Introduction

Currently, the prevalence of metastatic bone disease in developed countries is more than 280,000 new cases per year [1]; this number is expected to rise as patients with cancer live longer [2]. Bone is the third most common site of metastatic disease after the lung and the liver. The most common primary cancers are lung, breast, prostate, thyroid and renal cancer. Postmortem analysis shows that approximately 70 % of all patients with breast and prostate cancer and 35–42 % of patients with lung, thyroid and renal cancer have skeletal metastases [3]. The financial burden of treating patients with metastatic bone disease in the USA per year estimates approximately 12.6 billion dollars, which accounts for 17 % of the total annual cost of cancer treatments [4].

In the past, the occurrence of a pathological fracture through bone sarcomas or skeletal metastases was an absolute contraindication for limb salvage; in this setting, treatment traditionally consisted of amputation proximal to the most superior aspect of the fracture hematoma. Currently, the decision for limb salvage surgery has been reconsidered [1–12]. Although malignant primary bone tumors are usually referred for treatment at tertiary tumors centers, patients with metastatic bone disease may be treated by general orthopedic surgeons at community hospitals [2]. In any case, surgical considerations of patients with bone metastases should include multiple factors such as the location of the tumor within bone and the skeleton, the histology of the primary tumor, the pain, comorbidities and expected life span of the patients. Impending or actual pathological fractures of the long bones in patients with primary and metastatic bone tumors are a difficult and challenging complication that may alter management and prognosis, decrease quality of life and jeopardize survival [1–12]. In general, stabilization of an impending or pathological fracture involves techniques and concepts that differ from those used for patients with non-pathologic fractures [2]. Bone involved by metastatic cancer is weakened and requires stabilization or reconstruction with an implant or prosthetic device that should last the remaining of patient’s life and to stabilize the entire diseased bone [2]. Surgical complications should be minimized, as complications in cancer patients are unwanted. Methyl methacrylate is often used in combination with prostheses or intramedullary devices to supplement the fixation [2]. Radiation therapy and embolization often are used as a local adjuvant after surgical treatment or for palliation [13, 14].

Pathological long bones fractures pose many difficulties to the most experienced surgeons. Their management may alter prognosis, affecting both the quality of life and survival of the patients [12]. Previous studies have reported on the diagnosis, management and survival of cancer patients with metastatic bone disease and pathological fractures [2–38]; their results cannot be decisive regarding the optimal management of the patients and the survival of the reconstructions because of the lack of control groups and short term survival of these patients. Moreover, studies that propose treatment guidelines for cancer patients with bone metastases are limited [12, 39], and most surgeons treat these patients according to standard practice for fractures or their own preference. Therefore, to enhance the literature, this study aims to provide practical guidelines for the treatment of patients with long bone metastases based on a systematic review of the literature and to propose an algorithm to guide the treating orthopedic surgeons in their decision-making for these patients. We believe that the findings of the present article and the proposed treatment algorithm based on the experience and current practice of a tertiary tumor center with a relatively large experience on the treatment of tumor patients would be useful for the treatment approach of patients with long bone metastases.

Materials and methods

The search strategy included a computerized literature search in MEDLINE, EMBASE and Scopus. A systematic review of clinical studies that evaluated any treatment of long bone metastases was done using as keywords “long bones”, “metastases” and “treatment”. The reference lists of the selected papers were also checked for further relevant publications. Papers in other than English language and publication date before 2000 were excluded. The articles were then censored if they were case reports, review or opinion articles, or technique descriptions. From a total of 398 articles found, 19 articles were related to treatment of a clinical cohort of patients with metastatic disease of the long bones (Table 1) [2, 6–9, 21, 24, 25, 27–37]. There was no disagreement between the authors of the present study regarding the level of evidence of the included 19 articles. These articles were studied to determine the accuracy of surgical treatments for long bone metastases in every anatomic location, regardless of cancer type, stage and grade of the oncologic disease. Last, guidelines for the treatments of long bone metastases were inferred from the review analysis.

