To investigate the efficacy and significance of surgical treatment for patients with metastatic cancer of the femur. We retrospectively analyzed 39 cases of patients with metastatic cancer of the femur treated surgically between March 2005 and August 2013 in our hospital. There were 18 female cases, aged 39 to 83 years, with a mean age of 63 years. There were 21 male cases, aged 30 to 86 years, with a mean age of 63 years. Their expected survival time and actual survival time were evaluated and compared. Mirels score was performed preoperatively in patients who were on the verge of fracture. There were 25 cases of proximal femoral metastatic cancer, including 2 cases with bilateral proximal femoral metastatic lesions. The lesions were located in the femoral neck in 8 cases, intertrochanteric in 12 cases, and subtrochanteric in 7 cases. There were 12 cases of metastatic carcinoma to the femoral stem, of which 1 case had bilateral pathological fracture of the femoral stem. Metastatic cancer of the distal femur was found in 2 cases. Pain scoring was performed preoperatively and postoperatively.
Postoperatively, patients were evaluated for postoperative function using the Enneking scale at 3, 6, 12 months, and the final follow-up time, respectively. [RESULTS]: The mean follow-up time was 14 months (1 to 63 months), of which 28 patients died and 11 patients are currently alive. The median survival time of the deceased patients was 8.5 months (1 to 63 months). The difference in preoperative and postoperative pain scores was statistically significant (P<0.05). The actual survival time was greater than the expected survival time and the difference was statistically significant (p<0.05). The enneking function scores at 3, 6, and 12 months and at the time of the final follow-up after surgery ranged from 14 to 26 points, respectively. < a="">[Conclusion]: Surgical treatment was selected according to the presence of pathological fracture, near fracture, site of lesion, and extent of involvement of the femur. As one of the means of comprehensive treatment, it can effectively relieve pain, improve limb function, and enhance the quality of survival.
With the improvement of diagnosis level and patients’ quality of life, the treatment of bone metastatic tumors is also getting more and more attention from clinicians. Among metastatic bone tumors, the incidence of metastatic cancer of the femur is second only to that of the spine and pelvis. As the femur is the most important weight-bearing bone in the human body, the pain and functional impairment caused by pathological fracture of metastatic cancer will seriously affect the quality of life of patients. For pathological fractures of the femur, internal fixation or prosthetic reconstruction is usually required. For patients who are on the verge of fracture, prophylactic internal fixation is often required to reduce pain, restore function and improve quality of life as soon as possible. We retrospectively analyzed 39 patients with metastatic cancer of the femur treated surgically in our hospital. Their pre-surgical evaluation, surgical treatment methods, perioperative complications, postoperative functional assessment and prognosis were analyzed and summarized.
1.Data and methods
1.1, Clinical data
From March 2005 to August 2013, a total of 39 cases of metastatic cancer of the femur were treated in our hospital. There were 18 cases in women, aged 39 to 83 years, with a mean age of 63 years. There were 21 cases in males, aged 30 to 86 years, with a mean age of 63 years. The source was lung cancer in 19 cases, gastrointestinal cancer in 4 cases, breast cancer in 3 cases, prostate cancer in 3 cases, esophageal cancer in 2 cases, thyroid cancer in 1 case, cervical cancer in 1 case, kidney cancer in 3 cases, nasopharyngeal cancer in 1 case, and no primary foci were found in 2 cases. There were 25 cases of proximal femoral metastases, among which 2 cases had bilateral proximal femoral metastases. The lesions were located in the femoral neck in 8 cases, between the coarctation in 12 cases, and under the coarctation in 7 cases. There were 12 cases of metastatic carcinoma to the femoral stem, of which 1 case had bilateral pathological fracture of the femoral stem. There were 2 cases of distal femoral metastases. Pathological fractures accounted for 53.5% and near fractures accounted for 46.5%.
There were 5 cases of intramedullary femoral nail fixation, 5 cases of intramedullary femoral nail fixation + bone cement filling, 1 case of locking titanium plate fixation, 1 case of locking titanium plate fixation + bone cement filling, 3 cases of proximal femoral intramedullary nail fixation + bone cement filling, 1 case of femoral reconstruction nail fixation + bone cement filling, 7 cases of custom-made proximal femoral tumor-type prosthesis reconstruction, 7 cases of long gamma nail fixation, 5 cases of long gamma nail fixation + bone cement filling, and bone cement type bipolar artificial femoral head replacement in 7 cases.
