Long-term results after treatment for recurrent thymoma: a multicenter analysis

The treatment for recurrent thymoma remains a very controversial issue. This study aims to investigate the long-term outcomes in patients with relapse according to treatment strategies and clinicopathological features.

We retrospectively analyzed the database of three tertiary centers of thoracic surgery with the aim of reviewing the clinical records of 81 patients who experienced a recurrent thymoma after radical thymectomy, in the period between January 2001 and June 2013. The staging of both primitive and recurrent thymomas were based on the surgical and pathological criteria described by Masaoka. Experienced pathologists reassessed independently the histology of the initial thymoma and its relapse, according to the WHO classification. To the purposes of this study R+ resection or thymic carcinoma were considered as exclusion criteria. The overall outcome for long-term (5 years and 10 years) survival and disease-free survival after initial thymectomy and after treatment of recurrent thymoma were analyzed using standard statistics.

The population was gender balanced (41 M, 40 F), mean age: 46.4 ± 12.3 years. Fifty-four patients (66.7%) were affected by myasthenia gravis, while the other 14 by other paraneoplastic conditions. Surgery was performed in 61 patients (75.3%,), and radiotherapy and/or chemotherapy in 14 patients (17.3%). The mean follow-up duration after recurrence onset was 66.3 ± 56.4 months. Adjuvant therapy had no effect on prolonging the disease-free survival: no differences were found when investigating the administration of adjuvant chemotherapy (no CHT = 91.5 ± 76.4 months versus yes CHT=64.0 ± 41.3) and radiotherapy (no RT=86.2 ± 72.8 months versus yes RT= 93.0 ± 62.3; p = 0.8). Relapses were mostly local (mediastinum: 15 cases, pleura: 44 cases); hematogenous distant recurrences were observed in 15 cases (lung: 12; liver: 1; bone: 2 cases). An upgrade in the WHO class (defined as the "migration" of WHO class at initial thymectomy to more aggressive WHO class assigned at thymic recurrence resection) was found in 25/61 cases (40.9%), but this phenomenon apparently did not influence patient's prognosis. Overall, the 5- and 10-year survival rates after the initial thymectomy were 94.8% and 71.7%, respectively, while the 5- and 10-year survival rates after the treatment of the recurrence at the thymic level were 73.6% and 48.3%, respectively (82.4% at 5 years and 65.4% at 10 years when a R0-re-resection was obtained). The analysis on the trends of disease-free survival indicated that the site of recurrence (hematogenous diffusion) seems to be associated to a higher risk of re-relapse (p = 0.01).

Even following a thymectomy performed with radical intent, thymoma may recur several years later, usually as a locoregional relapse. A rewarding long-term survival may be expected after treatment, especially when a re-resection (radical) is performed (82.4% at 5 years). An histopathological "WHO upgrade" (from "low-risk" WHO classes at thymectomy to "high-risk classes" at relapse) may be observed in a remarkable percentage of patients (nearly 40% in this series), but this phenomenon seems to be not correlated with any worsening of the prognosis.