essential to avoid starting NACT with an ovarian cancer–specific chemotherapy regimen solely on the basis of detecting malignant tumor cells in pleural or peritoneal fluid [46]. For such patients, one of the primary goals of NACT is to control malignant pleural effusion (MPE). Before or early during chemotherapy, thoracentesis with drainage should be performed promptly to alleviate dyspnea; however, caution is warranted, as excessive drainage may lead to protein loss, malnutrition, and impaired immune function. Concurrent nutritional support and measures to prevent complications are necessary to ensure the smooth continuation of chemotherapy. When indicated, after draining and evacuating the pleural effusion, intrapleural administration of cisplatin and/or bevacizumab may be considered to achieve rapid control of the effusion. Large volumes of MPE can affect drug distribution and metabolism; therefore, adverse reactions should be closely monitored throughout treatment. Furthermore, assessment of chemotherapy response should take into account changes in pleural effusion volume, pleural lesions, and intra‑abdominal/pelvic lesions. Multidisciplinary team (MDT) discussions should be convened as needed to evaluate the feasibility of an individualized disease‑staging system (IDS) and to determine the extent of surgical intervention.

7.2.3. Tumor Debulking Surgery Numerous clinical studies have confirmed that the size of residual disease after surgery is one of the most important prognostic factors in advanced ovarian cancer. Therefore, whether performing PDS or IDS, the ultimate goal of surgery is to remove all macroscopically visible lesions, thereby laying a solid foundation for subsequent chemotherapy [47]. The diaphragm serves as a critical gateway for ovarian cancer metastasis into the thoracic cavity; during surgery, careful exploration is essential, and any involved diaphragmatic tissue should be either stripped or resected. In recent years, with advances in surgical techniques and the widespread adoption of multidisciplinary team (MDT) care models, debulking procedures targeting intrathoracic metastases in advanced ovarian cancer have gradually been implemented. A study from Memorial Sloan Kettering Cancer Center demonstrated that intrathoracic surgery (VATS or transdiaphragmatic approaches) performed during PDS for advanced ovarian cancer is both safe and effective: among 178 patients, 63% underwent supra‑diaphragmatic or cardiophrenic angle lymph node dissection, 12% had mediastinal lymph node dissection, 7% received pleural nodule resection, and 1% underwent pulmonary parenchymal resection. The median operative time was 430 minutes, with a median blood loss of 900 mL. Forty-one percent of patients had chest drains placed intraoperatively, and the median postoperative hospital stay was 8 days; the median interval between surgery and the first postoperative chemotherapy cycle was 37 days. Seventy-four percent achieved R0 resection of the thoracoabdominal region, 25% achieved R1 resection, and only two patients had postoperative residual lesions larger than 1 cm. Seven percent of patients experienced grade ≥3 complications, eight of which were related to thoracic surgery (seven cases of pleural effusion and one case of respiratory failure), with no deaths within 30 days. Median progression-free survival (PFS) and overall survival (OS) were 33.6 months and 81.3 months, respectively [48]. The study also emphasizes that such procedures should be performed at medical centers capable of managing complex operations, ensuring both safety and thoroughness of tumor removal. Patients with intrathoracic metastases often have concomitant upper abdominal involvement, requiring combined resections of multiple organs and presenting high surgical difficulty. It is recommended that these patients be managed at specialized oncology hospitals or large general hospitals adept at implementing MDT‑guided, optimal tumor debulking. Preoperative MDT discussions are essential to define the extent of surgery, while intraoperative collaboration among multidisciplinary surgical teams is crucial to achieve satisfactory debulking [41]. Furthermore, these patients face a markedly increased risk of postoperative pulmonary complications—such as worsening pleural effusions, atelectasis, and pneumonia—making meticulous anesthetic recovery, effective postoperative pain management, and early respiratory rehabilitation indispensable.

