Intralesional treatment versus wide resection for central low‐grade chondrosarcoma of the long bones Edited (no change to conclusions)

Abstract

Abstract 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.

Author(s)

Edwin F Dierselhuis, Krista A Goulding, Martin Stevens, Paul C Jutte

Abstract

Plain language summary

The effect of type of surgery for outcome in low‐grade chondrosarcoma

Background and review question
 Chondrosarcomas are one of the most common types of bone cancer, with varying degrees of severity. These tumours grow from cartilage forming cells, within the bone, or on the surface of the bone. Low‐grade chondrosarcomas (LGCS) are tumours that grow slowly over time and do not generally metastasize and people do not usually die from this disease. In the late 20th century, the condition was treated by cutting out large portions of bone surrounding the tumour (wide resection). However, surgeons today more commonly treat these tumours by scraping the tumour out of the bone (intralesional treatment). In this way, the bone structure is preserved and more extensive surgery can be avoided. Therefore, people are potentially less disabled and complications can be reduced. This is only appropriate if the survival outcome of the cancer treatment is not compromised compared to wide resection. We reviewed the evidence for the harms and benefits of both types of surgery on outcomes in people with LGCS, including tumour recurrence after surgery (local recurrence), level of physical functioning and complications after surgery.

Search date
 The evidence is current to April 2018.

Study characteristics
 We identified 14 studies that were suitable for analysis with a total of 511 participants; 92 were treated by wide resection compared to 419 by intralesional treatment. Age of the participants varied from 13 to 82 years with a mean age of 48 years. Women outnumbered men in the studies by just over one and a half times, which reflects that LGCS are more common in women. People were followed‐up for between 24 to 300 months after surgery. In addition, there were four studies including 270 participants, from which we could not extract the exact data, but were used to confirm the statistical analysis.

Key results
 We found that there was little or no difference in rates of local recurrence between treatment types. In 94% to 96% of the cases, the tumour was successfully removed after a single operation. In the few cases where disease recurred, a second operation was needed. People with LGCS probably have better functionality after less aggressive intralesional treatment, and complication rates were probably lower compare to wide surgical resection. Less than 0.3% of all people with LGCS died due to their disease, irrespective of the surgical technique.

Certainty of evidence
 Overall certainty of the studies was very low, as all studies only described the results of the treatment in hindsight and none of the studies randomly selected patients between treatment groups.

Author(s)

Edwin F Dierselhuis, Krista A Goulding, Martin Stevens, Paul C Jutte

Reviewer's Conclusions

Authors' conclusions

Implications for practice

There was very limited and very low‐certainty evidence on how to treat central low‐grade chondrosarcoma (LGCS) of the long bones. We only found retrospective comparative studies or case series, which are greatly biased by patient selection. Based on these data, there is evidence of very low certainty that recurrence‐free survival is equal between intralesional treatment and wide resection. There is evidence of very low certainty that intralesional surgery increases functional outcome as reported by Musculoskeletal Tumor Society (MSTS) scores. The included studies described many forms of adjuvants, such as phenolisation, the use of nitrogen, anhydrous alcohol and the application of polymethyl methacrylate (PMMA). Details regarding the use of these adjuvants were lacking in most studies and so we could not assess them.

Among the papers included in the meta‐analysis and Kaplan Meyer calculation, there were no local recurrences after 41 months. Only three cases have been reported in modern literature where local recurrence occurred beyond five years for this tumour subtype. Verdegaal 2012 and Meftah 2013 reported cases of local recurrence at 64 months, 91 months and 67 months respectively.

Implications for research

Considering the low incidence of this disease and the oncologic sequelae, such as local recurrence, future research is best performed in a multinational setting. The current level of evidence supporting intralesional treatment of LGCS is of very low certainty. Nevertheless, in our opinion a prospective randomised controlled trial comparing intralesional treatment versus wide resection may be unwarranted for both practical and ethical reasons. As this review has demonstrated, local recurrence after intralesional treatment occurs in approximately 5% of people only, with no demonstrable negative effect on patient survival. Future research should, perhaps, instead focus on less invasive treatment strategies for these tumours by identifying predictors that help to stratify people for surgical intervention or close observation. During the development of this review, the World Health Organization (Fletcher 2013), renamed LGCS as an atypical cartilaginous tumour (ACT). By definition, they are now tumours of borderline or low malignant potential. Although outside the scope of this review, considering the very low number of reported local recurrences and the fact the metastasis is so rare, there may even be a case for observation of smaller, less active lesions, especially those without cortical scalloping.

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