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Annals of Translational Medicine logoLink to Annals of Translational Medicine
. 2020 Apr;8(7):482. doi: 10.21037/atm.2020.03.55

Incidence of patients with bone metastases at diagnosis of solid tumors in adults: a large population-based study

Jin-Feng Huang 1, Jianfei Shen 2, Xiao Li 3, Ramesh Rengan 4, Nicola Silvestris 5,6, Minqi Wang 7, Lisa Derosa 8, Xuanqi Zheng 1, Andrea Belli 9, Xiao-Lei Zhang 1, Yan Michael Li 10,✉, Aimin Wu 1,✉
PMCID: PMC7210217  PMID: 32395526

Abstract

Background

Bones are one of the most common metastatic sites for solid malignancies. Bone metastases can significantly increase mortality and decrease the quality of life of cancer patients. In the United States, around 350,000 people die each year from bone metastases. This study aimed to analyze and update the incidence and prognosis of bone metastases with solid tumors at the time of cancer diagnosis and its incidence rate for each solid cancer.

Methods

We used the Surveillance, Epidemiology, and End Results (SEER) database to find patients diagnosed with solid cancers originating from outside the bones and joints between 2010 and 2016. Data were stratified by age, sex, and race. Patients with a tumor in situ or with an unknown bone metastases stage were excluded. We then selected most of the sites where cancer often occurred, leaving 2,207,796 patients for the final incidence analysis. For the survival analysis, patients were excluded if they were diagnosed at their autopsy or on their death certificate, or had unknown follow-ups. The incidence of bone metastases and overall survival was compared between patients with different primary tumor sites.

Results

We identified 2,470,634 patients, including 426,594 patients with metastatic disease and 113,317 patients with bone metastases, for incidence analysis. The incidence of bone metastases among the metastatic subset was 88.74% in prostate cancer, 53.71% in breast cancer, and 38.65% in renal cancer. In descending order of incidence, there were patients with other cancers in the genitourinary system (except for renal, bladder, prostate, and testicular cancer) (37.91%), adenocarcinoma of the lung (ADC) (36.86%), other gynecologic cancers (36.02%), small-cell lung cancer (SCLC) (34.56%), non-small cell lung cancer not otherwise specified and others [NSCLC (NOS/others)] (33.55%), and bladder (31.08%) cancers. The rate of bone metastases is 23.19% in SCLC, 22.50% in NSCLC (NOS/others), 20.28% in ADC, 8.44% in squamous cell carcinoma of the lung (SCC), and 4.11% in bronchioloalveolar carcinoma [NSCLC (BAC)]. As for the digestive system, the overall bone metastases rate was 7.99% in the esophagus, 4.47% in the gastric cancer, 4.42% in the hepatobiliary cancer, 3.80% in the pancreas, 3.26% in other digestive organs, 1.24% in the colorectum, and 1.00% in the anus. Overall, the incidence rate of bone metastases among the entire cohort in breast and prostate cancer was 3.73% and 5.69%, respectively.

Conclusions

The results of this study provide population-based estimates for the incidence rates of patients with bone metastases at initial diagnosis of their solid tumor. The findings can help clinicians to early detect bone metastases by bone screening to anticipate the occurrence of symptoms and favorably improve the prognosis.

Keywords: Bone metastases; Surveillance, Epidemiology, and End Results (SEER); incidence; prognosis

Introduction

Bones are one of the most common sites of metastases for many types of solid cancers (1-4). Bone metastases have an increased risk of serious skeletal-related events (SREs), such as pathological fractures, pain, hypercalcemia, and spinal cord compressions, which can seriously impair patients’ quality of life (5-9). Bone metastases also lead to a significant increase in mortality and morbidity (10-12).

In the United States, around 350,000 people die each year from bone metastasis (13). Several patients with bone metastasis and SREs are affected by breast or prostate cancer, while lower rates are observed in patients with lung, kidney, thyroid, or other cancers (4,14). The incidence rate of bone metastases in the United States is still unknown, and estimates have varied from 21,000–400,000 per annum. Though bone metastases can impact the mortality and quality of life of patients with cancer, more extensive population-based studies researching the incidence and prognosis of patients with bone metastases are lacking. Previous studies have shown that the prevalence of bone metastases is more than 70% in patients with metastatic breast and prostate cancer, and approximately 30% in metastatic renal cell carcinoma (1,12,15-18). However, there are no studies which provide information on the incidence of bone metastasis in other common cancers or systemic malignancies. Also, earlier studies cannot reflect the recent incidence and survival trends of patients with bone metastases (19).

Our study was conducted to estimate the incidence and prognosis of patients with bone metastases using the Surveillance, Epidemiology, and End Results (SEER) database that includes information on cancer incidence, treatment, and survival for approximately 30% of the American population (20). Specifically, we estimated the incidence proportion of patients’ bone metastases among solid tumors, considering tumor histology at the time of initial diagnosis.

Methods

Data source and cohort population

For our study, the SEER database was used. Inclusion criteria were adult patients (age ≥18 years) with a diagnosis of an invasive solid tumor originating outside of the bone and joints between January 1, 2010, and December 31, 2016. Patients were excluded if information relating to the presence or absence of bone metastases was unavailable. Other exclusion criteria were patients with diagnosis of carcinoma in situ and patients with a diagnosis of a rare tumor such as thymus cancer, heart cancer, mediastinum cancer, pleura cancer, spleen cancer, reticuloendothelial cancer, skin cancer, connective and soft tissue cancer, adrenal gland cancer, parathyroid gland cancer, other endocrine gland cancer, mesothelioma, Kaposi sarcoma, and lymphoma. For the survival analysis, patients were excluded if they were diagnosed at the time of the autopsy or at the issuing of the death certificate, or if they had unknown survival time or survival status.

Statistical analysis

Total numbers and incidence proportions of patients who were diagnosed with bone metastases were computed and then stratified by cancer type. The patients with lung cancer were classified by tumor histology using the International Classification of Disease for Oncology, 3rd Edition (ICD-O-3). Metastatic stage was conducted following the 7th edition of the American Joint Committee on Cancer staging manual, and then we defined patients with metastatic cancer as a subset with metastatic disease. We defined patients with bone metastases as a subset with bone metastases. The incidence proportion was defined as the number of patients diagnosed with bone metastases and a specific primary cancer divided by the total number of individuals diagnosed with that primary cancer; we also defined a second incidence proportion in which the denominator was restricted to patients with metastatic disease. The metastatic status of the brain, lung, and liver was also available, and we used it to characterize the extent of systemic disease, and subsequently calculated the incidence and median survival of patients with bone metastases classified by the extent of systemic disease. For survival estimates, we used the Kaplan-Meier method, taking into account a P value ≤0.05 as significant. The statistical analysis was generated and visualized with SPSS software (version 18; IBM Corp., USA).

Results

First, we identified 9,316,084 patients aged ≥18 years who were diagnosed with an invasive solid malignancy originating outside of the bone and joints between January 1, 2010 and December 31, 2016. The SEER database includes information on cancer incidence, treatment, and survival for approximately 30% of the American population. Patients were excluded in the cohort if the carcinoma is was in situ. Patients with an unknown bone metastases stage were excluded, leaving 2,470,634 patients for analysis. We then selected most of the sites where cancer often occurred, leaving 2,207,796 patients for the final incidence analysis (Figure 1).

Figure 1.

Figure 1

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Selection of study patients.

Between 2010–2016, a total of 2,207,796 patients had a diagnosis of cancer from common solid organs, and 426,594 patients had metastatic disease. We found 113,317 patients with bone metastases, which accounted for 5.13% of all patients, and 26.56% of those patients had metastatic disease.

