Narrative review of the progress in the treatment of hemoptysis among patients with advanced lung cancer

Introduction

Hemoptysis refers to the expectoration of blood from the lower respiratory tract and is commonly caused by bronchial artery hemoptysis. According to examinations such as angiography and bronchoscopy, approximately 90% of hemoptysis cases originate from the bronchial arteries, 5% from the pulmonary arteries, and 5% from the nonbronchial arteries (1). In 90% of severe hemoptysis cases that require treatment, the bleeding originates from the bronchial artery (2). The most common causes of hemoptysis are acute respiratory infections, cancer, bronchiectasis, and chronic obstructive pulmonary disease (3), and hemoptysis can be classified as infectious hemoptysis, tumorous hemoptysis, vascular hemoptysis, autoimmune hemoptysis, and drug-related hemoptysis (4). Hemoptysis must be distinguished from pseudohemoptysis, which refers to the presence of blood-tinged sputum from the nasopharynx or gastrointestinal tract (5). In clinical practice, it is necessary to comprehensively consider the medical history, physical examination, and examination information of patients with hemoptysis in order to accurately differentiate between these conditions.

Hemoptysis is one of the clinical manifestations of lung cancer, with the other symptoms being coughing, shortness of breath, loss of appetite, or weight loss (6). Fewer than 10% of patients are asymptomatic (7). Although targeted therapy and immunotherapy have fundamentally improved the treatment of advanced lung cancer (8), lung cancer remains one of the leading causes of cancer-related death worldwide (9). It is worth noting that hemoptysis is highly common in lung cancer. Nearly 20% of patients with lung cancer will experience hemoptysis, and the mortality rate associated with hemoptysis due to lung cancer is higher than that from other causes (10). Moreover, patients with lung cancer who have hemoptysis are more susceptible to recurrence (11). Immune checkpoint inhibitor therapy can significantly improve the progression-free survival and overall survival of patients with lung cancer, and massive hemoptysis is one of the adverse events related to immunotherapy (12). Meanwhile, secondary hemoptysis after lung metastasis is rare (13), with only a few reported cases (14).

Hemoptysis itself is a potentially life-threatening disease, and patients with advanced lung cancer have a worse prognosis. Nonspecific and conservative methods can be used to treat mild hemoptysis, while moderate-to-severe hemoptysis can be treated by the embolization of bleeding vessels or palliative surgical resection. Timely and appropriate treatment can improve the outcomes of hemoptysis in patients with advanced lung cancer, reduce mortality, and provide opportunities for subsequent etiological treatment. This review analyzes the safety and efficacy of the currently available treatment methods for hemoptysis in patients with advanced lung cancer in order to characterize the progress in this field. We present this article in accordance with the Narrative Review reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1100/rc).

Methods

A comprehensive literature search of the PubMed and Web of Science databases was conducted for studies published from January 2000 to December 2024. The search keywords included “lung cancer”, “cancer of the lung”, “hemoptysis”, “bronchial artery embolization”, and “bronchial arterial chemoembolization”. Only studies on the treatment of hemoptysis in patients with advanced lung cancer that were published in peer-reviewed journals and in the English language were included (Table 1).

Mechanism of hemoptysis in advanced lung cancer

The lungs are supplied from two sources: the bronchial arteries and pulmonary arteries. The pulmonary arteries flow toward the alveoli for gas exchange, while the bronchial arteries supply oxygenated blood to the bronchi and visceral pleura. Although the contribution of the bronchial arteries to pulmonary blood flow is smaller than that of the pulmonary arteries, they are more likely to cause hemoptysis, with bronchial artery system bleeding accounting for almost 90% of hemoptysis sources (15). Unfortunately, it is not always possible to determine the arterial origin of bleeding in clinical diagnosis and treatment. In the case of cancer, hemoptysis may occur through various pathophysiological mechanisms and affect the amount and speed of bleeding. These mechanisms include the formation of blood vessels within and around the tumor, the detachment of the outer layer of the tumor, necrosis within the tumor, irritation caused by coughing, the erosion of airway tissue into nearby blood vessels, and bleeding caused by medical procedures or treatments (16). Some drugs targeting vascular endothelial growth factor may also cause hemoptysis (17). Other medications commonly used in patients with cancer, including anticoagulation and antiplatelet therapy, may also cause or exacerbate bleeding.

