Surgical resection of primary tumors improves survival in patients with lung metastases: a population-based SEER analysis
Original Article

Surgical resection of primary tumors improves survival in patients with lung metastases: a population-based SEER analysis

Tianyu Liu, Xiaolong Lv, Lei Yang, Zelin Yang, Chenhao Jia, Huanwen Chen

Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China

Contributions: (I) Conception and design: T Liu, X Lv, L Yang; (II) Administrative support: H Chen; (III) Provision of study materials or patients: T Liu; (IV) Collection and assembly of data: T Liu, X Lv, Z Yang; (V) Data analysis and interpretation: T Liu; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

Correspondence to: Huanwen Chen, MD, PhD. Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, No. 1, Youyi Road, Yuzhong District, Chongqing 400010, China. Email: coolstarchw9527@163.com.

Background: The lung is a common site for cancer metastasis. Some cancer patients would develop lung metastases throughout the course of their illness. However, choosing surgical resection of the primary tumor (SRPT) or palliative treatment in patients with lung metastases remains controversial.

Methods: Lung metastatic patients diagnosed from 2010 to 2016 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Selected patients were divided into two subgroups (surgery and non-surgery). Further, all the 58 tumor types were classified into 13 subtypes. The clinical and demographic features were examined by the Fisher’s exact test, chi-squared test, or z-test. Overall survival (OS) was analyzed using the Kaplan-Meier (K-M) estimator and a log-rank test for each primary tumor type. Multivariable survival analyses of OS were performed using the Cox proportional hazards model.

Results: Among the 118,088 patients selected for study, 18,688 (15.83%) patients had undergone surgery. The analyses demonstrated that there was a significant association between SRPT and better OS in patients with lung metastases. The median survival time increased from 4.0 months in the non-surgery group to 19.0 months in the surgery group. Multivariate Cox regression analyses further validated that patients who underwent SRPT had an improved OS.

Conclusions: The current study demonstrated that patients with lung metastases can benefit from SRPT. SRPT should be considered in patients with lung metastases. Properly designed prospective randomized clinical trials would be required to further verify the conclusion.

Keywords: Primary tumor; lung metastasis; surgical resection of the primary tumor (SRPT); survival; Surveillance, Epidemiology, and End Results (SEER)


Submitted Oct 25, 2022. Accepted for publication Apr 07, 2023. Published online Apr 20, 2023.

doi: 10.21037/tcr-22-2459


Highlight box

Key findings

• The current study demonstrated that patients with lung metastases can benefit from SRPT.

What is known and what is new?

• SRPT resulted in better OS in several types of metastatic cancer.

• SRPT should be considered for lung metastatic patients.

What is the implication, and what should change now?

• In addition to radiotherapy and systemic chemotherapy, SRPT should also be seriously considered for lung metastatic patients. It is appreciated that the conclusion here will be validated and surgical inclusion criteria could be further clarified through well-designed, prospective, and randomized clinical trials.


Introduction

Distant metastases are the main cause of death in cancer patients, and are mostly found in the brain, liver, lungs, kidneys, and lymph nodes (1). The mechanism of distant metastasis is unclear. For cancer patients who exhibit no obvious symptoms, the tumors are difficult to be detected at earlier stage using present methods. Hence, for many patients, tumors were already in their advanced stages or had metastasized to other sites at the point of diagnosis, which further complicated the treatments. Many tumors are prone to distant metastases. For example, in osteosarcoma (2) and early-stage breast cancer (3), 13% and 20–30% of patients experienced distant metastases respectively. The lung is one of the most common metastatic sites for cancer metastasis, which accounts for 30–50% of all metastasis-related cases. Although distant lung metastases could occur in most types of cancer, they are most common in cancers involving melanoma, breast, colorectal, thyroid, head and neck and renal cell cancer (4). However, compared to other types of distant metastases, lung metastasized tumors have relatively lower growth rate and better overall survival (OS) (5). Therefore, treatment options for lung metastases could be different to that of metastases at other sites.

Although multiple treatment options, including locoregional and/or lung surgery, chemotherapy, immunotherapy and radiotherapy, could be used for lung metastatic cancer, the potential curative treatment approach would be comprehensive treatment for lung metastatic tumors. However, patients with lung metastasized tumors, which are already in advanced stages, are not recommended by the clinical guidelines to remove the primary tumors. Surgical resection of the primary tumor (SRPT) treated patients could have a 30–40% 5-year survival rate. Furthermore, previous studies revealed that SRPT resulted in better OS in several types of metastatic cancer, such as pancreatic cancer (6), gastroenteropancreatic neuroendocrine neoplasms (7), colorectal cancer (8), prostate cancer (9,10), and Ewing’s sarcoma (11). Nevertheless, none of these studies revealed a survival difference between lung metastases and other sites of metastases, as all these studies have relatively small sample size.

Given that the lungs are the predominant metastatic sites, it will be vital to understand how SRPT would affect the OS of patients with lung metastases. In the present study, we took advantage of the SEER database, which has a relatively large sample size, to assess whether SRPT should be considered for lung metastatic patients. We present this article in accordance with the STROBE reporting checklist (available at https://tcr.amegroups.com/article/view/10.21037/tcr-22-2459/rc).


Methods

Ethical statement

The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The data on cancer in the Surveillance, Epidemiology, and End Results (SEER) database is continually reported in every state of the United States and retrieved with no need for informed patient consent.

Patient cohort

Eligible patients and their related information were obtained from the SEER database by employing a specific software (SEER*Stat, version 8.3.5, National Center Institute, USA). The SEER database recorded various clinical information including tumor characteristics, demographics, cancer incidence and prevalence, treatments and mortality. The SEER database has been widely used for clinical cancer studies. Patients diagnosed between 2010 and 2016 were included. The exclusion criteria were as following: (I) patients diagnosed before 2010 or after 2016, (II) diagnosed at autopsy or via death certificate, (III) patients with no clear lung metastasis information or surgery information. Detailed patient selection procedures are displayed in Figure 1.

Figure 1 The flow-chart for the subject selection in the present study. SEER, Surveillance, Epidemiology, and End Results.

Data collection

For each patient, the following clinical data were obtained: primary tumor type, age at diagnosis, gender, marital status, insurance status, income level, laterality, tumor grade, tumor stage, lymph node stage, metastasis sites (bone, brain, or liver), OS, and surgery status (yes or no). OS was used as the major endpoint outcome in the study. OS was defined as the duration from diagnosis to death due to any causes. Selected patients were classified into two subgroups (surgery and non-surgery). Additionally, 58 types of cancer identified from the SEER database were further divided into 13 cancer subtypes based on the primary tumor sites, including the oral cavity and pharynx, bones and joints, digestive, respiratory, soft tissue and skin, urinary, endocrine, male genital, female genital, blood, nervous, lymphatic, and the remaining systems.