Next, we found that the rate of bone metastases varied widely by primary cancer type (Table 1; Figure 2). As shown in Table 1, the bone metastasis rate is the highest in lung cancer. More specifically, the rate of bone metastases is 23.19% for small-cell lung cancer (SCLC), 22.50% in non-small cell lung cancer not otherwise specified and others [NSCLC (NOS/others)], 20.28% for adenocarcinoma of the lung (ADC), 8.44% in squamous cell carcinoma of the lung (SCC), and 4.11% in bronchioloalveolar carcinoma [NSCLC (BAC)]. In analyzing the gastrointestinal tumors, the rate of bone metastases is 7.99% in the esophagus, 4.47% in the gastric system, 4.42% in the hepatobiliary system, 3.80% in the pancreas, 3.26% in other digestive organs, 1.24% in colorectum, and 1.00% in the anus. Among patients with renal cancer, prostate and breast cancer,16.08%, 5.69%, and 3.73% of patients were respectively found to have bone metastases.

Table 1. Incidence proportion and median survival of patients with identified bone metastases at diagnosis by primary cancer site.

Site Sub-site Number of patients with cancer (any stage) Number of patients with metastatic disease Number of patients with bone metastases at diagnosis Incidence proportion of bone metastases among entire cohort (%) Incidence proportion of bone metastases among subset with metastatic disease (%) Median survival in months (interquartile range) among patients with bone metastases (months)
Head and neck1 Head and neck1 77,610 11,267 1,114 1.44 9.89 8 [3–18]
Thyroid Thyroid 88,356 3,347 679 0.77 20.29 23 [4–82]
Breast Breast 436,347 30,285 16,266 3.73 53.71 27 [8–57]
Respiratory system SCLC 39,765 26,686 9,223 23.19 34.56 5 [1–10]
SCC 93,240 33,839 7,867 8.44 23.25 3 [1–7]
ADC 147,194 80,981 29,846 20.28 36.86 5 [1–13]
NSCLC (BAC) 4,475 1,024 184 4.11 17.97 7 [3–20]
NSCLC (NOS/others) 20,622 13,224 4,434 21.50 33.53 3 [1–8]
Digestive system Esophagus 25,955 10,005 2,075 7.99 20.74 11 [4–36]
Gastric 43,570 15,525 1,947 4.47 12.54 3 [1–8]
Hepatobiliary 72,015 16,454 3,186 4.42 19.36 3 [1–7]
Pancreatic 74,660 39,535 2,835 3.80 7.17 2 [1–6]
Colorectal 249,273 52,311 3,085 1.24 5.90 5 [1–15]
Anal 12,150 1,584 121 1.00 7.64 3 [NR–7]
Other digestive organs 23,514 8,229 767 3.26 9.32 3 [1–8]
Genitourinary Renal 101,121 14,498 5,630 16.08 38.65 6 [2–17]
Bladder 124,279 5,921 1,840 1.48 31.08 4 [1–10]
Prostate 346,844 22,257 19,750 5.69 88.74 25 [11–55]
Testicular 16,661 1,993 143 0.86 7.18 NR [7–NR]
Other GU 8,467 757 287 3.39 37.91 4 [1–9]
Gynecologic Ovarian 37,468 23,890 422 1.13 1.77 5 [1–17]
Endometrial 93,149 8,304 847 0.91 10.20 6 [2–15]
Cervical 22,774 3,585 558 2.45 15.56 6 [2–15]
Other gynecologic 15,160 497 179 1.18 36.02 6 [2–16]
Brain and other nervous system Brain and other nervous system 33,127 596 59 0.18 9.90 15 [3–NR]
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1, lip, tongue, gum, floor of mouth, & other mouth, salivary gland, oropharynx, nasopharynx, hypopharynx, pharynx, nasal cavity (including nasal cartilage), accessory, sinuses, middle & inner ear, larynx, trachea, orbit & lacrimal gland, retina, eyeball, eye, NOS. GI, gastrointestinal; GU, genitourinary; GYN, gynecologic; SCLC, small-cell lung cancer; NSCLC (NOS/others), non-small cell lung cancer not otherwise specified or non-small cell lung cancer other lung cancer; ADC, adenocarcinoma of the lung; SCC, squamous cell carcinoma of the lung; NSCLC (BAC), bronchioloalveolar carcinoma; NR, not reached.

Figure 2.

Figure 2

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Incidence proportion of patients diagnosed with bone metastases within the entire cohort. SCLC, small-cell lung cancer; NSCLC, non-small cell lung cancer; BAC, bronchioloalveolar carcinoma; NOS, not otherwise specified; ADC, adenocarcinoma of the lung; SCC, squamous cell carcinoma of the lung; GI, gastrointestinal; GU, genitourinary; GYN, gynecologic.

Moreover, Table 1 and Figure 3 show the incidence proportion of patients with bone metastases among the metastatic subset (patients with stage IV disease at diagnosis). The incidence of bone metastases among the metastatic subset is 88.74% in prostate cancer, 53.71% in breast cancer, and 38.65% in renal cancer. In descending order, patients with other cancers of the genitourinary system (except renal, bladder, prostate, testicular) (37.91%), ADC (36.86%), other gynecologic cancers (except ovarian, endometrial, and endometrial cancer) (36.02%), SCLC (34.56%), NSCLC (NOS/others) (33.55%), and bladder cancer (31.08%), showed an incidence proportion of bone metastases of >30%.

Figure 3.

Figure 3

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Incidence proportion of patients diagnosed with bone metastases within subset with metastatic disease. SCLC, small-cell lung cancer; NSCLC, non-small cell lung cancer; BAC, bronchioloalveolar carcinoma; NOS, not otherwise specified; ADC, adenocarcinoma of the lung; SCC, squamous cell carcinoma of the lung; GI, gastrointestinal; GU, genitourinary; GYN, gynecologic.

Table 1 and Figure 4 show the median survival time of patients with bone metastases in different systemic malignancies. The median survival time among patients with breast cancer and bone metastases, prostate cancer, and bone metastases and thyroid cancer, and bone metastases are 27, 25, and 23 months, respectively. The survival time of the 3 cancers mentioned above is higher than the others. The median survival time of other tumors with bone metastases is less than 10 months. In general, survival is worse in patients with digestive system cancer and bone metastases compared with other types of primary cancer. The median survival time in patients with hepatobiliary, gastric, and anal tumors is 3 months. Among patients with pancreatic tumor and bone metastases, the median survival time is 2 months.

Figure 4.

Figure 4

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Median survival of patients with identified bone metastases. SCLC, small-cell lung cancer; NSCLC, non-small cell lung cancer; BAC, bronchioloalveolar carcinoma; NOS, not otherwise specified; ADC, adenocarcinoma of the lung; SCC, squamous cell carcinoma of the lung; GI, gastrointestinal; GU, genitourinary; GYN, gynecologic.

Incidence proportion and median survival time of patients with bone metastases, as organized based on the presence or absence of brain, liver, and lung metastases, are shown in Table 2. In summary, the incidence of bone metastasis was higher, and survival time was shorter among patients with more extensive metastases at diagnosis. The incidence of bone-only metastasis was 13.98% in NSCLC (NOS/others), 12.64% in SCLC, and 11.81% in ADC. In descending order, patients with bladder cancer (5.14%), SCC (4.90%), esophageal cancer (4.52%), gastric cancer (2.86%), hepatobiliary cancer (2.74%), renal cancer (2.65%), breast cancer (2.22%), and NSCLC (BAC) (2.02%) showed an incidence proportion of bone metastases of >2%. The median survival time among patients with bone-only metastases in thyroid cancer, breast cancer, prostate cancer, and anal cancer was 60, 35, 27, and 20 months, respectively.

Table 2. Incidence proportion and median survival of patients with bone metastases by extent of systemic disease.

