Abstract
Aim: This multicenter retrospective study aimed to clarify the surgical and oncological outcomes of patients with high-grade soft tissue sarcoma (STS) who underwent prosthetic replacement reconstruction after lower extremity tumor resection. Patients and Methods: We retrospectively collected the data of 27 patients with high-grade STS. The mean follow-up duration after prosthetic replacement was 44.7 months. Results: The mean age at surgery was 63 years. The mean tumor size was 16 cm. For reconstruction, proximal femur replacement was performed in 15 patients, distal femur replacement in six, and total femur replacement in six. The major complications were infections in nine patients and aseptic loosening in four. Nine patients developed local recurrence. The cause of revision surgery was infection in five patients, aseptic loosening in three, and metal allergy in one. The 5-year prosthetic survival rate was 51.1%. At the final follow-up, amputation was performed in five patients. The 5-year limb salvage rate was 76.8%. The mean functional score of the 25 patients who could be assessed was 16.0 (53%). Of the 27 patients, five were excluded from the survival analysis because they underwent prosthetic replacement for local recurrence. The 5-year overall survival rate in the remaining 22 patients was 45.3%. Conclusion: We identified a high rate of surgical complications and poor survival in patients with high-grade STS who underwent tumor resection and reconstruction using prosthetic replacement of the lower extremities, although limb salvage was achieved in 81.5% of the patients. Careful follow-up is needed for surgical complications and oncological events after surgery.
In the past few decades, limb salvage has been considered the standard procedure for the majority of patients with soft-tissue sarcoma (STS) of the extremities because considerable advances have been made in the management of patients owing to improved imaging techniques and surgical expertise (1-3). Generally, the margins comprise soft tissue, such as the fascia and muscle, although STSs may directly abut the bone. Nevertheless, STSs invading the bone are uncommon (3). In a review of 874 patients with STS of the extremities, Ferguson et al. identified 48 patients (5.5%) with evidence of bone invasion (3). They reported that patients with bone invasion presented with significantly larger tumors that were frequently deep in the extremities, and more often had metastases at presentation. In addition to STS with bone invasion, when the attachment to the bone is detected on magnetic resonance imaging, reconstruction such as prosthetic replacement may be considered after STS removal from the bone (4, 5). We hypothesized that oncological and prosthetic outcomes may be poor in patients with STS who require bone resection and reconstruction using prostheses because they have large, deep STS and undergo massive bone and muscle resection. This multicenter retrospective study aimed to clarify the surgical and oncological outcomes of patients with high-grade STS who underwent prosthetic replacement reconstruction after lower extremity tumor resection.
Patients and Methods
The Tokai Musculoskeletal Oncology Consortium was formed in 2014 to improve the care of patients in central Japan with musculoskeletal tumors. All the physicians in this consortium specialize in orthopedic oncology. This study was approved by the institutional review boards of the authors’ affiliated institutions. Informed consent was waived owing to the retrospective nature of the study, and an opt-out option was permitted, whereby patients had the opportunity to discontinue participation in the study. This study was performed in line with the principles of the Declaration of Helsinki.
We retrospectively collected the data of 27 patients with high-grade STS between 2006 and 2020. The patients underwent tumor resection with adjacent or involved bone resection and prosthetic replacement for reconstruction after resection in the lower extremities. The mean age at surgery was 63 (range=11-84) years. The mean follow-up duration after prosthetic replacement was 44.7 (range, 3.3-134) months. We estimated prosthetic survival in 27 patients and evaluated oncological outcomes in 22 patients who underwent prosthetic replacement as the primary surgery. The causes of prosthetic failure were classified using Henderson’s classification as follows: type 1: soft-tissue failure, type 2: aseptic loosening, type 3: structural failure, type 4: infection, and type 5: tumor progression (6). Functional outcomes were assessed using the Musculoskeletal Tumor Society scoring system (7).
Statistical analysis. The relationship between patient and tumor characteristics was analyzed using the Mann-Whitney U-test for quantitative data and the chi-square test for qualitative data. The survival rate was estimated as the time from surgery to death or the final follow-up date. The prosthetic survival rate was estimated as the time from surgery to revision surgery owing to implant failure. Implant failure was defined as the replacement or removal of any part of the prosthesis because of local recurrence, polyethylene bushing failure, fracture, stem breakage, aseptic loosening, or infection. The Iimb salvage rate was calculated as the time from surgery to amputation for any reason. Survival curves were constructed using the Kaplan-Meier method. The Cox proportional hazards model was used to analyze the prognostic variables. Statistical significance was set at p<0.05. All statistical analyses were performed using the EZR graphical user interface (Saitama Medical Center, Jichi Medical University, Saitama, Japan) for R (R Foundation for Statistical Computing, Vienna, Austria), a modified version of R Commander designed to add statistical functions frequently used in biostatistics.
