Durability of oncological outcomes of combination chemotherapy as a monotherapy for a select patient subset with non-metastatic non-alveolar bladder/prostate rhabdomyosarcoma.

INTRODUCTION AND OBJECTIVES: We aim to assess the long-term oncological outcomes of children with bladder/prostate rhabdomyosarcoma (B/P RMS) treated with multiagent chemotherapy as a monotherapy. We hypothesize that a highly select patient subset can be treated with multiagent chemotherapy as a monotherapy and spared the morbidity of local treatment with similar oncological outcomes. METHODS: Patients (≤21-year-old) treated for non-metastatic non-alveolar B/P RMS at a tertiary center and followed for>one year, were retrospectively reviewed. After pathological confirmation, patients received 12 weeks of induction VAC chemotherapy (IC) followed by second-look biopsies. Between 1996 and 2006 (group A), patients with>50% tumor size reduction and negative second-look biopsies following IC were spared local treatment and followed-up closely. Between 2007 and 2020 (group B), local treatment was routinely given at 12 weeks according to the COG protocols, irrespective of IC response. For all patients, consolidation chemotherapy was administered for additional 12-18 months. RESULTS: Between 1996 and 2020, 27 patients (10 stage II, 17 stage III) with a median age of 3(1-21) years were included. Median follow-up was 87.5(15.3-247.1) months. Among 15 patients in group A, 3 were ineligible for the monotherapy protocol and received local treatment. The remaining 12 patients [9 complete (CR) and 3 incomplete response (IR) to IC] were treated exclusively with chemotherapy, of whom 9 were alive free of relapse at last follow-up. Two patients with IR to IC had disease relapse: one had pulmonary relapse at 8.2 months and one had local relapse at 35 months. The 5-year OS and EFS of group A were 86.7% and 80%, respectively. Analyzing survival according to IC response, CR to IC was achieved in 10 patients (9 group A and one group B) and was associated with significantly better OS and EFS than IR(p = 0.026 and 0.004, respectively) (Summary figure). All patients with CR to IC were alive free of relapse at last follow-up. DISCUSSION: Treatment of RMS is traditionally multimodal. Local treatment of B/P RMS is associated with significant patient morbidity. In this study, CR to IC predicted better OS and EFS. Patients who achieved CR (radiological and pathological) to IC remained alive free of relapse irrespective of local treatment. CONCLUSIONS: Our results suggest that patients with non-metastatic non-alveolar B/P RMS who achieve CR to IC can be treated with combination chemotherapy as a monotherapy and spared the morbidity of local treatment with durable survival outcomes. Prospective validation in a larger patient cohort is needed to support our hypothesis.