Statistical analyses

Depending on different variables, differences in the clinical and demographic features between surgery and non-surgery groups were analyzed by the Fisher’s exact test, chi-squared test, or z-test. For each type of cancer, OS was evaluated by the Kaplan-Meier (K-M) estimator or a log-rank test. OS was further estimated by K-M curves. In addition, survival analyses were also performed for the 13 cancer subtypes. Median survival times and the associated 95% confidence intervals (CIs) were calculated by the K-M method. Multivariable survival analyses of OS were performed utilizing the Cox proportional hazards model. The loss to follow-up or follow-up interruption at the end of the observation was treated as a censoring event. Moreover, we applied a subgroup analysis to test the robustness of our results. For the above analyses, the following software was used: SPSS Statistics 22.0 software (IBM, NY, USA) for the chi-square test, z-test, K-M curves, log-rank test, and Cox regression analysis; GraphPad Prism 8.3 software (GraphPad, CA, USA) was used to generate the histograms; Comprehensive Meta-Analysis (CMA) Software 2.0 (Biostat, NJ, USA) was employed for the forest plotting. A two-tailed P value smaller than 0.05 was recognized as statistically significant.


Results

Patient and tumor characteristics

Detailed demographic and clinical parameters of the patients were summarized in Table 1; 118,088 selected patients with lung metastases were collected from the SEER database, of whom 18,688 (15.83%) had undergone surgery and 99,400 (84.17%) had not (Figure 1). The median age at diagnosis was 68.0 years; 77.85% and 94.18% of patients were white and insured, respectively. Selected patients in the non-surgery group were older than those in the surgery group (median age: 69.0 vs. 62.0 years, P<0.001). Younger age was also associated with improved OS from univariate and multivariable Cox proportional hazard regression analyses (Table 2). There was a larger proportion (41.37% vs. 28.98%) of patients with N0 stage cancer in the surgery group. Patients undergoing surgery were at lower T and N stage, but with higher grade. Univariate and multivariable Cox proportional hazard regression analyses showed that patients with lower N stage had a better OS (Table 2). Patients with cancer of the urinary (21.62%) and the female genital systems (12.92%) had higher ratio of SRPT. Moreover, the ratio of patients who underwent SRPT increased through the years from 2010 to 2016. This suggests that SRPT might be a mainstream treatment option for patients with lung metastasis in the future (Figure 2). Additionally, the survival rates in the surgery and non-surgery groups were 38.86% (n=7,263) and 16.19% (n=16,090), respectively.

Table 1

Demographic and clinical characteristics for lung metastases patients of non-surgery and surgery

Subject characteristics Total, n (%) Non-surgery, n (%) Surgery, n (%) χ2/Z P value
All patients 118,088 (100.00) 99,400 (100.00) 18,688(100.00)
Age, years 71.33 <0.001
   ≤18 979 (0.83) 305 (0.31) 674 (3.61)
   19–40 4,050 (3.43) 2,281 (2.29) 1,769 (9.47)
   41–64 42,972 (36.39) 34,938 (35.15) 8,024 (42.94)
   ≥65 70,097 (59.35) 61,876 (62.25) 8,221 (43.99)
Sex 86.82 <0.001
   Male 60,907 (51.58) 51,713 (50.03) 9,194 (49.20)
   Female 57,181 (48.42) 47,687 (49.97) 9,494 (50.80)
Race 72.25 <0.001
   White 91,927 (77.85) 77,172 (77.64) 14,775 (79.06)
   Black 15,385 (13.03) 13,198 (13.28) 2,187 (11.70)
   Others* 10,482 (8.88) 8,812 (8.87) 1,670 (8.94)
   Unknown 274 (0.23) 218 (0.22) 56 (0.30)
Marital status 1,295.19 <0.001
   Married 56,233 (47.62) 46,897 (47.18) 9,336 (49.96)
   Unmarried 56,431 (47.79) 47,874 (48.16) 8,557 (45.79)
   Unknown 5,424 (4.59) 4,629 (4.66) 795 (4.25)
Insurance 66.20 <0.001
   Insured 111,218 (94.18) 93,521 (94.09) 17,697 (94.70)
   Uninsured 4,568 (3.87) 3,841 (3.86) 727 (3.89)
   Unknown 2,302 (1.95) 2,038 (2.05) 264 (1.41)
Income 3.04 0.002
   <6,000 28,325 (23.99) 24,090 (24.24) 4,235 (22.66)
   6,000–7,000 35,641 (30.18) 29,830 (30.01) 5,811 (31.10)
   7,000–8,000 16,864 (14.28) 14,103 (14.19) 2,761 (14.77)
   >8,000 37,255 (31.55) 31,375 (31.56) 5,880 (31.47)
Laterality 1,951.55 <0.001
   Right 35,852 (30.36) 31,169 (31.36) 4,683 (25.06)
   Left 29,051 (24.60) 24,577 (24.72) 4,474 (23.94)
   Bilateral 3,687 (3.12) 3,062 (3.08) 625 (3.34)
   Unknown 49,498 (41.92) 40,592 (40.84) 8,906 (47.66)
Grade 97.84 <0.001
   I 3,291 (2.79) 2,571 (2.59) 720 (3.85)
   II 16,654 (14.10) 12,368 (12.44) 4,286 (22.94)
   III 24,478 (20.73) 19,297 (19.41) 5,181 (27.73)
   IV 6,212 (5.26) 2,885 (2.91) 3,327 (17.80)
   Unknown 67,450 (57.12) 62,277 (62.65) 5,173 (27.68)
T stage 68.69 <0.001
   T1 11,166 (9.46) 9,022 (9.08) 2,144 (11.47)
   T2 16,070 (13.61) 12,732 (12.81) 3,338 (17.86)
   T3 28,352 (24.01) 21,531 (21.66) 6,821 (36.50)
   T4 35,547 (30.10) 31,058 (31.25) 4,489 (24.02)
   Unknown 26,953 (22.82) 25,057 (25.21) 1,896 (10.15)
N stage 63.24 <0.001
   N0 36,542 (30.94) 28,810 (28.98) 7,732 (41.37)
   N1 24,467 (20.72) 19,316 (19.43) 5,151 (27.56)
   N2 25,395 (21.51) 22,318 (22.45) 3,077 (16.47)
   N3 13,226 (11.20) 12,429 (12.50) 797 (4.26)
   Unknown 18,458 (15.63) 16,527 (16.63) 1,931 (10.33)
Bone MET 3,186.79 <0.001
   None 81,588 (69.09) 66,229 (66.63) 15,359 (82.19)
   Yes 32,925 (27.88) 29,940 (30.12) 2,985 (15.97)
   Unknown 3,575 (3.03) 3,231 (3.25) 344 (1.84)
Brain MET 2,184.96 <0.001
   None 99,823 (84.53) 82,478 (81.98) 17,345 (92.81)
   Yes 13,934 (17.80) 13,005 (13.08) 929 (4.97)
   Unknown 4,331 (3.67) 3,917 (3.94) 414 (2.22)
Liver MET 1,168.42 <0.001
   None 76,782 (65.02) 63,119 (63.50) 13,663 (73.11)
   Yes 37,991 (32.17) 33,269 (33.47) 4,722 (25.27)
   Unknown 3,315 (2.81) 3,012 (3.03) 303 (1.62)
Cancer system
   Oral cavity and pharynx 1,690 (1.43) 1,440 (1.45) 250 (1.34)
   Digestive system 31,829 (26.95) 27,171 (27.34) 4,658 (24.93)
   Respiratory system 47,679 (40.38) 45,156 (45.43) 1,523 (8.15)
   Bones and joints 626 (0.53) 318 (0.32) 308 (1.65)
   Soft tissue including heart 1,800 (1.52) 1,154 (1.16) 646 (3.46)
   Skin excluding basal squamous 2,777 (2.35) 2,039 (2.05) 738 (3.95)
   Breast 7,777 (6.59) 6,090 (6.13) 1,687 (9.03)
   Female genital system 6,478 (5.49) 4,064 (4.09) 2,414 (12.92)
   Male genital system 3,710 (3.14) 2,330 (2.34) 1,380 (7.38)
   Urinary system 10,652 (9.02) 6,611 (6.65) 4,041 (21.62)
   Eye and orbit 39 (0.03) 20 (0.02) 19 (0.10)
   Brain and other nervous system 63 (0.05) 30 (0.03) 33 (0.18)
   Endocrine system 1,768 (1.50) 947 (0.95) 821 (4.39)
   Lymphoma 571 (0.48) 498 (0.50) 73 (0.39)
   Myeloma 59 (0.05) 50 (0.05) 9 (0.05)
   Leukemia 111 (0.09) 93 (0.09) 18 (0.10)
   Mesothelioma 456 (0.39) 298 (0.30) 58 (0.31)
   Kaposi sarcoma 18 (0.02) 16 (0.02) 2 (0.01)
   Miscellaneous 85 (0.07) 75 (0.08) 10 (0.05)
Overall survival 8,038.88 <0.001
   Survival 23,353 (19.78) 16,090 (16.19) 7,263 (38.86)
   Death 94,735 (80.22) 83,310 (83.81) 11,425 (61.14)