Site Sub-site Type of systemic metastasis Number of patients Number of patients with bone metastases Proportion with bone metastases (%) Median survival in months (interquartile range)
Head and neck1 Head and neck1 Lung 1,284 217 16.90 6 [3–13]
Liver 372 158 42.47 8 [3–18]
Brain 77 21 27.27 5 [1–18]
2 of 3 273 122 44.69 4 [2–12]
All 3 18 12 66.67 5 [1–13]
None 75,371 532 0.71 10 [4–23]
Thyroid Thyroid Lung 1,076 224 20.82 11 [2–49]
Liver 95 31 32.63 4 [1–13]
Brain 48 17 35.42 5 [2–NR]
2 of 3 142 63 44.37 5 [2–12]
All 3 8 5 62.50 2 [1–6]
None 86,987 339 0.39 60 [12–NR]
Breast Breast Lung 4,926 2,414 49.01 24 [7–50]
Liver 3,690 2,042 55.34 18 [4–42]
Brain 752 418 55.59 15 [4–34]
2 of 3 2,504 1,692 67.57 11 [2–30]
All 3 349 280 80.23 4 [1–17]
None 424,126 9,415 2.22 35 [14–69]
Respiratory system SCLC Lung 2,279 523 22.95 6 [1–11]
Liver 7,849 2,916 37.15 5 [1–9]
Brain 3,489 580 16.62 5 [2–10]
2 of 3 3,930 1,710 43.51 4 [1–8]
All 3 517 299 57.83 3 [1–7]
None 20,444 2,584 12.64 7 [2–12]
SCC Lung 6,065 1,051 17.33 3 [1–7]
Liver 2,445 968 39.59 3 [1–6]
Brain 2,354 490 20.82 3 [1–6]
2 of 3 1,904 832 43.70 2 [1–5]
All 3 284 160 56.34 2 [1–4]
None 79,077 3,877 4.90 4 [1–9]
ADC Lung 14,485 4,233 29.22 5 [2–14]
Liver 5,265 2,829 53.73 3 [1–9]
Brain 11,839 3,357 28.36 5 [2–14]
2 of 3 8,273 4,402 53.21 3 [1–10]
All 3 1,353 990 73.17 3 [1–9]
None 102,527 12,106 11.81 6 [2–15]
NSCLC (BAC) Lung 352 38 10.80 11 [4–15]
Liver 24 13 54.17 2 [1–10]
Brain 53 15 28.30 10 [3–19]
2 of 3 55 27 49.09 7 [3–21]
All 3 3 1 33.33 6 [NA]
None 3,953 80 2.02 11 [3–23]
NSCLC (NOS/others) Lung 1,881 538 28.60 3 [1–8]
Liver 1,093 482 44.10 2 [1–7]
Brain 2,124 485 22.83 3 [1–8]
2 of 3 1,358 604 44.48 2 [1–5]
All 3 223 129 57.85 2 [1–4]
None 13,306 1,860 13.98 4 [1–9]
Digestive system Esophagus Lung 1,242 239 19.24 10 [4–42]
Liver 2,722 505 18.55 10 [3–30]
Brain 228 58 25.44 9 [4–30]
2 of 3 1,206 310 25.70 11 [4–43]
All 3 87 38 43.68 14 [7–NR]
None 20,470 925 4.52 13 [4–36]
Gastric Lung 979 191 19.51 4 [1–7]
Liver 5,342 406 7.60 3 [1–9]
Brain 137 34 24.82 3 [1–4]
2 of 3 1,186 267 22.51 2 [NR–8]
All 3 52 22 42.31 3 [1–4]
None 35,874 1,027 2.86 4 [1–9]
Hepatobiliary Lung 3,238 472 14.58 2 [0–6]
Liver 4,598 399 8.68 3 [1–9]
Brain 125 45 36.00 4 [1–10]
2 of 3 1,314 298 22.68 2 [1–5]
All 3 36 17 47.22 2 [0–7]
None 61,751 1,692 2.74 3 [1–8]
Pancreatic Lung 2,846 304 10.68 6 [2–19]
Liver 23,754 1,140 4.80 5 [1–14]
Brain 71 16 22.54 2 (1–7)
2 of 3 5,011 762 15.21 1 [0–4]
All 3 92 40 43.48 2 [0–3]
None 42,886 573 1.34 3 [1–9]
Colorectal Lung 3,425 261 7.62 6 [2–18]
Liver 26,849 1,102 4.10 5 [1–14]
Brain 190 18 9.47 2 [1–7]
2 of 3 8,472 983 11.60 5 [1–14]
All 3 205 68 33.17 2 [1–10]
None 210,132 653 0.31 6 [2–18]
Anal Lung 129 11 8.53 6 [5–8]
Liver 317 26 8.20 9 [4–27]
Brain 9 1 11.11 NA
2 of 3 116 15 12.93 4 [1–9]
All 3 3 0 0.00 NA
None 11,576 68 0.59 20 [6–36]
Other digestive organs Lung 748 122 16.31 2 [1–7]
Liver 3,714 255 6.87 3 [1–11]
Brain 66 15 22.73 2 [1–6]
2 of 3 728 179 24.59 2 [0–5]
All 3 36 16 44.44 1 [0–2]
None 18,222 269 1.48 3 [1–11]
Genitourinary Renal Lung 5,624 1,605 28.54 6 [2–15]
Liver 1,237 372 30.07 3 [1–9]
Brain 449 137 30.51 5 [2–15]
2 of 3 2,360 949 40.21 3 [1–8]
All 3 219 118 53.88 3 [1–7]
None 91,232 2,422 2.65 10 [3–30]
Bladder Lung 1,437 1,131 78.71 4 [1–10]
Liver 660 485 73.48 2 [1–6]
Brain 184 154 83.70 2 [1–11]
2 of 3 359 286 79.67 2 [1–5]
All 3 24 19 79.17 1 [0–2]
None 344,200 17,675 5.14 5 [2–12]
Prostate Lung 1,133 191 16.86 20 [8–47]
Liver 497 148 29.78 10 [4–22]
Brain 724 68 9.39 10 [3–24]
2 of 3 1,185 345 29.11 9 [3–24]
All 3 347 164 47.26 14 [4–NR]
None 277,125 296 0.11 27 [11–57]
Testicular Lung 883 44 4.98 NR [8–NR]
Liver 87 12 13.79 9 [7–19]
Brain 14 1 7.14 NA
2 of 3 261 30 11.49 13 [4–NR]
All 3 56 8 14.29 8 [0–NR]
None 15,360 48 0.31 NR [8–NR]
Other GU Lung 217 48 22.12 5 [2–12]
Liver 155 50 32.26 2 [0–6]
Brain 14 5 35.71 4 [1–7]
2 of 3 110 44 40.00 1 [0–6]
All 3 4 0 0.00 NA
None 7,967 140 1.76 7 [2–11]
Gynecologic Ovarian Lung 1,515 60 3.96 4 [1–19]
Liver 1,928 72 3.73 2 [0–11]
Brain 56 10 17.86 NR [NR–10]
2 of 3 650 88 13.54 4 [1–9]
All 3 17 8 47.06 2 [NR–6]
None 33,302 184 0.55 7 [1–34]
Endometrial Lung 1,898 225 11.85 7 [2–18]
Liver 638 66 10.34 6 [2–15]
Brain 87 15 17.24 2 [2–6]
2 of 3 593 156 26.31 3 [1–9]
All 3 36 18 50.00 3 [1–10]
None 89,897 337 0.37 8 [2–19]
Cervical Lung 702 116 16.52 6 [3–13]
Liver 250 63 25.20 6 [2–11]
Brain 35 15 42.86 3 [1–6]
2 of 3 259 103 39.77 4 [1–9]
All 3 8 5 62.50 3 [1–10]
None 21,514 256 1.19 10 [4–20]
Other gynecologic Lung 457 47 10.28 4 [1–10]
Liver 187 17 9.09 6 [3–14]
Brain 9 1 11.11 2 [2–2]
2 of 3 137 17 12.41 2 [0–5]
All 3 13 3 23.08 1 [NR]
None 14,357 94 0.65 8 [3–22]
Brain and other nervous system Brain and other nervous system Lung 32 4 12.50 19 [3–NR]
Liver 14 4 28.57 1 [NR–8]
Brain 200 4 2.00 3 [NR]
2 of 3 9 2 22.22 4 [NR–8]
All 3 NA NA NA NA
None 32,872 45 0.14 16 [2–NR]
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1, lip, tongue, gum, floor of mouth, & other mouth, salivary gland, oropharynx, nasopharynx, hypopharynx, pharynx, nasal cavity (including nasal cartilage), accessory, sinuses, middle & inner ear, larynx, trachea, orbit & lacrimal gland, retina, eyeball, eye, NOS. GI, gastrointestinal; GU, genitourinary; GYN, gynecologic; SCLC, small-cell lung; NSCLC (NOS/others), non-small cell lung cancer not otherwise specified or non-small cell lung cancer other lung cancer; ADC, adenocarcinoma of the lung; SCC, squamous cell carcinoma of the lung; NSCLC (BAC), bronchioloalveolar carcinoma; NR, not reached; NA, not applicable.

