Structure of residual metastases in patients with advanced testicular non-seminomatous germ cell tumors and incomplete serological and radiological response to chemotherapy
Authors: Volkova M. I. , Arakelyan G. A. , Klimov A. V. , Fainstein I. A. , Sergeev Yu. S. , Fedyanin M. Yu. , Rumyantsev A. A. , Tryakin A. A. , Tyulyandin A. S. , Matveev V. B. , Stilidi I. S. 
Published: May 2022

Objective: to analyze histological structure and identify predictors of detecting malignant non-seminoma in residual tumor masses obtained from patients with testicular non-seminomatous germ cell tumors (TNSGCTs) who had not achieved complete serological and radiological response to chemotherapy (CT).

Materials and methods. This study included 96 out of 703 patients with TNSGCTs (13.7 %) operated on in N.N. Blokhin National Medical Research Center of Oncology. The inclusion criteria were as follows: verified advanced TNSGCT, elevated levels of alpha-fetoprotein and/or chorionic gonadotropin at the moment of CT initiation, at least 3 completed courses of first-line or second-line platinum-based CT, residual tumor foci after CT visualized with radiological methods, alpha-fetoprotein >7.29 IU/mL or chorionic gonadotropin >5 mIU/mL 3 weeks after the initiation of the last CT course, and surgery after CT. Histological examination of the primary tumors demonstrated that they contained elements of seminoma (n = 14; 14.6 %), teratoma (n = 29; 30.2 %), choriocarcinoma in (n = 23; 23.9 %), embryonal carcinoma (n = 45; 46.9 %), and yolk sac (n = 18; 18.8 %). All study participants received first-line CT; 58 of them (60.4 %) also received second-line CT. All patients underwent surgery after CT, including retroperitoneal lymph node dissection (RPLND) (n = 96; 100 %) and excision of extra-retroperitoneal lesions (n = 8; 8.3 %).

Results. Histological examination of excised retroperitoneal masses showed that they contained areas of necrosis and fibrosis (n = 25; 26.0 %), teratoma (n = 29; 30.2 %), and viable malignant non-seminoma (n = 42; 43.8 %). There was a strong positive correlation between the existence of residual malignant non-seminomatous components in retroperitoneal masses and presence of choriocarcinoma (r = 0.300; р = 0.004), as well as the absence of embryonal carcinoma in the primary tumor (r = –0.300; р = 0.004), invasion of retroperitoneal metastases into major vessels and/or adjacent organs (r = 0.243; р = 0.017), and second-line CT prior to RPLND (r = 0.413; р <0.0001). Patients having ≥3 risk factors were significantly more likely to have residual malignant non-seminoma in retroperitoneal masses than patients who had 0–2 risk factors (73.5 % vs 27.3 %; р <0.0001). Excised residual extra-retroperitoneal masses contained areas of necrosis and fibrosis (n = 3; 37.5 %), teratoma (n = 1; 12.5 %), and malignant non-seminoma (n = 4; 62.5 %). Concordant structure of retroperitoneal and extra-retroperitoneal lesions was observed in 4 patients (50.0 %).

Conclusion. Malignant non-seminomas were detected in 43.8 % of retroperitoneal and 62.5 % of extra-retroperitoneal residual tumorsremoved after CT in patients with advanced TNSGCTs and incomplete serological and radiological response. Discordant structure of metastases at different locations was observed in 50 % of patients. Our finding can be used to select candidates for surgical excision of residual tumors among these patients.