*, American Indian/Alaska Native, Asian or Pacific Islander. MET, metastases.

Table 2

Univariate and multivariate survival analyses of overall survival in patients who underwent surgery

Subject characteristics Univariable Multivariable
OR (95% CI) P value OR (95% CI) P value
Age, years
   ≤18 Reference Reference
   19–40 1.822 (1.539–2.157) <0.001 1.781 (1.500–2.116) <0.001
   41–64 3.505 (3.005–4.088) <0.001 2.877 (2.453–3.374) <0.001
   ≥65 4.826 (4.139–5.627) <0.001 3.835 (3.269–4.499) <0.001
Sex
   Male Reference Reference
   Female 0.935 (0.901–0.970) <0.001 0.876 (0.843–0.909) <0.001
Race
   White Reference Reference
   Black 1.133 (1.072–1.197) <0.001 1.214 (1.148–1.284) <0.001
   Others* 0.903 (0.845–0.966) 0.003 0.910 (0.851–0.973) 0.006
   Unknown NA NA
Grade
   I Reference Reference
   II 1.364 (1.221–1.524) <0.001 1.331 (1.190–1.488) <0.001
   III 1.788 (1.603–1.994) <0.001 2.004 (1.796–2.237) <0.001
   IV 2.255 (2.017–2.521) <0.001 2.962 (2.646–3.315) <0.001
   Unknown NA NA
T stage
   T1 Reference Reference
   T2 1.256 (1.167–1.353) <0.001 1.195 (1.109–1.288) <0.001
   T3 1.256 (1.176–1.343) <0.001 1.104 (1.031–1.182) 0.005
   T4 1.818 (1.697–1.947) <0.001 1.462 (1.361–1.570) <0.001
   Unknown NA NA
N stage
   N0 Reference Reference
   N1 1.066 (1.019–1.115) 0.006 1.087 (1.037–1.139) <0.001
   N2 1.356 (1.288–1.428) <0.001 1.333 (1.261–1.409) <0.001
   N3 0.994 (0.903–1.095) 0.904 1.139 (1.032–1.257) 0.01
   Unknown NA NA
Bone MET
   None Reference Reference
   Yes 1.494 (1.425–1.566) <0.001 1.305 (1.242–1.371) <0.001
   Unknown NA NA
Brain MET
   None Reference Reference
   Yes 1.729 (1.602–1.867) <0.001 1.826 (1.684–1.980) <0.001
   Unknown NA NA
Liver MET
   None Reference Reference
   Yes 1.679 (1.613–1.748) <0.001 1.716 (1.643–1.792) <0.001
   Unknown NA NA
Radiotherapy
   No Reference Reference
   Yes 0.865 (0.827–0.905) <0.001 0.853 (0.813–0.895) <0.001
   Unknown NA NA
Chemotherapy
   No Reference Reference
   Yes 0.587 (0.566–0.610) <0.001 0.592 (0.569–0.616) <0.001

*, American Indian/Alaska Native, Asian or Pacific Islander. OR, odds ratio; CI, confidence interval; NA, not available; MET, metastases.

Figure 2 Variation of surgery quantity with time.

Survival analyses

Of the 118,088 patients, 94,735 (80.22%) were deceased by the end of follow-up. The median survival time was 19.0 months (95% CI: 18.45–19.55 months) and 4.0 months (95% CI: 3.94–4.06 months) for the surgery and non-surgery groups, respectively (P<0.001) (Table 3). After adjustment for parameters including age, gender, marital status, insurance status, income level, laterality, tumor grade, tumor stage, lymph node stage, metastasis sites (bone, brain, or liver), OS, and surgery status (yes or no), the multivariate Cox regression analysis indicated that recipients of SRPT were significantly related to a better OS [hazard ratio (HR) =0.49; 95% CI: 0.48–0.51, P<0.001] (Table 3).

