Conditional survival by primary extranodal site in diffuse large B-cell lymphoma: A population-based landmark analysis.

Abstract

7071 Background: Diffuse large B-cell lymphoma (DLBCL) frequently presents with extranodal involvement. Prior population-based studies report site-specific survival differences from diagnosis, but these estimates are influenced by early mortality and may not reflect prognosis among longer-term survivors. We therefore evaluated conditional survival by primary site using landmark analyses. Methods: Adolescents and adults (≥15 years) with primary extranodal DLBCL diagnosed in the Surveillance, Epidemiology, and End Results (SEER) database (2002–2022) were identified. Overall survival was assessed using multivariable Cox models adjusted for age, sex, race/ethnicity, and era. Landmark Cox models at 12 and 24 months estimated survival among patients alive at each timepoint. Gastrointestinal (GI) tract served as the reference site. Results: Among 30,963 patients, survival differed significantly by primary site (p<0.001). From diagnosis, CNS/brain involvement was associated with markedly worse survival compared with GI disease (HR 2.09, 95% CI 2.00–2.19), while several sites appeared favorable at diagnosis. Among 12-month survivors (n=20,497), excess risk for CNS persisted (HR 2.46). In contrast, early advantages for bone/bone marrow and head/neck diminished, and breast, skin/soft tissue, and testis were associated with higher subsequent hazards (HR ~1.2 each). At 24 months (n=17,614), increased risk remained for CNS (HR 2.47), lung/pleura (HR 1.41), breast (HR 1.35), skin/soft tissue (HR 1.23), and testis (HR 1.26), while most other differences were small or no longer significant. Conclusions: Prognostic differences by primary site change after conditioning on early survival. CNS involvement remains high risk, while several sites that appear favorable at diagnosis lose this advantage over time. Landmark analyses provide more meaningful risk estimates for survivors but cannot account for site-specific treatment differences in SEER. Adjusted hazard ratios for overall survival by primary extranodal site among 12- and 24-month survivors. Site (ref: GI) 12m HR (95% CI) 24m HR (95% CI) Site (ref: GI) 12m HR (95% CI) 24m HR (95% CI) Bone/Bone marrow 1.01 (0.93–1.11) 0.96 (0.87–1.07) Breast 1.24 (1.09–1.42) 1.35 (1.17–1.55) CNS/Brain 2.46 (2.29–2.65) 2.47 (2.27–2.68) Head/Neck 1.03 (0.96–1.11) 1.08 (1.00–1.17) Hepatobiliary/Pancreas 1.18 (1.04–1.34) 1.12 (0.97–1.29) Kidney/Adrenal 1.26 (1.07–1.48) 1.07 (0.88–1.29) Lung/Pleura 1.39 (1.26–1.54) 1.41 (1.26–1.58) Skin/Soft tissue 1.23 (1.14–1.33) 1.23 (1.13–1.34) Spleen 0.91 (0.80–1.04) 0.92 (0.80–1.06) Testis 1.23 (1.11–1.37) 1.26 (1.12–1.41) Adjusted for age, sex, race/ethnicity, and diagnosis era. Landmark Cox models among patients alive at 12 and 24 months.