Description of the condition
Chondrosarcomas (CS) are the most common primary malignant bone tumours after osteosarcoma (Bauer 1995; Eriksson 1980; Healey 1986; Rosenthal 1984). CS are a heterogeneous group of bone malignancies that all arise from cartilaginous origin (Fletcher 2002), and constitute 20 to 27% of all primary bone tumours (Murphey 2003). Reported overall incidence is 1:200,000 to 500,000, with male and female more or less equally affected (ESMO 2012; Giuffrida 2009). Peak incidence is between the 3th and 7th decade of life (ESMO 2012; Jundt 2008). CS vary from low grade, relatively benign to high grade or dedifferentiated tumours with very poor survival. Conventional CS can originate outside the bone (periosteal or peripheral CS) or within the bone (central CS) and the latter accounts for 75% of all tumours. The outcome is predominately determined by histological grading, ranging from I to III, with higher grade tumours showing worse prognosis. Central grade I CS tumours tend to grow slowly and rarely metastasise, resulting in an 83% to 89% 10-year survival rate (Bjornsson 1998; Evans 1977; Fiorenza 2002). Microscopically, they have a matrix rich of hyaline cartilage (Gelderblom 2008). Most important clinical symptom is persistent (night) pain, although CS can be asymptomatic. Treatment of grade I CS is primarily surgery, since these tumours are generally resistant to radiation or systemic therapy (Eriksson 1980; Lee 1999).
In clinical practice, the treating physician is presented with a diagnostic dilemma. In a substantial number of cases, it is difficult to differentiate central grade I CS from its benign equivalent, enchondroma, or higher grade tumours (Eefting 2009; Geirnaerdt 1997; Mirra 1985; Randall 2005). Enchondroma can be treated conservatively (wait-and-see) or treated with curettage. Transformation towards malignancy in solitary enchondromas is extremely rare. Alternatively, intermediate- and high-grade CS have a 53 to 64% and a 29 to 38% 10-year survival rate, respectively, and show a higher number of local recurrence and distant metastases (Bjornsson 1998; Fiorenza 2002; Giuffrida 2009). They are treated with en bloc resection with reconstruction (prosthesis) or amputation, which hampers joint and limb function. Historically, orthopaedic surgeons tended to treat grade I CS similar as higher grade tumours. More recently, there is a tendency to perform intralesional surgery in grade I CS by curettage, preferably with local adjuvant therapy (Donati 2010; Leerapun 2007; Schreuder 1998; van der Geest 2008; Veth 2005). Grade I CS tumours located in the pelvis and axial skeleton are more aggressive and require other treatment strategies (Gelderblom 2008). Therefore, only treatment of tumours in the long bones will be described in this review.
Description of the intervention
Intralesional surgery in CS is carried out by curettage. During this procedure, the tumour is reached through a cortical window and resected using a curette. After curettage, local adjuvant therapy can be applied, either by phenolization or cryotherapy (see How the intervention might work). In a large number of cases, bone cement is used as an additional adjuvant. Once the cavity is filled, the cortical window is placed back and fixated followed by routine wound closure. In some cases, prophylactic hardware is needed to prevent fracturing. Depending on the site of the tumour, patients are prohibited from weight bearing 6 to 12 weeks after surgery. Curettage is indicated if the joint is not affected and if the tumour does not grow outside the bone. The most serious complications after curettage are fracture of the treated site and infection.
How the intervention might work
Curettage removes the malignant tumour cells. However, as the exact tumour margins are unknown during surgery, local adjuvant therapy is often performed. Phenol has a proven cytotoxic effect on CS cells and is used with the intention to kill tumour cells that can not be reached with the curette. Cryotherapy is also used, whereby liquid nitrogen is sprayed or poured into the bone cavity. It is thought that local freezing extends the surgical margins. In some centres, the bone cavity is filled with polymethyl methacrylate. Heat released due to the exothermic reaction of polymethyl methacrylate during hardening has an additional tumour cytotoxic effect. Given the relatively mild nature of grade I CS, we hypothesise that these measures are sufficient to cure patients. The major benefit of curettage compared to wide resection is that it is joint and limb sparing, thereby improving functional outcome. Although patients might be temporarily disabled due to decreased weight bearing after curettage, long-term functionality can be restored.
Why it is important to do this review
CS has an overall incidence rate that is relatively low compared to other types of cancer. To our knowledge, there are no prospective, randomised controlled trials (RCTs), given the low number of patients affected. In the literature, only small, retrospective case series have been published, in which intralesional treatment has been compared to wide resection (Aarons 2009; Bauer 1995; Donati 2010; Etchebehere 2005; Leerapun 2007; Schreuder 1998; van der Geest 2008). This type of study is often subject to bias and the numbers are often too small for meaningful statistical analysis. A systematic review is necessary to search for and summarise the available evidence. Hickey 2011 was a meta-analysis on this specific topic and it showed that intralesional therapy is not necessarily inferior to wide resection. In the meantime, several studies have been published, which justifies an updated overview. This review will be important, since intralesional treatment has great functional benefits compared to resection. Therefore, if the intralesional treatment is equally beneficial oncologically, it will be beneficial to perform curettage instead of wide resection.