Table 3

The median survival time and multivariable Cox regression for analyzing the overall survival of lung metastases of non-surgery and surgery

Cancer system Cancer site Non-surgery (months), median (95% CI) Surgery (months), median (95% CI) Log Rank P value HR (95% CI) P
All patients 4.00 (3.94–4.06) 19.00 (18.45–19.55) 8792.07 <0.001 0.49 (0.48–0.51) <0.001
Oral cavity and pharynx system Lip 1.00 (0.37–1.63) 5.00 2.46 0.117 0.00 (0.00–0.01) 0.013
Tongue 7.00 (5.28–8.72) 11.00 (6.17–1.83) 7.46 0.006 0.54 (0.37–0.80) 0.002
Salivary gland 8.00 (5.42–10.56) 23.00 (16.93–29.07) 27.19 <0.001 0.38 (0.26–0.56) <0.001
Floor of mouth 5.00 (2.94–7.06) 20.00 (4.90–35.11) 8.12 0.004 0.28 (0.11–0.71) 0.007
Gum and other mouth 5.00 (3.47–6.53) 8.00 (4.06–11.94) 3.72 0.054 0.60 (0.36–1.00) 0.051
Larynx 6.00 (5.07–6.93) 12.00 (8.86–15.14) 11.61 0.001 0.55 (0.39–0.80) 0.001
Nasopharynx 13.00 (8.67–17.33) 20.00 2.60 0.107 0.64 (0.25–1.64) 0.411
Tonsil 9.00 (7.50–10.51) 17.00 (1.35–32.65) 4.03 0.045 0.64 (0.36–1.13) 0.122
Oropharynx 5.00 (2.99–7.01) 6.00 (0.00–12.20) 1.21 0.271 0.65 (0.30–1.40) 0.272
Hypopharynx 6.00 (4.23–7.77) 16.00 (3.60–28.40) 4.59 0.032 0.50 (0.26–0.96) 0.037
Other oral cavity and pharynx 3.00 (1.24–4.76) 12.00 (0.00–25.72) 0.73 0.391 1.23 (0.35–4.29) 0.742
Nose, nasal cavity and middle ear 7.00 (0.78–13.22) 14.00 (8.91–19.09) 2.37 0.124 0.65 (0.31–1.34) 0.241
Subtotal 7.00 (6.42–7.58) 16.00 (12.68–19.32) 74.99 <0.001 0.50 (0.43–0.58) <0.001
Digestive system Esophagus 4.00 (3.72–4.29) 10.00 (6.63–13.37) 14.60 <0.001 0.56 (0.40–0.79) 0.001
Stomach 3.00 (2.72–3.28) 6.00 (4.22–7.78) 13.36 <0.001 0.62 (0.50–0.77) <0.001
Small intestine 5.00 (3.36–6.64) 12.00 (7.36–16.64) 10.02 0.002 0.74 (0.55–1.01) 0.059
Colon cancer 4.00 (3.66–4.34) 15.00 (13.94–16.06) 739.75 <0.001 0.58 (0.55–0.62) <0.001
Rectum and rectosigmoid junction 11.00 (10.27–11.73) 26.00 (23.04–28.07) 294.04 <0.001 0.55 (0.50–0.60) <0.001
Anus, anal canal and anorectum 9.00 (6.80–11.20) 10.00 (5.51–14.49) 0.17 0.68 1.01 (0.69–1.48) 0.970
Liver and intrahepatic bile duct 2.00 (1.90–2.11) 20.00 (11.33–28.67) 178.43 <0.001 0.29 (0.22–0.37) <0.001
Gallbladder cancer 3.00 (2.46–3.54) 6.00 (3.67–8.33) 4.89 0.027 0.74 (0.53–1.05) 0.095
Other biliary 2.00 (1.65–2.36) 11.00 (4.56–17.44) 14.46 <0.001 0.58 (0.35–0.99) 0.045
Pancreas 2.00 (1.89–2.12) 12.00 (8.45–15.55) 79.77 <0.001 0.41 (0.33–0.52) <0.001
Retroperitoneum 5.00 (2.52–7.48) 18.00 (11.09–24.92) 7.96 0.005 0.68 (0.44–1.05) 0.078
Peritoneum, omentum and mesentery 7.00 (3.69–10.31) 29.00 (25.32–32.68) 26.19 <0.001 0.53 (0.36–0.79) 0.002
Other digestive organs 2.00 (1.77–2.23) 6.00 (0.16–11.84) 2.62 0.015 1.06 (0.50–2.23) 0.876
Subtotal 3.00 (2.92–3.08) 17.00 (16.16–17.84) 2653.93 <0.001 0.47 (0.46–0.49) <0.001
Respiratory system Lung and bronchus 4.00 (3.91–4.09) 16.00 (14.19–17.81) 752.60 <0.001 0.42 (0.40–0.45) <0.001
Pleura 0.00 3.00 0.14 0.702 0.08
Trachea, mediastinum and other respiratory organs 7.00 (4.35–9.66) 17.00 (8.57–25.43) 16.66 <0.001 0.42 (0.25–0.71) 0.001
Subtotal 4.00 (3.91–4.09) 16.00 (14.23–17.77) 777.86 <0.001 0.42 (0.40–0.45) <0.001
Bones and joints system Bones and joints 10.00 (8.02–11.98) 29.00 (23.00–35.00) 59.78 <0.001 0.62 (0.49–0.79) <0.001
Soft tissue and skin system Melanoma of the skin 5.00 (4.61–5.39) 11.00 (9.60–12.40) 72.16 <0.001 0.70 (0.63–0.78) <0.001
Soft tissue including heart 5.00 (4.35–5.65) 16.00 (13.73–18.27) 181.85 <0.001 0.50 (0.44–0.57) <0.001
Other non-epithlia skin 6.00 (2.75–9.25) 9.00 (6.31–11.69) 0.98 0.323 0.62 (0.35–1.09) 0.097
Mesothelioma 4.00 (3.09–4.91) 9.00 (5.99–12.01) 9.21 0.002 0.72 (0.52–1.00) 0.050
Eye and orbit 4.00 (1.70–6.30) 37.00 (4.26–69.74) 6.32 0.012 0.80 (0.15–4.28) 0.791
Kaposi sarcoma 0.28 0.597 0.00 0.599
Subtotal 5.00 (4.68–5.32) 13.00 (11.85–14.15) 269.51 <0.001 0.59 (0.54–0.63) <0.001
Female genital system Cervix uteri 6.00 (5.34–6.66) 12.00 (10.09–13.91) 16.94 <0.001 0.63 (0.48–0.82) 0.001
Breast cancer 15.00 (14.11–15.89) 29.00 (26.71–31.29) 216.38 <0.001 0.71 (0.66–0.76) <0.001
Corpus and uterus, NOS 3.00 (2.61–3.39) 14.00 (12.60–15.40) 341.18 <0.001 0.50 (0.45–0.56) <0.001
Ovary 3.00 (2.53–3.47) 30.00 (27.68–32.32) 607.92 <0.001 0.37 (0.32–0.43) <0.001
Vagina 5.00 (2.92–7.08) 18.00 (2.81–33.19) 2.15 0.143 0.68 (0.32–1.44) 0.316
Vulva 3.00 (1.90–4.11) 6.00 (2.73–9.27) 4.80 0.029 0.48 (0.30–0.75) 0.001
Other female genital organs 16.00 (7.05–24.95) 47.00 (32.50–61.50) 14.17 <0.001 1.09 (0.69–1.74) 0.708
Subtotal 9.00 (8.53–9.47) 24.00 (22.69–25.31) 675.06 <0.001 0.69 (0.66–0.73) <0.001
Male genital system Penis 2.00 (0.21–3.79) 7.00 (5.24–8.76) 2.05 0.152 0.51 (0.20–1.34) 0.170
Testis 8.00 (4.25–11.75) 0.00 181.87 <0.001 0.33 (0.24–0.47) <0.001
Subtotal 7.00 (3.31–10.69) 204.66 <0.001 0.37 (0.27–0.51) <0.001
Urinary system Prostate 12.00 (10.99–13.01) 18.00 (14.19–21.81) 11.36 0.001 0.84 (0.70–1.00) 0.054
Urinary 2.00 (1.63–2.37) 5.00 (4.46–5.54) 54.33 <0.001 0.83 (0.74–0.93) 0.001
Kidney and renal pelvis 4.00 (3.82–4.18) 19.00 (17.47–20.54) 1597.74 <0.001 0.40 (0.37–0.43) <0.001
Ureter 4.00 (2.63–5.37) 7.00 (5.18–8.82) 4.27 0.039 0.90 (0.47–1.70) 0.740
Other urinary organs 2.00 (0.95–3.05) 9.00 (7.13–10.88) 2.69 0.101 0.76 (0.44–1.31) 0.318
Subtotal 5.00 (4.77–5.23) 13.00 (12.30–13.70) 837.30 <0.001 0.69 (0.66–0.73) <0.001
Nervous system Cranial nerves other nervous system 1.00 46.00 (0.00–106.01) 1.10 0.294 0.00 (0.00–0.001) 0.474
Brain 6.00 (0.00–15.79) 7.00 (2.85–11.15) 0.08 0.766 0.54 (0.20–1.48) 0.230
Subtotal 5.00 (0.00–11.09) 10.00 (0.00–20.76) 2.11 0.146 0.33 (0.15–0.76) 0.009
Endocrine system Other endocrine including thymus 9.00 (6.27–11.74) 48.00 (40.69–55.31) 59.12 <0.001 0.31 (0.23–0.42) <0.001
Thyroid 2.00 (1.49–2.51) 59.00 (41.39–70.61) 412.80 <0.001 0.28 (0.23–0.33) <0.001
Subtotal 4.00 (3.27–4.73) 53.00 (43.22–63.78) 409.71 <0.001 0.26 (0.22–0.30) <0.001
Lymphatic system Non-Hodgkin lymphoma 12.00 (8.52–15.48) 32.00 (23.88–40.13) 5.97 0.015 0.55 (0.35–0.87) 0.010
Hodgkin lymphoma 1.43 0.232 1.72 (0.00–2.86) 0.964
Subtotal 15.00 (11.50–18.50) 32.00 (11.82–52.19) 6.64 0.01 0.52 (0.33–0.82) 0.004
Blood system Leukemia 6.00 (2.83–9.17) 42.00 (20.61–63.39) 15.75 <0.001 0.31 (0.15–0.66) 0.002
Myeloma 6.00 (1.61–10.39) 7.00 (0.76–13.24) 0.41 0.522 0.46 (0.12–1.78) 0.262
Subtotal 6.00 (3.43–8.57) 27.00 (14.08–39.92) 15.58 <0.001 0.42 (0.23–0.77) 0.005
Other system Miscellaneous 6.00 (1.89–10.11) 23.00 (1.12–44.88) 4.20 0.041 0.49 (0.20–1.17) 0.107

