Pediatric Rhabdomyosarcoma Surgery Treatment & Management

Current recommendations stem from IRS-V, in which treatment is stratified according to risk: low, intermediate, and high, based on the risk of disease recurrence and overall survival. Patients are then staged based on the site of the primary tumor. Favorable sites include the orbit, nonparameningeal head/neck, and genitourinary nonbladder/prostate sites; all other sites are unfavorable. Staging continues based on the size of the primary tumor (< 5 cm or >5 cm), regional lymph node involvement, distant metastases, and histologic subtype. Alveolar subtypes are now stratified based on gene fusion status.

Low-risk patients receive vincristine weekly for 9 doses and actinomycin D with or without cyclophosphamide (VAC regimen) and granulocyte colony-stimulating factor (G-CSF) for 4 doses every 12 weeks (at weeks 0, 12, 24, and 36). Radiation therapy is added in patients with residual localized disease. The protocol for intermediate-risk patients includes radiation therapy and either VAC or VAC and topotecan (according to randomized assignment) for nearly 1 year. A 2008 pilot study suggests that a regimen of alternating vincristine, doxorubicin, and cyclophosphamide with ifosfamide and etoposide (VDC/IE) is also effective.^[8] High-risk patients begin therapy with irinotecan followed by VAC and radiation therapy.

Recent investigations using the vinca alkaloid vinorelbine have been instituted for use in recurrent, advanced rhabdomyosarcoma.^[9] The VDC/IE regimen and irinotecan are being explored for use in high-risk tumors.

Radiation therapy

Radiation therapy is administered to patients who are at increased risk for local tumor recurrence. Intraoperative radiotherapy (IORT) or brachytherapy, implemented at the time of surgical intervention, has played a valuable role in patients whose tumors have positive or questionable margins.

Patients with group II disease (microscopic residual disease) have a high risk of local recurrence if prescribed radiotherapy is omitted or reduced, as demonstrated by Million et al. They noted that more than half the patients who relapsed at the original tumor site received nonstandard radiation therapy, and, of these, three quarters died of their disease.^[10]

Using clinical, chemotherapeutic, and radiotherapeutic data, another study reviewed the outcomes of 4230 patients who were at least 5-year survivors of secondary carcinomas, sarcomas, and hematological malignancies occurring after childhood cancer. After a median follow-up of 28 years, the results found that only the patients who received the highest dose of radiation (dose >150 joules) had a higher risk of mortality due to a sarcoma or second carcinoma; the risk of death due to carcinoma and sarcoma as second malignant neoplasms (SMNs) was 5.2-fold and 12.5-fold higher, respectively.^[11]

First, the surgeon must obtain a tissue diagnosis. The initial surgical intervention may consist of wide local excision or incisional or excisional biopsy. Complete excision should be attempted only when the tumor is clearly resectable, with negative margins. Incisional biopsies should be planned to ensure that the scar does not impede later attempts at resection, particularly when dealing with extremity tumors. Thus, biopsy incisions on the extremity should always be longitudinal. Patients who have unknown or positive margins should be considered for re-excision.

Anesthetic administration should be planned to incorporate any procedures that the child will need. For example, the surgeon should discuss the possible need for a central venous line, bone marrow aspiration, lymph node evaluation, and biopsy with the oncologist, the patient, and the family, so that, if needed, all procedures can be performed on the same day.

Thorough preoperative planning is essential because of the various surgical options that may be necessary in children with rhabdomyosarcoma, and the surgeon should take into consideration the possibility of obtaining clear margins when determining the initial surgical approach. In the event of resection after chemotherapy and radiation, if the surgeon is unsure that complete excision can be obtained safely, the placement of brachytherapy catheters or the administration of intraoperative radiotherapy may be discussed prior to operative intervention. Unlike with adult sarcomas, pediatric rhabdomyosarcoma may be present in the lymphatics in approximately 40% of cases.

It is important to evaluate the lymphatics in all children with rhabdomyosarcoma. This is best performed at the time of the initial procedure, particularly if lymphatic mapping with sentinel node biopsy is planned, as prior biopsy and/or excision may disrupt the lymphatics. Surgical options for evaluating the lymphatics include aggressive node sampling or sentinel node biopsy. Formal lymph node dissection is not recommended because it has not been shown to significantly improve survival, even in patients with histologically positive nodes.

Exceptions to wide local excision include head and neck tumors, vaginal/uterine tumors, and bladder tumors.

Preoperatively, all radiographic studies should be reviewed for evidence of metastases or signs of local invasion that may complicate resection. The surgeon should be prepared to perform a complete resection, when indicated, in order to afford the child the best possible prognosis.

Regardless of the tumor site, the surgeon should strive for a complete resection, without causing mutilation or disability. When the margins are in doubt, send frozen sections for analysis. Frequently, major neurovascular structures are in the resection field. When these structures are essential, a careful resection should be undertaken to remove as much of the tumor as possible. In these cases, brachytherapy, intraoperative radiotherapy, or postoperative radiation therapy may be beneficial. Recent studies suggest that debulking has no advantage over biopsy in terms of survival. Therefore, it is likely that biopsy followed by medical therapy and excision, when feasible, is the best option.^[12]

Patients should be observed postoperatively to ensure adequate wound healing and to examine for signs of local or distant recurrence.

Postoperatively, the tumor is graded based on extent of resection. This should be determined once the pathology is completed to determine the need for additional medical or surgical therapy. When possible, tumors with positive margins should be re-excised.

Complications vary based on tumor site. Because of the frequency of preoperative radiation therapy, the surgeon should be aware of the possibility of impaired wound healing.

The use of multimodal therapy and the long-term investigations by the IRS Group have allowed for steady improvement in prognosis for pediatric patients with rhabdomyosarcoma. The IRS-IV revealed that the failure-free survival rate and overall 3-year survival rate are 77% and 86%, respectively, in patients without metastatic disease. Recent emphasis is on stratification of therapy to provide local control with less impairment in functionality or cosmetics.

Investigations are under way through the Soft Tissue Sarcoma Committee of the Children’s Oncology Group. These studies seek to verify the stratification-based treatment algorithm. Future studies will aim to continue to improve survival while minimizing morbidity and mortality resulting from not only the malignancy but also the treatment.