Abstract
Background
Combined ambulatory thoracoscopic talc poudrage and tunneled indwelling pleural catheter (TIPC) placement may facilitate early pleurodesis while preserving outpatient management for malignant pleural effusion (MPE). Predictors of pleurodesis success after this combined approach remain incompletely defined. In this study, we aimed to identify the predictors of successful pleurodesis after this combined approach among patients with expandable and non-expandable lung subgroups.
Methods
We performed a retrospective cohort study of 100 patients who underwent outpatient thoracoscopic talc poudrage with TIPC placement for MPE. Pleurodesis success was assessed at 3 and 6 months. Multivariable logistic regression was used to identify predictors of success among 97 evaluable patients. Additional analyses were performed in the non-expandable lung subgroup.
Results
Among 97 patients, 77 (79.4%) had expandable lungs. In multivariable analysis, lung expandability was independently associated with pleurodesis success at 3 months [odds ratio (OR), 15.2; 95% confidence interval (CI): 4.22–71.0; P<0.001] and 6 months (OR, 7.97; 95% CI: 2.07–33.9; P=0.003). Cancer group was associated with 3-month success in adjusted analysis (global P=0.046): compared with the lung/mesothelioma group, the other-malignancy group had lower odds of success (OR, 0.19; 95% CI: 0.04–0.73), whereas breast cancer did not differ significantly. No group difference persisted at 6 months (global P=0.46). Lung/mesothelioma-associated MPE had higher early pleurodesis success than other malignancy groups, but not at 6 months. In the non-expandable lung subgroup, complete visceral restriction, airway obstruction and adhesions were associated with lower 6-month pleurodesis success on univariate analysis.
Conclusions
Lung expandability was the strongest independent predictor of pleurodesis success after combined outpatient thoracoscopic talc poudrage and TIPC placement. Selected patients with non-expandable lung may still achieve successful pleurodesis.
Keywords: Malignant pleural effusion (MPE), pleurodesis, talc poudrage, tunneled indwelling pleural catheter (TIPC), non-expandable lung
Highlight box.
Key findings
• In this retrospective cohort of patients with malignant pleural effusion (MPE) undergoing combined outpatient thoracoscopic talc poudrage and tunneled indwelling pleural catheter (TIPC) placement, lung expandability was the strongest independent predictor of pleurodesis success at both 3 and 6 months.
• Patients with non-expandable lung were less likely to achieve pleurodesis overall, but selected patients, particularly those with partial rather than complete visceral restriction, still achieved successful pleurodesis.
What is known and what is new?
• Successful pleurodesis generally depends on apposition of the visceral and parietal pleura, and non-expandable lung has traditionally been viewed as a barrier to pleurodesis.
• This study adds data from a combined outpatient same-day approach using thoracoscopic talc poudrage and TIPC placement and further characterizes outcomes among patients with non-expandable lung.
What is the implication, and what should change now?
• Lung expandability should be considered when counseling patients and selecting management strategies for MPE.
• Non-expandable lung should not be treated as a single binary exclusion category; the degree of visceral restriction may help identify patients who can still achieve pleurodesis with a combined approach.
Introduction
Malignant pleural effusion (MPE) is a common complication of advanced malignancy, associated with significant respiratory symptoms and reduced quality of life. It is considered the second leading cause of exudative pleural effusions and accounts for over 125,000 hospital admissions each year in the United States (1). Management of MPE is primarily palliative and aims to relieve dyspnea through minimally invasive procedures while minimizing repeated interventions and healthcare interactions (2).
Traditionally, two main strategies are used: tunneled indwelling pleural catheter (TIPC) placement for outpatient fluid drainage, and chemical pleurodesis, usually with talc, via chest tube, which typically requires hospital admission. Both approaches can be used, and they provide equal symptomatic relief with no significant difference in survival in randomized trials (3).
However, there are some limitations to each one. TIPC allows for shorter hospital stays but often requires ongoing outpatient drainage, and only a subset of patients achieve spontaneous pleurodesis; therefore, many patients remain dependent on TIPC. In contrast, talc pleurodesis is associated with higher pleurodesis success rates but necessitates hospitalization, with associated procedural risks, resource utilization, and increased time spent in the hospital (4).
To mitigate the limitations of both strategies, we used planned outpatient medical thoracoscopy with talc poudrage and concurrent TIPC placement, followed by same-day discharge when clinically appropriate. Unlike conventional surgical pleurodesis, this medical thoracoscopy procedure was performed under local anesthesia, with occasional moderate sedation but without general anesthesia. The TIPC allowed continued home drainage while awaiting pleurodesis and provided ongoing symptom control if pleurodesis was unsuccessful; it was removed once prespecified drainage and imaging criteria were met.
In addition to assessing the success of this combined technique, we examined factors that may be associated with pleurodesis success and catheter independence, particularly in patients with non-expandable lungs. We evaluated these factors at 3 and 6 months and analyzed the non-expandable lung subgroup.
In a prior descriptive report of this institutional cohort, we described the overall pleurodesis success rates achieved with this approach. The present study analyses the same cohort to identify the factors associated with that success, including age, sex, cancer type, lung expandability status and Eastern Cooperative Oncology Group performance status (ECOG PS). We also assessed factors predicting pleurodesis success in patients with non-expandable lungs, a category of patients who have been previously excluded from most studies due to the belief that they are less likely to achieve pleurodesis (1). We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1845/rc).
Methods
This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Institutional Review Board of University of Florida (IRB No. #IRB202500112). The requirement for individual informed consent was waived because of the retrospective design and use of de-identified clinical data.
