Prognostic factors for patients undergoing surgery for femur metastases following systemic treatment

Abstract

BACKGROUND

Patients with bone metastases often receive systemic treatments, including hormone and anti-cancer drug therapies. Systemic treatment may also be considered while planning for surgery. Consequently, accurate prognostic data and survival estimates for patients with bone metastases are indispensable for recommending the most appropriate treatment strategies.

AIM

To examined the prognosis and prognostic predictors in patients who received systemic treatment before surgery for femoral metastases.

METHODS

This retrospective cohort study included 24 patients who underwent surgery for femoral metastasis by orthopedic doctors and received preoperative systemic therapy at our hospital between 2014 and 2024. Kaplan-Meier analysis and Cox proportional hazards regression were employed to assess the relationship between overall survival (OS) and clinical parameters, including serum biochemical concentrations and blood cell counts.

RESULTS

Fourteen patients underwent postoperative systemic treatment. The median OS was 6 months [95% confidence interval (CI): 4-15 months], and the 1-year survival rate was 35%. Of the 24 patients, 17 were followed up until death. The multivariate analysis revealed that the administration of systemic treatment after surgery (hazard ratio, 0.27; 95%CI: 0.085-0.85, P = 0.025) was significantly associated with a favorable OS.

CONCLUSION

Orthopedic doctors should take into consideration that administering systemic treatment postoperatively may improve the prognosis of patients undergoing surgery for femoral metastasis who have also received preoperative systemic treatment.

Key Words: Femur metastasis; Surgery; Prognostic factors; Systemic treatment after surgery; Retrospective studies

Core Tip: This retrospective cohort study included 24 patients who underwent surgery for femoral metastasis by orthopedic doctors and received preoperative systemic therapy. We investigated the relationship between overall survival and clinical parameters, including serum biochemical concentrations and blood cell counts. Administering systemic treatment after surgery may be a favorable prognostic factor in patients undergoing surgery for femoral metastasis who have also received preoperative systemic treatment.

INTRODUCTION

Recent developments in the field of medicine have led to more prolonged survival in patients with cancer, even in the presence of bone metastasis[1]. The bone is the third most frequent site of metastasis after the lungs and liver[2]. Patients with cancer often undergo surgery for bone metastases in the extremities[3]. While this approach offers immediate pain relief and helps maintain quality of life, surgical complications pose a significant issue for patients with limited life expectancies.

One study reported prognostic factors in patients undergoing surgery for extremity bone metastases and found that primary cancer type, multiple bone metastases, presence of visceral metastases, low hemoglobin levels, and surgical procedure were associated with prognosis[4,5]. A study on femur metastases, the most commonly operated form of extremity bone metastases, also reported an association between cancer malignancy at the primary site and prognosis[6].

Patients with bone metastases often undergo systemic treatments such as hormone therapy and anti-cancer drug therapy and may also undergo systemic treatment when considering surgery. Although several studies have investigated the prognosis of patients undergoing surgery for femoral bone metastases, none have focused on cases in which systemic treatment was administered before surgery[6-8].

Patients undergoing surgery for femoral bone metastases have diverse clinical backgrounds. For instance, some patients present with femoral bone metastases at the time of cancer diagnosis and require surgery, whereas others develop femoral bone metastases after undergoing multiple cycles of chemotherapy.

Furthermore, Katagiri et al[9] reported that preoperative chemotherapy is a poor prognostic factor in patients with bone metastases. Therefore, we believe that a study focusing on patients undergoing preoperative chemotherapy before surgery for femoral bone metastases is useful.

In this study, we investigated the prognosis and prognostic predictors in patients who underwent surgery for femoral metastases after preoperative systemic therapy.

MATERIALS AND METHODS

This single-center retrospective cohort study included 24 patients who underwent surgery for femoral metastasis by orthopedic doctors and received preoperative systemic therapy at our hospital between July 2014 and August 2024. In this study, systemic treatment included hormone therapy, anticancer drug therapy, molecular targeted drugs, and immune checkpoint inhibitors.

The associations between overall survival (OS) and clinical parameters that could be potential prognostic factors, including age, sex, type of cancer, surgical method, type of systemic treatment before surgery for femur metastasis, presence or absence of visceral metastasis, number of bone metastases, presence or absence of pathological fractures, and presence or absence of systemic treatment after surgery for femur metastasis, were evaluated. OS was defined as the time from the date of surgery for femoral metastasis to the date of the last follow-up or death.

