Academic advantage without survival benefit? a national cancer database analysis of primary effusion lymphoma

Abstract Background: Primary effusion lymphoma (PEL) is a rare and aggressive HHV8-associated B-cell lymphoma that typically presents as malignant effusions without a detectable tumor mass. It disproportionately affects immunocompromised and socioeconomically vulnerable individuals, particularly those with HIV infection or residing in HHV8-endemic regions (Blood PMID: 30154110). Standardized treatment approaches are lacking, and outcomes remain dismal, with median survival near six months (J Clin Oncol PMID: 15994147). Due to its rarity, complexity, and frequent need for multidisciplinary management, patients with PEL may benefit from treatment at Academic Cancer Programs (ACPs), which often provide greater access to specialized expertise and supportive services. However, the influence of treatment facility type - ACPs versus Community Cancer Programs (CCPs) - on outcomes in PEL has not been previously described. We conducted a national analysis to evaluate demographic, socioeconomic, treatment, and survival differences among patients with PEL treated at ACPs versus CCPs. Methods: We conducted a retrospective analysis of patients diagnosed with PEL in the United States between 2004 and 2022 using the National Cancer Database. Demographic, clinical, and survival data were compared between patients treated at ACPs and CCPs. ACPs included academic and research programs, including NCI-designated comprehensive cancer centers. CCPs comprised community, comprehensive community, and integrated network cancer programs. Kaplan-Meier and Cox proportional hazards models were used to compare overall survival (OS), adjusting for age, race/ethnicity, insurance status, comorbidity score (Charlson-Deyo), and distance from the treating facility. Results: Of 563 patients identified with PEL, 314 (56%) were treated at ACPs and 140 (25%) at CCPs. The remaining 109 (19%) had unknown facility type and were excluded. The majority were male (85. 4% ACP vs. 79. 3% CCP, p 0. 001). Median age at diagnosis was 60 years at ACPs and 76 at CCPs (p 0. 001). Patients under 60 were more common at ACPs (49. 4% vs. 27. 1%), while those ≥75 were more often treated at CCPs (54. 3% vs. 32. 5%). ACPs treated significantly more Black (23. 9% vs. 4. 3%, p 0. 001) and Hispanic patients (18. 8% vs. 13. 6%, p = 0. 021). HIV positivity was more frequent at ACPs (14. 3% vs. 6. 4%, p 0. 001). Medicaid coverage was more common at ACPs (17. 2% vs. 10. 7%), while Medicare predominated at CCPs (67. 1% vs. 47. 5%, p 0. 001). Uninsured patients were more often treated at ACPs (5. 4% vs. 0%). Patients from neighborhoods in the highest educational disadvantage quartile (≥15. 3% without a high school diploma, 2016–2020 Census) were more often treated at ACPs (25. 2% vs. 21. 4%). Those from the lowest income quartile (46, 277) were similarly distributed (12. 1% vs. 12. 9%). Most patients lived in metropolitan areas in both groups (90. 1% ACP vs. 83. 6% CCP). Charlson–Deyo scores ≥2 were comparable (4. 8% ACP vs. 6. 4% CCP). Stage IV disease at presentation was more common at ACPs (47. 8% vs. 30. 0%, p 0. 001). Radiation therapy was rare (1%). Median time to chemotherapy initiation was shorter at ACPs (17 vs. 25. 5 days, p = 0. 020), and distance to care was slightly less (6. 3 vs. 7. 5 miles, p = 0. 012). Survival outcomes were poor across both settings. Median survival was 0. 73 years at ACPs and 0. 62 at CCPs. Two-year survival was 41% at ACPs and 32% at CCPs; five-year survival was 23% and 17%, respectively. On adjusted analysis, treatment at an ACP was not independently associated with improved OS. Conclusions: In this national cohort, ACPs cared for a younger, more racially and ethnically diverse, and socioeconomically vulnerable population with PEL. These patients more often had advanced disease and initiated treatment sooner. However, despite these differences, survival remained uniformly poor and was not significantly improved at ACPs compared to CCPs. These findings highlight the aggressive and treatment-refractory nature of PEL and emphasize the urgent need for dedicated clinical trials, standardized treatment strategies, and broader access to multidisciplinary care regardless of setting. Improving outcomes in PEL will require system-level solutions that bridge disparities and support timely intervention for high-risk populations.