In adult RCC, removal of lymph nodes doesn’t improve survival compared with radical tumor nephrectomy. Current COG protocol, however, indicates that lymph node sampling should be performed in all pediatric kidney cancers. Yet debate remains regarding whether, if lymph nodes are not resected or if a lymph node tests positive, further surgery should be performed to remove additional lymph nodes. Some studies suggest that lymphadenectomy leads to improved outcomes in pediatric RCC — but the evidence is limited due to small sample sizes — and this study couldn’t conclusively settle the issue.

“The reality is that our data did not prove that NX did worse,” said Dr Geller. “Our data set is too small to prove that.”

While patients with localized disease did well regardless of lymph node status, once the cancer spreads, the prognosis is much less certain. Among patients with metastatic disease, the survival rate was only 29%. Although the AREN0321 study intended to report on which medical treatments worked best for these kids, there were only 8 patients with metastasis, and not enough information was collected to draw a conclusion.

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“We did characterize the disease a bit,” said Dr Geller. Nearly all of the metastatic events occurred in patients with either translocation RCC (tRCC) or renal medullary carcinoma. To further study those tRCC cases across all age groups, COG has launched AREN1721 ( Identifier: NCT03595124), a cooperative study with SWOG,

Eastern Cooperative Oncology Group (ECOG), and the National Clinical Trials Network (NCTN). AREN1721 will test the efficacy of the targeted therapies axitinib and nivolumab in treating tRCC. The randomized trial will compare axitinib alone, nivolumab alone, and a combination of both drugs.

While the translocation phenotype accounts for around 50% to 60% of RCC in children and adolescents, only 1% to 4% of adult RCCs are diagnosed as tRCC. This may be an undercount, because the histology of the cells can resemble clear cell or papillary cancers. “If you don’t do the TFE3 gene stain, you will miss it,” Dr Geller said. Most labs do not routinely perform the stain, and indeed, the translocation type was only first described in 2004. “We are trying to raise awareness, because we don’t think [tRCC tumors] necessarily respond to the same therapies in the same way.” Translocation RCC is much more likely to metastasize, for instance, even if the primary tumor is smaller. As the prospective trial gets underway, it’s increasingly important to identify these patients to better understand which therapies will work best.

International collaboration will be key to increasing the number of patients studied, said Dr van den Heuvel-Eibrink. “I think it’s important that it’s now become a global responsibility,” she said. She and Dr Geller are working together to expand beyond American and European cohorts. “We have been to China to see whether we can recruit a Chinese cohort, because they have lots of patients,” she said. “We aim to have a worldwide registration.”


  1. Geller JI, Cost NG, Chi Y-Y, et al. A prospective study of pediatric and adolescent renal cell carcinoma: A report from the Children’s Oncology Group AREN0321 study. Cancer. Published online September 14, 2020. doi:10.1002/cncr.33173
  2. van der Beek JN, Geller JI, de Krijger RR, et al. Characteristics and outcome of children with renal cell carcinoma: A narrative review. Cancers (Basel). 2020;12(7):1776. doi:10.3390/cancers12071776