Assessment and diagnosis of hemoptysis

The degree of hemoptysis is typically classified based on the amount of blood discharged. Mild hemoptysis usually refers to the amount of hemoptysis less than 100 mL within 24 hours. In this case, the patient may only present with blood in the sputum, and the impact on the body is relatively small. However, even mild hemoptysis should not be ignored. Moderate hemoptysis refers to the amount of hemoptysis between 100 and 500 mL within 24 hours. At this point, hemoptysis is already quite obvious, and the patient may experience whole mouth bleeding. Severe hemoptysis is the most serious condition, referring to the amount of hemoptysis exceeding 500 mL within 24 hours, or a single hemoptysis exceeding 100 mL. In this case, the patient may experience shock due to massive blood loss, and even endanger their life, requiring immediate emergency measures. However, the definition based on bleeding volume may not accurately reflect the clinical impact of hemoptysis (16). Mild hemoptysis may only involve blood streaks in the mucus, while severe hemoptysis can lead to impaired cardiovascular function or even death. According to a report, the recurrence rates in mild, moderate, and severe hemoptysis are 8.0%, 40.7%, and 33.8%, respectively, while the mortality rates are 4.7%, 13.4%, and 13.5%, respectively (18). Mild hemoptysis accounts for over 90% of cases and has a good prognosis, while the mortality rate of severe hemoptysis can reach over 30% (19). Massive hemoptysis is rare, accounting for about 5% of all hemoptysis cases, but it can be life-threatening (5,20), being one of the acute and critical respiratory diseases. Massive hemoptysis is a common emergency in lung cancer and one of the common causes of death in those with advanced lung cancer (21,22). There is a wide range of bleeding volumes for severe hemoptysis reported in the literature, for instance, a single dose of 50 mL, a dose of 100 mL within 24 hours, and a dose of 1,000 mL within 48 hours. Some researchers also suggest that, beyond a sole focus on hemoptysis volumes, the patient’s respiratory, mental, and cardiovascular status should also be considered as key factors (21,23). According to Chinese experts, every case of hemoptysis larger than 100 mL can be considered as massive hemoptysis (24). Massive hemoptysis usually indicates the presence of underlying severe respiratory or systemic diseases, but the amount of hemoptysis is difficult to estimate accurately. The cause of death from massive hemoptysis is commonly shock caused by airway obstruction or excessive bleeding, with suffocation being the main cause of death. Therefore, massive hemoptysis can be defined as any life-threatening hemoptysis or any hemoptysis that may cause airway obstruction and suffocation.

Based on the patient’s basic medical history and physical examination findings, a preliminary diagnosis of hemoptysis can generally be made, but auxiliary examinations are usually needed to confirm the diagnosis. A complete panel of laboratory tests such as blood routine, urine routine, stool routine, coagulation function, liver and kidney function are necessary. Among imaging examinations, chest X-ray examination is a fast and convenient preliminary examination, but its sensitivity in determining the location and cause of bleeding is limited. For patients with relatively stable conditions, further computed tomography (CT) and angiography are recommended for determining the cause of bleeding. CT is an important noninvasive tool for evaluating patients with hemoptysis, and it can not only detect parenchymal and airway bleeding but also determine the mechanism of hemoptysis and whether a specific vascular supply is involved (25). Recurrent hemoptysis, defined as hemoptysis that recurs after initial successful hemostasis, is best reassessed through chest X-ray and CT or CT angiography (CTA) comparison (26). Multirow CTA can accurately identify the blood supply vessels missed by conventional angiography, guide clinical re-embolization treatment, and improve the success rate of treatment (27). If chest X-ray or multislice CT cannot determine the cause of hemoptysis, bronchoscopy should be performed (28). Bronchoscopy can effectively locate the anatomical site of bleeding, enabling the clearing of airway blood to maintain adequate oxygenation and ventilation (29). The above-mentioned examination methods can be used individually or in combination depending on clinical practice, availability, and patient condition stability. Understanding and adopting appropriate examination methods can assist clinical doctors in accurately assessing the condition of hemoptysis in patients and guide subsequent treatment.

Treatment strategy for hemoptysis in patients advanced lung cancer

For patients with hemoptysis, it is necessary to assess the stability of the patient’s condition and the severity of bleeding before treatment begins. Hemoptysis that endangers life can lead to severe airway obstruction and abnormal gas exchange. Any patient with life-threatening hemoptysis requires immediate treatment, and it is important to first ensure airway safety and stable hemodynamics. In acute situations, nonsurgical control of bleeding is preferable to surgery (30).