Table 1 Peer-reviewed studies included in this review
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Results

The most common primary cancer was breast followed by lung, prostate, renal and thyroid cancer; the femur was the most commonly affected site. Long bone metastatic lesions did not always require surgical intervention; the size and location of the metastatic lesion, the general health status and expected survival of the patients influenced the decision-making regarding the optimal treatment. The indications for surgery of long bone metastases were an impending or an actual pathological fracture and/or severe, constant pain; patients were operated if an expected survival of more than 6 weeks was estimated. Patients with a long bone metastasis to the lower extremities were more commonly operated compared to those with a long bone metastasis to the upper extremities.

There was no clear evidence to support resection of the metastatic lesion at the same surgical setting with internal fixation or prosthetic reconstruction of the metastatic lesion. The overall incidence of local disease progression was 11.5 %, while subsequent development of new lesions in the diseased bone was only 1 %. However, wide resection of a solitary bone metastasis, especially from renal cancer was associated with a more beneficial effect on survival of the patients compared with that of patients treated with less than a wide resection.

Internal fixation preferably with a reconstruction type intramedullary nail was indicated for meta-diaphyseal lesions; their rate of mechanical failure ranged from 2 to 22 %, but perioperative deaths from cardiopulmonary complications ranged from 1 to 10 %. Prosthetic reconstruction was indicated for extensive lytic lesions or pathological fractures in meta-epiphyseal locations; their rate of mechanical failure rate was less than 3.7 %, with an overall complications rate ranging from 6 to 35 %. Most of the internal fixation-related complications occurred more than 1 year after diagnosis and treatment, in contrast to prosthetic reconstruction-related complications that occurred earlier.

Local adjuvants were extensively used as per surgeons’ own preference. Cement augmentation was used for additional mechanical stability of the fixation. Radiation therapy or embolization has been used to slow local disease progression and avoid any subsequent failure of the fixation.

Discussion

Improvements in imaging, surgery and medical oncology treatments have greatly increased the survival of cancer patients [3–5], including those with metastatic disease [6]. However, the occurrence of a skeletal event from cancer significantly influences the quality of life of these patients. In these cases, the indications for surgical treatment vary from pain to impending or actual pathological fracture, and seem to differ between countries [5]; in the USA, up to 71 % of patients with metastatic cancers have been treated due to impending pathological fractures compared to only 18 % in the Nordic countries [6]. Decisions regarding potential surgery for metastatic bone disease require reliable data about the patients’ expected survival and quality of life [15].

Patients with metastatic bone disease are often treated at community hospitals [2]. To our opinion and the related literature, these patients should be better referred for treatment at tertiary tumor centers [1–6, 12]. In cases that a musculoskeletal tumor trained orthopedic surgeon will not be the treating physician, general orthopedic surgeons should be familiar with the management of these patients. More importantly, the treating orthopedic surgeon should know that a metastatic bone lesion may not reliably heal [2]. As the treatment of metastatic bone disease is multidisciplinary, it is imperative that orthopedic surgeons are involved at an early stage and not only follow the patients with pathological fractures, as early treatment, management of pain, and improvement in the functional status is particularly important for cancer patients, especially those with a short life expectancy [6].

Prognostic life expectancy of patients with skeletal metastasis is important for the choice of the appropriate treatment. Previous studies by orthopedic surgeons [40–42] and radiation oncologists [43–45] reported on the prognostic factors for patients with skeletal metastasis. Tomita et al. [40] and Bauer et al. [42] involved analysis of patients who had undergone surgery. Tokuhashi et al. [41] studied both surgically and conservatively treated patients. In a recent prospective study, the number of surgeries performed was approximately 7 % of that of radiotherapies [46]. Therefore, previously published studied in orthopedic oncology literature might not be representative of patients with bone metastasis [47]. Katagiri et al. [47] identified six significant prognostic factors for survival: the primary lesion, visceral or cerebral metastases, abnormal laboratory data, poor performance status, previous chemotherapy and multiple skeletal metastases. The prognostic score was calculated by adding together all the scores for individual factors. With a prognostic score of ≥7, the survival rate was 27 % at 6 months and only 6 % at 1 year; in contrast, patients with a prognostic score of ≤ 3 had a survival rate of 91 % at 1 year and 78 % at 2 years. This scoring system was able to predict the survival rates of patients with skeletal metastases more accurately than previous scoring systems and may be useful for selecting an optimal treatment [47].