1.2. Surgical treatment and evaluation
The Dutch model scoring system was used preoperatively. The Kamofsky Performance Scale (KPS) was used to assess the survival time of the patients according to the long-term quality of life, the primary focus and the involvement of internal organs, and the Mirels score was used to score the proximal femoral endangered fracture. Patients were assessed for postoperative function using the Enneking score at 3 months, 6 months, 12 months, and at the final follow-up visit. Follow-up was performed by telephone or outpatient, every three months, with final follow-up at the time of the most recent outpatient follow-up or at the time of the patient’s death. Pre- and postoperative pain assessment of patients was evaluated using the VAS (Visual Analogue Scale, VAS) scoring method.
2. Results
The mean follow-up time was 14 months (1-63 months), of which 28 patients died and 11 patients are still alive. The median survival time of all patients was 8 months (1-63 months) by the time of the last follow-up. The median survival time of the deceased patients was 8.5 months (1 to 63 months). The incidence of pathological fractures was 53.5%. There were 19 cases of lung cancer disease, accounting for 49% of the total patients with metastatic cancer to the femur, with a median survival time of 9 months (3 to 24 months) by the time of the last follow-up. The actual survival time was 13.9±14.2 months and the expected survival time was 4.4±2.6 months, and the actual survival time was greater than the expected survival time and the difference was statistically significant (P<0.05).
Postoperative pain was significantly reduced, with a preoperative pain score of 6.7±1.7 and a postoperative pain score of 3.2±1.3, a preoperative pain score of 8.0±0.7 and a postoperative score of 4.0±1.1 for pathological fractures, and a preoperative pain score of 5.2±1.2 and a postoperative pain score of 2.2±0.7 for near fractures, with a statistically significant difference in preoperative and postoperative pain scores (P<0.05). Functional scores were performed postoperatively at 3, 6, 12 months, and at the final follow-up time. The functional scores at 3 months postoperatively were 15.4< span="">±5.4 for pathological fractures, 24.0±3.0 for near fractures, 18.9±3.2 for normal femoral prosthesis reconstruction, and 23.0±3.5 for custom proximal femoral prosthesis reconstruction, and the difference in postoperative functional scores between these two patients was statistically significant (P<0.05).
Postoperative enneking functional scores ranged from 14 to 26 points until the time of the last follow-up. The longest survival time by far was for patients with bone metastases from prostate cancer. The mean survival time was 51 months. < span="">Surgical complications were postoperative fat liquefaction of the incision in three cases, which healed well after multiple incisional extrusion and dressing changes. one patient had suspected pulmonary embolism, and pulmonary CT did not reveal a significant embolic lesion, which improved after observation and treatment in the ICU. one case presented with a distal fracture of the custom-made prosthesis, and a locking titanium plate and steel cable internal fixation with bone graft fusion was performed. There were no cases of reoperative treatment after internal fixation failure in this group of patients.
3. Discussion
3.1. Principles and objectives of surgical treatment
Bone metastasis cancer is the most common cause of bone destruction in elderly patients. In the bones of extremities, bone metastatic cancer is most likely to invade the femur. The primary cancers are usually breast cancer, lung cancer, kidney cancer, prostate cancer, thyroid cancer, gastrointestinal tract cancer, metastatic cell carcinoma, neurogenic tumor, etc. The first principle is that the recovery period after surgery should be shorter than the patient’s expected survival time; the second principle is that the fixation provided must be stable enough to provide full weight bearing as well as to provide continuous stability during the patient’s survival; and the third principle is that the surgical reconstruction needs to cover all of the destroyed bone. The goals of surgical treatment are to fix the fracture, reduce pain, and restore function and early activity.
Some authors suggest that the shortest expected survival time is 30 to 90 days to consider surgical treatment. Bone metastases are often end-stage tumors, so aggressive treatment of pathologic fractures and prevention of pathologic fractures to allow early return to activity, reduce the stress of care, and alleviate patient pain are the main goals of their treatment during the patient’s limited survival. In the present study, the incidence of pathological fractures was 53.5%. Unlike non-pathological fractures, patients with pathological fractures take a long time to heal, with as many as 50% of patients failing to heal at all.
Therefore, the strength of the internal fixation must be sufficient to maintain this non-healing or delayed healing for the limited time the patient has to survive. With the continuous improvement of medical treatment, including chemotherapy, radiation therapy and external radiation therapy with additional application of bisphosphonates, the survival of patients with bone metastases is significantly longer than in the past.