The conservative treatment of hemoptysis mainly includes monitoring, oxygen therapy, positional drainage, administration of hemostatic drugs, and application of bronchoscopy. Conservative treatment is primarily suitable for mild-to-moderate hemoptysis and has the advantages of usability and convenience (31). The commonly used hemostatic drugs include posterior pituitary hormone, thrombin, and vitamin K, among others. In addition, tranexamic acid and adrenaline can be inhaled to achieve hemostasis. To stop bleeding, tranexamic acid can also be administered intravenously. If necessary, blood products can also be infused, but the effect is often weak during emergency treatment. When patients with lung cancer have mild hemoptysis, bronchoscopy is usually not necessary, but conservative treatment may likely result in recurrence (32). When a patient experiences life-threatening hemoptysis, sufficient oxygenation and ventilation should be immediately provided to ensure airway safety. The patient should be positioned on their side with the bleeding side facing down, the source of blood isolated, and blood clots prevented from overflowing into the healthy lung, blocking the airway, and hindering the alveolar gas exchange (33). If airway hematoma cannot be effectively cleared and suffocation cannot be relieved, progressive respiratory distress or hypoxemia will occur, and endotracheal intubation should be performed immediately. Subsequent bronchoscopy examination can be applied to clear the accumulated blood in the airway, cold saline sprayed locally, diluted adrenaline administered or tranexamic acid, thrombin or fibrin complex applied to constrict blood vessels and stop bleeding, or a balloon placed to block the bleeding airway. Laser, electrotomy, and local freezing/thermal ablation can also be used for treatment, especially for hemoptysis caused by central lung cancer (20). Among them, bronchoscopic argon plasma coagulation is a useful technique for endobronchial management of hemoptysis in patients with central malignancies. Once the airway is safe and appropriate resuscitation begins, the primary focus should be to locate the source of bleeding and accurately resolve it.

The further treatment of hemoptysis begins with vascular CT, which can determine the location of bleeding, bleeding vessels, and causes of hemoptysis. Intravascular treatment is the first-line treatment for hemoptysis, with 90% of successful applications being achieved through bronchial artery embolization (BAE) and 10% through pulmonary artery occlusion (34). There is evidence suggesting that endovascular treatment is effective for treating hemoptysis associated with primary lung cancer (35), especially when the examination clearly identifies the affected artery. BAE was introduced in 1973 to treat hemoptysis caused by benign diseases and was subsequently used to treat hemoptysis caused by cancer. BAE is considered to be the first choice for treating life-threatening hemoptysis (36,37). Its embolic materials include polyvinyl alcohol particles, gelatin sponge, gel foam, and microcoil, which can safely and effectively control hemoptysis (38). In Abid et al.’s study, 97.5% of cases were successfully embolized, 95% of patients experienced immediate cessation of hemoptysis, and 12% of cases experienced hemoptysis recurrence, but no major life-threatening or functional BAE-related complications were encountered (39). Early intervention strategies should be considered to shorten hospitalization time and prevent early recurrence (40). Compared with conservative treatment alone, BAE can provide superior control of hemoptysis recurrence in the long term and improve quality of life (41). BAE remains an effective and safe choice for treating hemoptysis in patients with hepatocellular carcinoma and lung metastasis, with a good clinical success rate and a low recurrence rate of hemoptysis (13). In patients with lung cancer and life-threatening hemoptysis who are treated with BAE, CTA-identified severe hemoptysis and pulmonary artery injury are independent predictive factors of recurrent hemoptysis (42). Other research suggests that BAE treatment has good clinical efficacy for patients with nonmassive hemoptysis and does not cause significant complications after treatment. Minor complications reported in literature include fever, dizziness, nausea, chest pain, and difficulty swallowing, among which chest pain is the most common. These events can be easily controlled through symptomatic treatment and will not affect clinical outcomes; serious complications are rare, manifested as spinal cord ischemia, which may be accompanied by splenic, renal, and pancreatic infarction (31). Therefore, the absolute contraindication for BAE is that bleeding vessels supply the heart, spinal cord, or skull simultaneously and cannot be avoided. These blood vessels are crucial for supplying blood to important organs, and once they become blocked, it can lead to serious consequences.