Regarding the type of cancer, patients were divided into two groups based on the new Katagiri score: Those classified as slow growth and those classified as moderate or high growth. The relationship of the type of growth with OS was evaluated[9].

Regarding systemic treatment, the patients were divided into two groups: Those who received hormone therapy and those who did not, and their relationship with OS was evaluated.

Additionally, serum concentrations of biochemicals, such as albumin (ALB), C-reactive protein (CRP), and lactate dehydrogenase (LDH), were assessed within 1 month before surgery for femur metastasis.

The following cut-off values of biochemicals were determined as the new Katagiri score: ALB, 3.7 g/dL, CRP, 0.4 mg/dL, and LDH, 250 U/L[7].

Statistical analysis

Statistical analyses were performed using the EZR software[10]. OS was estimated using the Kaplan-Meier method, with the data cut-off in December 2024. Survival disparities were assessed via the log-rank test for univariate comparisons, while independent prognostic factors were determined through multivariate analysis using a Cox proportional hazards model. Results are presented as odds ratios (OR) with 95% confidence intervals (CI). Statistical significance was defined as P < 0.05.

RESULTS

Table 1 summarizes the clinical characteristics of the patients. This study included 10 men and 14 women who underwent surgery for femur metastasis and had a median patient age of 73.5 years (range: 48-86). Seventeen patients underwent osteosynthesis, and seven patients underwent artificial head replacement.

Table 1 Patient clinical characteristics.

Characteristic	n
Age at bone metastasis diagnosis	Median 73.5 (range, 50-87)
Sex
Male	11
Female	13
Type of cancer
Lung cancer
With molecularly targeted therapy	1
Without molecularly targeted therapy	3
Breast cancer
Hormone dependent	5
Hormone independent	2
Prostate cancer
Hormone dependent	2
Hormone independent	1
Colorectal cancer	2
Esophageal cancer	1
Hepatocellular carcinoma	1
Kidney cancer	1
Bladder cancer	1
Multiple myeloma	3
Malignant lymphoma	1
Surgical method
Osteosynthesis	17
Artificial head replacement	7
Systemic treatment before surgery
Hormone therapy	6
Anticancer drugs and/or molecularly targeted drugs	18
Visceral metastasis
Yes	14
No	10
Number of bone metastases
1	6
Multiple	18
Pathological fractures
Yes	6
No	18
Systemic treatment after surgery
Yes	14
No	10

The median follow-up duration was 5.5 months (range: 1-77). The median OS was 6 months (95%CI: 4-15), and the 1-year survival rate was 35% (Figure 1A). Of the 24 patients, 17 were followed up until death.

Figure 1 Patients receiving systemic treatment before and after surgery. A: Overall survival of the 24 patients who underwent surgery for femur metastasis after receiving preoperative systemic treatment; B: Kaplan-Meier curves of the overall survival of patients classified by systemic treatment after surgery. OS: Overall survival; CI: Confidence interval.

Univariate analysis identified the following factors as significant predictors of favorable OS: Low-growth cancer (P = 0.020), osteosynthesis (P = 0.0040), visceral metastasis (P = 0.017), and systemic treatment after surgery (P = 0.0030) (Table 2). Systemic treatment was selected following surgery for visceral metastasis. We considered the surgical method to be subject to selection bias and did not include this in the multivariate analysis. The multivariate analysis revealed that the administration of systemic treatment after surgery (hazard ratio, 0.27; 95%CI: 0.085-0.85, P = 0.025) was significantly associated with a favorable OS (Table 3).

Table 2 Univariate analysis of the overall survival.

