The Treatment of Malignant Pleural Effusion With Permanent Indwelling Pleural Catheters

Pleural effusion (PE)—abnormal accumulation of fluid in the pleural cavity—is a ubiquitous nosological entity. The estimated annual incidence for Germany is between 400 000 and 500 000 (1). Initial diagnostic aspiration for laboratory, cytological and microbiological examinations and subsequent conservative, medical therapy (diuresis) are the main priorities when treating non-malignant pleural effusions secondary to cardiac, renal and/or hepatic failure. Multiple pleural aspirations or the use of a permanent implantable tunneled pleural catheter (indwelling pleural catheter, IPC) are exceptions when treating transudates which usually have a good response to diuresis.

Malignant pleural effusion (MPE) is the cause of exudative PE in 42 to 77% of cases (2). The presence of MPE is regarded as a sign of an advanced or generalized tumor stage (3). The incidence of MPE is reported to be between 500 and 700 cases per million population, which means that 40 000 to 60 000 new cases can be expected in Germany each year (4, 5). The most common primary diseases are lung and breast cancer. The prognosis of patients with pleural carcinomatosis is significantly limited, with a median survival time of approximately four months and a one-year survival rate of approximately 18% (6). Focus here is on rapid, symptomatic therapy for patients suffering from MPE and dyspnea (7). Single or repeated pleural aspirations are rarely successful with MPE because the effusion is constantly reproduced by the underlying pleural carcinomatosis, or reabsorption is impaired by tumor-related obstruction of the pleural lymphatic channels (8). Therefore, rapid symptom control is achieved only by draining the MPE, combined with pleurodesis (surgical obliteration of the pleural space between the visceral and parietal pleura), or by continuous drainage of the MPE (9). The European Respiratory Society (ERS) and the European Association for Cardio-Thoracic Surgery (EACTS) have defined both talc pleurodesis (TP) and IPC as effective treatment options for MPE (10).

Based on registry data (German Federal Statistics Office, Pleural Tumor Registry of the German Society for Thoracic Surgery [DGT], IPC Registry of the ewimed company), the present article outlines the state of care of patients with IPC in Germany and develops treatment recommendations in comparison with TP.

Available data from the Federal Statistics Office

For the year 2020, the Federal Statistics Office lists 29 167 inpatients with an intervention for the primary or secondary diagnosis J90 (pleural effusion, not classified elsewhere) or J91 (pleural effusion, in conditions classified elsewhere) (eMethods). Therefore, in Germany, approximately 7% of hospitalized patients undergo an intervention in the form of catheter insertion (n = 24 577), thoracoscopic TP (n = 3949), or a combination of thoracoscopic TP and IPC (n = 641) (Table 1); the majority of PEs are assessed and treated on an outpatient basis.

Table 1

Data from the Federal Statistics Office for patients with a diagnosis of pleural effusion and treatment by IPC placement and/or VATS talc pleurodesis

In only 20.8% of patients with IPC was an underlying malignant condition (MPC) recorded. The small proportion of underlying malignancy and also the large proportion of emergency catheter insertions (56.1%) in the IPC group suggest that in many cases, despite coding an IPC (German procedure classification [OPS]: 8–144.1), a non-tunneled temporary pleural catheter was in fact inserted, for example, during internal medical or intensive care treatment. This assumption is supported by the fact that more than 60% of the patients were cared for in non-surgical departments.

According to the Federal Statistics Office, the proportion of MPEs is significantly higher (63.3% and 62.6%, respectively) in patients with thoracoscopic TP alone (OPS: 5–345.5) and also in combination with IPC (OPS: 8–144.1) than in the group with IPC insertion alone (20.8%) (Table 1).

Indications for thoracoscopy versus IPC

The indication for either thoracoscopy or placement of an IPC is made during the course of establishing the diagnosis of MPE and its treatment (Figure). Thoracoscopy should be indicated for an underlying malignant condition only if there is so far no histopathologic evidence of pleural carcinomatosis and the patient is in good general condition with a good prognosis. There should be no evidence of a trapped lung on the chest x-ray after the initial pleural aspiration. A trapped lung means that lung compression caused by effusion has led to the development of a thick fibrous membrane over the visceral pleura which does not allow re-expansion of the lung after drainage of the effusion. TP can only be successful if the visceral pleura makes contact with the parietal pleura. With MPE and trapped lung, extensive dissection of the fibrous membrane (decortication) should not be performed in the hope of improving lung expansion. It is usually unsuccessful and associated with a high complication rate.

Figure

Treatment algorithm for malignant pleural effusion

There is only little evidence available in cases of underlying malignant disease and/or detection of malignant cells in the pleural aspirate (= MPE) as to the amount of effusion above which a recommendation for renewed aspiration is in place or how often effusion aspiration should be repeated. The indication for pleural aspiration in MPE is primarily for the presenting symptoms (dyspnea, feeling of pressure in the chest); the indication for repeat pleural aspiration is when symptoms improve after tapping. Repeat therapeutic pleural aspiration may also be performed in patients with slow fluid accumulation and those with very short life expectancy or poor performance status (11). Otherwise, multiple effusion aspirations should be avoided for recurrent, symptomatic PE, as the time delay risks the development of a trapped lung and increases the risk of infection. From our own experience, we recommend that no more than two to three pleural aspirations be performed. This is also consistent with data from the IPC registry, where the average aspiration rate before IPC insertion was 1.5 in 2021 (down from 3.8 in 2011).

