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Patterns of Outcome and Prognostic Factors in Primary Large-Cell Lymphoma of the Testis in a Survey by the International Extranodal Lymphoma Study Group

E. Zucca, A. Conconi, T.I. Mughal, A.H. Sarris, J.F. Seymour, U. Vitolo, R. Klasa, M. Ozsahin, G.M. Mead, M.A. Gianni, S. Cortelazzo, A.J.M. Ferreri, A. Ambrosetti, M. Martelli, C. Thiéblemont, H. Gomez Moreno, G. Pinotti, G. Martinelli, R. Mozzana, S. Grisanti, M. Provencio, M. Balzarotti, F. Laveder, G. Oltean, V. Callea, P. Roy, F. Cavalli, M.K. Gospodarowicz

From the Division of Haematology/Medical Oncology, Peter MacCallum Cancer Institute, East Melbourne, Australia; Department of Radiation Oncology, Princess Margaret Hospital, Toronto; Division of Medical Oncology, British Columbia Cancer Agency, Vancouver, Canada; Service de Hématologie and Service de Biostatistique, Centre Hospitalier Lyon Sud, Lyon, France; Divisione di Oncologia Medica, Ospedale S. Martino, Belluno; Divisione di Ematologia, Ospededali Riuniti di Bergamo, Bergamo; Divisione di Medicina I, Azienda Ospedaliera S. Antonio Abate, Gallarate; Divisione di Oncologia Medica, Istituto Nazionale per lo Studio e la Cura del Tumori, Servizio di Radiochemioterapia, Ospe ale San Raffaele, Divisione di Ematoncologia Clinica, Istituto Europeo di Oncologia, and Dipartimento di Oncologia Medica ed Ematologia, Istituto Clinico Humanitas, Milano; Divisone Ematologia, Azienda Ospedaliera "Bianchi-Melacrino-Morelli," Reggio Calabria; Dipartimento di Biotecnologie Cellulari ed Ematologia, Università degli Studi "La Sapienza," Roma; Divisione di Ematologia, Azienda Ospedaliera S. Giovanni Battista, Torino; Servizio di Oncologia Medica, Ospedale di Circolo Fondazione Macchi, Verase; Divisione di Ematologia, Policlinico G.B. Rossi, Verona, Italy; Instituto de Enfermedades Neoplasticas, Lima, Peru; Clin Med 1, Spit Clin Jud, Tirgu-Mures, Romania; Servicio de Oncologia Medica, Clinica Puerta de Hierro, Madrid, Spain; Divisione di Oncologia Medica, Instituto Oncologico della Svizzera Italiana, Bellinzona; Rare Cancer Network, Service de Radio-Oncologie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; Department of Lymphoma and Myeloma, M.D. Anderson Cancer Center, Houston, TX; Department of Haematology/Medical Oncology, Christie Hospital NHS Trust, Manchester; and Cancer Research Campaign, Wessex Medical Oncology Unit, Southampton General Hospital, Southampton, United Kingdom.

Address reprint requests to Emanuele Zucca, MD, International Extranodal Lymphoma Study Group, c/o Oncology Institute of Southern Switzerland, Ospedale San Giovanni, 6500 Bellinzona, Switzerland; email: ielsg{at}ticino.com.

Purpose: To determine clinical features and patterns of outcome of primary testicular diffuse large B-cell lymphomas (DLCL).

Patients and Methods: A retrospective international survey of 373 patients with primary testicular DLCL.

Results: Most patients presented with localized disease (stage I to II), and the median age at diagnosis was 66 years (range, 19 to 91 years). Anthracycline-based chemotherapy was administered to 255 patients (68%), and prophylactic intrathecal chemotherapy was given to 68 patients (18%); 133 patients (36%) received prophylactic scrotal radiotherapy. Median overall survival was 4.8 years, and median progression-free survival was 4 years. The survival curves showed no clear evidence of a substantial proportion of cured patients. A favorable international prognostic index score (IPI), no B-symptoms, the use of anthracyclines, and prophylactic scrotal radiotherapy were significantly associated with longer survival at multivariate analysis. However, even for patients with stage I disease and good-risk IPI, the outcome seems worse than what was reported for DLCL at other sites. At a median follow-up of 7.6 years, 195 patients (52%) had relapsed. Extranodal recurrence was reported in 140 cases. Relapses in CNS were detected in 56 patients (15%) up to 10 years after presentation. A continuous risk of recurrence in the contralateral testis was seen in patients not receiving scrotal radiotherapy.

Conclusion: Testicular DLCL is characterized by a particularly high risk of extranodal relapse even in cases with localized disease at diagnosis. Anthracycline-based chemotherapy, CNS prophylaxis, and contralateral testicular irradiation seem to improve the outcome. Their efficacy is under evaluation in a prospective clinical trial.

On behalf of the International Extranodal Lymphoma Study Group (IELSG).

Supported in part by the Swiss Cancer League/Cancer Research Switzerland, Bern, Switzerland.

E. Zucca and A. Conconi contributed equally to this work; F. Cavalli and M. K. Gospodarowicz are co-senior authors.

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