Surgical considerations for metastatic lesions in the cardiophrenic lymph nodes (CPLN): The CPLN are located at the cardiophrenic angle, where the pericardium and diaphragm meet, and typically comprise supradiaphragmatic and parapericardial lymph nodes. With advances in imaging diagnostics, CPLN metastases and the associated clinical management challenges have garnered increasing attention, as they enable both accurate staging and satisfactory tumor debulking. Relevant surgical resection should be guided by multidisciplinary team (MDT) discussion and collaboration, with a thorough assessment of the clinical utility of CPLN removal and adherence to the following criteria: (1) Preoperative imaging—MRI, CT, PET‑CT, or PET‑MRI—demonstrates CPLN enlargement suggestive of metastasis. (2) Surgical approach: either an abdominal route (open or laparoscopic) or a thoracoscopic approach. (3) CPLN resection is indicated only when the abdominopelvic cavity can achieve a satisfactory level of tumor cell reduction (R0 or R1). (4) Surgical technique must strictly adhere to the “no‑tumor” principle and employ no‑tumor techniques. (5) Malignant pleural effusion (MPE) should be well controlled, and the patient must be able to tolerate surgery. (6) The institution must possess a high‑level MDT and adequate intensive care resources and capabilities.

7.2.4. Postoperative Adjuvant Therapy Postoperative adjuvant therapy is primarily based on chemotherapy, and the selection and administration of chemotherapy regimens should adhere to the standard treatment guidelines for advanced ovarian cancer. In addition, maintenance therapy should be considered according to the patient’s genetic testing results. During both chemotherapy and maintenance therapy, changes in malignant pleural effusion (MPE) should be monitored dynamically, and symptomatic effusions should be managed promptly with local interventions. Given the poor prognosis and limited treatment tolerance in this patient population, physical performance status should be thoroughly assessed during chemotherapy, with individualized adjustments made to chemotherapy drug dosages and treatment cycles. The use of anti-angiogenic agents, such as bevacizumab, should be actively considered.

Recommendation 9: For ovarian cancer patients with malignant pleural effusion (MPE), in addition to adhering to standard treatment principles, the following considerations are essential: (1) Prior to initiating neoadjuvant chemotherapy (NACT), a definitive pathological diagnosis must be established to avoid empirical or indiscriminate NACT. (2) Before or during the early phase of NACT, thoracentesis with drainage can provide rapid symptomatic relief; intrapleural administration of chemotherapeutic agents may be considered. Concurrently, adequate nutritional support should be provided, and adverse drug reactions closely monitored to ensure chemotherapy safety. (3) Whether performing primary debulking surgery (PDS) or interval debulking surgery (IDS), the ultimate surgical goal is R0 resection. Given the complexity of these procedures, management of such patients should be conducted at specialized oncology centers or large general hospitals with well‑established multidisciplinary teams (MDTs). (4) Resection of intrathoracic lesions, including chest wall lymph nodes (CPLN), should be undertaken cautiously under the guidance of an experienced MDT, with meticulous perioperative management. (5) Postoperative adjuvant chemotherapy should be administered according to standardized protocols and tailored to individual patient needs; combination regimens incorporating anti‑angiogenic agents are strongly recommended, with close monitoring and timely management of MPE. (Recommendation level: Grade 2A.)

7.3. Local Therapy Local therapy serves as an important adjunct to systemic treatment in advanced ovarian cancer, aiming to alleviate symptoms and improve patients’ tolerance to antitumor therapies. For symptomatic patients, pleural local therapy should be initiated promptly. Currently, the main modalities for managing malignant pleural effusion (MPE) include indwelling pleural catheterization (IPC), pleurodesis, and intrapleural drug administration. Traditional techniques such as thoracentesis and closed‑chest drainage are typically performed after confirmation by imaging and physical examination; however, due to their relatively high invasiveness and a higher incidence of complications, these approaches are now used less frequently.

Recommendation 10: For patients with symptomatic malignant pleural effusion, early pleural local therapy is recommended. Prior to treatment, clear indications must be established, contraindications excluded, and informed consent obtained (recommendation grade: 2A).