Mirels’ scoring system [16] seems to be the most detailed used classification system for the evaluation and decision-making for treatment of a long bone metastatic lesion (Fig. 1) [2]. This system is based on the size, site and imaging of the lesion, and the presence of pain [16]; a score higher than 8 points is associated with an impending fracture and indicates the need for prophylactic surgery [16]. However, this method does not take into account the life expectancy of the patient and which type of prophylactic surgery is better to use [38]. Conventional implants may not achieve rigid fixation in patients with long bone metastasis. Acrylic bone cement augmentation and/or adjuvant treatments, such as embolization or radiation therapy, are often mandatory to obtain local disease control and to avoid mechanical failure of the implant [2].

Fig. 1
figure 1

Protocol for decision-making and treatment of patients with long bone metastases

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There is controversy regarding the optimal surgical treatment for patients with a solitary bone metastasis, especially for patients with renal cancer [6, 17–20]. Some authors reported that en bloc resection of a solitary metastasis was a positive prognostic factor for an improved survival [6, 17]; however, other authors reported that en bloc resection did not affect the survival of the patients [18–20]. Additionally, there is no agreement that en bloc resection of a metastasis in patients with multiple metastases affects the survival of the patients when compared with intralesional surgery [6]. There is also controversy regarding the complications and reoperation rates after surgery for bone metastases. Some authors reported that the complications rate seems to be lower after en bloc resection compared to marginal or intralesional surgery [6, 7, 21, 22]. We concur that en bloc resection of a metastatic lesion may prevent local progression of the disease and therefore mechanical complications and reoperations [6, 8, 23–25]. However, most complications after intramedullary nailing for long bone metastases occur late, more than 1 year after diagnosis and treatment, which should be considered in treatment decision-making [7]. In contrast, prosthetic reconstruction usually allows for immediate postoperative stability and weight bearing, and has been associated with lower mechanical failure rates compared to intramedullary nailing [8, 23–25]. Therefore, prosthetic reconstruction seems to be the more durable surgical option for patients with a longer expectancy survival, especially if e bloc resection of the metastatic lesion can be obtained [24, 26].

Based on the analysis of the literature [2, 6–9, 21, 24, 25, 27–37, 39], the questions raised by this manuscript are still challenging. After decades of treating tumor patients with different methods and approaches, we obtained great experience for the management of these patients, and we propose treatment guidelines for patients with long bone pathological fractures from metastatic bone tumors (Fig. 2). Surgeons should follow oncological principles in treating tumor patients. Referral to a specialized orthopedic oncology center is generally recommended. Treatment decision requires complete staging and oncological principles. Intramedullary fixation or prosthetic reconstruction should be chosen on the basis of the location of the lesion, the extent of bone destruction and the ability of the construct to last the life expectancy of the patients. If surgical treatment is necessary, the life expectancy of the patients should be considered. We consider expected survival of less than 6 weeks as a relative contraindication for surgical management of any impending or actual pathological fractures, especially if in the upper extremity. For patients with a life expectancy of 3–12 months, we opt for less invasive surgical reconstruction procedures that do not need prolonged rehabilitation [5]. For patients with longer life expectancy (>12 months), we aim for en bloc resection of a metastasis and opt for durable reconstruction procedures such as prosthetic reconstructions, even if associated with longer rehabilitation times [5]. The histology, response to chemotherapy and radiation therapy of the primary cancer, the presence of visceral metastases, the number of skeletal metastases and the overall health status of the patients seem to be the most important predictors of survival [5, 6]. We believe that this algorithm based on our experience and analysis of the literature, would be helpful for decision-making and treatment approach of patients with long bone pathological fractures from metastatic bone tumors.

Fig. 2
figure 2

Mirels’ classification for impending pathological fractures [16]

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