Intravenous but not intrathecal central nervous system–directed chemotherapy improves survival in patients with testicular diffuse large B-cell lymphoma

• Published in: European journal of cancer (1990) Vol. 115; pp. 27 - 36
• Main Authors: Mannisto, S., Vähämurto, P., Pollari, M., Clausen, M.R., Jyrkkiö, S., Kellokumpu-Lehtinen, P.-L., Kovanen, P., Karjalainen-Lindsberg, M.-L., d’Amore, F., Leppä, S.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-07-2019; Elsevier Science Ltd
• Subjects: Anthracycline; B-cell lymphoma; Central nervous system; Chemotherapy; CNS-directed therapy; Confidence intervals; Disease control; Geriatrics; Hazard assessment; Hazard identification; Identification methods; Impact analysis; Intravenous administration; Irradiation; Lymphocytes B; Lymphoma; Malignancy; Medical prognosis; Medical treatment; Monoclonal antibodies; Nervous system; Older people; Patients; Primary testicular lymphoma; Prophylactic testicular irradiation; Radiation; Risk groups; Rituximab; Survival; Targeted cancer therapy; Testes; Rituximab; Primary testicular lymphoma; Survival; Prophylactic testicular irradiation; CNS-directed therapy
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2019.04.004

Testicular lymphoma is a rare malignancy affecting mainly elderly men, the majority representing diffuse large B-cell lymphoma (DLBCL). Its relapse rate is higher than that of nodal DLBCL, often affecting the central nervous system (CNS) with dismal prognosis.
We searched for patients with testicular DLBCL (T-DLBCL) involvement from the pathology databases of Southern Finland University Hospitals and the Danish Lymphoma Registry. Clinical information was collected, and outcomes between treatment modalities were evaluated. Progression-free survival (PFS), disease-specific survival (DSS) and overall survival (OS) were assessed using Kaplan–Meier and Cox proportional hazards methods.
We identified 235 patients; of whom, 192 were treated with curative anthracycline-based chemotherapy. Full survival data were available for 189 patients. In univariate analysis, intravenous CNS-directed chemotherapy, and irradiation or orchiectomy of the contralateral testis translated into favourable PFS, DSS and OS, particularly among the elderly patients (each p ≤ 0.023). Intrathecal chemotherapy had no impact outcome. In multivariate analyses, the advantage of intravenous CNS-directed chemotherapy (hazard ration [HR] for OS, 0.419; 95% confidence interval [CI], 0.256–0.686; p = 0.001) and prophylactic treatment of contralateral testis (HR for OS, 0.514; 95% CI, 0.338–0.782; p = 0.002) was maintained. Rituximab improved survival only among high-risk patients (International Prognostic Index≥3, p = 0.019). The cumulative risk of CNS progression was 8.4% and did not differ between treatment modalities.
The results support the use of CNS-directed chemotherapy and prophylactic treatment of the contralateral testis in patients with T-DLBCL involvement. Survival benefit appears resulting from better control of systemic disease rather than prevention of CNS progression.
•Intravenous central nervous system (CNS)–directed chemotherapy translates to superior survival in testicular lymphoma.•Phophylactic treatment of contralateral testis is associated with improved survival.•Intrathecal CNS-directed chemotherapy does not have impact on survival.•The benefit of rituximab is seen only among the patients with high International Prognostic Index.