Favorable Outcome of Abbreviated R-CHOP in Patients with Primary Testicular Lymphoma
Authors: Al-Sarayfi Diana , Brink Mirian , Bellido Mar , Plattel Wouter , Huls Gerwin A. , Nijland Marcel 
Published: December 2023

Background
Primary testicular lymphoma (PTL) is a rare type of extranodal large B-cell lymphoma with an increased risk of relapse mostly involving the contralateral testis or central nervous system (CNS). To minimize the risk of relapse, Vitolo et al. (2011) introduced a multimodality approach in limited stage PTL including radical orchiectomy, 6 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) with 4 intrathecal methotrexate (MTX IT) administrations and radiotherapy of the contralateral testis. In limited stage diffuse large B-cell lymphoma, without involvement of the testis, 4 cycles of R-CHOP proved non-inferior to 6 cycles of R-CHOP (Poeschel et al. 2019; Persky et al. 2020). However, it is unknown whether the number of cycles of R-CHOP can be reduced in PTL. Therefore, we aimed to evaluate the impact of the number of R-CHOP cycles on outcome in PTL patients in the Netherlands.
Methods
PTL patients ≥18 years, Ann Arbor stage I-II, diagnosed in 2014-2021, who received at least 3 cycles of R-CHOP were identified in the Netherlands Cancer Registry, with survival follow-up through 2022. Patients with CNS involvement at diagnosis were excluded. Treatment modalities were categorized as 3 cycles R-CHOP or 6 cycles R-CHOP. Patients who received 4, 5 or more than 6 cycles of R-CHOP were included in the 6 cycles modality. The primary endpoints were progression-free survival (PFS), and overall survival (OS). PFS was defined as the time between end of primary treatment and relapse, or death from any cause, whichever came first, and OS was defined as the time between end of primary treatment and death from any cause. The secondary endpoint was cumulative incidence function (CIF) of CNS relapse, defined as the number of CNS relapses divided by the total number of patients in the study population at risk for a specific time. Uni- and multivariable analyses were conducted to establish independent predictors of risk of relapse and mortality among patients who received 3 cycles of R-CHOP versus 6 cycles of R-CHOP. Uni- and multivariable analysis to calculate risk of relapse and mortality after adjustment for the baseline and treatment characteristics was performed using Cox regression.
Results
A total of 139 patients were identified: median age, 68 years (range, 37-86 years); stage I, 68%; IPI 0, 87%. Of these patients, 43 received 3 cycles R-CHOP and 96 received 6 cycles R-CHOP (number of cycles 4:4%; 5:6%; 6 or more: 90%). Patients with stage I disease more commonly received 3 cycles of R-CHOP compared to patients with stage II ( p&lt;0.01; Table 1). In combination with R-CHOP, most patients received MTX IT (93%), high-dose MTX (4%) or did not receive prophylaxis (4%). The median number of MTX IT cycles was 5 in patients who received 3 cycles R-CHOP and 6 in patients who received 6 cycles R-CHOP ( p=0.08). Of the patients who received 3 cycles R-CHOP, 29% received &lt;4 MTX IT cycles, compared to 11% in patients who received 6 cycles R-CHOP ( p=0.02). Overall, 82% received radiotherapy, 5% orchidectomy and 13% no consolidation. The median follow-up from end of treatment was 42 months (inter quartile range [IQR], 22-70 months). Overall response rate (ORR; partial remission or greater) for patients who received 3 cycles R-CHOP and 6 cycles R-CHOP were similar (79% versus 86%, respectively, p=0.27).
The 5-year PFS and OS were 66% and 75%, respectively. Regarding 3 versus 6 R-CHOP, the 5-year PFS and OS were similar, i.e. 65% versus 67% ( p=0.81) and 73% versus 76% ( p=0.69), respectively (Figure 1). In univariable analysis, risk of relapse and mortality were similar for patients who received 3 cycles of R-CHOP or 6 cycles R-CHOP. In multivariable analysis, none of the covariables influenced the risk of relapse or mortality. The 5-year CIF of CNS was 6.7%, with a median time from end of treatment to CNS relapse of 25 months. 6 (14%) out of 43 PTL patients with 3 cycles R-CHOP relapsed to CNS, and 1 (1%) out of 96 patients with 6 cycles R-CHOP ( p&lt;0.01). The number of MTX cycles was not related on developing a CNS relapse (p=0.81).
Conclusion
In this nationwide population of PTL patients, nearly one-third of patients received 3 cycles of R-CHOP instead of 6 cycles. No difference in survival was observed between the two groups. These data support investigating reduction of systemic treatment from 6 cycles of R-CHOP in this patient group.