Results
Patient characteristics (Table I). The participants comprised 21 men and six women. The tumors were located in the thigh in 23, knee in two, buttock in one, and in the inguinal region in one. Regarding tumor types, eight were liposarcomas, eight were undifferentiated pleomorphic sarcomas, six were myxofibrosarcomas, three were synovial sarcomas, one was a fibrosarcoma, and one was a leiomyosarcoma. The mean tumor size was 16 (range=5-33) cm. Three patients had already developed lung metastases at initial presentation. Preoperatively, bone invasion was suspected on magnetic resonance imaging in 15 patients, and bone invasion was detected pathologically in 10 patients. A preoperative pathological fracture was observed in one patient.
Patient characteristics.
All 27 patients underwent surgical tumor resection and reconstruction using prosthetic replacement of the lower extremities. R0 resection was performed in 23 patients, whereas R1 resection was performed in four. For reconstruction, proximal femur replacement (PFR) including one total hip replacement was performed in 15 patients, distal femur replacement (DFR) in six patients, and total femur replacement (TFR) in six patients. Cement and cementless stem fixations were performed in 14 and 13 patients, respectively. Twelve patients required soft-tissue reconstruction. Perioperative chemotherapy and radiotherapy were administered to 15 patients (pre and post surgery in eight, pre surgery in five and post surgery in two) and seven patients (pre surgery in five and post surgery in two), respectively.
Surgical complications, prosthetic survival, and function. Complications were observed in 19 out of 27 patients. The major complications were infections in nine patients, followed by aseptic loosening in four patients, two patients had wound dehiscence, one had lymphorrhea, and one had metal allergy. Nine patients developed local recurrence. Infection was also associated with perioperative chemotherapy (p=0.0192) (Table II). Of the nine patients with infection, five underwent revision, one underwent amputation, one underwent debridement, one underwent debridement with mesh removal, and one underwent debridement with a pedicle flap. Age, sex, tumor size, bone involvement, joint replacement, soft-tissue reconstruction, and adjuvant radiotherapy were not associated with the development of infection.
The analysis of risk factors for infection in patients with soft-tissue sarcoma undergoing prosthetic replacement reconstruction.
Out of the 27 patients, revision surgery or amputation was required in 13 during follow-up. According to the Henderson classification, the causes of prosthetic failure were type 2 in four, type 4 in six, and type 5 in four patients. The cause of revision surgery was infection in five patients, aseptic loosening in three, and metal allergy in one; one patient who underwent revision surgery for aseptic loosening developed local recurrence and subsequently underwent amputation.
The 5-year prosthetic survival rate was 51.1% (95% confidence interval=28.6-69.8%) (Figure 1). At the final follow-up, amputation was performed in five patients (infection, n=1; local recurrence, n=4) (18.5%). The 5-year limb-salvage rate was 76.8% (95% confidence interval=48.3-90.9%) (Figure 2). The mean functional score of the 25 patients who could be evaluated was 16.0 (53%) out of 30 total points [PFR: 17 (57%), DFR: 16.8 (56%), and TFR: 15.6 (52%)].
Kaplan-Meier curve demonstrating prosthetic survival (with 95% confidence interval) in 27 patients with soft-tissue sarcoma of the lower extremities.
Kaplan-Meier curve demonstrating the limb salvage rate (with 95% confidence interval) in 27 patients with soft-tissue sarcoma of the lower extremities.
Overall survival. Of the 27 patients, five were excluded from the survival analysis because they underwent prosthetic replacement for local recurrence. At the final follow-up, 11 patients were alive, 10 had died from sarcoma, and one patient had died from other causes. Eleven patients had developed metastasis, including three patients with metastasis at initial presentation. The 5-year overall survival rate in the 22 evaluable patients was 45.3% (95% confidence interval=21.5-66.4%) (Figure 3). Tumor size (p=0.006, Cox hazard proportion model) was a prognostic variable for predicting survival (Table III). Age, sex, joint replacement, metastasis at initial presentation, and pathological bone invasion were not associated with prognosis.