For patients with head and neck cancer, the incidence of comorbidity with liver metastases and bone metastasis was 42.47%. Among patients with was cancer, the incidence of comorbidity with liver metastasis and bone metastasis is higher in NSCLC (BAC) (54.17%), ADC (53.73%), and NSCLC (NOS/others) (44.10%) than in SCC (39.59%) and SCLC (37.15%). Furthermore, we found that the incidence of comorbidity of brain metastases and bone metastasis was higher than other sites among patients with digestive system cancer and gynecologic cancer.

Table S1 shows the incidence proportions of patients diagnosed with bone metastases, classified according to primary cancer, age, race, and gender. Median survival estimates, and those of age, race, gender, and cancer type, are displayed in Table S2.

Table S1. Incidence proportion of patients with identified bone metastases at diagnosis by primary cancer site as stratified by age, race, and gender.

Site Sub-site Age Race Gender
Age category in years Number of patients with bone metastases Entire cohort Incidence proportion of bone metastases among entire cohort (%) Incidence proportion of bone metastases among subset with metastatic disease (%) Race Number of patients with bone metastases Entire cohort Incidence proportion of bone metastases among entire cohort (%) Incidence proportion of bone metastases among subset with metastatic disease (%) Gender Number of patients with brain metastases (total number of patients in subcategory) Number of entire cohort Number of metastatic disease Incidence proportion of brain metastases among entire cohort Incidence proportion of brain metastases among subset with metastatic disease
Head and neck Head and neck1 18–40 57 3,399 1.68 18.69 White 819 59,043 1.39 9.55 Male 780 54,314 7,862 1.44 9.92
41–60 395 29,942 1.32 8.73 Black 103 6,300 1.63 11.12 Female 334 23,296 3,405 1.43 9.81
61–80 522 36,216 1.44 9.53 Hispanic 99 6,062 1.63 12.04
>80 96 8,053 1.19 10.00 Asian or Pacific Islander 80 5,093 1.57 10.99
American Indian/Alaska Native 5 480 1.04 7.81
Unknown 8 632 1.27 8.99
Thyroid Thyroid 18–40 37 24,002 0.15 9.16 White 380 57,307 0.66 19.84 Male 309 21,708 1,427 1.42 21.65
41–60 186 39,558 0.47 19.79 Black 103 6,109 1.69 34.92 Female 370 66,648 1,920 0.56 19.27
61–80 370 22,434 1.65 24.25 Hispanic 92 14,305 0.64 13.61
>80 86 2,362 3.64 18.03 Asian or Pacific Islander 100 9,179 1.09 23.75
American Indian/Alaska Native 3 532 0.56 11.11
Unknown 1 924 0.11 7.69
Breast Breast 18–40 1,140 24,616 4.63 50.11 White 10,908 298,403 3.66 55.70 Male 210 3,414 335 6.15 62.69
41–60 6,294 176,055 3.58 52.34 Black 2,447 48,090 5.09 50.19 Female 16,051 432,933 29,981 3.71 53.54
61–80 7,022 194,444 3.61 56.07 Hispanic 1,707 48,576 3.51 48.72
>80 1,805 41,232 4.38 51.69 Asian or Pacific Islander 1,067 36,476 2.93 51.37
American Indian/Alaska Native 85 2,392 3.55 47.22
Unknown 47 2,410 1.95 48.45
Respiratory system Small cell 18–40 25 115 21.74 34.72 White 7,793 32,785 23.77 35.42 Male 5,103 19,710 13,736 25.89 37.15
41–60 2,320 9,373 24.75 35.73 Black 714 3,547 20.13 29.86 Female 4,120 20,059 12,950 20.54 31.81
61–80 6,070 25,894 23.44 35.34 Hispanic 399 1,823 21.89 32.28
>80 808 4,387 18.42 27.45 Asian or Pacific Islander 271 1,348 20.10 30.08
American Indian/Alaska Native 42 230 18.26 29.37
Unknown 4 36 11.11 25.00
Squamous cell carcinoma 18–40 32 441 7.26 19.05 White 5,869 71,748 8.18 22.49 Male 5,351 61,490 22,226 8.70 24.08
41–60 1,615 18,183 8.88 24.13 Black 1,107 11,761 9.41 25.89 Female 2,516 31,750 11,617 7.92 21.66
61–80 5,100 60,633 8.41 23.33 Hispanic 440 5,281 8.33 22.94
>80 1,120 13,983 8.01 21.87 Asian or Pacific Islander 402 3,696 10.88 30.99
American Indian/Alaska Native 41 556 7.37 21.35
Unknown 8 198 4.04 11.76
Adenocarcinoma 18–40 345 1,109 31.11 44.92 White 21,226 107,687 19.71 37.07 Male 16,070 76,262 41,174 21.07 39.03
41–60 7,992 32,581 24.53 39.62 Black 3,373 16,920 19.93 33.42 Female 13,776 70,932 39,807 19.42 34.61
61–80 17,748 90,582 19.59 37.44 Hispanic 2,122 9,477 22.39 37.54
>80 3,761 22,922 16.41 29.75 Asian or Pacific Islander 2,961 12,234 24.20 39.50
American Indian/Alaska Native 133 626 21.25 35.75
Unknown 41 280 14.64 36.94
Bronchioloalveolar adenocarcinoma 18–40 3 29 10.34 27.27 White 123 3,383 3.64 16.97 Male 96 1,701 585 5.64 16.41
41–60 38 657 5.78 25.85 Black 23 380 6.05 21.10 Female 88 2,774 439 3.17 20.05
61–80 111 2,935 3.78 17.62 Hispanic 15 308 4.87 18.07
>80 32 854 3.75 13.56 Asian or Pacific Islander 23 391 5.88 21.50
American Indian/Alaska Native 0 8 0.00 0.00
Unknown 0 5 0.00 0.00
Non-small cell and other 18–40 30 102 29.41 38.96 White 3,297 15,419 21.38 34.00 Male 2,681 11,654 7,699 23.00 34.82
41–60 1,163 4,471 26.01 35.49 Black 522 2,733 19.10 29.03 Female 1,758 8,968 5,525 19.60 31.82
61–80 2,631 12,521 21.01 33.47 Hispanic 310 1,977 15.68 36.56
>80 615 3,528 17.43 30.60 Asian or Pacific Islander 291 1,119 26.01 36.28
American Indian/Alaska Native 14 119 11.76 22.58
Unknown 5 35 14.29 27.78
Digestive system Esophagus 18–40 29 279 10.39 21.80 White 1,626 19,952 8.15 21.28 Male 1,788 20,367 8,211 8.78 21.78
41–60 703 6,829 10.29 22.55 Black 197 2,584 7.62 19.13 Female 287 5,588 1,749 5.14 16.41
61–80 1,142 15,024 7.60 20.19 Hispanic 157 2,009 7.81 19.48
>80 201 3,823 5.26 18.31 Asian or Pacific Islander 73 1,181 6.18 16.74
American Indian/Alaska Native 22 165 13.33 28.95
Unknown 0 64 0.00 0.00
Gastric 18–40 130 1,696 7.67 15.31 White 1,114 23,122 4.82 13.51 Male 1,283 26,580 10,021 4.83 12.80
41–60 674 11,615 5.80 14.09 Black 198 5,931 3.34 9.56 Female 664 16,990 5,504 3.91 12.06
61–80 936 22,168 4.22 12.25 Hispanic 374 8,099 4.62 11.84
>80 207 8,091 2.56 9.19 Asian or Pacific Islander 239 5,889 4.06 12.71
American Indian/Alaska Native 20 371 5.39 13.42
Unknown 2 158 1.27 9.09
Hepatobiliary 18–40 44 1,085 4.06 12.68 White 1,816 38,991 4.66 19.67 Male 2,365 47,281 9,859 5.00 23.99
41–60 1,104 22,942 4.81 21.48 Black 441 8,931 4.94 20.89 Female 821 24,734 6,595 3.32 12.45
