It’s a question that surgeons often face: How much surrounding healthy tissue should they take out when removing a patient’s cancer to be sure it is fully eliminated? Removing more can sacrifice nearby nerves, blood vessels, tendons and even joints, with lasting effects on quality of life.
A new study led by UC Davis researchers finds that in at least one type of cancer, control may be achieved with much narrower margins than previously thought.
Until now, surgeons have had no scientific evidence on the optimal surgical margins for pediatric patients with non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) . In this first-ever large prospective clinical trial, scientists evaluated the risk of local cancer recurrence after surgical and chemoradiation therapies to non-metastatic NRSTS in children and young adult patients.
The trial (ARST0332) by the Children’s Oncology Group showed that close surgical margins as little as a millimeter — less than one tenth of the traditional surgical margin — would preserve precious healthy tissue and maintain low risk of recurrence. The findings were published today in JAMA Surgery .
“When we remove a tumor, our goal is to leave no cancer behind. So, when we operate on a child or young adult with soft tissue sarcomas, we ask how surgically aggressive we need to be in obtaining this negative margin?” said UC Davis Health orthopedic surgeon R. Lor Randall , the study’s senior author.
Randall specializes in pediatric oncology and is The David Linn Endowed Chair for Orthopaedic Surgery. He is also a professor and chair of the Department of Orthopaedic Surgery and director of Sarcoma Advanced Research and Clinical Fellowships at UC Davis Health.
“For a child, a few millimeters can make a lifelong difference when a tumor is next to an important nerve or blood vessel,” Randall said.
About non-rhabdomyosarcomas therapies
NRSTS include many different types of cancers that start in tissues that normally develop into muscles, nerves and tendons. They make up over half of soft tissue sarcomas in children and young adults. Every year, around 550 new cases are diagnosed in children in the United States alone.
The standard treatment for NRSTS is surgery with a complete resection (known as R0) to fully remove the tumor with no cancer cells at the microscopic edges of the removed tissue. This is called a negative, or cancer-free margin. Traditionally, the recommended protocol is to have a 1-2 centimeter margin when feasible. However, in a child’s smaller body, this may be difficult to do without damaging important structures.
Some patients also need chemotherapy and radiation therapy. This will depend on the type of cancer, size and grade, as well as whether it can be completely removed. The objective is to prevent cancer from returning.
First study in children looking at non-rhabdomyosarcomas
This is the largest prospective trial to evaluate surgical margins in relation to risk of cancer recurrence.
The researchers assessed the impact of margin extent on local cancer recurrence and survival outcomes in 266 patients. The patients were under the age of 30 (median age 13.7 years) and had non-metastatic NRSTS. All had their tumors completely removed (via resection) with no cancer cells at the margins. Of these, 178 received surgery alone. The other 88 also received chemotherapy and radiation, either before or after surgery.
The team reviewed the patients’ diagnostic imaging, tumor biopsies and resection specimens and operative records. They followed the patients for a median of 6.2 years. They classified them into three groups: low risk with surgery and no other treatment; intermediate risk with upfront surgery followed by chemoradiation; and intermediate risk with upfront chemoradiation followed by surgery.
Low rates of cancer returning with narrow margins
Exact margin widths were available for 132 patients, about half of those studied. In this group, the estimated risk of cancer returning at the surgical site within five years was 4.9% with a 1-millimeter margin, 2.0% with a 2- to 5-millimeter margin, and 0% with a margin of 6 millimeters or more.
“For the first time, we have evidence from a large prospective trial to help answer how closely we can safely get to these tumors,” Randall explained. “So, it is very exciting to find that getting close to the tumor — within a millimeter — can potentially save a blood vessel or healthy tissue and meet the standard of care, something that had never been shown before.”
Randall explained that most smaller tumors (less than 5 cm) do well with close margins even without chemotherapy and radiation. Larger tumors (more than 5 cm), on the other hand, would likely require chemotherapy and radiation.
The study also showed that with surgery and no chemoradiation treatment, the risk of local return of cancer was 5.6% for patients with smaller tumors. For patients with large tumors and who received chemotherapy, the risk of local recurrence was 3.7%.
Randall noted that wider margins may also be more important for patients treated with surgery alone.
“These findings can help surgeons decide when a close, but cancer free margin may be enough, allowing them to preserve more of a young person’s limb and its function,” said Sheri Spunt, coauthor and principal investigator on the trial. Spunt was an endowed professor of pediatric cancer at Stanford University and is now a senior medical director at AbbVie.
Expert teams help tailor treatment
The researchers emphasized that decisions about surgical margins require a team experienced in treating these rare cancers. They must consider the type and behavior of the tumor, nearby structures such as nerves and blood vessels, and whether chemotherapy or radiation are needed.
“Children with these rare cancers should be cared for at centers with extensive experience treating pediatric sarcoma,” Randall said. “They need access to pediatric oncologists, radiation therapists and surgeons who meet regularly to plan their care.”
This study was funded by St. Jude Children’s Research Hospital (Grants P01CA23099, P30CA21765). It was supported by the St. Baldrick’s Foundation, the Seattle Children’s Foundation from Kat’s Crew Guild via the Sarcoma Research Fund and the American Lebanese Syrian Associated Charities. It was also funded by the National Institutes of Health to the Children’s Oncology Group (Grants U10CA098543, U10CA098413, U10CA29511, U10CA180803, U10CA180886 and U10CA180899).
Susan M. Hiniker of Stanford University is the study’s first and corresponding author. For the complete list of coauthors, check the article .
JAMA Surgery
Surgical Margin and Risk of Local Recurrence in Children and Young Adults With Nonrhabdomyosarcoma Soft Tissue Sarcoma
28-Oct-2026
No conflict of interest.