Kaplan-Meier curve demonstrating the overall survival (with 95% confidence interval) in 22 patients with primary soft-tissue sarcomas.
Cox proportional hazard model for predicting survival.
Discussion
In the present multicenter study, surgical complications were common, and prosthetic survival in patients with high-grade STS was poor, although 81.5% of the patients (22 of 27 patients) had preserved limbs. The main causes of prosthetic failure were found to be infection and local recurrence. The prognostic variables for predicting survival were tumor size and metastasis at initial presentation.
However, reports on resection and reconstruction using prosthetic replacements in patients with STS are few (4, 5). Yan et al. conducted a study on 30 patients with STS who underwent reconstruction using a prosthetic replacement (5). They included eight patients with proximal humerus replacement and 10 patients with local recurrence. Chemotherapy was administered preoperatively in eight patients and postoperatively in 23 patients. At a mean follow-up duration of 25 months, the 2- and 5-year survival rates were 61.6% and 30.0%, respectively, although they included nine patients with metastasis at initial presentation. The poor prognosis was consistent with our study. Moreover, some authors have reported that bone involvement may indicate poor prognosis in STS (3, 4, 8). However, we did not observe a significant difference in survival between patients with STS with or without bone invasion. Thus, our cohort itself may have a mortality risk despite bone invasion because tumor size, depth, and histological grade are critical factors for survival (9, 10). The mean tumor size in our study was 15 cm, and all the STSs were deep and high-grade. Yan et al. have also reported that three patients underwent revision or amputation (5). Stem fracture was observed in two patients and infection in one patient. Four patients developed local recurrence. The rate of surgical complications was low. However, large and deep STS are commonly associated with surgical complications (9, 11-14). Recently, Rowell et al. described the surgical and oncological outcomes in 29 patients with high-grade STS and bone involvement in the lower extremities (4). Twelve patients underwent neoadjuvant radiation and eight underwent adjuvant radiation treatment. Only one patient underwent neoadjuvant chemotherapy. They demonstrated that 14 out of 29 patients underwent reoperations for surgical complications, with nine related to infection. Five patients developed local recurrence. This high incidence of surgical complications is consistent with the results of our study. Infection is a serious complication because it is the main cause of additional surgeries. Providing adequate soft-tissue coverage after reconstruction may be a critical factor in reducing infections (15, 16). Although we did not identify a relationship between soft-tissue reconstruction and infection in this study, the use of a musculocutaneous flap may be a useful option for reducing infection. In the present study, the functional outcome rate was 53% in 27 patients. Goryn et al. have reported that the functional outcomes in adult patients with prostheses for osteosarcoma were a mean Musculoskeletal Tumor Society score of 85% for DFR, followed by 81% for PFR and 71% for TFR (17). In addition to bone resection, massive muscle resection along with STS resection may have affected the functional outcomes in our cohort. Hagi et al. reported the outcomes in 55 patients with primary STS who underwent amputation including 46 patients with lower extremity STS (18). The 5-year disease-specific survival rate was 53.7%. The level of amputation (above or below the knee) was significantly different in terms of achieving an independent gait. Patients who underwent above-knee amputation required wheelchairs, with an odds ratio of 14.8. Therefore, we should consider preserving the limb using prosthetic replacements such as PFR, TFR and DFR in our setting because the patients are at a high risk of reduced activities of daily living owing to above-knee amputation.
This study had some limitations. Firstly, the number of patients included in this study was small. Secondly, this study had a retrospective design.
In conclusion, we identified a high rate of surgical complications and poor survival in patients with high-grade STS who underwent tumor resection and reconstruction using prosthetic replacement of the lower extremities, although limb salvage was achieved in 81.5% of the patients. Careful follow-up is required for surgical complications and oncological events after surgery.
Footnotes
Authors’ Contributions
Tomoki Nakamura contributed to the study conception and design. Material preparation, data collection and analysis were performed by all Authors. The first draft of the manuscript was written by Tomoki Nakamura and all Authors commented on previous versions of the article. All Authors read and approved the final article.
Funding
The Authors declare that no funds, grants, or other support were received during the preparation of this article.
Conflicts of Interest
The Authors have no relevant financial or non-financial interests to disclose.
- Received July 15, 2023.
- Revision received August 31, 2023.
- Accepted September 1, 2023.
- Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).
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