Adjustment factors: adjusted for Ages at diagnosis, Sex, Marriage, Insurance, Race, Income, Grade, T stage, N stage, Radiation, Chemotherapy, Bone metastases, Brain metastases, Liver metastases. CI, confidence interval; HR, hazard ratio; NOS, not otherwise specified.

Of the 58 types of cancer, subjects who underwent SRPT had improved OS to varying degrees compared to those who did not. Moreover, the 58 types of cancer were divided into 13 subtypes and subjects with SRPT were associated with improved OS (Table 3). Among the patients whose primary tumors were in the oral cavity and pharynx system, median survival time was 16.00 months (95% CI: 12.68–19.32 months) and 7.00 months (95% CI: 6.42–7.58 months) for the surgery and non-surgery groups, respectively (P<0.001). Similarly, the median survival time of patients in the surgery group was significantly longer than that of those in the non-surgery group in cancer of the digestive system (17.00 months, 95% CI: 16.16–17.84 months vs. 3.00 months, 95% CI: 2.92–3.08 months; P<0.001), bones and joints (29.00 months, 95% CI: 23.00–35.00 months vs. 10.00 months, 95% CI: 8.02–11.98 months; P<0.001), soft tissue and skin (13.00 months, 95% CI: 11.85–14.15 months vs. 5.00 months, 95% CI: 4.68–5.32 months; P<0.001), female genital (24.00 months, 95% CI: 22.69–25.31 months vs. 9.00 months, 95% CI: 8.53–9.47 months; P<0.001), urinary (13.00 months, 95% CI: 12.30–13.70 months vs. 5.00 months, 95% CI: 4.77–5.23 months; P<0.001), endocrine (53.00 months, 95% CI: 43.22–63.78 months vs. 4.00 months, 95% CI: 3.27–4.73 months; P<0.001), lymphatic (32.00 months, 95% CI: 11.82–52.19 months vs. 15.00 months, 95% CI: 11.50–18.50 months; P=0.01), blood (27.00 months, 95% CI: 14.08–39.92 months vs. 6.00 months, 95% CI: 3.43–8.57 months; P<0.001), and the remaining miscellaneous systems (23.00 months, 95% CI: 1.12–44.88 months vs. 6.00 months, 95% CI: 1.89–10.11; P=0.041). However, a log-rank test revealed no difference of survival time between surgery and non-surgery groups in the nervous system (P=0.146). The K-M OS curves for the surgery and non-surgery groups were shown in Figure 3. At each time point, the survival time of patients in the surgery group was longer than that of those in the non-surgery group.

Figure 3 Kaplan-Meier analyses for survival in different cancer system surgery or non-surgery. Overall survival: (A) patients with oral cavity and pharynx system: surgery vs. non-surgery; (B) patients with digestive system: surgery vs. non-surgery; (C) patients with respiratory system: surgery vs. non-surgery; (D) patients with bones and joints system: surgery vs. non-surgery; (E) patients with soft tissue and skin system: surgery vs. non-surgery; (F) patients with female genital system: surgery vs. non-surgery; (G) patients with male genital system: surgery vs. non-surgery; (H) patients with urinary system: surgery vs. non-surgery; (I) patients with nervous system: surgery vs. non-surgery; (J) patients with endocrine system: surgery vs. non-surgery; (K) patients with lymphatic system: surgery vs. non-surgery; (L) patients with blood system: surgery vs. non-surgery; (M) patients with other system: surgery vs. non-surgery.