This retrospective cohort study evaluated patients undergoing pleurodesis for recurrent pleural effusion in the setting of malignancy at University of Florida Health Shands Hospital in Gainesville, Florida, USA. Clinical data were obtained from the hospital’s electronic health records. A total of 100 patients were initially identified and followed longitudinally to assess pleurodesis success at 3 and 6 months. Patients who died prior to the 6-month time point were retained if pleurodesis success had been established before death; those without documented success prior to death (n=3) were excluded due to inability to determine the outcome. A total of 97 patients were included in the final analyses.
Procedure and follow-up
Medical thoracoscopy was performed under moderate sedation using intravenous midazolam and fentanyl titrated to maintain patient comfort. A 10-mm STORZ rigid thoracoscope was introduced through a thoracoscopy port after blunt entry into the pleural space. Pleural fluid was evacuated under direct thoracoscopic visualization with negative pressure applied during the procedure, with the port still in place, and the pleural space was systematically inspected for pleural abnormalities, including adhesions and lung re-expansion. When required, blunt adhesiolysis was performed to facilitate drainage, visualization, and lung expansion. After pleural drainage and thoracoscopic assessment, 4 g of sterile talc was insufflated into the pleural space.
A TIPC (PleurX) was placed at the conclusion of the procedure. A separate skin exit site was created approximately 5 cm inferior and anterior to the thoracoscopy incision, and the catheter was passed through a subcutaneous tunnel and introduced into the pleural space through the existing thoracoscopy entry site. Therefore, a second pleural puncture was not required. No additional chest tube was placed. The TIPC was connected to wall suction at −40 cm H2O for approximately 20 minutes to evacuate residual pleural air and fluid and was then capped. A chest radiograph was obtained before discharge. Patients requiring additional observation or management were admitted.
Drainage and follow-up
After discharge, patients were advised to drain the TIPC every other day. Patients were provided with the contact information of a pleural nurse navigator, who monitored drainage volumes. Once drainage decreased to <50 mL during three consecutive drainage attempts, patients were scheduled for chest radiography and evaluation for possible catheter removal. Chest radiographs obtained after the procedure and before catheter removal were used to assess residual pleural air or fluid and procedural complications.
The primary outcomes were factors predicting pleurodesis success at 3 and 6 months. Pleurodesis success was defined as sustained symptom relief with decreased drainage from the pleural catheter of <50 mL over 3 subsequent drainage events leading to the removal of TIPC, repeat imaging showing <25% opacification in the hemithorax and no requirement for further pleural intervention on the same hemithorax during subsequent follow-up. This pleurodesis success criterion reflects definitions commonly used in prior published studies (5,6). Baseline variables included age, sex, same-day discharge status, lung expandability, ECOG PS, and primary malignancy. Gender was abstracted from the electronic medical record and analyzed as a binary variable as recorded in the clinical chart. Race and ethnicity were not included in the primary models due to limited relevance to the study hypothesis.
The TIPC was removed once these criteria were met; it was not retained for a fixed duration. Patients continued scheduled drainage and clinical follow-up until the criteria were satisfied or until death. Pleurodesis success was assessed at two landmark timepoints, 3 and 6 months after the index procedure. These outcomes are cumulative rather than competing: patients meeting the criteria by 3 months are also counted as successes at 6 months, and the 6-month assessment additionally confirms durability by requiring that no further ipsilateral pleural intervention was needed.
Non-expandable lung was defined as failure of the lung to oppose the chest wall after complete pleural fluid drainage, despite spontaneous respiration and application of negative intrapleural pressure. Although non-expandable lung could sometimes be suspected on preprocedural imaging, it was often confirmed only after complete pleural fluid drainage and intraprocedural assessment of lung re-expansion. Intraprocedural assessment during medical thoracoscopy further subclassified non-expandable lung as either partially expandable or completely non-expandable. Partially expandable lung was defined as incomplete lung expansion, in which the lung partially inflated and approached the chest wall without achieving full apposition during spontaneous breathing. Completely non-expandable lungs were defined as absence of any visible lung re-expansion despite the application of negative intrapleural pressure. Finally, post-procedure chest radiographs were obtained as part of routine clinical care and were used to evaluate for procedural complications and residual pleural air/fluid; however, they were not used as the primary criterion for classification of lung expansibility.
Additional variables, including the presence or absence of pleural adhesions were collected on visual inspection during medical thoracoscopy. Adhesiolysis was defined as the mechanical disruption and division of pleural adhesions during pleuroscopy to facilitate pleural drainage, improve lung re-expansion, and allow adequate visualization and access to the pleural space. Adhesions were lysed using blunt or sharp dissection techniques at the discretion of the operator. All patients had their computed tomography of the chest evaluated to assess the presence or absence of airway obstruction due to tumor on the ipsilateral side of MPE.
Lung expandability and same-day discharge were treated as binary variables. ECOG was analyzed as an ordinal variable. Primary malignancies were grouped into clinically relevant categories to improve model stability, including a Lung/Mesothelioma group, breast cancer, and an “others” category comprising gastrointestinal (GI), genitourinary (GU), ovarian, and other malignancies. Lung cancer and mesothelioma were pooled a priori because only 7 patients had mesothelioma, a number insufficient to support a separate category in a multivariable model. Because these two tumour types differ biologically, a sensitivity analysis modelling mesothelioma as its own category (with lung cancer as the reference) was performed to confirm that any effect attributed to the pooled group was not driven by mesothelioma.