It should be noted, however, that for patients with hemoptysis caused by tumors, traditional embolization materials have a low tumor necrosis rate and a high incidence of rebleeding after embolization, which affects the patient’s hemoptysis control rate, tumor remission rate, and long-term survival rate (43). To address these limitations, researchers have turned to a new embolic material, drug-loaded embolic microspheres, which have dual functions of vascular embolization and chemotherapy drug release when applied to bronchial arterial chemoembolization (BACE). As an emerging treatment method, BACE has been scrutinized in clinical studies, which has confirmed its efficacy and safety in the treatment of patients with advanced lung cancer and hemoptysis (44,45), confirming it to be palliative option with good hemostatic effects (46). BACE treatment for patients with advanced lung cancer with hemoptysis is safe, effective, and tolerable (47). Additionally, it was found that BACE, as compared to BAE, significantly prolonged the median overall survival of patients with advanced lung cancer and massive hemoptysis, further supporting its safety and efficacy (48). Microspheres can physically embolize tumor blood vessels, quickly preventing bleeding while reducing tumor volume; moreover, they can transport chemotherapy drugs to facilitate a high local drug concentration, thus continuously inhibiting the growth of tumor cells (49). This combination of local and systemic treatment—providing both the hemostatic effect of BAE and the antitumor effect of chemotherapy drugs—not only improves treatment outcomes but also reduces the side effects associated with systemic chemotherapy, representing a novel treatment option for patients with advanced lung cancer. Its clinical significance is not limited to direct hemostasis but also represents a strategic shift toward a more comprehensive treatment strategy for advanced lung cancer to address acute bleeding events and potential malignant tumors. However, the superiority of BACE over BAE still needs to be further validated through rigorously designed prospective studies.

Although BAE has been proven to be safe and effective in the embolization treatment of hemoptysis in patients with primary and metastatic lung cancer (50), there is currently a lack of in-depth understanding of pulmonary artery embolism in clinical practice. Research has shown that pulmonary artery involvement is associated with the increased mortality rate of hemoptysis in patients with lung cancer (51). A study has evaluated the safety and efficacy of pulmonary embolism in treating patients with lung cancer-related hemoptysis, reporting a 30-day mortality rate of 31% and a 3-year survival rate of 3.6%. It has also been found that tumor size, tumor cavity, and necrosis are significantly correlated with hemoptysis recurrence and higher mortality rates (52). Although the technical success rate and initial clinical efficacy of treatment for pulmonary embolism are promising, the recurrence rate of hemoptysis remains high and the overall survival rate low (53).

Surgery is crucial for treating potentially fatal pulmonary hemoptysis, but it is only suitable for patients for whom drug therapy and embolism have failed (54). The types of palliative resection aimed at achieving complete hemostasis include lobectomy and segmentectomy, among others. Research suggest that performing pulmonary resection in the early stages can help save the lives of patients with hemoptysis (50). Most patients with hemoptysis are treated with traditional open surgery, and one study found that for patients with pulmonary diseases who experience hemoptysis, thoracoscopic surgery can also be an effective and safe option if the hemoptysis is not complicated and the patient’s vital signs are stable (55).

Tumor-related hemoptysis is an important risk factor for recurrent hemoptysis after interventional therapy (56), and patients may be frequently hospitalized due to hemoptysis (57). Therefore, in addition to supportive treatment, potential causes should also be treated. Palliative treatment for advanced lung cancer aims to control local lung lesions, adjacent mediastinal structures, or distant metastatic sites. The current standard treatment for patients with advanced lung cancer with cancer-causing driver gene mutations in the tumor is chemotherapy plus immune checkpoint inhibitors or oral targeted drugs, such as tyrosine kinase inhibitors (58,59). In addition, multiple antibody-drug conjugates are currently being evaluated individually or in combination with different molecules (such as chemotherapy drugs or immune checkpoint inhibitors). Their principle mechanisms of effect include the precise delivery of cytotoxic drugs through antibody-mediated processes, the targeting of antigens specifically expressed by tumor cells, the protection of normal tissues, and selective damage to tumors (60). In addition, matching targeted therapy with circulating tumor DNA testing may improve the prognosis of patients with advanced lung cancer (61). For patients in the advanced stage, it is important that safe and effective treatment methods are selected to optimally control tumor growth, reduce adverse events, lower medical costs, and minimize disruptions to patients’ lives. There remains a need to continuously improve our understanding of biomarkers and antibody targets in order to further refine treatment strategies for patients with advanced lung cancer.

Conclusions

Among patients with advanced lung cancer, the incidence of severe hemoptysis is higher and is associated with a poor prognosis. Early identification and active intervention can prevent fatal outcomes to a certain extent and improve prognosis. Mild hemoptysis can be treated conservatively, while for life-threatening hemoptysis, airway safety and hemodynamic stability should be first prioritized. Depending on the condition, BAE, BACE, and other treatments can be administered. When medication or endovascular treatment is ineffective and the condition stable, palliative resection surgery can also be applied. To reduce the recurrence of hemoptysis, active etiological treatment should be carried out after hemostasis. Further research is needed to develop standardized treatment and prevention strategies for hemoptysis in patients with advanced lung cancer.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1100/rc

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