Primary Diffuse Large B-Cell Lymphoma of the Testis (PTL): A Prospective Study of Rituximab (R)-CHOP with CNS and Contralateral Testis Prophylaxis. Results of the IELSG 10 Study.
Authors: Vitolo Umberto , Zucca Emanuele , Martelli Maurizio , Chiappella Annalisa , Baldi Ileana , Balzarotti Monica , Conconi Annarita , Gomez Henry , Lopez-Guillermo Armando , Martinelli Giovanni , Orsucci Lorella , Pavone Vincenzo , Rossi Giuseppe , Storti Sergio , Gospodarowicz Mary K. , Cavalli Franco , Sarris Andreas H. 
Published: October 2019

Abstract
Introduction: Diffuse large B-cell lymphoma (DLBCL) of the testis (PTL) is a rare presentation of extranodal lymphoma at poor prognosis with a 5-yr overall survival of 40-55%. Contralateral testis, CNS and extranodal sites relapses are the main cause of failures. IELSG 10 study is a prospective phase II international trial for patients with stage I or II PTL and was designed to define a standard treatment for PTL. It aims to evaluate efficacy and toxicity of a combined treatment of R-CHOP, intrathecal methotrexate and prophylactic scrotal radiotherapy (RT) with the addition, in stage II, of loco-regional RT. The trial was conducted by IELSG and Intergruppo Italiano Linfomi.
Patients and methods: From June 2001 to June 2006, 50 pts with stage I-II PTL were enrolled from 26 centres. Treatment plan was: R-CHOP21 (R 375mg/m2, Ctx750 mg/m2, Doxo50 mg/m2, Vcr1.4 mg/m2 day 1 and Pdn40 mg/m2 days 1–5) for 6 courses and 2 additional ones in stage II patients with slow response; intrathecal methotrexate (IT MTX) 15mg for 4 doses during courses 1 and 2; at the end of chemotherapy 30 Gy scrotal RT to contralateral testis was planned to all pts and 30–36 Gy nodal loco-regional RT for those with stage II disease.
Results: To date 45 pts who completed the treatment are evaluable. Median age was 64 (range 22–80); 36 stage I and 9 stage II disease; 3 had bilateral testicular involvement; 4 LDH>normal and 2 B symptoms. All received R-chemotherapy as planned. Forty-two (93%) pts received adequate CNS prophylaxis (at least 4 IT MTX); 3 less than 4 IT MTX because of poor tolerance or toxicity. Scrotal RT was given to 40 pts (89%) as planned; 5 did not performe it (3 refusal, 1 progressive disease and 1 bilateral orchiectomy). Forty-four patients (98%) achieved a CR and one progressed after 4 R-CHOP courses. With a median follow-up of 28 months, 3-yr OS, 3-yr PFS and 3-yr EFS were: 88% (95% CI 69–96%), 82% (95% CI 63–92%) and 78% (95% CI 58–89%). Seven patients relapsed or progressed: 2 in nodal sites, 3 in extranodal ± nodal sites and 2 in CNS (1 isolated meningeal and 1 eningeal + nodal relapse). The actuarial risk of CNS relapse at 3 years is 2.5% (95% CI 0–7%). No contralateral testis relapses were observed. Five patients died: three because of DLBCL; one of peripheral T-cell lymphoma and one of ANLL 21 months off therapy while in CR. No toxic death occurred during treatment. Main grade 3–4 toxicities were: hematological 27% and neurological 15%.
Conclusions: Although the follow-up is short, these results compare favorably with those previously reported in IELSG retrospective study in PTL (Zucca et al J Clin Oncol 2003). Contralateral testis relapses has not been observed and the incidence of CNS relapse seems to be reduced. If these results are confirmed with a longer follow-up, a combined treatment of R-CHOP, IT MTX and prophylactic scrotal RT ± nodal RT in stage II patients would improve the prognosis of these pts and should be regarded as the standard treatment in localized stage PTL. However, if further relapses are observed there will be a need for innovative strategies to address the issues of systemic and CNS relapse.