The therapeutic decision for or against insertion of an IPC should also always take into account the patient’s prognosis, quality of life, and preferences (8). A shorter stay in hospital may be another argument in favor of IPC (12).

The indication for insertion of an IPC is predominantly made by oncologists, thoracic surgeons and pulmonologists. The most frequently recorded underlying conditions are lung and breast cancer (Table 2).

Table 2

Data from the IPC registry for the registration of patients with malignant pleural effusion in Germany

Insertion of a tunneled pleural catheter

After sonographic identification of the puncture site (6th or 7th intercostal space in the anterior/mid-axillary line) and application of local anesthesia, pleural puncture is performed using the Seldinger technique with insertion of a sheath. After making a second stab incision (approximately 10 cm anterior to the first puncture site), subcutaneous tunneling is performed between the two incisions and the end of the catheter is inserted via the sheath into the pleural cavity. The catheter is secured in place with a suture. Insertion takes about 10 to 20 minutes.

In 2020, insertion of an IPC for pleural effusion during inpatient treatment was most frequently performed in Germany by departments for internal medicine (62.5%). Insertion of an IPC for malignant pleural effusion (IPC registry) was mainly performed by thoracic surgeons (68%) (Table 2).

Thoracoscopic talc pleurodesis versus insertion of a tunneled pleural catheter

A total of 387 thoracoscopic TPs and 191 IPC placements for primary pleural cancer (malignant pleural mesothelioma—circa 25%) and secondary pleural carcinomatosis (approx. 75%) were documented in the DGT Pleural Tumor Registry from January 2015 to December 2021 (Table 3). In contrast to the data of the Federal Statistics Office, the DGT Pleural Tumor Registry reports that the proportion of patients who received an IPC for MPE (33%, 191/578) is significantly lower than the proportion of patients who underwent thoracoscopic TP (67%, 387/578). Reasons for this are often the still pending confirmation of pleural carcinomatosis or the prospect of a successful TP and thus, possibly, the decision to refrain from an IPC (Figure). By far the majority of patients (98%) were admitted electively to the thoracic surgery department (Table 3). The gender and age distribution largely matches the corresponding data from the Federal Statistics Office and the IPC registry. The clear difference in the Karnofsky index between the groups of patients with IPC and those with TP is particularly notable, with a significantly worse symptomatic limitation of physical activity in the IPC patient group (Table 3). ECOG (Eastern Cooperative Oncology Group) status and the patient’s prognosis play an important role in determining treatment with either IPC or TP. The longer postoperative stay for the group with thoracoscopic TP (mean: 8.8 days) is due to the need for insertion of a chest drain, which is removed after surgery once the effusion subsides and the lung expands. Not so with IPC: Here, the patient can be discharged home significantly sooner after catheter insertion (postoperative stay on average 4.5 days) and regular effusion drainage is performed on an outpatient basis (Table 3). Two meta-analyses also demonstrated that hospital stay was significantly shorter for patients with IPC management as compared with patients after TP (13, 14). Thus, Yeung et al. demonstrated a slightly more than two-day shorter hospital stay (weighted mean difference [WMD]: 2.19 days; 95% confidence interval: [0.70; 3.67]) for the IPC group in comparison with the TP group (14).

Table 3

Data from the Pleural Tumor Registry of the German Society for Thoracic Surgery for the period 01/2015 to 12/2021

There is no difference in postoperative complication rates between the two treatment modalities (IPC versus TP) in the patients we treated surgically (Table 3), nor in the meta-analyses (13, 14). The 30-day mortality of patients with IPC is significantly increased (12.3%) as compared with patients after thoracoscopic TP (5.4%). Since 30-day mortality was essentially determined by the underlying malignant disorder, the question arises as to whether the indication for IPC was established too late and other palliative procedures, such as pleural aspiration or best supportive care (BSC), would have been better indicated.

Long-term course

Over the long-term, some patients with IPC experience spontaneous pleurodesis with no recurrence of PE. In a randomized clinical trial (ASAP trial), Wahidi et al. showed that the autopleurodesis rate, defined as complete or partial response (primary endpoint), was 47% with daily drainage and 24% with drainage every other day (p = 0.003) (15). Time to autopleurodesis (secondary endpoint) was also significantly (p = 0.005) shorter with daily (median: 54 days) as compared with every-other-day (median: 90 days) drainage (15). Repeated drainage may cause pleural inflammation and induce local release of proinflammatory cytokines, which may subsequently lead to fibrin formation in the MPE (16).

The findings of the ASAP study were confirmed by the AMPLE-2 study, which was also randomized. Here, daily drainage compared with symptomatic drainage resulted in an increase in the pleurodesis rate (secondary endpoint) from 11% to 37% after 60 days of treatment (17).

