Management
Due to the paucity of data on young patients with RCC, there are no established guidelines for the management of this disease in children. Although treatment recommendations are extrapolated from adult RCC guidelines, genetic and pathological differences in the diseases are a cause for concern. The Children's Oncology Group (COG) prospectively enrolled patients under 30 years with pathologically confirmed RCC in the COG AREN03B2 Renal Tumor Biology and Classification Study (NCT#00898365) protocol from August 2006 to July 2016. Patient demographics, stage (including TNM 6th edition stage, lymph node status, presence of metastasis), radiologic assessment (tumor laterality, radiologic lymph node status), primary surgical management, and pathology (histology and genetics) were assessed. An advantage of this study is the central review of pathology and radiographic images. Out of the 3250 patients enrolled in the study, 120 (3.7%) patients with unilateral tumors had pathologically confirmed RCC. Translocation tumors and RCC NOS constituted 46.7 and 20.8% of the population, respectively. Radiologically positive lymph nodes (>1 cm) were observed in 27.1% of patients and 60.8% of these patients had pathologically positive lymph nodes. Of the patients with positive lymph nodes, radiologic evidence was observed in 35 of 73 patients and preoperative imaging predicted positive lymph nodes in 20 of these patients (sensitivity 57%, specificity 95%). A majority of the patients had a radical nephrectomy (73.3%) but only 59% of patients had lymph node sampling at the time of the procedure.
Nephron-sparing surgical approaches with extended lymph node dissection have been successfully utilized.[27] In 2019, Saltzman et al. evaluated factors that predicted lymph node sampling and found that nephron-sparing approaches and low stage was associated with a lack of lymph node sampling. They attributed these practices to clinician adoption of adult guidelines that do not recommend lymph node sampling in patients without clinical suspicion of positive lymph nodes.[28,29]
Patients with positive lymph nodes had primary tumors with median tumor size of 6.5 cm (0.8–19.7 cm) contradicting the dogma that forms the basis for active surveillance in adult patients with T1 RCC. The high rate of positive lymph nodes in children without clinical suspicion on preoperative imaging should make practitioners have a low threshold for lymph node dissection in individuals aged 10–21 years with renal tumors. Focused genetic testing of patients enrolled in AREN03B2 from 2006 to 2016 helped re-classify patients previously classified as RCC NOS. Forty-two percent of patients were MiTF RCC, and TFE3 translocations were found in 93.2% of patients.[2,30]
Positive lymph nodes predict poor outcomes in adult patients (5-year survival of 20%),[28,29] however, survival approaches 70% in children.[16] Indolfi et al. studied prognostic factors of lymph node involvement in 16 patients with RCC enrolled in the Italian Rare Tumors Pediatric Age (TREP) project. Seventy-five percent of patients had retroperitoneal or limited lymph node dissection (RPLND) at primary surgery. Five patients recurred between 2 and 34 months, one patient progressed, and 5 died from disease. Of the nine patients with complete RPLND, eight survived whereas only one of seven patients with limited dissection survived. Malouf et al. evaluated the effect of lymph node status on recurrence free survival in patients with TFE3 tumors enrolled in the Juvenile RCC Network.[31–33] Patients with positive lymph nodes had lower 3-year recurrence free survival compared with those with negative nodes (28.9 vs. 76.9%). Three-year overall survival was 14.3% in patients with distant metastasis.[6] Although current literature in children with RCC suggests a more important role for a comprehensive lymph node dissection in children, further studies are necessary to fully elucidate the prognostic and therapeutic implications.[18] A recent abstract by Geller et al. evaluated whether omitting adjuvant therapy in patients with completely resected lymph nodes maintained a favorable outcome in children with renal cell carcinoma. In the 93.5% of patients with completely resected N1M0 disease, 4-year event free survival and overall survival (OS) was 87.2 and 94.6%, respectively. They concluded that favorable outcomes could be achieved without adjuvant therapy if the local disease is completely resected despite lymph node involvement.[34]
Curr Opin Urol. 2019;29(5):500-504. © 2019 Wolters Kluwer Health, Inc.
