Effects of Surgical Intervention for Bone Metastases on Survival in Patients with Advanced Cancer: A Nationwide Population-Based Cohort Study

Figures & data

Figure 1 Flowchart of the study design and participant selection.

Table 1 Patient Characteristics Based on the Longitudinal Health Insurance Database

Patient	Total		With Surgery		Non- Surgery		p^a
Characteristics	n	%	n	%	n	%
Total	74,900		8802	11.8	66,098	88.2
Mortality							< 0.001
Without	46,209	61.7	6004	68.2	40,205	60.8
With	28,691	38.3	2798	31.8	25,893	39.2
Sex							< 0.001
Male	39,225	52.4	4052	46.0	35,173	53.2
Female	35,675	47.6	4750	54.0	30,925	46.8
Age (years)	65.94 ± 14.29		67.45 ± 14.55		65.74 ± 14.25		< 0.001
18–44	6,318	8.4	688	7.8	5630	8.5
45–64	27,115	36.2	2867	32.6	24,248	36.7
≥ 65	41,467	55.4	5247	59.6	36,220	54.8
Location of BM							<0.001
Axial	8687	10.0	2374	28.0	6313	8.1
Appendicular	1437	1.7	546	6.4	891	1.1
Multiple	76,345	88.3	5553	65.5	70,792	90.8
Length of hospital days	12.9 ± 13.2		11.9 ± 12.9		13.1 ± 13.3		< 0.001
RT/CT							< 0.001
Without	18,092	20.9	1436	16.9	16,656	21.4
With	68,377	79.1	7037	83.1	61,340	78.6
Hospital levels
Medical center	40,195	46.5	3913	46.2	36,282	46.5	0.78
Regional hospital	36,838	42.6	3640	43.0	33,198	42.6
District hospital	9436	10.9	920	10.9	8516	10.9
HTN							< 0.001
Without	66,928	89.4	7204	81.8	59,724	90.4
With	7972	10.6	1598	18.2	6374	9.6
DM							< 0.001
Without	67,250	89.8	7596	86.3	59,654	90.3
With	7650	10.2	1206	13.7	6444	9.7
COPD							0.11
Without	71,143	95.0	8330	94.6	62,813	95.0
With	3757	5.0	472	5.4	3285	5.0
CKD							0.30
Without	70,781	94.5	8297	94.3	62,484	94.5
With	4119	5.5	505	5.7	3614	5.5
IHD							< 0.001
Without	72,391	96.7	8391	95.3	64,000	96.8
With	2509	3.3	411	4.7	2098	3.2
CHD							< 0.001
Without	72,862	97.3	8495	96.5	64,367	97.4
With	2038	2.7	307	3.5	1731	2.6
Stroke							0.01
Without	72,691	97.1	8500	96.6	64,191	97.1
With	2209	2.9	302	3.4	1907	2.9
Pneumonia							< 0.001
Without	60,898	81.3	7477	84.9	53,421	80.8
With	14,002	18.7	1325	15.1	12,677	19.2
Injury							< 0.001
Without	70,630	94.3	7600	86.3	63,030	95.4
With	4270	5.7	1202	13.7	3068	4.6
Hyperthyroidism							0.73
Without	74,817	99.9	8794	99.9	66,023	99.9
With	83	0.1	8	0.1	75	0.1
Liver disease							< 0.001
Without	69,755	93.1	8041	91.4	61,714	93.4
With	5145	6.9	761	8.6	4384	6.6
Depression							< 0.001
Without	74,384	99.3	8714	99.0	65,670	99.4
With	516	0.7	88	1.0	428	0.6
Sepsis							0.004
Without	64,578	86.2	7676	87.2	56,902	86.1
With	10,322	13.8	1126	12.8	9196	13.9
Zoledronic acid							< 0.001
Without	52,415	70.0	6386	72.6	46,029	69.6
With	22,485	30.0	2416	27.4	20,069	30.4
Pamidronate disodium							< 0.001
Without	53,614	71.6	6791	77.2	46,823	70.8
With	21,286	28.4	2011	22.8	19,275	29.2
Clodronate Tetrahydrate							< 0.001
Without	52,635	70.3	6654	75.6	45,981	69.6
With	22,265	29.7	2148	24.4	20,117	30.4
Denosumab							0.47
Without	52,286	69.8	6174	70.1	46,112	69.8
With	22,614	30.2	2628	29.9	19,986	30.2

Note: ^aChi-square/Fisher’s exact test for categorical variables and t-test for continuous variables. A p-value < 0.001 was considered statistically significant.