3.2. Survival time, pathology and assessment of imminent fracture and pain
There are also many reports on the survival assessment of patients with bone metastatic cancer, but most of them focus on spinal metastatic cancer. The Dutch model scoring system is the most commonly used clinical scale to assess survival. This score predicts survival based on the Kamofsky Performance Scale (KPS), the primary site, and the involvement of internal organs.
The prognosis was divided into three groups according to the results: group A, with a total score of 0 to 3 and a median survival of 3 months; group B, with a total score of 4 to 5 and a median survival of 9 months; and group C, with a total score of 6 and a median survival of 18.7 months [1]. In the present study, the median survival time was 8 months until the last follow-up time, which was higher than the median survival time of the Dutch model scoring system (3 months). This may be related to the continuous improvement of medical treatment, including a combination of chemotherapy, radiotherapy, external radiation therapy, and application of diphosphonates, which prolong the survival time of patients. Assessing the risk of pathological fracture in patients with metastatic cancer who are on the verge of fracture is highly subjective.
In 1971, Beals et al. showed that patients with breast cancer with painful bone destruction greater than 62.5 px had a 58% likelihood of pathologic fracture. In 1973 and 1981, Filder et al. found that fractures occurred in 2.3% of untreated patients with less than 50% cortical destruction and in 80% of patients with greater than 75% cortical destruction. The most commonly used criterion for assessing near fracture is the Mirels scoring system, which has a 12-point scale based on anatomic site, type of bone destruction, degree of destruction, and pain associated with activity. A composite score of 9, 8, and 7 is associated with a fracture incidence of 33%, 15%, and 4%, respectively. Therefore, prophylactic fixation was performed in patients with metastatic bone cancer with a near fracture score of 8 or higher.
In our group of patients with metastatic cancer of the femur, all patients with near fracture scores of 8 or higher also underwent prophylactic internal fixation or prosthetic reconstruction. Although the Mirels’ scale provides a good guide for physicians in treating patients with near fractures in bone metastases, it is based on 78 radiation-treated patients, a small number of patients, and is a retrospective study, and there is overlap between the fracture and nonfracture groups. In a study by Van der Linden et al [9], it was shown that a lesion invading more than 30 mm of cortex and more than 50% of circumference in cross-section alone was a predictor of pathological fracture.
And the Mirels’ score did not predict pathological fractures with sufficient specificity. Also, the experience of the clinician is important. Patients with progressive pain who are not sensitive to radiation therapy should be treated with prophylactic surgery regardless of the Mirels’ score. As assessed in terms of early function (three months), the functional scores of patients with near fractures are better than those of patients with pathological fractures, which may be an advantage of prophylactic internal fixation to reduce patient pain and improve quality of life. Pain was significantly reduced after fixation in this group of patients, and the difference between preoperative and postoperative pain was significant and statistically significant.
3.3. Selection of surgical treatment modality
The proximal femur is a high stress transmission zone, and stable fixation is very important. Due to delayed healing or non-healing of the fracture, patients with metastatic cancer of the femoral neck mostly choose the surgical option of artificial prosthesis reconstruction, and cemented artificial femoral head prosthesis replacement is a good choice. We performed cemented bipolar femoral head replacement in 7 patients with metastatic cancer of the femoral neck, and they recovered well and could walk on the ground at an early stage after surgery. Prosthetic reconstruction is not dependent on bone healing, while improving function, reducing pain, and providing stable reconstruction as early as possible. However, replacement of the proximal femoral prosthesis has its drawbacks, and despite anatomic reconstruction of the muscle, weakness of the abductor muscle, infection, and dislocation often occur.
In patients with a single metastatic lesion in the proximal femur and a long expected survival period, an enlarged lesion is excised and a custom-made artificial bipolar proximal femoral prosthesis is reconstructed; such patients require approximately 6 weeks of postoperative immobilization to facilitate adductor muscle reconstruction and functional recovery. In patients who are on the verge of fracture, in addition to prosthetic reconstruction, the lesion can be treated with intramedullary nail fixation, intracapsular scraping, and if the defect is large, cement filling. Good treatment results are reported in the literature.
