Effectiveness of Regional Hyperthermia With Chemotherapy for High-Risk Retroperitoneal and Abdominal Soft-Tissue Sarcoma After Complete Surgical Resection: A Subgroup Analysis of a Randomized Phase-III Multicenter Study

Retroperitoneal and abdominal soft-tissue sarcomas are rare tumors with a reported incidence of 2.7 cases per million.1 For localized abdominal and retroperitoneal tumors, surgical resection with gross negative margins remains the standard of care. As opposed to extremity sarcoma, mortality from tumors located in the retroperitoneum occurs mainly because of local relapse. Local recurrence is responsible for 3 of 4 tumor-related deaths.2 Systematic compartmental resection, that is, removal of the tumor en bloc with a rim of normal tissue, including macroscopically unaffected structures, has been shown to reduce local recurrence rates.3–5 These studies indicate that complete removal of the tumor represents the most important prognostic factor in patients with retroperitoneal soft-tissue sarcoma. Despite gross complete multivisceral resections, small surgical margins may occur in the retroperitoneum in patients with large soft-tissue sarcoma.3,6 To improve local tumor control, multimodal therapeutic concepts with radiation and systemic perioperative chemotherapy have been developed in addition to radical surgery.7–9 The prospective randomized multicenter trial EORTC (European Organisation for Research and Treatment of Cancer) 62961 indicated that hyperthermia combined with systemic chemotherapy with etoposide, ifosfamide, and doxorubicin (EIA) significantly increased local progression-free survival (LPFS) and disease-free survival (DFS) compared to chemotherapy alone in patients with high-risk sarcoma (diameter > 5 cm, FNCLCC grading 2 or 3).10 This study, however, included a heterogeneous patient collective with retroperitoneal and extremity soft-tissue sarcomas, as well as different resection status (R0/R1 vs R2 resections). Therefore, it remains unknown whether hyperthermia in addition to chemotherapy compensates for insufficient surgery or is also effective in decreasing local recurrence in patients after macroscopically complete resection of sarcomas. Because from a surgical, anatomical, and prognostic perspective, extremity, abdominal, and retroperitoneal sarcoma represent different entities, this manuscript will focus only on abdominal and retroperitoneal sarcoma.11,12 Aim of this study was to evaluate the effect of hyperthermia in the subgroup of patients with R0/R1 resection of retroperitoneal and abdominal sarcoma on local-recurrence, progression-free, and overall long-term survival. Moreover, the effect of the intensified treatment in the regional hyperthermia (RHT) group on perioperative morbidity and mortality was evaluated.