Introduction

Primary testicular diffuse large B-cell lymphoma (PTL) is characterized by a high risk of relapse in both the contralateral testis and central nervous system (CNS). Intrathecal (IT) CNS prophylaxis and contralateral testis irradiation have been shown to prevent contralateral recurrences and reduce CNS relapses. However, the impact of CNS prophylaxis on overall survival (OS) and progression-free survival (PFS) remains inadequately studied, with limited evidence available from real-world cohorts. Consequently, further research is warranted to clarify the prognostic significance of CNS-directed strategies in the management of PTL.

Methods

We conducted a single-center, retrospective study at Qilu Hospital of Shandong University, enrolling patients diagnosed with primary testicular diffuse large B-cell lymphoma, from January 2014 to December 2024. We collected and analyzed demographic data, laboratory examinations, treatment patterns, and survival outcomes. Progression-free survival (PFS), overall survival (OS) and prognostic factors were assessed using Kaplan-Meier survival analysis and Cox proportional hazards models.

Results

A total of 46 cases were included in the study with a median age of 61 years (range, 22-89). Bulky testicular masses were present in 8.7% of patients, B symptoms in 13.0%, and elevated LDH levels in 26.1%. Most patients had localized disease (stage I-II, 71.7%), low risk IPI score (0-1, 47.8%), and most patients demonstrated favorable performance status, with an ECOG performance score of 0-1 observed in 82.6%. 12 patients (26.1%) had more than one extranodal site affected, 2 (4.3%) had central nervous system (CNS) involvement and 6 patients (13%) had bone marrow involvement at diagnosis. According to the Hans classification, 11 patients (23.9%) had the germinal center B-cell (GCB) subtype, and 32 patients(69.6%) had the non-GCB subtype. Among them, 20 patients (43.5%) exhibited double expression of Bcl-2 and MYC on immunohistochemistry.

Most patients received chemotherapy (44, 95.7%) as first-line treatment, among whom 25 patients (54.3%) received consolidative radiotherapy (RT). The majority of patients received first-line therapy with R-CHOP (63%), 3 patients (6.5%) received R-CHOP+BTKi, and the remainder receiving other chemotherapy regimens. 28 (60.9%) patients received CNS prophylaxis including IT alone (n = 20), IT plus HD-MTX (n = 2) and HD-MTX alone (n = 6).

Across the entire cohort, factors associated with both progression-free survival (PFS) and overall survival (OS) included LDH level, hemoglobin (Hb) level, lymphocyte count, B symptoms, IPI score, and CNS prophylaxis. In addition, radiotherapy was associated with improved OS.

In univariate Cox regression analysis, lower hemoglobin levels, presence of B symptoms, and elevated LDH levels were significantly correlated with poorer prognosis. Although not statistically significant, radiotherapy appeared to be associated with better OS (P = 0.08). In addition, normal lymphocyte count and low IPI score ,were associated with longer PFS. Double expression of Bcl-2 and MYC, as assessed by immunohistochemistry, was not significantly associated with survival. Patients who received R-CHOP had similar OS and PFS to those who received other chemotherapy. Multivariate analysis demonstrated that a normal LDH level was significantly associated with improved OS, while a normal hemoglobin level was associated with improved PFS. Total objective response rates (ORR) is 92.3%. Patients who received chemotherapy combined with CNS prophylaxis, achieved an ORR of 100%.

Age, IPI score, IHC results, and treatment regimens did not differ significantly between the CNS prophylaxis and non-prophylaxis groups. PFS was significantly longer in the CNS prophylaxis group than in the non-prophylaxis group (P = 0.008).

Conclusions

Our findings suggest that both CNS prophylaxis and radiotherapy demonstrated a positive impact on patient outcomes. In contrast, elevated LDH levels, decreased hemoglobin, abnormal lymphocyte counts, presence of B symptoms, and a high IPI score were all significantly associated with poorer outcomes. These results highlight the potential importance of CNS-directed strategies and consolidative radiotherapy in PTL and warrant validation in larger, prospective studies.

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2025
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