Statistical analysis
Descriptive statistics were used to summarize baseline characteristics. Continuous variables were reported as mean ± standard deviation or median (interquartile range), and categorical variables as counts and percentages. Multivariable logistic regression models were constructed separately for 3- and 6-month outcomes, incorporating age, sex, same-day discharge, lung expandability, ECOG, and cancer group as predictors. Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were reported.
To distinguish crude from adjusted associations, unadjusted ORs and absolute pleurodesis success rates (n/N, %) for each predictor category are reported alongside the adjusted estimates. Global P values for the three-level cancer group variable were obtained by likelihood ratio test.
Model performance was evaluated using multiple complementary metrics. Discrimination was assessed using the area under the receiver operating characteristic curve (AUC), while calibration was evaluated using the Hosmer-Lemeshow goodness-of-fit test. Overall model performance was assessed using the Brier score, and explained variance was quantified using pseudo-R2 statistics (McFadden and Nagelkerke). Multicollinearity was assessed using variance inflation factors.
A predefined subgroup analysis was performed among patients with non-expandable lungs. Within this subgroup, additional variables, including degree of visceral restriction (partial vs. complete), presence of adhesions, and airway obstruction, were evaluated. Univariate logistic regression analyses were first performed to explore associations with pleurodesis success. Given the small sample size and evidence of separation, penalized logistic regression using Firth’s method was subsequently applied to obtain stable estimates, with variable selection guided by clinical relevance and univariate trends.
An additional exploratory analysis was conducted among patients with non-expandable lung and adhesions to assess the association between successful adhesiolysis and pleurodesis outcomes. Due to the limited sample size, this analysis was performed using Fisher’s exact test, and results were summarized as proportions and exact P values.
All statistical analyses were performed using R (version 4.4.1), and a two-sided P value <0.05 was considered statistically significant.
Results
A total of 97 patients were included in the final analysis. The mean age was 66.2±8.7 years, and 62.9% of patients were female. The majority of patients (87.6%) underwent same-day discharge and the remaining were admitted for post procedural complications including infection, pneumothorax or simply remained under ambulator status but kept for 1 day to allow full recovery post procedure. Also, 79.4% of our cohort were found to have an expandable lung. Pleurodesis success was achieved in 69.1% of patients at 3 months and 86.6% at 6 months. Two patients developed cellulitis at the catheter insertion site and were successfully treated with antibacterial therapy. Neither patient developed empyema or required catheter removal because of uncontrolled infection. No catheter blockage requiring removal, catheter fracture, significant bleeding, or catheter-tract metastasis was observed. Two patients developed persistent post-procedural air leaks and required hospital admission.
Table 1 summarizes the baseline characteristics of the study sample.
Table 1. Baseline characteristics of the study population.
| Variable | Value |
|---|---|
| Age (years) | 66.2±8.7; 66 [42–85] |
| Sex | |
| Male | 36 (45.4) |
| Female | 61 (62.9) |
| Same-day discharge | 85 (87.6) |
| Hospitalization | 12 (12.4) |
| Expandable lung | 77 (79.4) |
| Pleurodesis success | |
| 3 months | 67 (69.1) |
| 6 months | 84 (86.6) |
| Primary malignancy | |
| Lung | 34 (35.1) |
| Breast | 31 (32.0) |
| Mesothelioma | 7 (7.2) |
| Ovarian | 8 (8.2) |
| Gastrointestinal | 8 (8.2) |
| Genitourinary | 8 (8.2) |
| Other | 1 (1.0) |
Continuous variables are presented as mean ± standard deviation and median [interquartile range], and categorical variables are presented as counts (percentages).
Lung cancer was the most common primary malignancy (34/97, 35.1%), followed by breast cancer (31/97, 32.0%); mesothelioma accounted for a small minority of the cohort (7/97, 7.2%). The remaining 25 patients (25.8%) had ovarian (n=8), GI (n=8), GU (n=8) or other (n=1) primary malignancies. Outcomes by primary malignancy are presented in Table 2.
Table 2. Lung expandability and pleurodesis outcomes by primary malignancy (n=97).
| Primary malignancy | Total, n (%) | Expandable lung, n (%) | 3-month success, n (%) | 6-month success, n (%) |
|---|---|---|---|---|
| Lung | 34 (35.1) | 29 (85.3) | 28 (82.4) | 29 (85.3) |
| Mesothelioma | 7 (7.2) | 1 (14.3) | 4 (57.1) | 6 (85.7) |
| Lung/mesothelioma (pooled) | 41 (42.3) | 30 (73.2) | 32 (78.0) | 35 (85.4) |
| Breast | 31 (32.0) | 26 (83.9) | 20 (64.5) | 29 (93.5) |
| Ovarian | 8 (8.2) | 7 (87.5) | 4 (50.0) | 6 (75.0) |
| Gastrointestinal | 8 (8.2) | 7 (87.5) | 6 (75.0) | 7 (87.5) |
| Genitourinary | 8 (8.2) | 6 (75.0) | 4 (50.0) | 6 (75.0) |
| Other | 1 (1.0) | 1 (100.0) | 1 (100.0) | 1 (100.0) |
| Other malignancies (pooled) | 25 (25.8) | 21 (84.0) | 15 (60.0) | 20 (80.0) |
| Total | 97 (100.0) | 77 (79.4) | 67 (69.1) | 84 (86.6) |
Fisher’s exact test P<0.001 for expandable lung in mesothelioma versus all other malignancies. Crude between-group differences in pleurodesis success were not statistically significant at either timepoint (3 months, P=0.23; 6 months, P=0.29).