7.3.1. Local Treatment for MPE Associated with Ovarian Cancer: Pleural Catheter Drainage is the first‑line approach. Ultrasound guidance can facilitate intraoperative localization and real-time monitoring of the puncture and catheter placement; therefore, routine use of ultrasound‑guided pleural drainage is recommended to ensure both success and safety. Several studies have demonstrated that IPC is as effective as pleurodesis in alleviating dyspnea and improving quality of life in patients with malignant pleural effusion, independent of lung reexpansion status [49–50], making it suitable for all symptomatic patients. Key considerations include: (1) Given that advanced ovarian cancer often coexists with malnutrition and reduced cardiopulmonary reserve, the initial volume of fluid drained during IPC should generally not exceed 600–800 mL, while maintaining a controlled drainage rate [51] and closely monitoring vital signs. (2) If no significant discomfort occurs after the first drainage, subsequent daily volumes may be maintained at 1,000–1,200 mL; prolonged, large‑volume drainage is discouraged to avoid excessive protein loss, which could exacerbate hypoalbuminemia and render the pleural effusion difficult to control. (3) When bilateral pleural effusions are both substantial, alternate drainage between sides is advised. Two randomized controlled trials have shown that compared with every‑other‑day or on‑demand drainage, daily active drainage significantly increases the success rate of spontaneous pleurodesis and improves long-term quality of life [52–53]. (4) During drainage, dynamic assessment of effusion removal and lung reexpansion is essential; when symptoms markedly improve, drainage volume decreases substantially (to <100 mL per day), and imaging demonstrates adequate lung reexpansion, tube removal may be considered. (5) If pleural effusion remains uncontrolled, intrapleural chemotherapy is typically administered following drainage to limit rapid effusion recurrence; prolonged, high‑volume drainage alone is not advisable. (6) Should severe coughing, production of white frothy sputum, or an oxygen saturation below 90% occur during drainage, immediate cessation of pleural drainage is required, along with supplemental oxygen and diuretic therapy, to vigilantly monitor for the development of reexpansion pulmonary edema.

Patients requiring long-term catheterization should undergo regular catheter maintenance and take precautions to prevent and manage the following complications [51]: (1) Pain: Caused by catheter irritation of the parietal pleura, intercostal nerves, or local inflammation; it is the most common complication. In some patients, pain can be alleviated by adjusting the catheter’s position. (2) Poor drainage or absence of drainage: First assess the volume of pleural effusion using imaging. If the effusion remains substantial, consider the possibility of loculated effusion or catheter obstruction. Begin by flushing the catheter with sterile saline to relieve blockage; if this is ineffective, perform intrathoracic fibrinolytic therapy to dissolve septa or clots. If these measures fail, remove and replace the catheter. (3) Catheter dislodgement or migration: Often related to inadequate fixation or accidental traction by the patient. If the catheter partially dislodges, do not attempt to reinsert it; immediately perform ultrasound to confirm its position and, if necessary, reposition it. If the catheter is completely dislodged, promptly apply pressure dressing to the wound to prevent pneumothorax, and urgently evaluate the patient’s condition, providing appropriate symptomatic management. (4) Infection: For infections at the catheter exit site or within the catheter tract, select antibiotics that cover common skin pathogens. If adequate antimicrobial therapy proves ineffective, consider removing the catheter. Intrathoracic infection is a serious complication, frequently associated with poor aseptic technique by the operator and/or compromised host immunity. Once established, administer broad-spectrum systemic antibiotics and obtain a pleural fluid culture to identify the causative pathogen, while actively managing local thoracic symptoms. In cases of empyema, perform closed thoracic drainage and, if indicated, surgical intervention. If both catheter‑related and intrathoracic infections are present, initiate broad-spectrum antibiotics and proceed with early catheter removal. After infection control, reconsider re‑placement. Strict asepsis, standardized procedures, and meticulous management form the cornerstone of complication prevention, while early recognition and prompt intervention are critical to averting adverse clinical outcomes.

Recommendation 11: For the local management of malignant pleural effusion associated with ovarian cancer, ultrasound-guided thoracocentesis with drainage tube placement is recommended as the first-line approach; strict aseptic technique and standardized procedures must be observed. Following tube placement, regular daily drainage is advised, with the volume and rate of drainage determined by the extent of fluid accumulation and the degree of symptom relief. The initial drainage should generally not exceed 600–800 mL, and close monitoring of vital signs and prevention of hypoproteinemia are essential. Patients with long-term indwelling catheters should undergo routine catheter maintenance, with proactive measures to prevent and manage complications (recommendation grade: 2A).

