Management of Low and Intermediate Risk Adult Rhabdomyosarcoma: A Pooled Survival Analysis of 553 Patients

Abstract

This is the second-largest retrospective analysis addressing the controversy of whether adult rhabdomyosarcoma (RMS) should be treated with chemotherapy regimens adopted from pediatric RMS protocols or adult soft-tissue sarcoma protocols. A comprehensive database search identified 553 adults with primary non-metastatic RMS. Increasing age, intermediate-risk disease, no chemotherapy use, anthacycline-based and poor chemotherapy response were significant predictors of poor overall and progression-free survival. In contrast, combined cyclophosphamide-based, cyclophosphamide + anthracycline-based, or cyclophosphamide + ifosfamide + anthracycline-based regimens significantly improved outcomes. Intermediate-risk disease was a significant predictor of poor chemotherapy response. Overall survival of clinical group-III patients was significantly improved if they underwent delayed complete resection. Non-parameningeal clinical group-I patients had the best local control, which was not affected by additional adjuvant radiotherapy. This study highlights the superiority of chemotherapy regimens -adapted from pediatric protocols- compared to anthracycline-based regimens. There is lack of data to support the routine use of adjuvant radiotherapy for non-parameningeal group-I patients. Nonetheless, intensive local therapy should be always considered for those at high risk for local recurrence, including intermediate-risk disease, advanced IRS stage, large tumors or narrow surgical margins. Although practically difficult (due to tumor's rarity), there is a pressing need for high quality randomized controlled trials to provide further guidance.

Figure 1

PRISMA flowchart.

Figure 2

(a) Kaplan-Meier (KM) OS and PFS curves for the whole cohort; (b) KM OS and PFS curves for the whole cohort according to the IRS risk group (low risk vs. intermediate risk); (c) Comparative efficacy of different chemotherapeutic regimens on PFS outcomes; (d) Comparative efficacy of different chemotherapeutic regimens on OS outcomes.

Figure 3

(a) KM OS curves for the response to chemotherapy; (b) The effect of delayed complete resection on OS of clinical group III patients; (c) KM LRFS curves of non-PM group I patients who did vs. who didn’t receive adjuvant radiotherapy.