Characteristics	n	Median OS	95%CI	P value
Age				0.19
> 70	15	5	1-15
< 71	9	10	4 to not censored
Sex				0.67
Male	11	6	2-15
Female	13	7	1 to not censored
Type of cancer				0.020
Low growth	11	29	1 to not censored
Moderate or rapid growth	13	6	2-9
Surgical method				0.0040
Osteosynthesis	17	6	1-9
Artificial head replacement	7	77	4 to not censored
Type of systemic treatment before surgery				0.064
Hormone therapy	6	29	1 to not censored
Anticancer drugs and/or molecularly targeted drugs	18	5	3-9-not censored
Visceral metastasis				0.017
Yes	14	6	1-7
No	10	15	1 to not censored
Number of bone metastases				0.94
1	6	9	1 to not censored
Multiple	18	6	4-29
Pathological fractures				0.153
Yes	6	9	4 to not censored
No	18	6	2-15
Systemic treatment after surgery				0.0030
Yes	14	29	5 to not censored
No	10	4	1-6
Albumin				0.057
≥ 3.7	13	15	3 to not censored
< 3.7	11	6	1-7
CRP				0.867
> 0.4	16	7	4-29
≤ 0.4	8	5	1 to not censored
LDH				0.58
≥ 250	11	6	1-28
< 250	13	7	3 to not censored

OS: Overall survival; CI: Confidence interval; CRP: C-reactive protein; LDH: Lactate dehydrogenase.

Table 3 Multivariate analysis of the overall survival.

Characteristics		HR	95%CI	P value
Systemic treatment after the surgery	Yes	0.27	0.085-0.85	0.025
Visceral metastasis	No	0.35	0.11-1.1	0.080

HR: Hazard ratio; CI: Confidence interval.

The 1-year survival rate of the 14 patients who underwent systemic treatment after surgery was 51%, whereas that of the 10 patients who did not undergo systemic treatment was 12% (Figure 1B).

DISCUSSION

Our study investigated the survival and prognostic factors in patients who underwent surgery for femoral metastasis following preoperative systemic therapy. The 1-year survival rate of patients who underwent surgery for femoral metastasis after receiving preoperative systemic treatment was 35%.

The New Katagiri Score considers prior chemotherapy as a prognostic factor[9]. Similarly, the presence or absence of preoperative systemic treatment may also affect prognosis, suggesting that these factors should be considered separately. Our findings are therefore significant in this context.

Our first finding regarding the administration of systemic treatment after surgery being a favorable prognostic factor in patients with femoral metastasis, provided it was also administered preoperatively. The Katagiri score, a well-established prognostic system, does not account for postoperative systemic therapy[9]. However, based on our results, it is desirable to confirm the possibility of systemic treatment after surgery, estimate OS, and manage patients with femur metastasis requiring surgery and preoperative systemic treatment accordingly.

Furthermore, we identified low-growth cancer, osteosynthesis, and presence of visceral metastasis as other favorable prognostic factors in the univariate analysis. Similar to our study, studies on patients undergoing surgery for femoral bone metastasis have reported that the type of cancer and presence of visceral metastases were associated with life prognosis[6,7]. One study reported that the choice of surgical procedure for femoral bone metastasis surgery was influenced by selection bias[6], and the favorable life prognosis of patients who underwent osteosynthesis in our study may have been similarly influenced.

Nonetheless, our study had some limitations. First, our study focused on bone metastasis of various types of malignant tumors. Although the drugs used and treatment indications vary depending on the type of malignant tumor, they are currently being studied in a single population. However, all malignant tumors require systemic treatment to prolong patient lifespan, making our study meaningful.

Second, selection bias may have been present in the surgical cases. Because no standardized guidelines exist for surgical indication, each case was discussed individually at orthopedic conferences. Consequently, the absence of clear selection criteria may have introduced bias that affected the survival outcomes.

Third, another source of selection relates to decisions regarding the administration of chemotherapy after surgery. The study included more than 10 different cancer types, and the criteria for systemic therapy varied based on these cancer types. Therefore, patients who were able to receive systemic therapy after surgery were likely in better overall health and had a more favorable baseline prognosis. Although we conducted multivariate analysis including systemic treatment after surgery and visceral metastasis; however, additional variables reflecting the patients' overall condition should be incorporated.

Fourth, the sample size was small. Although statistical analysis was conducted, in future, research including more cases is necessary, to ensure validity of the findings.

CONCLUSION

Administering systemic treatment after surgery may be a favorable prognostic factor for patients who have undergone surgery for femoral metastasis after receiving preoperative systemic treatment. Our study suggests that clinicians should assess the feasibility of postoperative systemic treatment, as patients eligible for such therapy may have a more favorable prognosis after surgery for femoral bone metastases.