7.3.2. Pleurodesis For patients with malignant pleural effusion (MPE), pleurodesis is an extremely important therapeutic modality. Its core principle involves inducing adhesion between the visceral and parietal pleura through chemical or mechanical means, thereby creating a sealed pleural space to achieve long-term control of MPE. The primary prerequisite for performing pleurodesis is that, following adequate drainage, imaging assessment demonstrates complete lung reexpansion or near‑complete reexpansion (with less than 25% of the lung collapsed) [54]. Talc is the most effective sclerosing agent for inducing pleural adhesion; it can be administered either by VATS spray or via a drainage tube, and there is no significant difference in pleurodesis success rates between these two delivery methods [55]. A case series involving 24 patients with ovarian cancer reported that talc spray performed under VATS was well tolerated, with 92% of patients remaining recurrence‑free at 6 months [56]. The presence or absence of peritoneal effusion does not affect the response to sclerosing agents, the total volume of drained fluid, or the duration of drainage tube placement [57]. Currently, intrapleural talc is poorly accessible in China, and talc‑based pleurodesis has not yet been routinely implemented in clinical practice. Other available sclerosing agents include povidone‑iodine, bleomycin, doxycycline, autologous blood, silver nitrate, and others; the success rate of pleurodesis generally exceeds 70%–80% [58–59], indicating considerable therapeutic potential. For ovarian cancer patients with recurrent aspiration and ineffective drainage who continue to have persistent MPE despite systemic antitumor therapy, pleurodesis may be considered after comprehensive multidisciplinary team (MDT) evaluation, provided the patient expresses a strong preference. If pleurodesis fails, indwelling IPC should be contemplated. However, this treatment should be avoided in patients with marked pulmonary atelectasis leading to poor pleural apposition, significantly elevated intrathoracic negative pressure, or an expected survival of less than 3 months.

Recommendation 12: Pleurodesis is an important therapeutic modality for managing malignant pleural effusion (MPE) and is indicated in patients whose lungs can re-expand following adequate drainage. For ovarian cancer–associated MPE patients who require repeated drainage and have not responded to systemic therapy, pleurodesis may be considered after comprehensive multidisciplinary team (MDT) evaluation, provided the patient expresses a strong preference. If pleurodesis fails, indwelling chest tube drainage is recommended (recommendation grade: 2B).

7.3.3 Intrathoracic Antitumor Drug Infusion Therapy Intrathoracic infusion therapy enables antitumor agents to efficiently eradicate pleural metastases while significantly reducing systemic toxicity, and has become an important treatment modality for malignant pleural mesothelioma, lung cancer, and thymoma [51]. Available agents include chemotherapeutic drugs, anti-angiogenic agents, biologics, and immune checkpoint inhibitors, among others.

7.3.3.1 Chemotherapy Drug Infusion Chemotherapy drugs can directly inhibit the proliferation of tumor cells, thereby reducing the incidence of malignant pleural effusion (MPE) associated with ovarian cancer. Compared with systemic administration, intrathoracic chemotherapy achieves higher drug concentrations at the site of disease, resulting in better control while minimizing systemic adverse effects. In clinical practice, intrathoracic chemotherapy is primarily indicated for primary thoracic malignancies, such as non–small cell lung cancer and malignant pleural mesothelioma. Although MPE is frequently observed in patients with ovarian cancer, clinical evidence supporting intrathoracic chemotherapy in this patient population remains limited. Cisplatin is a commonly used agent for intrathoracic chemotherapy [60], typically administered at a dose of 30–60 mg per infusion, dissolved in normal saline and delivered via intrathoracic injection. Data from clinical studies indicate that among patients with secondary MPE due to ovarian cancer, the disease control rate (DCR) following intrathoracic chemotherapy reaches 87.5% [61]. Overall, intrathoracic platinum-based therapy is well tolerated, with common adverse events including bone marrow suppression (e.g., leukopenia and thrombocytopenia), gastrointestinal symptoms (e.g., nausea and vomiting), and systemic manifestations such as fatigue [60]. In addition to platinum agents, taxanes—such as paclitaxel—can also be employed for the local treatment of MPE associated with ovarian cancer. In patients with stage IV serous ovarian carcinoma, intrathoracic paclitaxel demonstrated significant antitumor activity; pharmacokinetic analyses further revealed that, compared with systemic intravenous administration, intrathoracic delivery markedly increases local drug exposure—by up to 1,160-fold [62]. Thus, intrathoracic chemotherapy represents an effective local therapeutic option.

Recommendation 13: For patients with ovarian cancer–related malignant pleural effusion, clinical practice recommends considering intrapleural chemotherapy for local treatment following adequate drainage (Category 2A).

