Prognostic value of tumor bulk in modern management of common lymphoma subtypes: an Australasian Lymphoma and Related Diseases Registry study

The presence of a single large site of disease or so-called tumor 'bulk' in lymphoma has been variably associated with outcomes and influenced management decisions. However, challenges arise in using bulk as a prognosticator due to varied definitions across different lymphoma subtypes but also within studies of each subtype, increased utility of positron emission tomography in decision-making and recent incorporation of novel therapies. We analyzed data from the Australasian Lymphoma Registry regarding presence and influence of bulk on outcomes and treatment decisions in six key subtypes: diffuse large B-cell, follicular, marginal zone, T-cell, Hodgkin and Burkitt lymphoma. Of the 5,090 eligible patients identified between 2016-2025, 88% had documented information on the presence of bulk (registry definition >5 cm). Patients with bulk were more likely to receive systemic chemotherapy alone, and less likely to have localized treatment alone (radiotherapy and/or surgery), compared to those without bulk. Bulk was associated with inferior overall survival in patients with diffuse large B-cell lymphoma, and superior overall survival in those with Hodgkin lymphoma, in the univariate analyses. Exploratory analyses using disease-specific bulk definitions from clinicians practicing in Australia and New Zealand showed inferior progression-free survival in patients with diffuse large B-cell lymphoma (bulk >7.5 cm) and inferior overall survival in those with Burkitt lymphoma (bulk >10 cm), but not other subtypes. We demonstrated real-world evidence of management heterogeneity for patients with bulk, with potential prognostic implications. International standardization of the definition of bulk is urged for uniform utility in positron emission tomography-based and molecular prognostication across clinical studies. Trial registered with the Australian New Zealand Clinical Trials Registry: ANZCTRN12617000050358.