Association of rituximab with survival outcomes in primary testicular diffuse large B-cell lymphoma: a systematic review and meta-analysis of retrospective studies

Abstract

Abstract Background Primary testicular diffuse large B-cell lymphoma (PT-DLBCL) is the most common subtype of primary testicular lymphoma (PTL). Standard treatment protocols generally encompass a multimodal approach, incorporating radical orchiectomy, rituximab-based chemotherapy, prophylactic radiotherapy, and central nervous system (CNS) prophylaxis. However, whether rituximab-containing therapy is associated with survival outcomes in patients with PT-DLBCL remains uncertain. This systematic review and meta-analysis aimed to evaluate the association between rituximab-containing frontline therapy and clinical outcomes in patients with PT-DLBCL. Methods A comprehensive literature search was conducted across both English and Chinese databases, encompassing PubMed, Embase, Web of Science, the Cochrane Library, ClinicalTrials.gov, CNKI, VIP, Wanfang, SinoMed, and ChiCTR, from database inception to June 19, 2024. Eleven retrospective comparative studies involving 663 patients were included. Only three studies (454 patients) provided extractable hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) and contributed to the quantitative survival meta-analysis. Data extraction and quality assessment were performed, and pooled analyses were conducted using random-effects models. Complete response (CR) was evaluated as an exploratory secondary endpoint. Results Based on these three studies, the pooled HR was 0.74 (95% CI 0.45–1.21; P = 0.23) for OS and 0.78 (95% CI 0.44–1.37; P = 0.38) for PFS. These pooled estimates were derived from limited retrospective evidence and were largely based on unadjusted HRs. Therefore, they should be interpreted as descriptive summaries rather than evidence of an independent association. Conclusions Given the limitations of the available evidence, this meta-analysis found insufficient evidence to determine the independent association between rituximab-containing frontline therapy and OS or PFS in patients with PT-DLBCL. The observed associations may reflect the broader evolution of multimodal treatment strategies rather than a rituximab-specific contribution. These findings do not exclude a potential clinically meaningful association. Further well-designed studies, including multicenter registries and unified reporting standards, are warranted to clarify this association. Trial registration This meta-analysis was registered in PROSPERO (CRD42024567721).