7.3.3.2. Chemotherapy Combined with Intrathoracic or Intraperitoneal Administration of Anti-Angiogenic Agents To enhance therapeutic efficacy, platinum-based agents are often combined with anti-angiogenic drugs. This treatment strategy leverages the synergistic effects of cisplatin’s cytotoxicity and the tumor‑inhibitory action of anti‑angiogenic agents, markedly improving local disease control and potentially prolonging overall survival. In a clinical controlled trial involving 45 patients with malignant pleural effusion (MPE)—including 3 ovarian cancer patients in the combination therapy group and 4 in the cisplatin monotherapy group—recombinant human endostatin combined with cisplatin (EP regimen) significantly increased both the objective response rate (ORR) (78.3% vs. 40.9%, P < 0.05) and the disease control rate (DCR) (87.0% vs. 59.1%, P < 0.05), while demonstrating a favorable safety profile with no serious adverse events reported [63]. The cisplatin–bevacizumab regimen has also been applied in the treatment of MPE secondary to lung cancer; clinical data indicate that the ORR with bevacizumab plus cisplatin was significantly higher than that of cisplatin monotherapy (88.37% vs. 67.44%, P < 0.05) [64]. Bevacizumab has further been used for managing ascites associated with ovarian cancer; a phase III clinical trial enrolling 58 patients with advanced ovarian cancer demonstrated that intraperitoneal administration of bevacizumab in combination with cisplatin provided substantial benefits in reducing ascites volume, improving overall response rates, and enhancing quality of life [65]. However, the use of anti‑angiogenic agents in MPE related to ovarian cancer remains unreported. Combination therapies can effectively control the progression of MPE while simultaneously alleviating patients’ clinical symptoms and psychological distress. At present, evidence‑based support for such combined infusion regimens remains limited; therefore, clinical practice should adhere to individualized principles, rigorously weigh potential benefits against treatment risks, and employ these approaches cautiously only after obtaining informed consent. If anti‑angiogenic agents are administered preoperatively, careful timing is essential to avoid dosing within 4–6 weeks prior to surgery.

Recommendation 14: Intrathoracic perfusion with a cisplatin-based regimen combined with anti-angiogenic agents can improve local tumor control and alleviate clinical symptoms. For patients with ovarian cancer–related malignant pleural effusion, individualized assessment of the benefit–risk ratio is required before initiating such combination therapy (recommendation grade: 2A).

7.3.3.3. Hyperthermic Intrathoracic Chemotherapy Hyperthermic intrathoracic chemotherapy (HITHOC) is an innovative multimodal treatment that leverages the synergistic effects of hyperthermia and chemotherapy to deliver heated chemotherapeutic agents directly into the pleural space, often serving as an adjunct to pleural tumor cytoreductive surgery [66]. It achieves precision and efficacy in the local management of malignant pleural effusions through the following mechanisms: (1) Hyperthermia itself exerts a cytotoxic effect; when temperatures reach 43°C, tumor cell mortality increases significantly [67]. (2) Localized chemotherapy enables higher concentrations of chemotherapeutic agents to remain within the pleural cavity for extended periods, thereby more effectively targeting and eliminating tumor cells. (3) The combined action of hyperthermia and chemotherapeutic agents enhances drug cytotoxicity while reducing cancer cell resistance, markedly improving therapeutic outcomes [68]. (4) Continuous circulation of large volumes of fluid helps flush out free tumor cells and necrotic debris from the pleural space, contributing further to its antitumor effects. HITHOC is typically administered following video-assisted thoracoscopic surgery. A mixture of 1,500–2,000 mL of saline or glucose solution with antineoplastic agents is warmed and infused into the patient’s pleural cavity at a constant temperature, usually set between 42 and 43°C, for a duration of 60 minutes. Studies have demonstrated that, compared with conventional intrathoracic chemotherapy, HITHOC significantly improves the overall response rate (80.70% vs. 31.03%, P < 0.001), while adverse event rates were comparable between the two groups [69]. A meta-analysis indicated that combining HITHOC with pleural cytoreductive surgery confers substantial clinical benefits, with patients receiving HITHOC exhibiting longer median survival times than those who did not undergo HITHOC (Hedges’ g = 0.763, P < 0.001) [70]. Cisplatin is the preferred agent for HITHOC; other options, such as anthracyclines, mitomycin, or gemcitabine, may also be employed [66]. In malignant pleural effusions associated with ovarian cancer, HITHOC has shown significant therapeutic value. A case report involving a patient with advanced ovarian cancer who received cisplatin-based HITHOC demonstrated no grade 3 or 4 treatment-related toxicities during the course of therapy following pleural tumor cytoreduction. The patient subsequently completed eight cycles of systemic chemotherapy and achieved 14 months of progression-free survival after the final treatment session [71]. Another case involved a 42-year-old patient with advanced ovarian cancer who underwent pleural decortication combined with HITHOC following pleural metastases; the patient recovered well, with no evidence of recurrence at a three-month follow-up [72]. Adverse reactions to HITHOC are generally mild and well-tolerated, typically including sweating, pain, and low-grade fever. The primary toxicity associated with cisplatin use is nephrotoxicity [70]. Contraindications to HITHOC include severe cardiopulmonary dysfunction, acute infectious diseases, fever (body temperature > 38°C), and bleeding tendencies or coagulation disorders [73]. While HITHOC can effectively control and treat malignant pleural effusions related to ovarian cancer, current studies are limited by small sample sizes and short follow-up durations, underscoring the need for additional high-quality, evidence-based data to confirm its long-term survival benefits and safety profile.

