Tumor Bulk Shows Divergent Prognostic Impact Across Lymphoma Subtypes

A large registry analysis published in Haematologica found that tumor bulk, defined as a single disease site greater than 5 cm, was associated with variable survival outcomes by lymphoma subtype, with inferior outcomes seen in patients with diffuse large B-cell lymphoma (DLBCL) and superior outcomes in patients with Hodgkin lymphoma.¹

The study, conducted using data from the Australasian Lymphoma and Related Diseases Registry (LaRDR), also demonstrated substantial heterogeneity in how bulk is defined and how it influences frontline treatment selection across 6 common lymphoma subtypes. Investigators noted that international standardization of the definition of bulk is needed to support consistent use of the measure in PET-based and molecular prognostication.

Study Design

The registry-based analysis included 5090 patients with newly diagnosed lymphoma identified from 38 hospital sites across Australia and New Zealand between January 1, 2016, and January 3, 2025. Eligible subtypes included DLBCL, follicular lymphoma (FL), marginal zone lymphoma (MZL), peripheral T-cell lymphoma (PTCL) Hodgkin lymphoma, and Burkitt lymphoma, classified according to the fourth edition World Health Organization criteria. Patients with primary mediastinal B-cell, mantle cell, and nodular lymphocyte-predominant Hodgkin lymphomas were excluded because of limited sample size, as were patients managed with active surveillance alone. The median follow-up was 23.5 months.

Prevalence and Treatment Patterns

Bulk was reported in 27.0% of patients with available data (n = 1372/5090). Rates of bulk varied by subtype, ranging from 16.4% in marginal zone lymphoma to 4.8% in Burkitt lymphoma. Among patients with a recorded maximum dimension, 36.2% had bulk exceeding 10 cm. Nodal sites accounted for 72.4% of bulky disease locations, with bone and gastrointestinal sites being the most common extranodal locations.

Across the overall cohort, patients with bulk were more likely to receive systemic chemotherapy alone and less likely to receive localized treatment such as radiotherapy or surgery. This pattern held for patients with FL and MZL. Patients with DLBCL and bulk were less likely to receive chemotherapy alone but more likely to receive chemotherapy with consolidative radiotherapy. In Hodgkin lymphoma, bulk was associated with a higher likelihood of receiving high-intensity systemic chemotherapy (22.3% vs 14.9% without bulk).

Key Findings: Survival Outcomes

Using the registry-defined 5-cm threshold, patients with bulky DLBCL had inferior overall survival (HR, 1.26; 95% CI, 1.05-1.50) and inferior progression-free survival (PFS; HR, 1.27; 95% CI, 1.07-1.50) compared with those without bulk. In contrast, patients with Hodgkin lymphoma across all stages who had bulky disease had superior overall survival (HR, 0.28; 95% CI, 0.11-0.73), an association that remained after adjustment for the International Prognostic Score but was no longer significant after further adjustment for age. Bulk was not associated with survival differences in FL, MZL, PTCL, or Burkitt lymphoma using the 5-cm definition.

In exploratory analyses using survey-derived cutoffs, inferior overall survival was observed in Burkitt lymphoma using a 10-cm threshold, and inferior PFS was observed in DLBCL using a 7.5-cm threshold; the DLBCL finding did not persist after adjustment for prognostic indices.

Clinical Implications

Historically, tumor bulk or bulky disease has been a consideration in prognostication and treatment decision-making across multiple lymphoma subtypes;² however, the increasing use of PET imaging and novel therapies have raised questions about its continued value in modern practice.

The authors concluded that the presence of bulk was associated with greater use of systemic therapy and less use of localized treatment overall but did not independently retain prognostic significance for most subtypes after multivariate adjustment. They noted that variability in definitions and documentation of bulk across sites and lymphoma subtypes limits its standalone utility as a prognostic marker and called for a data-driven, internationally standardized definition to support its use in future prognostic and molecular studies.

“Determining the optimal definition of disease bulk for each subtype, the associations with underlying biology, and evaluating the utility of this metric in the modern PET era, are priorities for future research,” authors Chung et al concluded.

REFERENCES

1. Chung E, Wang L, Wellard C, et al. Prognostic value of tumor bulk in modern management of common lymphoma subtypes: an Australasian Lymphoma and Related Diseases Registry study. Haematologica. Published online March 2026. doi:10.3324/haematol.2025.287919

2. Wilder RB, Rodriguez MA, Ha CS, et al. Bulky disease is an adverse prognostic factor in patients treated with chemotherapy comprised of cyclophosphamide, doxorubicin, vincristine, and prednisone with or without radiotherapy for aggressive lymphoma. Cancer. 2001;91(12):2440-2446.