**Background:** Malignant pleural effusion (MPE) affects over 150,000 new patients annually in the US, with lung and breast cancer being the most common primary histologies. MPE signifies advanced disease with poor prognosis; mean survival ranges from three to twelve months across cancer types, averaging 74 days for lung cancer and 192 days for breast cancer. While prior studies have identified prognostic factors and validated risk scoring systems (LENT, PROMISE), none have evaluated the relationship between treatment response (specifically resolution of pleural fluid accumulation) and survival. This study hypothesized that patients who experience resolution of pleural fluid accumulation have longer survival than those who continue to re-accumulate their effusion.
**Methods:** A retrospective chart review was conducted of patients with newly diagnosed MPE presenting to the Interventional Pulmonology service at a single institution between 1 September 2013 and 30 September 2017. Inclusion criteria were: pleural effusion with diagnostic thoracentesis by Interventional Pulmonary, positive cytology for malignant cells, and age >18 years. Exclusion criteria included prior thoracentesis diagnostic for malignancy, negative/indeterminate cytology, age <18, or index thoracentesis by other services. Data collected included demographics, ECOG performance status, pleural fluid chemistries and cytology, serum labs, PD-L1 status, targetable mutations, IPC placement, time to resolution of pleural fluid, systemic treatment information, and date of death. Resolution of PF accumulation was defined as improvement in symptoms with no need for subsequent procedures (serial thoracentesis group) or IPC drainage <50 mL for three consecutive drainages allowing catheter removal (IPC group). Overall survival was calculated from MPE diagnosis to death, with censoring at 4 December 2018. Sample size calculation required a minimum of 72 patients to detect a hazard ratio of 0.5 (power 0.8, alpha 0.05). Cox regression and multivariate modeling with stepwise selection were used.
**Key Results:** Data were obtained on 123 patients (71 female, 58%; median age 64.4 years, IQR 62.3–66.5). Cytologic diagnoses included adenocarcinoma of the lung (37.4%), breast cancer (26.8%), hematologic malignancy (9.8%), urogenital cancer (7.3%), small cell lung cancer (5.7%), and other (13%). Actionable mutations or PD-L1 ≥50% were identified in 60 of 104 tested patients (57.7%). Median survival for all patients was 4.8 months. Patients with resolution of PF accumulation (n=29) had significantly improved survival (HR 0.38, 0.21–0.69, p=0.001). In multivariate analysis controlling for IPC placement, cytotoxic chemotherapy, targeted/hormone/immune therapies, mutation/PD-L1 status, PF cytologic cell type, PF LDH, PF albumin, PF protein, PF % lymphocytes, and PF % neutrophils, resolution of PF accumulation remained strongly associated with improved survival (HR 0.12, 0.03–0.42, p=0.001). The multivariate model also showed IPC placement was associated with increased mortality (HR 6.87, 2.33–20.30, p=0.005) and PF cytology of "Other" cancers was associated with worse survival (HR 5.20, 1.55–17.45, p=0.008). Factors associated with resolution of PF accumulation included PF protein (OR 2.8, 1.28–6.15, p=0.01), IPC placement (OR 4.2, 1.46–11.83, p=0.01), targeted therapy (OR 12.33, 2.25–67.76, p=0.004), and hormone therapy (OR 5.14, 1.17–22.60, p=0.03).
**Clinical Implications:** This is one of the first studies to demonstrate an independent association between resolution of pleural fluid accumulation and improved survival in MPE, even after controlling for multiple confounders including treatment type and cancer type. The finding that patients achieving pleural fluid resolution had a median survival of 20.2 months versus 3.3 months for those without resolution suggests that pleural fluid control may serve as a clinically meaningful surrogate for treatment response. The study also highlights the importance of nutritional status (PF protein, albumin) and overall fitness (ECOG performance score) in MPE prognosis. The lack of survival benefit associated with targeted and immune therapies in this cohort (contrary to prior trials) likely reflects sample size limitations and heterogeneity. These findings support the need for prospective studies evaluating mechanisms of pleural fluid resolution and its relationship to survival, particularly in the era of targeted and immunotherapies.