The AREN0321 trial (ClinicalTrials.gov Identifier: NCT03595124) is the first-ever prospective study of pediatric renal cell carcinoma (RCC).1 Conducted by the Children’s Oncology Group (COG), the trial determined that unlike in adult RCC, complete surgical removal of the tumor produced favorable outcomes, regardless of lymph node status.

Renal cell carcinoma is the most common kidney cancer in adults, but extremely rare in children. Some 80% of pediatric kidney cancers are Wilms tumors, and the other 20% comprise an assortment of different cancers. Some, like clear cell sarcoma, are highly aggressive, but RCC can sometimes be successfully removed with surgery.

However, some pediatric RCC patients need additional treatment, and that’s a major gap in knowledge. “You have a fraction of a fraction of a rare cancer who don’t do well,” said James Geller, MD, pediatric oncologist at Cincinnati Children’s Hospital Medical Center, Ohio, and principal investigator on the trial. “It hasn’t been in the forefront of people’s attention.”

The AREN0321 trial set out to change that. The study included multiple arms for high-risk pediatric kidney cancers: anaplastic Wilms tumor, clear cell sarcoma of the kidney, rhabdoid tumor, and RCC. Over the 6-year study period, they prospectively enrolled 68 patients with RCC from all over the United States.


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A main objective of the trial was to determine whether surgery alone, without accompanying adjuvant therapy, was sufficient to ensure a favorable prognosis — regardless of lymph node involvement.

In adult RCC, if the cancer spreads to the lymph nodes, survival plummets to about 1 in 4 patients, but in 2004, Dr Geller published a retrospective study of children with RCC showing the opposite in kids.2 Pediatric patients who did not receive adjuvant therapy fared as well as those who did, the review reported.

The prospective study showed that after 4 years, complete resection of the tumor for children with local lymph node involvement but no metastasis delivered an overall survival rate of 91.4% (16 individuals).

“That was a meaningful finding,” Dr Geller said. “It was important to validate that prospectively, and it proves biological distinctness from adult RCC.”

Demonstrating that adjuvant therapy doesn’t provide measurable benefit protects patients, because no therapy is without side effects, and some of the events can be serious. “You’re exposing people to a cancer journey and all that comes with a cancer journey,” said Dr Geller. “Until we have a miracle pill that is 100% efficacious and completely bland, it’s hard to support using that medicine.”

In 26 patients, or 38% of the study participants, lymph node sampling was not done (NX). While lymph node sampling is important for accurate staging, it remains unclear whether it impacts the survival rate for patients.

“There’s been a lot of debate on what we should do,” said Marry van den Heuvel-Eibrink, MD, PhD, pediatric oncologist at Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands. “We are always advocating in children with renal cancer to take out 7 or more lymph nodes, because then you can really know whether there’s lymph node metastasis.”