61–80 1,735 38,658 4.49 19.53 Hispanic 544 13,552 4.01 18.39
>80 303 9,330 3.25 14.54 Asian or Pacific Islander 345 9,585 3.60 17.48
American Indian/Alaska Native 37 773 4.79 23.13
Unknown 3 183 1.64 15.00
Pancreatic 18–40 41 1,119 3.66 8.69 White 1,947 51,673 3.77 7.18 Male 1,695 38,321 20,973 4.42 8.08
41–60 727 16,856 4.31 7.77 Black 327 9,028 3.62 6.41 Female 1,176 36,339 18,562 3.24 6.34
61–80 1,691 41,976 4.03 7.49 Hispanic 301 7,957 3.78 7.00
>80 376 14,709 2.56 5.27 Asian or Pacific Islander 238 5,454 4.36 8.66
American Indian/Alaska Native 19 406 4.68 8.60
Unknown 3 142 2.11 5.26
Colorectal 18–40 131 9,175 1.43 5.76 White 1,969 166,744 1.18 5.76 Male 1,878 130,273 27,775 1.44 6.76
41–60 1,023 76,643 1.33 5.77 Black 468 30,329 1.54 6.18 Female 1,207 119,000 24,536 1.01 4.92
61–80 1,459 117,593 1.24 6.15 Hispanic 371 28,276 1.31 6.13
>80 472 45,862 1.03 5.49 Asian or Pacific Islander 244 20,419 1.19 6.08
American Indian/Alaska Native 27 1,850 1.46 6.35
Unknown 6 1,654 0.36 8.00
Anal 18–40 2 371 0.54 3.92 White 84 9,268 0.91 7.25 Male 53 4,481 524 1.18 10.11
41–60 52 5,328 0.98 7.69 Black 17 1,344 1.26 9.24 Female 68 7,669 1,060 0.89 6.42
61–80 56 5,184 1.08 8.05 Hispanic 10 1,097 0.91 6.25
>80 11 1,267 0.87 6.83 Asian or Pacific Islander 9 311 2.89 14.06
American Indian/Alaska Native 1 65 1.54 7.14
Unknown 0 65 0.00 0.00
Other GI 18–40 21 875 2.40 7.75 White 595 15,935 3.73 10.54 Male 344 10,793 3,542 3.19 9.71
41–60 237 7,051 3.36 9.84 Black 103 3,324 3.10 9.82 Female 512 12,720 4,687 4.03 10.92
61–80 457 12,285 3.72 10.36 Hispanic 95 2,624 3.62 10.16
>80 141 3,302 4.27 12.40 Asian or Pacific Islander 50 1,379 3.63 9.51
American Indian/Alaska Native 10 142 7.04 16.95
Unknown 3 109 2.75 20.00
Genitourinary Renal 18–40 128 4,916 2.60 37.21 White 3,921 68,184 5.75 39.25 Male 3,820 64,350 9,683 5.94 39.45
41–60 1,740 35,278 4.93 38.70 Black 557 12,112 4.60 38.23 Female 1,783 36,771 4,815 4.85 37.03
61–80 2,976 51,015 5.83 39.42 Hispanic 755 14,206 5.31 36.90
>80 759 9,912 7.66 36.01 Asian or Pacific Islander 315 5,234 6.02 37.54
American Indian/Alaska Native 51 885 5.76 34.93
Unknown 4 500 0.80 19.05
Bladder 18–40 15 1,296 1.16 26.79 White 1,423 102,014 1.39 31.54 Male 1,390 94,809 4,167 1.47 33.36
41–60 385 20,264 1.90 33.92 Black 171 7,255 2.36 28.31 Female 450 29,470 1,754 1.53 25.66
61–80 1,029 71,202 1.45 31.08 Hispanic 143 7,846 1.82 27.88
>80 411 31,517 1.30 28.96 Asian or Pacific Islander 88 5,196 1.69 35.48
American Indian/Alaska Native 14 415 3.37 35.90
Unknown 1 1,553 0.06 20.00
Prostate 18–40 14 327 4.28 73.68 White 12,788 234,522 5.45 88.66 Male 19,750 346,844 22,257 5.69 88.74
41–60 3,321 93,062 3.57 87.44 Black 3,396 53,642 6.33 88.92 Female 0 0 0 0 0
61–80 11,230 229,600 4.89 88.33 Hispanic 2,213 32,440 6.82 88.56
>80 5,185 23,855 21.74 90.54 Asian or Pacific Islander 1,119 16,142 6.93 89.88
American Indian/Alaska Native 135 1,316 10.26 88.82
Unknown 99 8,782 1.13 83.90
Testicular 18–40 87 11,893 0.73 6.14 White 89 11,001 0.81 7.60 Male 143 16,661 1,993 0.86 7.18
41–60 42 4,119 1.02 8.79 Black 10 506 1.98 12.99 Female 0 0 0 0 0
61–80 14 594 2.36 15.56 Hispanic 38 1,959 1.94 5.99
>80 0 55 0.00 0.00 Asian or Pacific Islander 4 712 0.56 5.13
American Indian/Alaska Native 1 180 0.56 3.45
Unknown 1 303 0.33 25.00
Other GU 18–40 6 158 3.80 60.00 White 207 6,130 3.38 37.57 Male 199 6,610 507 3.01 39.25
41–60 40 1,574 2.54 31.01 Black 25 703 3.56 41.67 Female 88 1,857 250 4.74 35.20
61–80 153 4,625 3.31 37.59 Hispanic 27 977 2.76 31.03
>80 88 2,110 4.17 41.71 Asian or Pacific Islander 26 549 4.74 46.43
American Indian/Alaska Native 2 41 4.88 66.67
Unknown 0 67 0.00 0.00
Gynecologic Ovarian 18–40 25 2,872 0.87 2.44 White 278 25,567 1.09 1.67 Male 0 0 0 0 0
41–60 121 14,266 0.85 1.51 Black 61 3,270 1.87 2.73 Female 422 37468 23890 1.13 1.77
61–80 202 16,029 1.26 1.73 Hispanic 49 5,073 0.97 1.64
>80 74 4,301 1.72 2.30 Asian or Pacific Islander 33 3,209 1.03 1.84
American Indian/Alaska Native 1 220 0.45 0.70
Unknown 0 129 0.00 0.00
Endometrial 18–40 17 3,935 0.43 6.34 White 327 12,015 2.72 16.93 Male 0 0 0 0 0
41–60 320 36,826 0.87 11.29 Black 93 3,084 3.02 15.25 Female 847 93149 8304 0.91 10.20
61–80 436 46,037 0.95 9.80 Hispanic 88 5,164 1.70 12.48
>80 74 6,351 1.17 9.81 Asian or Pacific Islander 47 2,124 2.21 15.67
American Indian/Alaska Native 3 208 1.44 8.57
Unknown 0 179 0.00 0.00
Cervical 18–40 75 6,351 1.18 15.66 White 120 120 100.00 33.06 Male 0 0 0 0 0
41–60 163 10,523 1.55 9.61 Black 22 1,347 1.63 47.83 Female 558 22,774 3,585 2.45 15.56
61–80 190 4,993 3.81 15.93 Hispanic 22 1,522 1.45 37.29
>80 30 907 3.31 13.95 Asian or Pacific Islander 13 751 1.73 59.09
American Indian/Alaska Native 1 104 0.96 16.67
Unknown 1 112 0.89 100.00
Other GYN 18–40 7 736 0.95 36.84 White 41 24,834 0.17 10.35 Male 0 0 0 0 0
41–60 49 4,491 1.09 33.11 Black 4 2,054 0.19 8.70 Female 179 15160 497 1.18 36.02
61–80 97 7,085 1.37 46.86 Hispanic 12 4,109 0.29 11.88
>80 26 2,848 0.91 21.14 Asian or Pacific Islander 2 1,858 0.11 4.26
American Indian/Alaska Native 0 144 0.00 0.00
Unknown 0 128 0.00 0.00
Brain and other nervous system Brain and other nervous system 18–40 10 5,505 0.18 10.10 White 380 57,307 0.66 19.84 Male 29 18,734 351 0.15 8.26
41–60 20 11,096 0.18 9.76 Black 103 6,109 1.69 34.92 Female 30 14,393 245 0.21 12.24
61–80 23 13,569 0.17 9.87 Hispanic 92 14,305 0.64 13.61
>80 6 2,957 0.20 10.17 Asian or Pacific Islander 100 9,179 1.09 23.75
American Indian/Alaska Native 3 532 0.56 11.11
Unknown 1 924 0.11 7.69
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1, lip, tongue, gum, floor of mouth, & other mouth, salivary gland, oropharynx, nasopharynx, hypopharynx, pharynx, nasal cavity (including nasal cartilage), accessory, sinuses, middle & inner ear, larynx, trachea, orbit & lacrimal gland, retina, eyeball, eye, NOS. GI, Gastrointestinal; GU, Genitourinary; GYN, Gynecologic; NOS, not otherwise specified.