In multivariable logistic regression analysis, the presence of an expandable lung was strongly associated with pleurodesis success at both timepoints (Table 3, Figure 1). At 3 months, expandable lung was associated with significantly increased odds of success (OR 15.2, 95% CI: 4.22–71.0, P<0.001). The success rate was 79.2% (61/77) among the expandable lungs group compared with 30% (6/20) among the non-expandable lungs group. This association remained significant at 6 months (OR 7.97, 95% CI: 2.07–33.9, P=0.003) with successful pleurodesis achieved in 71 of 77 patients (92.2%) among the expandable lungs, compared with 13 of 20 patients (65.0%) in the non-expandable lungs group.
Table 3. Multivariable logistic regression analysis of predictors of pleurodesis success at 3 and 6 months.
| Variable | 3-month | 6-month | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Success, n/N (%) | Unadjusted | Adjusted | Success, n/N (%) | Unadjusted | Adjusted | |||||
| OR (95% CI) | P value | OR (95% CI) | P value | OR (95% CI) | P value | OR (95% CI) | P value | |||
| Age (per year) | – | 0.99 (0.94–1.04) | 0.752 | 0.99 (0.93–1.05) | 0.681 | – | 1.02 (0.96–1.09) | 0.541 | 1.01 (0.94–1.08) | 0.862 |
| Female | 40/61 (65.6) | 0.64 (0.25–1.60) | 0.334 | 0.44 (0.12–1.47) | 0.195 | 54/61 (88.5) | 1.54 (0.48–5.01) | 0.471 | 1.00 (0.24–4.09) | 0.995 |
| Same-day discharge | 60/85 (70.6) | 1.71 (0.50–5.92) | 0.394 | 1.28 (0.23–6.12) | 0.760 | 73/85 (85.9) | 0.55 (0.07–4.68) | 0.587 | 0.38 (0.02–2.90) | 0.422 |
| Expandable | 61/77 (79.2) | 8.90 (2.95–26.8) | <0.001 | 15.2 (4.22–71.0) | <0.001 | 71/77 (92.2) | 6.37 (1.84–22.0) | 0.003 | 7.97 (2.07–33.9) | 0.003 |
| ECOG performance status per 1-point increase | – | 0.68 (0.38–1.22) | 0.198 | 0.75 (0.37–1.49) | 0.425 | – | 0.97 (0.45–2.10) | 0.942 | 1.15 (0.46–2.77) | 0.750 |
| Cancer group (global) | 0.239 | 0.046 | 0.295 | 0.463 | ||||||
| Lung/mesothelioma (reference) | 32/41 (78.0) | Reference | – | Reference | – | 35/41 (85.4) | Reference | – | Reference | – |
| Breast | 20/31 (64.5) | 0.51 (0.18–1.45) | 0.208 | 0.38 (0.09–1.48) | 0.180 | 29/31 (93.5) | 2.49 (0.47–13.3) | 0.286 | 1.73 (0.27–14.8) | 0.576 |
| Other malignancies | 15/25 (60.0) | 0.42 (0.14–1.25) | 0.121 | 0.19 (0.04–0.73) | 0.020 | 20/25 (80.0) | 0.69 (0.19–2.54) | 0.572 | 0.52 (0.11–2.31) | 0.388 |
Absolute pleurodesis success rates (n/N, %) are reported for each predictor category alongside both unadjusted and adjusted ORs. Adjusted models include age, sex, same-day discharge, lung expandability, ECOG performance status and cancer group. Global P values for the three-level cancer group variable are from likelihood ratio tests. Dashes indicate estimates that are not applicable: ECOG was modelled as a single ordinal term, so no OR is estimated for individual levels, and no success rate is defined for the continuous variables. The contrast between the unadjusted and adjusted columns shows that the association between cancer group and 3-month success emerges only after adjustment, principally for lung expandability. CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; OR, odds ratio.
Figure 1.
Forest plot demonstrating adjusted odds ratios and 95% confidence intervals for predictors of pleurodesis success at 3 and 6 months. Odds ratios are presented on a logarithmic scale. ECOG, Eastern Cooperative Oncology Group.
Lung expandability differed markedly by tumour type. An expandable lung was present in 29 of 34 patients with lung cancer (85.3%) but in only 1 of 7 patients with mesothelioma (14.3%; Fisher’s exact test P<0.001 for mesothelioma versus all other malignancies), and in 26 of 31 patients with breast cancer (83.9%) and 21 of 25 patients in the other-malignancy group (84.0%).
Unadjusted 3-month pleurodesis success was 82.4% (28/34) in lung cancer, 57.1% (4/7) in mesothelioma, 64.5% (20/31) in breast cancer and 60.0% (15/25) in the other-malignancy group; these crude differences were not statistically significant (global P=0.23). The corresponding 6-month rates were 85.3%, 85.7%, 93.5% and 80.0% (global P=0.29). Absolute success rates for every predictor category are shown in Table 3, and outcomes by primary malignancy in Table 2.
After adjustment for age, sex, same-day discharge, lung expandability, and ECOG PS, cancer group was associated with pleurodesis success at 3 months (global P=0.046). Relative to the lung/mesothelioma reference group (32/41, 78.0%), the other-malignancy group had significantly lower adjusted odds of success (15/25, 60.0%; OR 0.19, 95% CI: 0.04–0.73, P=0.02), whereas the breast cancer group did not differ significantly (20/31, 64.5%; OR 0.38, 95% CI: 0.09–1.48, P=0.18). The association was therefore evident only after adjustment, principally for lung expandability.