Surgical treatment of pathological fractures between the ramus remains controversial. If the lesion is confined to the intertrochanteric space and the internal wall destruction is small, a compression screw or nail plate system is traditionally applied. However, the lack of stress distribution between the implant and the residual bone increases the failure rate of this fixation method due to prolonged survival, local lesion progression, delayed healing or non-healing. The proximal femoral intramedullary nail has the distinct advantage of being placed close to the pressure side of the femur and away from the lateral tension side. However, it is prone to pathological fractures at the distal tip if there is a distal lesion. Proximal fixation to the femoral head and neck and distal interlocking intramedullary nailing of the femur is more advantageous.
If the lesion is extensively involved in the neck of the femur and between and under the trochanter, internal fixation is rarely able to deal with such lesions and artificial prosthetic reconstruction is mostly chosen, more so in cases where internal fixation has failed or in cases where radiotherapy is not sensitive. The disadvantage is that prosthetic reconstruction increases the chance of infection and dislocation of the prosthesis. Reconstruction of the prosthesis may also cause imbalance in gait due to reconstruction of the flexors and extensors. Despite these disadvantages, the patient can immediately bear weight and reduce pain. Pathologic fractures under the ramus are first intramedullary nailed. The literature reports Zickel nailing into the treatment of subtrochanteric pathological fractures and near fractures of the femur.Zickle and Mouradian reported [15] 35 cases of subtrochanteric pathological fractures and near fractures. Early function was good. However, difficulties in Zickle nail placement, femoral shortening, valgus displacement and rotational instability are its disadvantages.
Femoral reconstruction nail or long gamma nail can fix the full length of the femur, which helps to reduce the chance of pathological fracture with metastases in other parts of the femur in the future, and most patients with bone destruction undergo intracapsular scraping and cement filling of the lesion, which significantly reduces the patient’s pain after surgery. The patient is able to move to the ground as soon as possible. This method is relatively easy to operate compared with artificial prosthesis reconstruction, and the patient recovers quickly after surgery and has better stabilization effect.
For patients with metastatic carcinoma of the femoral stem, femoral intramedullary nail fixation can be used, and auxiliary scraping and bone cement filling can be performed when the lesion defect is large. The application of reconstructive nail fixation locks the proximal and distal ends, reducing the chance of fracture fragment shortening and intramedullary nail displacement. As the tumor progresses, screws fixed proximally in the femoral head provide stable fixation and protect other metastatic lesions in the femur. In addition to scraping the lesion, the fixation can be reinforced with bone cement to reduce the chance of failure.
Supracondylar or intercondylar fractures of the distal femur are less frequent and more difficult to manage. If sufficient bone mass is available, conventional internal fixation combined with cement filling provides adequate stability. Satisfactory pain relief and recovery of motor function can be obtained with the nail plate system and the dynamic compression nail plate system. The nail plate system is not recommended in cases of massive bone loss and extensive bone destruction. Immediate weight bearing and stability can be obtained with grouped distal femoral knee prosthesis reconstruction.
3.4. Functional assessment and complication prevention
The functional status of the patient is evaluated starting 3 months after surgery. The most commonly used assessment standard is the Enneking functional scoring system, which was adopted by the International Congress on Limb Preservation and the Bone and Soft Tissue Oncology Society in 1993.
In this study, the functional scores of patients with pathological fractures at 3 months after surgery were lower than those of patients with near fractures, suggesting that early treatment of near fractures can lead to better function. The lower functional scores in patients with generalized artificial femoral head prosthesis reconstruction than in patients with custom-made proximal femoral prosthesis reconstruction may be related to the choice of surgical treatment plan and the patient’s underlying status, with patients in good general status, with only a single metastatic lesion and a long expected survival time opting for extended tumor resection prosthesis reconstruction. Although sometimes the Enneking score has some subjective factors, it is simple and easy to perform and is commonly used in patients undergoing tumor preservation surgery.
Due to the small number of patients in this group, there were few postoperative complications. The surgical complications included three cases of postoperative incisional fat liquefaction, one patient with suspected pulmonary embolism, and one case with a distal fracture of a custom-made prosthesis, all of which were treated accordingly. Perioperative complications may lead to delayed postoperative radiotherapy and chemotherapy and therefore have a significant negative impact on the survival time of patients. Therefore, the treatment of patients with metastatic cancer should minimize the occurrence of complications. Careful intraoperative hemostasis and adequate incisional drainage reduce the complications of incision.
For elderly patients, postoperative anticoagulants are routinely applied to reduce deep vein thrombosis. Preoperative tumor vascular embolization may reduce intraoperative bleeding. Careful preoperative assessment and scoring of the patient’s overall status and detailed development of the surgical plan are effective ways to reduce complications.