Abbreviations: BM, bone metastases; RT, chemotherapy; CT, chemotherapy; DM, diabetes mellitus; CHD, congestive heart disease; CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease; HTN, hypertension; IHD, ischemic heart disease.

Table 2 Factors for Mortality Based on Multivariate Cox Regression Analysis

Variables	Crude HR	Adjusted HR^a	95% CI	95% CI	p
Surgery
With/Without	0.64	0.70	0.67	0.73	< 0.001
Sex
Male/Female	1.40	1.40	1.37	1.44	< 0.001
Age (years)
45–64/18–44	1.01	1.02	0.97	1.06	0.453
≥ 65/18–44	1.18	1.16	1.11	1.22	< 0.001
HTN
With/Without	1.44	1.54	1.52	1.57	< 0.001
DM
With/Without	1.65	1.77	1.74	1.81	< 0.001
COPD
With/Without	1.69	1.67	1.64	1.71	< 0.001
CKD
With/Without	1.08	1.30	1.04	1.93	0.005
IHD
With/Without	1.52	1.61	1.56	1.66	< 0.001
CHD
With/Without	1.76	1.86	1.80	1.92	< 0.001
Stroke
With/Without	1.64	1.73	1.68	1.79	< 0.001
Pneumonia
With/Without	2.43	2.26	2.22	2.29	< 0.001
Injury
With/Without	1.48	1.54	1.50	1.57	< 0.001
Hyperthyroidism
With/Without	1.38	1.44	1.27	1.74	0.002
Liver disease
With/Without	1.94	1.88	1.84	1.92	< 0.001
Depression
With/Without	1.61	1.72	1.61	1.84	< 0.001
Sepsis
With/Without	2.52	2.31	2.27	2.35	< 0.001
Zoledronic acid
With/Without	0.56	0.85	0.40	1.38	0.44
Pamidronate disodium
With/Without	0.84	1.03	0.57	1.60	0.57
Clodronate Tetrahydrate
With/Without	0.68	0.88	0.30	1.41	0.45
Denosumab
With/Without	0.90	1.27	0.71	1.77	0.60

Note: ^aAdjusted for the variables listed in the table. A p-value < 0.001 was considered statistically significant.

Abbreviations: HR, hazard ratio; CI, confidence interval; DM, diabetes mellitus; CHD, congestive heart disease; CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease; HTN, hypertension; IHD, ischemic heart disease.

Figure 2 Kaplan–Meier curves for cumulative survival and the Log rank test. The inpatients with bone metastases were aged ≥ 18 years and stratified by whether they underwent surgery.

Figure 3 The number of surgeries done for BM by years of follow-up presents an upward trend.

Table 3 Factors for Mortality Stratified by Sex, Age Groups, Comorbidities, and Certain Cancers Based on Multivariate Cox Regression Analysis

Surgery
Stratified	Adjusted HR^a	95% CI	95% CI	p
Total	0.70	0.67	0.73	< 0.001
Sex
Male	0.74	0.71	0.77	< 0.001
Female	0.66	0.64	0.69	< 0.001
Age group (years)
18–44	0.66	0.64	0.69	< 0.001
45–64	0.67	0.65	0.70	< 0.001
≥ 65	0.73	0.70	0.76	< 0.001
HTN	0.77	0.74	0.80	< 0.001
DM	0.86	0.83	0.89	< 0.001
COPD	0.77	0.74	0.81	< 0.001
CKD	0.82	0.79	0.86	< 0.001
IHD	0.82	0.79	0.85	< 0.001
CHD	0.75	0.72	0.78	< 0.001
Stroke	0.71	0.68	0.74	< 0.001
Pneumonia	0.76	0.73	0.79	< 0.001
Injury	0.84	0.80	0.87	< 0.001
Hyperthyroidism	0.95	0.91	0.99	0.034
Liver disease	0.79	0.76	0.82	< 0.001
Depression	0.79	0.76	0.82	< 0.001
Sepsis	0.93	0.89	0.97	0.011
Lung cancer	0.74	0.68	0.80	< 0.001
Female breast cancer	0.79	0.72	0.86	< 0.001
Prostate cancer	0.69	0.61	0.79	< 0.001

Notes: ^aAdjusted for the listed variables. A p-value < 0.001 was considered statistically significant.

Abbreviations: HR, hazard ratio; CI, confidence interval; DM, diabetes mellitus; CHD, congestive heart disease; CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease; HTN, hypertension; IHD, ischemic heart disease.