At 6 months, cancer group was no longer associated with pleurodesis outcomes (global P=0.46). This reflected convergence over time in the groups with lower early success: among patients who had not achieved pleurodesis at 3 months, 9 of 11 with breast cancer (81.8%) and 5 of 10 in the other-malignancy group (50.0%) did so by 6 months, compared with 3 of 9 (33.3%) in the lung/mesothelioma group.
In the sensitivity analysis modelling mesothelioma separately from lung cancer (Table S1), the adjusted odds of 3-month success in mesothelioma did not differ significantly from lung cancer (OR 1.60, 95% CI: 0.17–14.8, P=0.67), the lower odds in the other-malignancy group persisted (OR 0.21, 95% CI: 0.05–0.88, P=0.03), and lung expandability remained the dominant predictor (OR 17.3, 95% CI: 3.71–80.3, P<0.001). The early advantage of the pooled group was therefore not attributable to mesothelioma, although the small mesothelioma sample limits the precision of this estimate.
No statistically significant associations were observed for age, sex, same day discharge or PS as documented in Table 3.
Model discrimination was good, with AUC values of 0.78 at 3 months and 0.75 at 6 months. Calibration was adequate based on Hosmer-Lemeshow testing, and no significant multicollinearity was identified.
As shown in Table 4, among patients with non-expandable lung, univariate analysis demonstrated that complete visceral restriction was associated with lower odds of pleurodesis success, reaching statistical significance at 6 months (OR 0.07, 95% CI: 0.003–0.63, P=0.03), with a consistent direction of effect at 3 months (OR 0.11, P=0.07) (Table 4). Patients with complete restriction demonstrated pleurodesis success in 1 of 10 patients (10.0%) at 3 months and 4 of 10 patients (40.0%) at 6 months, whereas patients with partial restriction achieved success in 5 of 10 patients (50.0%) at 3 months and 9 of 10 patients (90.0%) at 6 months. Pleural adhesions, airway obstruction demonstrated a trend toward reduced pleurodesis success but did not reach statistical significance.
Table 4. Univariate logistic regression analysis of predictors of pleurodesis success in the non-expandable lung subgroup.
| Variable | 3-month | 6-month | ||
|---|---|---|---|---|
| OR (95% CI) | P value | OR (95% CI) | P value | |
| Age (per year) | 0.97 (0.87–1.06) | 0.46 | 0.96 (0.87–1.05) | 0.40 |
| Female sex | 0.08 (0.004–0.70) | 0.042 | 0.88 (0.13–5.65) | 0.88 |
| Same-day discharge | 0.55 (0.06–5.30) | 0.57 | 0.38 (0.02–3.38) | 0.42 |
| ECOG (per 1-point increase) | 2.75 (0.58–21.74) | 0.25 | 2.49 (0.61–12.79) | 0.22 |
| Restriction (complete) | 0.11 (0.005–0.94) | 0.07 | 0.07 (0.003–0.63) | 0.03 |
| Adhesions | 0.14 (0.01–1.03) | 0.06 | 0.64 (0.07–4.41) | 0.65 |
| Airway obstruction | <0.01 | >0.99 | 0.11 (0.005–1.14) | 0.08 |
CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; OR, odds ratio.
Given the small sample size of the non-expandable lung subgroup and the limited number of pleurodesis events, penalized logistic regression using Firth’s method was performed to reduce small-sample bias and improve estimate stability (Table 5). In this analysis, complete visceral restriction remained substantially and directionally associated with lower odds of pleurodesis success, particularly at 6 months, although this did not reach statistical significance (OR 0.14, 95% CI: 0.008–1.05, P=0.056). Female sex, pleural adhesions, and airway obstruction were not significantly associated with pleurodesis success after penalized regression. Overall, the Firth analysis yielded results that were generally directionally consistent with the univariate analysis, but with attenuated estimates and loss of statistical significance.
Table 5. Penalized logistic regression (Firth method) evaluating predictors of pleurodesis success in the non-expandable lung subgroup.
| Variable | 3-month | 6-month | ||
|---|---|---|---|---|
| OR (95% CI) | P value | OR (95% CI) | P value | |
| Female sex | 0.16 (0.008–1.79) | 0.136 | 1.59 (0.17–20.03) | 0.680 |
| Complete restriction | 0.30 (0.023–2.60) | 0.274 | 0.14 (0.008–1.05) | 0.056 |
| Adhesions | 0.57 (0.042–9.67) | 0.659 | 1.22 (0.116–12.82) | 0.862 |
| Airway obstruction | 0.16 (0.001–4.60) | 0.304 | 0.23 (0.012–2.73) | 0.246 |
CI, confidence interval; OR, odds ratio.
Among patients with non-expandable lung and pleural adhesions (n=13), the relationship between adhesiolysis and pleurodesis success was evaluated. At 3 months, pleurodesis success rates were similar between patients who underwent adhesiolysis and those who did not (12.5% vs. 20.0%, P>0.99). At 6 months, patients who underwent adhesiolysis had a higher observed success rate compared with those who did not undergo adhesiolysis (75.0% vs. 40.0%); however, this difference did not reach statistical significance (P=0.29).
