Background: A previous cooperative study of patients (pts) with ENKL who were diagnosed between 2000 and 2013 in 31 institutes in Japan reported that the most common first-line treatment for localized ENKL was radiotherapy with dexamethasone, etoposide, ifosfamide, and carboplatin (RT-DeVIC) (66%). The 2-year (yr) overall survival (OS) and progression-free survival (PFS) of pts with localized ENKL were 78% and 68%, respectively (JCO 2017). RT-DeVIC has been included as a preferred regimen of combined modality therapy in the NCCN guidelines. The treatments and outcomes of pts with localized ENKL in recent clinical practice are unknown. Methods: We conducted a cooperative study (NKEA-Next; UMIN000046300) by hemato-oncologists and radiation oncologists of pts with ENKL who were diagnosed between 2014 and 2021 in 45 institutes in Japan. The results were compared with those from the 2000-2013 cohort (JCO 2017). The primary endpoint was OS of pts with ENKL who received next-generation treatment in 2014-2021 at participating institutes. We analyzed the data of localized ENKL. Results: Of 351 pts in the 2014-2021 cohort, 235 (67%) had localized ENKL. First-line therapy was RT-DeVIC in 185 (79%) pts, sequential chemoradiotherapy in 17, RT alone in 15 pts, and chemotherapy alone in 12 pts. Six pts received no treatment due to poor performance status (PS). Only two pts (1%) received anthracycline-containing regimens. With a median follow-up of 3.4 yrs, the 2-yr OS and PFS of localized ENKL were 83% and 75%, respectively. Pts treated with RT-DeVIC showed the following clinical features: median age, 58 yrs (range, 13-82); age > 60 yrs, 45%; stage IIE, 34%; B symptoms present, 27%; elevated serum lactate dehydrogenase, 23%; ECOG PS 2, 4%; and soluble interleukin-2 receptor (sIL-2R) level > upper limit of normal (ULN), 31% (57/183). The complete response rate was 88% among the 179 pts who were evaluated for response. The 2-yr OS and PFS of RT-DeVIC were 87% and 79%, respectively. There was no treatment-related death due to RT-DeVIC. G3/4 mucositis was recorded in 32% (G3, n = 59; G4, n = 0). G3/4 febrile neutropenia occurred in 18% (G3, n = 32; G4, n = 2). sIL-2R > ULN was associated with worse OS (P< 0.01). In comparison with pts with localized disease in the 2000-2013 cohort, pts in the 2014-2021 cohort received RT-DeVIC more frequently (P< .001). There was no significant difference in OS (P = 0.24) or PFS (P = 0.10) between the two cohorts. Conclusions: RT-DeVIC was more frequently used for first-line treatment of localized ENKL, and its efficacy has been maintained, with 87% 2-yr OS in recent clinical practice in Japan, providing further evidence of RT-DeVIC as a preferred first-line regimen for localized ENKL. No obvious improvement in OS and a reduction in G3 mucositis were observed, suggesting that more efficacious and less toxic regimens need to be introduced.