Recommendation 15: For patients with ovarian cancer–related malignant pleural effusion, if pleural drainage or pleurodesis fails to control the effusion, it is recommended to develop a hyperthermic intrathoracic chemotherapy regimen through an MDT; this may be considered as an option for managing pleural effusion (recommendation grade: Category 3).

7.3.3.4. Other Pleural Infusion Therapies Existing drugs used in pleural infusion therapy for malignant pleural effusion (MPE) also include biologic response modifiers. Recombinant interleukin‑2 (IL‑2) is an important immunomodulator, primarily employed to enhance the function of the human immune system; numerous studies have demonstrated IL‑2’s efficacy in treating MPE. A meta‑analysis indicated that, compared with cisplatin alone, intrapleural administration of IL‑2 in combination with cisplatin significantly improved patients’ overall response rate (ORR) and disease control rate (DCR) (P < 0.001), and IL‑2 also enhanced patients’ quality of life (P < 0.001) [74]. Intrapleural infusion of biologic agents may cause fever; careful monitoring of adverse reactions and appropriate management are essential.

Intrathoracic administration of immune checkpoint inhibitors is currently in the exploratory phase, with research primarily focused on preclinical and early-phase clinical studies related to malignant pleural effusion (MPE). In preclinical settings, animal studies employing intrathoracic injection of anti‑PD‑1 antibodies have demonstrated that, compared with the control group, local delivery significantly reduced pleural fluid volume and tumor burden in MPE‑bearing mice, prolonged survival, and was accompanied by activation of intrathoracic CD8⁺ T cells and upregulation of pro‑inflammatory cytokine expression. These findings suggest that localized administration of immune checkpoint inhibitors can modulate the intratumoral immune microenvironment and enhance antitumor responses. Clinically, a prospective single‑arm phase I trial administered a single intrathoracic dose of 100 mg sintilimab to 16 patients with advanced non‑small cell lung cancer complicated by MPE. Results showed pleurodesis rates of 75% at day 35 and 56.3% at day 70, with a median progression‑free survival in the thoracic cavity of approximately 10.4 weeks. Partial response in extrathoracic tumors was observed in about 12.5% of patients, and overall tolerability was favorable, preliminarily indicating that this local delivery approach is both clinically feasible and safe [75]. However, these studies involved small sample sizes and were of low evidence level, lacking randomized controlled data; their long-term efficacy and optimal patient populations remain to be further validated, warranting additional in-depth investigation.

7.3.4. Video-assisted thoracoscopic surgery (VATS) refers to intrathoracic procedures performed under video‑assisted visualization. Existing retrospective studies and case reports indicate that, in carefully selected patients with advanced ovarian cancer, VATS can facilitate complete drainage of malignant pleural effusions, pleurodesis—including both chemical and mechanical approaches—and resection of intrathoracic lesions, demonstrating promising clinical potential [31, 76]. However, the optimal patient population, timing of intervention, and specific procedural protocols for VATS in cytoreductive surgery remain to be further investigated.

Recommendation 16: For carefully selected patients with advanced ovarian cancer and malignant pleural effusion, video-assisted thoracoscopic surgery (VATS) is an important diagnostic and therapeutic modality. Further research is needed to clarify the optimal patient population, timing of intervention, and strategies for integrating VATS with systemic therapy (recommendation grade: 2B).