Discussion
Combined thoracoscopic talc poudrage with TIPC placement has emerged as an effective strategy for the management of MPE (6). In our cohort, pleurodesis success was 69.1% at 3 months and 86.6% at 6 months. Reported success rates for related approaches vary considerably: the TACTIC trial reported pleurodesis in 53% of patients receiving combined medical thoracoscopy, talc poudrage and TIPC (7), while the TAPPS trial reported approximately 78% at 3 months with thoracoscopic talc pleurodesis and 51% with TIPC alone (7-10). Direct comparison across these studies is limited by differences in the definition of pleurodesis success, the timing of assessment and case mix; in particular, our cohort included all comers with MPE, among them 20 patients (20.6%) with non-expandable lung, who are excluded from most published series. Despite favourable outcomes with combined approaches, the predictors that influence pleurodesis success and catheter independence remain incompletely defined in the literature (11).
Key predictors of pleurodesis success
In our multivariable analysis, lung expandability was the dominant and only consistent independent predictor of pleurodesis success at both 3 and 6 months. At 3 months, pleurodesis success was achieved in 61 of 77 patients (79.2%) with expandable lungs compared with 6 of 20 patients (30.0%) with non-expandable lungs. This association remained significant at 6 months, with successful pleurodesis observed in 71 of 77 patients (92.2%) with expandable lungs versus 13 of 20 patients (65.0%) with non-expandable lungs.
This finding is highly consistent with prior literature which demonstrates the central role of pleural apposition in achieving durable pleurodesis (6,12). Previous studies have often underrepresented patients with non-expandable lungs due to traditional dogma that non-expandable lung cannot achieve successful pleurodesis (4). In our cohort, we included all comers with MPE including ones with non-expandable lung and studied this subgroup of patients with non-expandable lungs and the factors that might influence the success of pleurodesis.
From physiological standpoint, successful pleurodesis requires apposition of the visceral and parietal pleura which then allows talc to induce sustained inflammation, fibroblast activation, and pleural symphysis (1,12). Lung expandability directly determines these changes as they control if the visceral and parietal pleura will achieve sustained apposition. However, our findings suggest that non-expandable lungs represent a spectrum rather than an absolute contraindication to pleurodesis. In patients with partial restriction, preserved regional visceral–parietal pleural apposition, together with continued TIPC drainage, may promote progressive pleural-space obliteration. Septation, adhesions, and mediastinal shift could also reduce the residual pleural space and create localized areas of pleural apposition; however, these mechanisms were not systematically assessed and therefore remain hypotheses rather than observed explanations.
Cancer type and pleurodesis outcomes
Primary malignancies were grouped as lung/mesothelioma, breast, and other (GI, GU, ovarian and miscellaneous). Within the pooled lung/mesothelioma group, lung cancer predominated (34 of 41 patients, 83%); mesothelioma contributed only 7 patients, and the two tumor types behaved differently. Patients with mesothelioma were far more likely to have a non-expandable lung (6 of 7, 85.7%) than patients with lung cancer (5 of 34, 14.7%), consistent with the diffuse visceral pleural involvement characteristic of mesothelioma.
After adjustment, patients in the other-malignancy group had significantly lower odds of 3-month pleurodesis success than the lung/mesothelioma group, whereas patients with breast cancer did not, and no group difference persisted at 6 months. Because the crude between-group differences were not statistically significant, this association is best interpreted as one that emerges after accounting for lung expandability rather than as a large independent effect of tumor histology. These findings contrast with Bielsa et al., one of the largest studies evaluating tumor type and pleurodesis outcomes, where lung cancer and mesothelioma were associated with lower complete response rates after talc poudrage compared with breast and other metastatic cancers. In that study, tumor type and pleural tumor burden remained independent predictors of pleurodesis failure. Similarly, the TIME1 analysis found lower pleurodesis success in mesothelioma compared with non-mesothelioma malignancies (13-15).
However, other cohorts such as Kolschmann, Martínez-Moragón, Leemans, and Hanawa did not identify tumor type as a consistent independent determinant of success (16-19). Interestingly, the Dresler Intergroup trial suggested in post hoc analysis that patients with lung or breast cancer may benefit more from thoracoscopic talc poudrage than talc slurry, supporting the possibility that technique of talc delivery may influence outcomes in lung cancer predominant cohorts (20).
Our sensitivity analysis indicates that the higher early success observed in the pooled lung/mesothelioma group reflects the predominance of lung cancer rather than any mesothelioma-related advantage. Indeed, patients with mesothelioma had the lowest crude 3-month success of any histology in our cohort (57.1%), which is directionally consistent with Bielsa et al. and TIME1 (13,14), and their markedly lower rate of lung expandability offers a plausible mechanism. The difference from prior series may therefore relate to our use of thoracoscopic talc poudrage under direct visualization combined with continuous TIPC drainage, and to the inclusion of patients with non-expandable lung who would have been excluded elsewhere, rather than to a histology effect per se.
Thus, the higher early success observed in our lung/mesothelioma group may reflect the predominancy of lung cancer rather than mesothelioma, the use of thoracoscopic talc poudrage with direct visualization, and the addition of TIPC-mediated continuous drainage rather than a true mesothelioma-related advantage. Additional factors leading to lower pleurodesis success in abdominal and pelvic malignancies could be due to concurrent ascites which may prevent successful pleurodesis by limiting lung expansion through increased intra-abdominal pressure and by promoting continued pleural fluid accumulation via transdiaphragmatic fluid movement. These factors, however, were not assessed in our study.