A meta-analysis demonstrated that pleurodesis rates achieved by TP (87.95%) were significantly (relative risk [RR]: 1.56 [1.26; 1.92]; p <0.0001) higher than those resulting from IPC (56.41%) (18). The application of talc suspension via an IPC increases the pleurodesis rate. For instance, a randomized trial demonstrated that in the talc arm the pleurodesis rate after 35 days was 43%, which was significantly higher than that in the placebo arm at 23% (hazard ratio: 2.20 [1.23; 3.92]; p = 0.008) (19).

More important than pleurodesis, however, is the quality of life of patients with MPE in a predominantly palliative setting. Wang et al. reported no apparent difference between IPC and TP in their meta-analysis of quality of life (WMD: 1.50 [−3.80; 0.80], p = 0.20) (18). In their meta-analyses, Iyer et al. and Yeung et al. demonstrated that there was also no difference between thoracoscopic TP and IPC with respect to the main symptom of dyspnea (13, 14).

The relevance of complications, including infections, after IPC varies considerably in the studies due to their small number of cases. In a meta-analysis by Patil et al, the estimated mean rate of all IPC complications was 17.2%, including major complications such as empyema 2.3%, loculation 2.0%, dislodgement 1.3%, leakage 1.3%, and pneumothorax 1.2% (20). A large multicenter retrospective study reported a pleural infection rate of 4.9% for IPC, with 94% of cases successfully treated with antibiotic therapy alone (21). IPC removal was not necessary in the majority of patients with local infection (22). A multicenter study also found no increased risk of IPC-related infection for patients with MPE on antineoplastic therapy, so chemotherapy is not a contraindication for IPC (23). Pooled results showed higher local infection with IPC than with chemical pleurodesis (6.9% versus 0.5%; RR: 5.83 [1.56; 21.87]) (13).

In a retrospective study involving 395 patients with IPC for MPE, Frost et al. found the median catheter dwell time to be 1.2 months (24). Dwell time is determined by death or removal of the IPC after pleurodesis or infection. In daily clinical practice, there is a median drainage material consumption lasting 91 days for IPC patients with MPE and 104 days for patients with nonmalignant PE (in 2020 according to the IPC registry). The literature reports IPC removal rates to be as high as 36% (25).

Few data are available regarding long-term survival of patients with an IPC. In a randomized trial (TIME2), median survival time was 200 days (interquartile range [IQR]: 39−392 days) in the TP group and 153 days (IQR: 73−288 days) in the IPC group, with no statistically significant difference in survival time up to one year for a difference of −0.8 months [−2.4; 0.8]; p = 0.32) (26). In daily clinical practice, the majority of patients with an IPC inserted as indicated by their presenting findings will have worse survival times (Figure), given that an impaired ECOG score, limited prognosis, and trapped lung as signs of advanced pleural carcinomatosis/MPE are indications for IPC. Risk assessment of survival can be undertaken using the LENT scoring system (27). Two large meta-analyses failed to demonstrate differences in survival of patients with TP versus IPC (13, 18).

Conclusions

The focus for patients with MPE is on effective symptom management with the shortest possible hospital stay. An IPC achieves these goals, a fact reflected in the guidelines of the American Thoracic Society and its European counterparts (European Respiratory Society/British Thoracic Society) (28).

• IPC and thoracoscopic TP are comparable in terms of symptomatic management of MPE and quality of life.
• The decision about treatment must be made on an individual basis, taking into account survival prognosis, the patient’s general state of health, anatomic conditions (trapped lung), and the patient’s preferences.
• IPC is the preferred treatment option for patients with MPE and a high ECOG index score with limited survival time; prior multiple pleural aspirations and possible TP attempts should be avoided.
• IPC is the treatment of choice for symptomatic MPE patients with a trapped lung.
• In general, chemotherapy is not a contraindication for IPC.
• Pleurodesis via an IPC is possible and can be enhanced by daily removal of the effusion and, where appropriate, the use of talc, although this is not the mainstay of therapy.
• The main complication of IPC is local infection, which requires antibiotic and, where necessary, local treatment (irrigation). Removal of the IPC is rarely indicated here.
• Survival of MPE patients is not so much determined by the therapeutic approach used, but rather by the underlying condition.

Conflict of interest statement
Prof. Hofmann was president of the German Society for Thoracic Surgery from 2019 until 2021 and has been past president since 2021.

Prof. Scheule receives consulting fees from the ewimed company.

The other authors confirm that no conflict of interest exists.

Manuscript received on 7 March 2022, revised version accepted on 10 May April 2022

Translated from the original German by Dr. Grahame Larkin, MD

Corresponding author
Prof. Dr. med. Hans-Stefan Hofmann
Department for Thoracic Surgery

University Hospital of Regensburg

Franz-Josef-Strauss-Allee 11

93053 Regensburg

Cite this as:
Hofmann HS, Scheule AM, Markowiak T, Ried M: The treatment of malignant pleural effusion with permanent indwelling pleural catheters. Dtsch Arztebl Int 2022; 119: 595–600. DOI: 10.3238/arztebl.m2022.0229

►Supplementary material

eMethods:
www.aerzteblatt-international.de/m2022.0229

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