7.4. Management of Refractory MPE: For patients who respond well to treatment of pelvic and abdominal lesions but continue to have pleural effusion, the nature of the effusion should first be reassessed to determine whether it remains malignant, while excluding non‑malignant causes such as chemotherapy‑induced cardiac dysfunction, lymphatic drainage obstruction, or hypoproteinemia. If refractory MPE is confirmed, this suggests that the pleural lesions may harbor relatively independent mechanisms of drug resistance or inadequate drug distribution. In such cases, local therapy should be intensified in addition to ongoing systemic treatment: for patients with prominent symptoms or large volumes of effusion, IPC should be performed to relieve symptoms, and, depending on the patient’s performance status and life expectancy, pleurodesis or intrathoracic chemotherapy may be considered. If imaging reveals localized pleural thickening or nodules, the feasibility of lesion resection under thoracoscopy can be evaluated. Concurrently, an MDT discussion is recommended to optimize the systemic treatment regimen, including switching chemotherapy regimens, combining targeted or immunotherapy, or administering palliative radiotherapy directed at the pleural lesions. For those who remain unresponsive to these interventions, active referral to clinical trials is advised.

7.5. Management of Malignant Pleural Effusion in Recurrent Ovarian Cancer The management of malignant pleural effusion (MPE) in recurrent ovarian cancer should first follow the guidelines for the diagnosis and treatment of recurrent ovarian cancer. Local therapeutic strategies and approaches for MPE may be guided by the previously described recommendations.

8. Efficacy Evaluation Criteria

At present, there are no specific efficacy criteria for malignant pleural effusion (MPE) associated with ovarian cancer; however, the World Health Organization’s standards may be used to assess the effectiveness of local therapies [77]: (1) Complete response (CR): Pleural effusion has resolved and remains absent for at least 4 weeks. (2) Partial response (PR): Pleural effusion has decreased significantly by at least 50% and persists for at least 4 weeks. (3) No change: Effusion reduction is less than 50%, or effusion has increased but by no more than 25%. (4) Progression: Pleural effusion has increased markedly, or the patient has died. In clinical practice, a comprehensive assessment should integrate symptom relief, lung reexpansion, and response to antitumor therapy.

9. Conclusion

The presence of MPE indicates that ovarian cancer has already metastasized to distant sites and represents a common, severe complication of advanced-stage ovarian cancer. The underlying mechanism involves the dissemination of ovarian cancer cells from the pelvic and abdominal cavities to the pleural space via multiple pathways, disrupting the balance between fluid production and absorption within the thoracic cavity. The gold standard for diagnosis is the histopathological identification of ovarian cancer cells in pleural effusion or pleural tissue. Clinically, ascites and/or palpable pelvic–abdominal masses are often present; therefore, differential diagnosis should consider pleural and peritoneal metastases from gastric, colorectal, or breast cancers, as well as tuberculous involvement of the pleural space. Key diagnostic considerations include the patient’s medical history, clinical presentation, serum tumor markers, biochemical and cytologic analysis of pleural fluid, and imaging findings. Immunocytochemistry (ICC) and immunohistochemistry (IHC) play a critical role in making this distinction [78–79].

Antitumor therapy is key to managing malignant pleural effusion (MPE). Ovarian cancer patients with MPE should, while adhering to standard ovarian cancer treatment guidelines, actively incorporate local therapies. Pleural drainage via thoracentesis remains the preferred local intervention for reducing MPE and alleviating dyspnea in these patients. Other local treatments—including pleurodesis, intrapleural instillation, and video-assisted thoracoscopic surgery (VATS)—are also used to control MPE; however, the available evidence from studies on ovarian cancer is limited, consisting mainly of small retrospective series and case reports, with a notable lack of prospective, large‑scale clinical trials. Consequently, the optimal management and treatment strategies for MPE associated with ovarian cancer require further investigation. A multidisciplinary team (MDT) approach should be integrated throughout the entire diagnostic and therapeutic process, providing critical decision‑making at each stage and playing a pivotal role. Promoting MDT‑based collaborative care, precise risk assessment, and individualized interventions represents a crucial direction for improving the management of MPE in ovarian cancer—and constitutes a long‑term, challenging undertaking.