Performance status and clinical predictors
In our study, ECOG PS was not associated with pleurodesis success at either timepoint. This finding is consistent with several prior studies that similarly failed to demonstrate an independent association between performance status and pleurodesis success. In the largest single-center series of thoracoscopic talc pleurodesis (n=611), Steger et al. found that Karnofsky Performance Status (KPS) did not predict pleurodesis success, though it was significantly associated with 30-day mortality and long-term survival (21). Other similar studies, such as Kolschmann et al., reported no significant influence of KPS on pleurodesis success after thoracoscopic talc poudrage (16). Additionally, in the TAPPS trial, prespecified subgroup analysis by World Health Organization (WHO) performance status (0–1 vs. 2–3) showed no significant interaction between performance status and pleurodesis outcomes (9).
However, some studies have reported a positive association. Martínez-Moragón et al. found that KPS <70 was significantly associated with pleurodesis failure on univariate analysis in a cohort of 120 patients undergoing chemical pleurodesis (17).
Our findings can be explained by the fact that the use of a combined outpatient approach may attenuate the impact of performance status by reducing procedural burden and hospitalization.
Factors influencing success of pleurodesis in the non-expandable lung subgroup
A key strength of our study is the detailed evaluation of patients with non-expandable lungs. This population has historically been underrepresented in pleurodesis studies and often presumed to have unsuccessful pleurodesis (1,4). Within this subgroup, our univariate analysis showed that the degree of pleural restriction is an important determinant of successful pleurodesis. Within the non-expandable lung cohort, patients with complete restriction demonstrated 40% pleurodesis success at 6 months, whereas patients with partial restriction achieved 90% pleurodesis success at 6 months.
This is important as it suggests patients with non-expandable lungs should not be viewed as a binary entity, but rather as a spectrum in which the severity of pleural restriction significantly influences outcomes. Prior studies have often underrepresented patients with non-expandable lungs or grouped them as one entity (1,4). However, our analysis provides more insight into heterogeneity within this population and suggests that factors such as the degree of pleural restriction are important determinants of outcome.
Other factors, including adhesions and airway obstruction, demonstrated trends toward reduced success but were not statistically significant. Similarly, adhesiolysis did not significantly improve pleurodesis outcomes, although a higher success rate was observed at 6 months among patients with when adhesiolysis was performed.
Limitations and future directions
This retrospective, single-center study has several limitations. The non-expandable lung subgroup was small, resulting in less precise estimates. Pleural elastance, patient-reported outcomes, serial imaging, costs, pleural fluid pH and lactate dehydrogenase (LDH), molecular data such as epidermal growth factor receptor (EGFR) status, and standardized tumor-burden grading were not consistently available. Post-procedural pleural loculations and residual fluid collections were also not systematically abstracted or graded, precluding a formal comparison between patients with expandable and non-expandable lungs. Because many patients already had a confirmed MPE and underwent the procedure for symptom relief, pleural fluid was not routinely retested unless there was diagnostic uncertainty. Additionally, further studies are needed to clarify the physiological mechanisms underlying successful pleurodesis in patients with non-expandable lungs following pleural fluid drainage.
Furthermore, the mesothelioma subgroup comprised only 7 patients; therefore, the sensitivity analysis separating mesothelioma from lung cancer was imprecise and should be regarded as exploratory. The association between cancer group and early pleurodesis success was apparent only in the adjusted analysis and was based on a modest number of events in each group. Therefore, it requires confirmation in larger cohorts before it can be used to guide management.
Future studies should focus on prospective validation of these findings, incorporation of physiological measures of pleural mechanics, and development of integrated prediction models combining clinical, radiographic, and biological variables. Larger cohorts are also needed, particularly for studying patients with non-expandable lungs.
Conclusions
Our study explored the factors that might influence the success of pleurodesis and removal of TIPC following combined thoracoscopic talc poudrage and TIPC for MPE. Lung expandability emerged as the dominant and only consistent independent predictor at both 3 and 6 months. Importantly, our findings demonstrate that patients with non-expandable lungs should not be universally excluded, as a meaningful proportion of these patients will achieve successful pleurodesis when selected appropriately. Further studies with larger cohorts are needed to better define these predictors and refine patients’ selection strategies.
Supplementary
The article’s supplementary files as
Acknowledgments
The authors thank the clinical and procedural teams involved in the care of patients with malignant pleural effusion at the University of Florida.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Institutional Review Board of University of Florida (IRB No. #IRB202500112). The requirement for individual informed consent was waived because of the retrospective design and use of de-identified clinical data.
Footnotes
Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1845/rc
Funding: None.
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1845/coif). The authors have no conflicts of interest to declare.