Patients who underwent SRPT exhibited a significant improvement in rate of survival, a finding observed across diverse synchronous metastases patterns (Table 4). In lung metastasis only, the median survival times of the surgery and non-surgery groups, were 15.00 months (95% CI: 14.56–15.44 months) and 5.00 months (95% CI: 4.90–5.11 months) (P<0.001), respectively. In lung metastasis combined with liver metastasis, the median survival times of the surgery and non-surgery groups, were 10.00 months (95% CI: 9.46–10.55 months) and 2.00 months (95% CI: 1.91–2.09 months) (P<0.001), respectively. In lung metastases combined with bone metastases, the median survival times were 10.00 months (95% CI: 9.26–10.74 months) and 4.00 months (95% CI: 3.86–4.14 months) for the surgery and non-surgery groups, respectively (P<0.001). Similarly, the median survival time of patients in the surgery group was significantly longer than that of patients in the non-surgery group in lung metastases combined with brain metastases [respectively, 8.00 months (95% CI: 6.98–9.02 months) and 3.00 months (95% CI: 2.82–3.18 months); P<0.001] (Table 4). Furthermore, most of the subjects had received primary tumour resection as the first treatment. No radiation and/or cancer-directed surgery accounted for 93.1%. Radiation prior to surgery accounted for 6.0%. Radiation after to surgery accounted for 0.7%. The sum of intraoperative radiation, intraoperative rad with other rad before/after and sequence unknown, but both were given accounted for 0.1% (Figure 4). Patients who underwent SRPT and chemotherapy or radiotherapy experienced a significant survival improvement. In chemotherapy, the median survival times were 24.00 months (95% CI: 23.29–24.71 months) and 9.00 months (95% CI: 8.87–9.13 months) for the surgery and non-surgery groups, respectively (P<0.001). In radiotherapy, the median survival times were 20.00 months (95% CI: 18.71–21.29 months) and 6.00 months (95% CI: 5.87–6.13 months) for the surgery and non-surgery groups, respectively (P<0.001). Patients who underwent chemotherapy or radiotherapy were also associated with improved OS from multivariable Cox proportional hazard regression analyses (Table 2).

Table 4

Survival analysis of different metastatic organs and treatment modalities

Parameter Non-surgery (months), median (95% CI) Surgery (months), median (95% CI) Log Rank P value
Only lung metastasis 5.00 (4.90–5.11) 15.00 (14.56–15.44) 3,834.12 <0.001
Lung + liver metastasis 2.00 (1.91–2.09) 10.00 (9.46–10.55) 1,548.96 <0.001
Lung + bone metastasis 4.00 (3.86–4.14) 10.00 (9.26–10.74) 442.61 <0.001
Lung + brain metastasis 3.00 (2.82–3.18) 8.00 (6.98–9.02) 125.80 <0.001
Chemotherapy
   Yes 9.00 (8.87–9.13) 24.00 (23.29–24.71) 7,849.03 <0.001
   No 1.00 (0.97–1.03) 9.00 (8.37–9.63)
Radiotherapy
   Yes 6.00 (5.87–6.13) 20.00 (18.71–21.29) 8,923.70 <0.001
   No 3.00 (2.94–3.06) 18.00 (17.39–18.61)

CI, confidence interval.

Figure 4 Radiation sequence with surgery.

Multivariate Cox analyses in 13 subgroups displayed similar results. The HRs and 95% CIs for the surgery and non-surgery groups in each type of cancer were summarized in the forest plots (Figure 5). After adjustment for confounding factors, we found that SRPT improved OS among patients with cancer in the oral cavity and pharynx (HR =0.50; 95% CI: 0.43–0.58; P<0.001), digestive (HR =0.47; 95% CI: 0.46–0.49; P<0.001), bones and joints (HR =0.62; 95% CI: 0.49–0.79; P<0.001), female genital (HR =0.69; 95% CI: 0.66–0.73; P<0.001), soft tissue and skin (HR =0.59; 95% CI: 0.54–0.63; P<0.001), male genital (HR =0.37; 95% CI: 0.27–0.51; P<0.001), urinary (HR =0.69; 95% CI: 0.66–0.73; P<0.001), endocrine (HR =0.26; 95% CI: 0.22–0.30; P<0.001), nervous (HR =0.33; 95% CI: 0.15–0.76; P=0.009), lymphatic (HR =0.52; 95% CI: 0.33–0.82; P=0.004), and blood systems (HR =0.42; 95% CI: 0.23–0.77; P=0.005) (Table 3). Furthermore, we performed HR meta-analysis by using the random-effects model (Figure 5) and showed that SRPT was an independent prognostic factor corresponding to better OS (HR =0.34; 95% CI: 0.33–0.36; P<0.001).

Figure 5 Forest plot. CI, confidence interval.

Discussion

For decades, there is no effective therapy modality for patients with lung metastases. With the advancement of science and technology, new treatment methods, including systemic chemotherapy, radiotherapy, targeted therapy, immunotherapy and combination therapy, have emerged; however, their applicability and effectiveness are still limited. The curative treatment is still considered to be the complete removal of primary and metastatic tumors, and whether SRPT improves survival or not is still controversial. Thus, it is worth the in-depth investigation.

The results of the study demonstrated that there is a significant association between SRPT and better OS in patients with lung metastases based on the SEER dataset. The median survival time increased from 4.0 months in the non-surgery group to 19.0 months in the surgery group. Multivariate Cox regression analysis also validated that patients who received SRPT had a better OS. Thus, SRPT can be an alternative treatment strategy for cancer patients with lung metastases. The current study is believed to be the largest retrospective study that focused on evaluating the benefits of SRPT in patients with metastatic lung cancer.

In the subgroup analyses, we found that SRPT was beneficial for not only the general cancer patients but also the patients in each cancer subgroups. For primary tumors originated from the oral cavity and pharynx systems, the results suggested that SRPT could improve OS, which is consistent with previous reports. Harris et al. and Pan et al. suggested that compared to non-surgical patients, those who received SRPT showed a clear survival advantage with distant metastasis in laryngeal carcinoma (12,13). Tumors in the digestive system might cause bleeding, perforation, obstruction and malnutrition. SRPT can lower the risk of severe tumor-related complications and improve patients’ quality of life. Therefore, SRPT was recommended for patients with stage IV gastric cancer (14-16) and colorectal cancer (17,18). Additionally, Wang et al. also found that cancer patients with pancreas metastases who underwent SRPT had improved OS (19). Thus, the conclusion is also aligned with findings from previous studies.

