Mortality rates in this study group are consistent with literature. We report a 30-day mortality of 13.4% which is similar to that previously reported (2.6 to 12%) [14,15,16]. One-year and 2-year mortality in our patients were 67% and 85.7% respectively, compared to previously reported mortality rates of 60–83% at 1 year and 70–94% at 2 years [2,3,4,5,6,7,8,9].
Regarding short-term outcomes, poor ASA and functional status have been previously found to be significant risk factors for 30-day mortality [15]. Previous studies observed that patients who were underweight [14], had rapid-growth tumours, visceral metastases, internal fixation or no postoperative chemotherapy [15] have higher mortality at 30 days but results were not statistically significant. On the other hand, age, gender, blood loss, blood transfusion, duration of surgery, primary cancer type, major bony resection and CCI were not found to be related to survival [14,15,16].
Many studies had also investigated risk factors for longer-term survival. However, Sorenson et al. found that predictors of survival were inconsistent amongst previous studies and cited that the reason might be because these studies on patients undergoing surgical treatment for metastatic lesions exhibit a great extent of heterogeneity [7]. Furthermore, different primary cancers contribute unequally to the various study groups and other studies include metastatic lesions at other sites including shoulder and the spine with differing proportions.
The common risk factor of survival across all studies is the site of the primary cancer leading to the pathological fracture. The link between primary site of cancer and long-term survival in patients with pathological femur fracture has been well-established [2,3,4,5,6,7,8]. Multivariate analysis of the risk factors for survival in this study demonstrates that patients with breast cancer have significantly better prognosis than patients with lung cancer.
Other factors previously studied and found to be significant in at least one study include preoperative serum haemoglobin, presence of visceral metastases, presence of spinal metastases, presence of brain metastases, number of bony metastases, whether the fracture was an actual or impending fracture, duration from time of cancer diagnosis to incidence of pathological fracture, type of procedure performed, functional status, presence of adjuvant therapy and ASA status [2,3,4,5,6,7,8].
In this study, risk factors that were significant in univariate analysis but ultimately not found to be independent risk factors after multivariate analysis include serum haemoglobin, presence of visceral metastases and time from diagnosis of cancer to incidence of pathological fracture as risk factors for survival after treatment.
Apart from site of primary cancer, serum albumin is the other independent risk factor for mortality in this study. Serum albumin is a readily available parameter to evaluate patient’s nutritional status [17] and provides useful prognostic significance in cancer survival [18] and traumatic hip fractures [19,20,21]. Preoperative serum albumin may be an indicator of patient’s ability to withstand surgical impact and early rehabilitation. It has also been shown to be useful for reducing complications in orthopaedic patients by allowing us to screen and treat those at risk [17]. Advantages of using serum albumin as a prognostic tool include the fact that it is a simple, inexpensive, and reproducible laboratory marker. Normal albumin levels have been found to correlate with higher survival in metastatic lesions at other body sites, such as the pelvis [22]. Few studies however have studied the role of albumin as a prognostic factor in pathological femoral fractures.
Nathan et al. looked into the effect of albumin on survival after treatment of pathological femur fractures and found albumin significant only in univariate analysis and not after multivariate regression [2]. Katagiri et al. noted that even though laboratory data including albumin are known to be prognostic factors for some malignancies, they have not been sufficiently investigated as prognostic factors in the past [13]. Katagiri et al. demonstrated that laboratory data can be a significant prognostic factor and included albumin in their prediction model—patients with albumin < 37 g/L had poorer prognosis in their model [13]. This prognostic model was based largely on non-surgically treated patients and may not be applicable to potential surgical candidates [23]. Patients who present with an actual fracture or impending fracture requiring surgery are at a later stage of their malignancy and this may explain why the average serum albumin level in our study group with only surgical-treated patients is 32 g/L. Cox regression analysis in our study demonstrates worse prognosis for every 1 g/L decrease in albumin. This suggests that prognostic models may benefit from looking at the adverse effect that even lower levels of serum albumin have on prognosis; however, further studies are needed to fully validate this.
Serum albumin may be a useful prognostic factor for survival and commonly utilised as an indicator for malnutrition. Nevertheless, there is limited evidence that nutritional supplementation may improve prognosis in patients with low serum albumin levels. Gupta et al. suggested that since low levels of serum albumin are linked with poorer outcome in cancer patients, serum albumin can perhaps be utilised as an independent indicator of the need for nutrition intervention [18]. Nevertheless, the study noted the absence of clinical trials demonstrating that raising albumin levels, by means of intravenous infusion or hyperalimentation, decreases the excess risk of mortality in cancer patients, and by extension, patients with metastatic femoral fractures. A Cochrane review also found minimal evidence to suggest that nutritional supplementation can reduce mortality in patients with hip fractures [24].
This study found a significant correlation between albumin and presence of visceral metastases. This finding needs to be validated by further studies. If so, serum albumin may be interpreted as an indicator of general physiological well-being, and its potential for optimization be limited by the presence of visceral metastasis.
This study shows that there could be a role for albumin in prognostication of survival in patients with metastatic femur fractures. There may be value in measuring serum albumin routinely on admission to aid decision-making with regard to surgical treatment. Prudence is imperative before commencing surgical treatment on patients who have hypoalbuminaemia or are extremely cachectic and malnourished as they may not benefit from palliative surgery. Further research is required to determine if clinical scoring of prognosis to guide treatment in patients with metastatic pathological femur fractures will improve outcomes.
Limitations
This was a single-centre retrospective study using prospectively collected data with all the limitations inherent to such design.
This study did not include patients who were treated non-surgically as records were only obtained from our hospital surgical registry. This study was unable to capture date on patient who underwent adjuvant treatment modalities including chemotherapy, hormonal therapy and radiotherapy, which may affect their survival.
Data on the peri-operative functional outcomes which had been previously found to be significant risk factors for survival was not included in this study [2, 6, 7].
Strengths
This study represents a more homogenous cohort of pathological femur fractures compared to previous studies.