Data Sharing Statement
Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1845/dss
References
- 1. Feller-Kopman DJ, Reddy CB, DeCamp MM, et al. Management of Malignant Pleural Effusions. An Official ATS/STS/STR Clinical Practice Guideline. Am J Respir Crit Care Med 2018;198:839-49.. 10.1164/rccm.201807-1415ST [DOI] [PubMed] [Google Scholar]
- 2. Munavvar M, Bodtger U, Carus A, et al. Current Trends in Treating Malignant Pleural Effusion: Evidence, Guidelines, and Best Practice Recommendations. JCO Oncol Pract 2025;21:759-65.. 10.1200/OP.24.00387 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. Iyer NP, Reddy CB, Wahidi MM, et al. Indwelling Pleural Catheter versus Pleurodesis for Malignant Pleural Effusions. A Systematic Review and Meta-Analysis. Ann Am Thorac Soc 2019;16:124-31.. 10.1513/AnnalsATS.201807-495OC [DOI] [PubMed] [Google Scholar]
- 4. Thomas R, Fysh ETH, Smith NA, et al. Effect of an Indwelling Pleural Catheter vs Talc Pleurodesis on Hospitalization Days in Patients With Malignant Pleural Effusion: The AMPLE Randomized Clinical Trial. JAMA 2017;318:1903-12.. 10.1001/jama.2017.17426 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. Bhatnagar R, Keenan EK, Morley AJ, et al. Outpatient Talc Administration by Indwelling Pleural Catheter for Malignant Effusion. N Engl J Med 2018;378:1313-22.. 10.1056/NEJMoa1716883 [DOI] [PubMed] [Google Scholar]
- 6. Reddy C, Ernst A, Lamb C, et al. Rapid pleurodesis for malignant pleural effusions: a pilot study. Chest 2011;139:1419-23.. 10.1378/chest.10-1868 [DOI] [PubMed] [Google Scholar]
- 7. Dipper A, Sundaralingam A, Hedley E, et al. Medical thoracoscopy with talc poudrage and indwelling pleural catheter insertion versus medical thoracoscopy with talc poudrage alone for patients with symptomatic malignant pleural effusion (TACTIC): a randomised, controlled phase 3 trial. Lancet Respir Med 2026;14:341-9.. 10.1016/S2213-2600(25)00409-6 [DOI] [PubMed] [Google Scholar]
- 8. Davies HE, Mishra EK, Kahan BC, et al. Effect of an indwelling pleural catheter vs chest tube and talc pleurodesis for relieving dyspnea in patients with malignant pleural effusion: the TIME2 randomized controlled trial. JAMA 2012;307:2383-9.. 10.1001/jama.2012.5535 [DOI] [PubMed] [Google Scholar]
- 9. Bhatnagar R, Piotrowska HEG, Laskawiec-Szkonter M, et al. Effect of Thoracoscopic Talc Poudrage vs Talc Slurry via Chest Tube on Pleurodesis Failure Rate Among Patients With Malignant Pleural Effusions: A Randomized Clinical Trial. JAMA 2020;323:60-9.. 10.1001/jama.2019.19997 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10. Psallidas I, Hassan M, Yousuf A, et al. Role of thoracic ultrasonography in pleurodesis pathways for malignant pleural effusions (SIMPLE): an open-label, randomised controlled trial. Lancet Respir Med 2022;10:139-48.. 10.1016/S2213-2600(21)00353-2 [DOI] [PubMed] [Google Scholar]
- 11. Dipper A, Jones HE, Bhatnagar R, et al. Interventions for the management of malignant pleural effusions: a network meta-analysis. Cochrane Database Syst Rev 2020;4:CD010529.. 10.1002/14651858.CD010529.pub3 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12. Rodriguez-Panadero F, Montes-Worboys A. Mechanisms of pleurodesis. Respiration 2012;83:91-8.. 10.1159/000335419 [DOI] [PubMed] [Google Scholar]
- 13. Bielsa S, Hernández P, Rodriguez-Panadero F, et al. Tumor type influences the effectiveness of pleurodesis in malignant effusions. Lung 2011;189:151-5.. 10.1007/s00408-011-9283-6 [DOI] [PubMed] [Google Scholar]
- 14. Mercer RM, Macready J, Jeffries H, et al. Clinically important associations of pleurodesis success in malignant pleural effusion: Analysis of the TIME1 data set. Respirology 2020;25:750-5.. 10.1111/resp.13755 [DOI] [PubMed] [Google Scholar]
- 15. Rahman NM, Pepperell J, Rehal S, et al. Effect of Opioids vs NSAIDs and Larger vs Smaller Chest Tube Size on Pain Control and Pleurodesis Efficacy Among Patients With Malignant Pleural Effusion: The TIME1 Randomized Clinical Trial. JAMA 2015;314:2641-53.. 10.1001/jama.2015.16840 [DOI] [PubMed] [Google Scholar]
- 16. Kolschmann S, Ballin A, Gillissen A. Clinical efficacy and safety of thoracoscopic talc pleurodesis in malignant pleural effusions. Chest 2005;128:1431-5.. 10.1378/chest.128.3.1431 [DOI] [PubMed] [Google Scholar]
- 17. Martínez-Moragón E, Aparicio J, Sanchis J, et al. Malignant pleural effusion: prognostic factors for survival and response to chemical pleurodesis in a series of 120 cases. Respiration 1998;65:108-13.. 10.1159/000029240 [DOI] [PubMed] [Google Scholar]
- 18. Leemans J, Dooms C, Ninane V, et al. Success rate of medical thoracoscopy and talc pleurodesis in malignant pleurisy: A single-centre experience. Respirology 2018;23:613-7.. 10.1111/resp.13252 [DOI] [PubMed] [Google Scholar]
- 19. Hanawa S, Ejima M, Sugawara M, et al. Development and validation of a predictive model for pleural effusion control following talc pleurodesis in malignant pleural effusion. Int J Clin Oncol 2026;31:890-8.. 10.1007/s10147-026-03007-0 [DOI] [PubMed] [Google Scholar]
- 20. Dresler CM, Olak J, Herndon JE, 2nd, et al. Phase III intergroup study of talc poudrage vs talc slurry sclerosis for malignant pleural effusion. Chest 2005;127:909-15.. 10.1378/chest.127.3.909 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21. Steger V, Mika U, Toomes H, et al. Who gains most? A 10-year experience with 611 thoracoscopic talc pleurodeses. Ann Thorac Surg 2007;83:1940-5.. 10.1016/j.athoracsur.2007.02.061 [DOI] [PubMed] [Google Scholar]