The results of the study also showed that SRPT is associated with improved survival in surgery group with cancer in the bone and joint system. Likewise, several studies have found that SRPT improved OS of chondrosarcoma (20), osteosarcoma (21), and Ewing’s sarcoma in the bone system (11) with lung metastases. Melanoma is a type of skin cancer with increasing incidence and high malignancy (22). Melanoma patients with distant metastases usually have a worse prognosis regarding 5-year survival rates (<16%) and median survival time (<1 year) (23). The results of the study suggested that SRPT improved median survival time and OS for melanoma patients with lung metastases. A phase-2 clinical trial by Sosman et al. concluded that for certain selected patients, SRPT provided a promising treatment option that can improve OS of the patients (24). For breast cancer, the current study indicated that patients who received SRPT had improved OS. Some recent studies have also shown that SRPT in metastatic breast cancer was related to better OS (25,26). Moreover, SRPT has been shown to be effective in patients diagnosed with metastatic prostate (9), ovarian (27), and renal cell cancer (28). In addition, the current study also demonstrated that SRPT improved OS in other lung metastatic patients, which had not been reported previously.

The conclusions from the present study are consistent with that of the previous studies. We noticed that patients with metastatic lung cancer who received SRPT had improved OS. However, the underlying mechanisms are unclear. The possible mechanisms could be as following: (I) SRPT may reduce the number of blood circulating tumor cells which prevents micrometastases from becoming macrometastases (29,30) and eliminates the “seeding source” to blocking cancer progression (31); (II) SRPT may alleviate tumor burden to the body (32); (III) SRPT may associate with the recovery of the immune system by reversing systemic inflammation (33,34). In addition, SRPT can reduce severe tumor-related complications, and thus lead to better survival outcomes. The ratio of patients that had undergone SRPT was increasing from 2010 to 2016 except for 2015. This indicated that more and more lung metastasis patients tend to choose SRPT as a treatment option. With the advancement systemic therapies, surgical techniques and imaging techniques, distant metastases at earlier stages would be more capable of being detected. Further, neoadjuvant therapy provides another opportunity for clinicians to perform SRPT on these patients (35). In addition, the development of imaging techniques can help the clinicians to visualize the tumor borders and blood supply more clearly and thus help in developing surgical protocols that could remove tumors more safely and thoroughly.

Although the current study is supported by detailed analysis, it has limitations in several ways. Firstly, considering that the study design was based solely on the SEER database, it could not avoid the potential inherent subject selection bias. Secondly, the SEER database lacks information for factors such as disease burden, surgical margin status, preoperative status, smoking status, alcohol intake and other detailed factors (e.g., the presence of comorbidities and complications). How these factors would affect OS is unknown, which may influence the surgical decisions. It was not known for the reasons why the patients underwent SRPT. Thirdly, some factors were not described in detail in the SEER database. For example, types of surgery, whether palliative or radical surgery, open operation or minimally invasive surgery, were unknown. Chemicals and their doses used for chemotherapy or the radiation strategies used were also unknown. These unrecorded factors might affect the outcomes of survival analyses. Fourthly, apart from lung metastases, it is possible to combine data for metastases at other sites, which might have an impact on OS of patients. Finally, the SEER database does not provide computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), B-ultrasound and other imaging data, which has a certain impact on the evaluation of whether to perform surgical treatment and the prognosis. Despite the aforementioned limitations, this population-based study included a large number of lung metastasis patients and showed significant correlations with rigorous analyses, and thus should be very convincing and conclusive.


Conclusions

The results of the study showed that SRPT is effective for patients with lung metastases. However, at present, the criteria for suitability of undergoing surgery are unknown. Therefore, it is appreciated that the conclusion here will be validated and surgical inclusion criteria could be further clarified through well-designed, prospective, and randomized clinical trials. Finally, in addition to radiotherapy and systemic chemotherapy, SRPT should also be seriously considered for lung metastatic patients.


Acknowledgments

The authors acknowledge all the staff for their great efforts in the SEER program.

Funding: None.


Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tcr.amegroups.com/article/view/10.21037/tcr-22-2459/rc

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-22-2459/coif). The authors have no conflicts of interest to declare.

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. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The data on cancer in the SEER database is continually reported in every state of the United States and retrieved with no need for informed patient consent.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.


