Intralesional treatment versus wide resection for central low-grade chondrosarcoma of the long bones.

BACKGROUND Grade I or low-grade chondrosarcoma (LGCS) is a primary bone tumour with low malignant potential. Historically, it was treated by wide resection, since accurate pre-operative exclusion of more aggressive cancers can be challenging and under-treatment of a more aggressive cancer could negatively influence oncological outcomes. Intralesional surgery for LGCS has been advocated more often in the literature over the past few years. The potential advantages of less aggressive treatment are better functional outcome and lower complication rates although these need to be weighed against the potential for compromising survival outcomes. OBJECTIVES To assess the benefits and harms of intralesional treatment by curettage compared to wide resection for central low-grade chondrosarcoma (LGCS) of the long bones. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 4), MEDLINE and Embase up to April 2018. We extended the search to include trials registries, reference lists of relevant articles and review articles. We also searched 'related articles' of included studies suggested by PubMed. SELECTION CRITERIA In the absence of prospective randomised controlled trials (RCTs), we included retrospective comparative studies and case series that evaluated outcome of treatment of central LGCS of the long bones. The primary outcome was recurrence-free survival after a minimal follow-up of 24 months. Secondary outcomes were upgrading of tumour; functional outcome, as assessed by the Musculoskeletal Tumor Society (MSTS) score; and occurrence of complications. DATA COLLECTION AND ANALYSIS We used standard methodological procedures recognised by Cochrane. We conducted a systematic literature search using several databases and contacted corresponding authors, appraised the evidence using the ROBINS-I risk of bias tool and GRADE, and performed a meta-analysis. If data extraction was not possible, we included studies in a narrative summary. MAIN RESULTS We included 18 studies, although we were only able to extract participant data from 14 studies that included a total of 511 participants; 419 participants were managed by intralesional treatment and 92 underwent a wide resection. We were not able to extract participant data from four studies, including 270 participants, and so we included them as a narrative summary only. The evidence was at high risk of performance, detection and reporting bias.Meta-analysis of data from 238 participants across seven studies demonstrated little or no difference in recurrence-free survival after intralesional treatment versus wide resection for central LGCS in the long bones (risk ratio (RR) 0.98; 95% confidence interval (CI) 0.92 to 1.04; very low-certainty evidence). MSTS scores were probably better after intralesional surgery (mean score 93%) versus resection (mean score 78%) with a mean difference of 12.69 (95% CI 2.82 to 22.55; P value < 0.001; 3 studies; 72 participants; low-certainty evidence). Major complications across six studies (203 participants) were lower in cases treated by intralesional treatment (5/125 cases) compared to those treated by wide resection (18/78 cases), with RR 0.23 (95% CI 0.10 to 0.55; low-certainty evidence). In four people (0.5% of total participants) a high-grade (grade 2 or dedifferentiated) tumour was found after a local recurrence. Two participants were treated with second surgery with no evidence of disease at their final follow-up and two participants (0.26% of total participants) died due to disease. Kaplan-Meier analysis of data from 115 individual participants across four studies demonstrated 96% recurrence-free survival after a maximum follow-up of 300 months after resection versus 94% recurrence-free survival after a maximum follow-up of 251 months after intralesional treatment (P value = 0.58; very low-certainty evidence). Local recurrence or metastases were not reported after 41 months in either treatment group. AUTHORS' CONCLUSIONS Only evidence of low- and very low-certainty was available for this review according to the GRADE system. Included studies were all retrospective in nature and at high risk of selection and attrition bias. Therefore, we could not determine whether wide resection is superior to intralesional treatment in terms of event-free survival and recurrence rates. However, functional outcome and complication rates are probably better after intralesional surgery compared to wide resection, although this is low-certainty evidence, considering the large effect size. Nevertheless, recurrence-free survival was excellent in both groups and a prospective RCT comparing intralesional treatment versus wide resection may be challenging for both practical and ethical reasons. Future research could instead focus on less invasive treatment strategies for these tumours by identifying predictors that help to stratify participants for surgical intervention or close observation.