Table S2. Median survival of patients with bone metastases by age, race, and gender.

Site Sub-site Age Race Gender
Age category in years Number of patients with bone metastases Median survival in months (interquartile range) Race Number of patients with bone metastases Median survival in months (interquartile range) Gender Number of patients with bone metastases Median survival in months (interquartile range)
Head and neck Head and neck1 18–40 57 15 [8–32] White 819 8 [3–16] Male 780 8 [3–18]
41–60 395 9 [3–21] Black 103 8 [3–18] Female 334 8 [3–15]
61–80 522 7 [3–16] Hispanic 99 8 [3–20]
>80 96 4 [1–10] Asian or Pacific Islander 80 15 [8–35]
American Indian/Alaska Native 5 10 [5–15]
Unknown 8 11 [3–16]
Thyroid Thyroid 18–40 37 52 [9–NR] White 380 21 [4–82] Male 22 [4–82]
41–60 186 66 [7–NR] Black 103 27 [3–60] Female 23 [3–NR]
61–80 370 22 [4–NR] Hispanic 92 21 [3–64]
>80 86 6 [2–23] Asian or Pacific Islander 100 49 [9–NR]
American Indian/Alaska Native 3 2 [NR]
Unknown 1 5 [NR]
Breast Breast 18–40 1,140 42 [20–72] White 10,908 28 [8–59] Male 23 [8–54]
41–60 6,294 32 [13–66] Black 2,447 20 [6–43] Female 27 [8–57]
61–80 7,022 25 [6–53] Hispanic 1,707 32 [12–63]
>80 1,805 12 [2–32] Asian or Pacific Islander 1,067 31 [12–62]
American Indian/Alaska Native 85 34 [12–NR]
Unknown 47 NR [22–NR]
Lung Small cell 18–40 25 8 [4–10] White 7,793 5 [1–10] Male 5103 5 [1–10]
41–60 2,320 7 [2–11] Black 714 8.0 [2.0–16.0] Female 4,120 6 [1–10]
61–80 6,070 5 [1–10] Hispanic 399 4 [1–10]
>80 808 2 [0–6] Asian or Pacific Islander 271 6 [2–10]
American Indian/Alaska Native 42 3 [1–9]
Unknown 4 18 [5–18]
Squamous cell carcinoma 18–40 32 8 [2.0–15.0] White 5,869 3.0 [1.0–7.0] Male 5,351 3.0 [1.0–7.0]
41–60 1,615 4.0 [2.0–9.0] Black 1,107 3.0 [1.0–8.0] Female 2,516 3.0 [1.0–7.0]
61–80 5,100 3.0 [1.0–7.0] Hispanic 440 3.0 [1.0–9.0]
>80 1,120 2.0 [1.0–5.0] Asian or Pacific Islander 402 4.0 [1.0–9.0]
American Indian/Alaska Native 41 4.0 [1.0–11.0]
Unknown 8 2.0 [1.0–9.0]
Adenocarcinoma 18–40 3 14 [5–29] White 21,226 4 [1–12] Male 16,070 4 [1–11]
41–60 38 6 [2–16] Black 3,373 4 [1–11] Female 13,776 5 [2–15]
61–80 111 4 [1–12] Hispanic 2,122 6 [2–15]
>80 32 3 [1–8] Asian or Pacific Islander 2,961 11 [3–25]
American Indian/Alaska Native 133 5 [1–10]
Unknown 41 13 [2–32]
Bronchioloalveolar adenocarcinoma 18–40 - 22 [4–38] White 92 6 [2–16] Male 96 7 [2–19]
41–60 50 10 [5–21] Black 20 5 [1–16] Female 88 9 [3–2]
61–80 84 7 [2–21] Hispanic 11 11 [4–21]
>80 13 6 [2–12] Asian or Pacific Islander 23 22 [9–39]
American Indian/Alaska Native 1 NA
Unknown 0 NA
Non-small cell and other 18–40 30 7 [5–15] White 3,297 3 [1–7] Male 2,681 3 [1–7]
41–60 1,163 4 [1–9] Black 522 3 [1–7] Female 1,728 3 [1–9]
61–80 2,631 3 [1–8] Hispanic 310 3 [1–10]
>80 615 2 [1–5] Asian or Pacific Islander 291 4 [1–15]
American Indian/Alaska Native 14 2 [1–5]
Unknown 5 2 [1–5]
GI Esophagus 18–40 29 9 [2–31] White 198 11 [4–37] Male 287 11 [4–35]
41–60 703 13 [4–38] Black 14 12 [5–33] Female 1,788 11 [3–44]
61–80 1,142 11 [4–38] Hispanic 16 13 [4–43]
>80 201 11 [4–32] Asian or Pacific Islander 9 13 [4–43]
American Indian/Alaska Native 1 8 [4–19]
Unknown 0 NA
Gastric 18–40 130 5 [1–10] White 1,114 4 [1–9] Male 1,283 3 [1–8]
41–60 674 4 [1–9] Black 198 3 [1–7] Female 664 3 [1–8]
61–80 936 3 [1–9] Hispanic 374 3 [1–8]
>80 207 2 [0–5] Asian or Pacific Islander 239 3 [1–8]
American Indian/Alaska Native 20 5 [1–6]
Unknown 2 NA
Hepatobiliary 18–40 44 7 [3–13] White 1,816 3 [1–8] Male 2,365 3 [1–7]
41–60 1,104 3 [1–7] Black 441 3 [1–7] Female 821 3 [1–8]
61–80 1,735 3 [1–7] Hispanic 544 3 [1–8]
>80 303 2 [0–5] Asian or Pacific Islander 345 3 [1–7]
American Indian/Alaska Native 37 3 [1–9]
Unknown 3 5 [1–5]
Pancreatic 18–40 41 8 [2–20] White 51,673 2 [1–6] Male 1,695 2 [1–6]
41–60 727 3 [1–8] Black 9,028 2 [1–6] Female 1,176 2 [1–6]
61–80 1,691 2 [1–6] Hispanic 7,957 2 [1–8]
>80 376 1 [0–3] Asian or Pacific Islander 5,454 2 [1–6]
American Indian/Alaska Native 406 1 [0–5]
Unknown 142 0 [0–1]
Colorectal 18–40 131 10 [3–23] White 166,744 5 [1–14] Male 1,878 5 [1–15]
41–60 1,023 9 [3–20] Black 30,329 4 [2–15] Female 1,207 5 [1–14]
61–80 1,459 4 [1–13] Hispanic 28,276 5 [2–18]
>80 472 2 [0–5] Asian or Pacific Islander 20,419 7 [2–19]
American Indian/Alaska Native 1,850 6 [4–9]
Unknown 1,654 14 [2–14]
Anal 18–40 2 NA White 9,268 10 [5–27] Male 53 8 [4–22]
41–60 52 14 [5–46] Black 1,344 6 [5–22] Female 68 14 [4–27]
61–80 56 9 [4–24] Hispanic 1,097 4 [2–NR]
>80 11 3 [1–8] Asian or Pacific Islander 311 5 [1–6]
American Indian/Alaska Native 65 NA
Unknown 65 NA
Other GI 18–40 21 4 [1–11] White 15,935 3 [1–8] Male 344 3 [1–10]
41–60 237 2 [1–8] Black 3,324 2 [0–10] Female 512 2 [1–7]
61–80 457 3 [1–9] Hispanic 2,624 2 [0–6]
>80 141 2 [0–5] Asian or Pacific Islander 1,379 2 [1–10]
American Indian/Alaska Native 142 4 [1–6]