References

  1. Chaffer CL, Weinberg RA. A perspective on cancer cell metastasis. Science 2011;331:1559-64. [Crossref] [PubMed]
  2. Wang W, Yang J, Wang Y, et al. Survival and prognostic factors in Chinese patients with osteosarcoma: 13-year experience in 365 patients treated at a single institution. Pathol Res Pract 2017;213:119-25. [Crossref] [PubMed]
  3. Chen W, Hoffmann AD, Liu H, et al. Organotropism: new insights into molecular mechanisms of breast cancer metastasis. NPJ Precis Oncol 2018;2:4. [Crossref] [PubMed]
  4. Seo JB, Im JG, Goo JM, et al. Atypical pulmonary metastases: spectrum of radiologic findings. Radiographics 2001;21:403-17. [Crossref] [PubMed]
  5. Prasanna T, Karapetis CS, Roder D, et al. The survival outcome of patients with metastatic colorectal cancer based on the site of metastases and the impact of molecular markers and site of primary cancer on metastatic pattern. Acta Oncol 2018;57:1438-44. [Crossref] [PubMed]
  6. Feng T, Lv W, Yuan M, et al. Surgical resection of the primary tumor leads to prolonged survival in metastatic pancreatic neuroendocrine carcinoma. World J Surg Oncol 2019;17:54. [Crossref] [PubMed]
  7. Tsilimigras DI, Hyer JM, Paredes AZ, et al. Resection of Primary Gastrointestinal Neuroendocrine Tumor Among Patients with Non-Resected Metastases Is Associated with Improved Survival: A SEER-Medicare Analysis. J Gastrointest Surg 2021;25:2368-76. [Crossref] [PubMed]
  8. Peng P, Luan Y, Sun P, et al. Prognostic Factors in Stage IV Colorectal Cancer Patients With Resection of Liver and/or Pulmonary Metastases: A Population-Based Cohort Study. Front Oncol 2022;12:850937. [Crossref] [PubMed]
  9. Culp SH, Schellhammer PF, Williams MB. Might men diagnosed with metastatic prostate cancer benefit from definitive treatment of the primary tumor? A SEER-based study. Eur Urol 2014;65:1058-66. [Crossref] [PubMed]
  10. Jin K, Qiu S, Jin H, et al. Survival Outcomes for Metastatic Prostate Cancer Patients Treated With Radical Prostatectomy or Radiation Therapy: A SEER-based Study. Clin Genitourin Cancer 2020;18:e705-22. [Crossref] [PubMed]
  11. Ren Y, Zhang Z, Shang L, et al. Surgical Resection of Primary Ewing's Sarcoma of Bone Improves Overall Survival in Patients Presenting with Metastasis. Med Sci Monit 2019;25:1254-62. [Crossref] [PubMed]
  12. Harris BN, Bhuskute AA, Rao S, et al. Primary surgery for advanced-stage laryngeal cancer: A stage and subsite-specific survival analysis. Head Neck 2016;38:1380-6. [Crossref] [PubMed]
  13. Pan Y, Hong Y, Liang Z, et al. Survival analysis of distant metastasis of laryngeal carcinoma: analysis based on SEER database. Eur Arch Otorhinolaryngol 2019;276:193-201. [Crossref] [PubMed]
  14. Thrumurthy SG, Chaudry MA, Chau I, et al. Does surgery have a role in managing incurable gastric cancer? Nat Rev Clin Oncol 2015;12:676-82. [Crossref] [PubMed]
  15. Li Z, Ren H, Wang T, et al. Resection of the Primary Tumor Improves the Survival of Patients With Stage IV Gastric Neuroendocrine Carcinoma. Front Oncol 2022;12:930491. [Crossref] [PubMed]
  16. Xu J, Lu D, Zhang L, et al. Palliative resection or radiation of primary tumor prolonged survival for metastatic esophageal cancer. Cancer Med 2019;8:7253-64. [Crossref] [PubMed]
  17. Yi C, Li J, Tang F, et al. Is Primary Tumor Excision and Specific Metastases Sites Resection Associated With Improved Survival in Stage IV Colorectal Cancer? Results From SEER Database Analysis. Am Surg 2020;86:499-507. [Crossref] [PubMed]
  18. Yao YC, Chen JQ, Yin L, et al. Primary tumor resection with or without metastasectomy for left- and right-sided stage IV colorectal cancer: an instrumental variable analysis. BMC Gastroenterol 2022;22:114. [Crossref] [PubMed]
  19. Wang L, Yang L, Chen L, et al. Do Patients Diagnosed with Metastatic Pancreatic Cancer Benefit from Primary Tumor Surgery? A Propensity-Adjusted, Population-Based Surveillance, Epidemiology and End Results (SEER) Analysis. Med Sci Monit 2019;25:8230-41. [Crossref] [PubMed]
  20. Song K, Song J, Chen F, et al. Does Resection of the Primary Tumor Improve Survival in Patients With Metastatic Chondrosarcoma? Clin Orthop Relat Res 2019;477:573-83. [Crossref] [PubMed]
  21. Huang X, Zhao J, Bai J, et al. Risk and clinicopathological features of osteosarcoma metastasis to the lung: A population-based study. J Bone Oncol 2019;16:100230. [Crossref] [PubMed]
  22. Abdel-Rahman O. Clinical correlates and prognostic value of different metastatic sites in patients with malignant melanoma of the skin: a SEER database analysis. J Dermatolog Treat 2018;29:176-81. [Crossref] [PubMed]
  23. Korn EL, Liu PY, Lee SJ, et al. Meta-analysis of phase II cooperative group trials in metastatic stage IV melanoma to determine progression-free and overall survival benchmarks for future phase II trials. J Clin Oncol 2008;26:527-34. [Crossref] [PubMed]
  24. Sosman JA, Moon J, Tuthill RJ, et al. A phase 2 trial of complete resection for stage IV melanoma: results of Southwest Oncology Group Clinical Trial S9430. Cancer 2011;117:4740-06. [Crossref] [PubMed]
  25. Badwe R, Hawaldar R, Nair N, et al. Locoregional treatment versus no treatment of the primary tumour in metastatic breast cancer: an open-label randomised controlled trial. Lancet Oncol 2015;16:1380-8. [Crossref] [PubMed]
  26. Wang Z, Chen B, Chen J, et al. A Novel Nomogram Model to Identify Candidates and Predict the Possibility of Benefit From Primary Tumor Resection Among Female Patients With Metastatic Infiltrating Duct Carcinoma of the Breast: A Large Cohort Study. Front Oncol 2022;12:798016. [Crossref] [PubMed]
  27. Bristow RE, Tomacruz RS, Armstrong DK, et al. Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum era: a meta-analysis. J Clin Oncol 2002;20:1248-59. [Crossref] [PubMed]
  28. Mickisch GH, Garin A, van Poppel H, et al. Radical nephrectomy plus interferon-alfa-based immunotherapy compared with interferon alfa alone in metastatic renal-cell carcinoma: a randomised trial. Lancet 2001;358:966-70. [Crossref] [PubMed]
  29. Budd GT, Cristofanilli M, Ellis MJ, et al. Circulating tumor cells versus imaging--predicting overall survival in metastatic breast cancer. Clin Cancer Res 2006;12:6403-9. [Crossref] [PubMed]
  30. Wong NS, Kahn HJ, Zhang L, et al. Prognostic significance of circulating tumour cells enumerated after filtration enrichment in early and metastatic breast cancer patients. Breast Cancer Res Treat 2006;99:63-9. [Crossref] [PubMed]
  31. Pockaj BA, Wasif N, Dueck AC, et al. Metastasectomy and surgical resection of the primary tumor in patients with stage IV breast cancer: time for a second look? Ann Surg Oncol 2010;17:2419-26. [Crossref] [PubMed]
  32. Khan SA, Stewart AK, Morrow M. Does aggressive local therapy improve survival in metastatic breast cancer? Surgery 2002;132:620-6; discussion 626-7. [Crossref] [PubMed]
  33. DeNardo DG, Andreu P, Coussens LM. Interactions between lymphocytes and myeloid cells regulate pro- versus anti-tumor immunity. Cancer Metastasis Rev 2010;29:309-16. [Crossref] [PubMed]
  34. Turner N, Tran B, Tran PV, et al. Primary Tumor Resection in Patients With Metastatic Colorectal Cancer Is Associated With Reversal of Systemic Inflammation and Improved Survival. Clin Colorectal Cancer 2015;14:185-91. [Crossref] [PubMed]
  35. Barnes CA, Aldakkak M, Clarke CN, et al. Value of Pretreatment 18F-fluorodeoxyglucose Positron Emission Tomography in Patients With Localized Pancreatic Cancer Treated With Neoadjuvant Therapy. Front Oncol 2020;10:500. [Crossref] [PubMed]
Cite this article as: Liu T, Lv X, Yang L, Yang Z, Jia C, Chen H. Surgical resection of primary tumors improves survival in patients with lung metastases: a population-based SEER analysis. Transl Cancer Res 2023;12(5):1128-1144. doi: 10.21037/tcr-22-2459

Download Citation