Unknown 109 2 [2–NR]
GU Renal 18–40 128 10 [4–24] White 68,184 6 [2–17] Male 3,820 6 [2–18]
41–60 1,740 8 [3–26] Black 12,112 5 [2–14] Female 1,783 5 [2–15]
61–80 2,976 6 [2–17] Hispanic 14,206 7 [2–19]
>80 759 3 [1–7] Asian or Pacific Islander 5,234 6 [2–20]
American Indian/Alaska Native 885 6 [2–12]
Unknown 500 5 [5–50]
Bladder 18–40 15 8 [4–10] White 102,014 4 [1–10] Male 1,390 4 [1–10]
41–60 385 5 [2–11] Black 7,255 4 [2–8] Female 450 3 [1–8]
61–80 1,029 4 [1–11] Hispanic 7,846 4 [1–4]
>80 411 2 [1–6] Asian or Pacific Islander 5,196 5 [1–10]
American Indian/Alaska Native 415 1 [1–5]
Unknown 1,553 5 (NR)
Prostate 18–40 14 22 [13–38] White 234,522 25 [10–53] Male 19,750 25 [11–55]
41–60 3,321 34 [17–72] Black 53,642 25 [11–55] Female 0 NA
61–80 11,230 29 [12–65] Hispanic 32,440 24 [11–61]
>80 5,185 15 [5–33] Asian or Pacific Islander 16,142 34 [13–NR]
American Indian/Alaska Native 1,316 26 [10–55]
Unknown 8,782 NR
Testicular 18–40 87 NR [8–NR] White 11,001 21.0 [4.5–NR] Male 143 NR [7–NR]
41–60 42 32 [4–NR] Black 506 NA Female 0 NA
61–80 14 8 [3–NR] Hispanic 1,959 NR [NR–NR]
>80 - NA Asian or Pacific Islander 712 NR [14.0–NR]
American Indian/Alaska Native 180 14.0 [NR]
Unknown 303 NR
Other GU 18–40 6 5 [5–18] White 6,130 4 [1–9] Male 199 4 [1–9]
41–60 40 7 [2–14] Black 703 5 [3–9] Female 88 4 [1–10]
61–80 153 5 [1–9] Hispanic 977 4 [1–9]
>80 88 2 [1–7] Asian or Pacific Islander 549 5 [2–14]
American Indian/Alaska Native 41 7 [7–9]
Unknown 67 4 [1–9]
GYN Ovarian 18–40 25 5 [2–9] White 25,567 4 [1–15] Male 0 NA
41–60 121 7 [2–19] Black 3,270 7 [2–36] Female 422 5 [1–17]
61–80 202 5 [1–23] Hispanic 5,073 4 [1–10]
>80 74 2 [0–7] Asian or Pacific Islander 3,209 7 [1–14]
American Indian/Alaska Native 220 2 [NR–NR]
Unknown 129 NA
Endometrial 18–40 17 5 [5–10] White 12,015 6 [2–17] Male 0 NA
41–60 320 8 [2–20] Black 3,084 4 [1–12] Female 847 6 [2–15]
61–80 436 6 [1–15] Hispanic 5,164 6 [1–15]
>80 74 3 [1–10] Asian or Pacific Islander 2,124 9 [3–28]
American Indian/Alaska Native 208 10 [9–20]
Unknown 179 NA
Cervical 18–40 75 8 [3–15] White 120 6 [2–16] Male 0 NA
41–60 163 7 [3–18] Black 1,347 5 [3–12] Female 558 6 [2–15]
61–80 190 5 [2–13] Hispanic 1,522 6 [2–14]
>80 30 3 [1–7] Asian or Pacific Islander 751 12 [4–23]
American Indian/Alaska Native 104 1 [NR–13]
Unknown 112 NR [NR–NR]
Other GYN 18–40 7 8 [3–NR] White 24,834 5 [2–17] Male 0 NA
41–60 49 9 [3–29] Black 2,054 3 [2–16] Female 179 6 [2–16]
61–80 97 4 [2–12] Hispanic 4,109 4 [2–16]
>80 26 3 [1–16] Asian or Pacific Islander 1,858 9 [6–14]
American Indian/Alaska Native 144 1 [1–1]
Unknown 128 1 [1–1]
Brain and other nervous system Brain and other nervous system 18–40 10 NR [15–NR] White 57,307 10 [3–NR] Male 29 15 [3–NR]
41–60 20 NR [3–NR] Black 6,109 19 [1–NR] Female 30 19 [2–NR]
61–80 23 8 [2–NR] Hispanic 14,305 NR [2–NR]
>80 6 NR [NR–2] Asian or Pacific Islander 9,179 1 [NR]
American Indian/Alaska Native 532 NA
Unknown 924 NA
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1, lip, tongue, gum, floor of mouth, & other mouth, salivary gland, oropharynx, nasopharynx, hypopharynx, pharynx, nasal cavity (including nasal cartilage), accessory, sinuses, middle & inner ear, larynx, trachea, orbit & lacrimal gland, retina, eyeball, eye, NOS. GI, gastrointestinal; GU, genitourinary; GYN, gynecologic; SCLC, small-cell lung cancer; NSCLC (NOS/others), non-small cell lung cancer not otherwise specified or non-small cell lung cancer other lung cancer; ADC, adenocarcinoma of the lung; SCC, squamous cell carcinoma of the lung, NSCLC (BAC), bronchioloalveolar carcinoma; NR, not reached; NA, not applicable.

Discussion

In our study, we showed the number and incidence proportion of patients with bone metastases and the prognosis of identified bone metastases among patients with cancer of the digestive system with the lowest median survival time. To our knowledge, this is the first epidemiologic study of bone metastases using the entire SEER database. Roodman et al. pointed out that the exact prevalence of bone metastasis remains unknown, and patients with bone metastases are usually incurable (21). Therefore, it is probable that our study may have widespread applications and could be useful in the formation of screening paradigms for bone metastases, clinical treatment and trial design, and counseling of different subsets of patients with cancer.

Incidence of bone metastasis

In 1997, Coleman et al. reported that the incidence of bone metastasis was 30–40% for patients with lung cancer, which is higher than our results (22). In 2013, Sathiakumar et al. reported that the incidence of bone metastasis among lung cancer patients was 19.8%, based on data from 1999 to 2006 (23). Al Husaini et al. pointed out that the incidence of skeletal metastasis in advanced-stage lung cancer was 30–40% (24).

In our study, we found that the incidence of bone metastases was 16.89% in patients with newly diagnosed lung cancer and 33.10% in patients with metastatic lung cancer. A comparison of our findings with those of other studies confirms that the rate of bone metastasis among lung cancer is gradually decreasing, which has contributed to the popularization of screening and the development of effective treatment strategies. Additionally, we found the incidence of bone metastases among patients with SCLC to be higher than that of patients with non-small cell lung cancer (NSCLC). Yerushalmi et al. found that the incidence of bone metastases among patients with breast cancer had decreased steadily over 3 time periods (25) (1989–1991: 7.5%, 1992–1997: 5.3%, 1998–2001: 3.5%). Jensen et al. noted that the incidence rate of bone metastases among patients with breast cancer was 3.6% in a population of 35,912 patients (19). In this study, the incidence was slightly lower than that reported by earlier studies. Pietropaoli et al. indicated that only approximately 1% of patients with stage IV carcinoma of the head and neck had concomitant bone metastases (26), which is similar to our results.

Previous studies have reported that the incidence rate of bone metastases in patients with hepatocellular carcinoma ranges from 3% to 20% (27,28). These findings are consistent with our results. However, the studies just mentioned above only discussed the incidence rate of bone metastases in single cancers. There is no study which systematically analyzes the incidence of bone metastases in different cancers types. Our study shows that lung cancer is most likely to present with bone metastasis, which may support recent screening guidelines. Previous studies have shown that the incidence rate of bone metastases in metastatic prostate cancer is over 80%, while bone metastases occur in 65–80% of patients with metastatic breast cancer (29-34). Our study also indicates that the incidence proportion of bone metastases is high in patients with breast or prostate cancer. Previous studies have shown that bone metastases occur in approximately 30% of patients with invasive bladder cancer and renal cancer (35-38). In our study, the incidence rate of bone metastases was 16.08% and 1.48% in renal cancer and bladder cancer, respectively. Furthermore, bone metastases accounted for 38.65% and 31.08% of metastatic renal and bladder cancers, respectively. Though the rate of bone metastases is not high in bladder cancer, bone cancer accounts for a relatively large portion of the metastatic sites among patients with metastatic bladder cancer. Therefore, we must pay attention to the screening of bone metastases in this setting.

Survival

Our results show that cancer presented at diagnosis with bone metastases with the longest median survival time is breast cancer (27 months), followed by prostate cancer (25 months), and thyroid cancer (23 months). Previous studies had shown that the median survival time is 30 and 28 months among breast cancer patients with bone metastases and prostate cancer patients with bone metastases (39,40). These results are similar to ours. Bhatia reported that the prognosis of hepatocellular carcinoma with bone metastasis is extremely poor, with a median survival of only 1–2 months (41). We also found that the median survival time is the shortest in cancers of the digestive system. Silvestris et al. indicated that the median survival was 6 months in gastric cancer patients after bone metastasis diagnosis (42). Our results showed the median survival is 3 months among gastric cancer patients with bone metastases, which was a little shorter than the earlier study.

Clinical implications

Bone metastases are associated with an increased risk of mortality for patients with cancer and may lead to a poor quality of life (17,43,44). The early detection of bone metastases may minimize morbidity and mortality and lead to a better quality of life (45-47), while also being a fundamental step in anticancer treatment (48-50). The National Comprehensive Cancer Network (NCCN) clinical practice guidelines in oncology also recommended routine screening bone metastases in patients with SCLC, prostatic cancer, and high-metastasis-risk renal cancer (51-54). Our results support the current guidelines as these cancers are all at high risk of the development of bone metastases, although the routine use of bone screening is not recommended in NSCLC. Our data showed that the incidence of bone metastases at diagnosis in NSLCLC is relatively high. Therefore, in patients with a diagnosis of stage IV NSCLC, special focus should be dedicated to the screening of the bones.

Furthermore, screening of bone metastases is not routinely performed for patients with esophagus cancer (55). However, our data revealed a 7.99% and 20.74% incidence proportion of bone metastases in patients with esophagus cancer and metastatic esophagus cancer, respectively. Therefore, routine screening of bone metastases is necessary for patients with these cancers.

As screening was not routinely performed in these patients, bone metastases are always discovered only as a result of SREs, which may be a more advanced disease that shortens survival (56) and often requires surgical intervention or a more complex treatment plan. However, surgery for pathological fracture and loss of motor function and mobility might also increase mortality (5). Our data show a relatively high rate of bone metastasis in these populations—one which may be underestimated. Therefore, our findings may support the need to routinely screen for bone metastases at diagnosis for these patients.

As for patients with head and neck cancers, the incidence of comorbidity for liver metastasis and bone metastases is high. Patients with breast and bladder cancer have a high incidence of comorbidity with bone metastasis and brain, liver, or lung metastasis. Therefore, a diagnosis of bone metastases may be a strong signal that other sites of metastases may exist in patients. For lung cancer, we should pay attention to the comorbidity of bone metastases and liver metastases, while for digestive system cancer and gynecologic cancer, we may be more concerned about the comorbidity of bone metastases and brain metastases.

Previous studies have shown that patients with bone-only metastases have a better prognosis (57-59). For instance, previous investigators pointed out that the median survival time of patients with breast cancer and bone-only metastasis was about 20–50 months, which is much longer than multiple sites metastasis (60-63). This result is consistent with our findings. The incidence of bone-only metastasis is high in NSCLC (NOS/others), SCLC, ADC, bladder cancer, and esophageal cancer. So, for patients with these cancers, we must find a specific metastasis status. Because the treatment of bone-only metastasis is different from other sites or multiple sites metastasis (60), identifying bone-only metastasis may help clarify the clinical course, improve the prognosis for patients with bone-only metastasis, and estimate median survival time more accurately (64,65).

Our data also have value for the design of clinical trials. The data in our study may help investigators quantify the specific number of patients needed to be excluded from the trial enrollment, with bone metastasis as an exclusion criterion. Moreover, for studies or trials which are related to bone metastases, our study can provide generalizable estimates of incidence and prognosis for use in calculations and some trial design.

Limitations

The present study has some potential limitations. Firstly, we only identified bone metastases at initial cancer diagnosis, and, because SEER cannot provide information relating to disease recurrence, we could not screen patients with bone metastases after initial diagnosis. Secondly, we do not have information relating to the number size and exact location of the bone metastases. Thirdly, screening was not conducted across all malignancies, and therefore some data of metastases might have been missed. Finally, treatment information for the metastatic sites was not provided, so we could not study the treatment received by each patient.

Although this study has several limitations, it provides new information regarding the epidemiology of bone metastasis. Incidence of bone metastasis and the specific proportion of patients with bone metastases among different cancer types could help in the development of the formation of screening paradigms for bone metastases, clinical treatment and trial design, and counseling of different subsets of patients with cancer.

Conclusions

The results of this study provide population-based estimates of the incidence of bone metastasis and the specific incidence proportion of patients with bone metastasis diagnosis of solid tumors. We have shown that prostate cancer and breast cancer are most likely to occur with bone metastases. Additionally, the rate of bone metastasis was more than 20% in patients with lung, renal, bladder, thyroid, and esophageal cancers. We also found that the median survival time was more than 20 months in bone metastatic breast cancer, prostate cancer, and thyroid cancer. Conversely, the median survival time was the shortest in gastrointestinal, lung, and gynecologic cancer with bone metastases. These data may help clinicians in their justification of using of bone screening, which may also have an important role in clinical trial design and better prognosis. The findings can support the decision of screening of the bone and extracranial metastases for patients with high-risk primary malignancy.

Supplementary

The article’s supplementary files as

atm-08-07-482-coif.pdf (191.8KB, pdf)
DOI: 10.21037/atm.2020.03.55

Acknowledgments

Funding: This work was funded by the National Natural Science Foundation of China (No. 81501933), the Zhejiang Provincial Medical and Health Technology Foundation of China (No. 2018KY129), Wenzhou Leading Innovative Talent Project (No. RX2016004) and the Wenzhou Municipal Science and Technology Bureau (No. Y20170389). The funders had no role in the design, execution, or writing of the study.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Footnotes

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm.2020.03.55). The authors have no conflicts of interest to declare.

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DOI: 10.21037/atm.2020.03.55

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