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. 2018 Jul 3;7(8):4146–4155. doi: 10.1002/cam4.1656

Trends in incidence and associated risk factors of suicide mortality in patients with non‐small cell lung cancer

Huaqiang Zhou 1,2,3,4, Wei Xian 4, Yaxiong Zhang 1,2,3, Gang Chen 1,2,3, Shen Zhao 1,2,3, Xi Chen 1,2,3, Zhonghan Zhang 1,2,3, Jiayi Shen 4, Shaodong Hong 1,2,3, Yan Huang 1,2,3, Li Zhang 1,2,3,
PMCID: PMC6089196  PMID: 29971970

Abstract

Lung cancer patients have an increased risk for committing suicide. But no comprehensive study about the suicide issues among non‐small‐cell lung cancer (NSCLC) patients has been published. We aimed to estimate the trend of suicide rate and identify the high‐risk group of NSCLC patients. Patients diagnosed with primary NSCLC were identified from Surveillance, Epidemiology, and End Results (SEER) database (1973‐2013). Suicide mortality rate (SMR) were calculated. Multivariable logistic regression was employed to find out independent risk factors for suicide. Among 495 889 NSCLC patients, 694 (0.14%) of them died from suicide. The suicide mortality rates have significantly decreased (before 1993: 0.21%, 1994‐2003: 0.16%, after 2004: 0.09%, < .001). Male (OR 6.22, 95% CI: 4.96‐7.98, < .001), white (OR 3.89, 95% CI: 2.66‐5.97, < .001), being unmarried (OR 1.43, 95% CI: 1.22‐1.67, < .001), the elderly (60‐74 vs <60: OR 1.24, 95% CI: 1.03‐1.50, = .024, >75 vs <60: OR 1.31, 95% CI: 1.05‐1.63, = .018) were independently associated with higher risk of suicide mortality. Surgery (OR: 1.44, 95% CI: 1.19‐1.73, < .001) was also relative with higher risk of suicide. Our study observed significant decrease in suicide mortality among NSCLC patients in US over past decades. Older age, male sex, unmarried status, and surgery were risk factors of committing suicide. Clinicians should be aware of these high‐risk groups.

Keywords: non‐small cell lung carcinoma, prognosis, risk factors, SEER, suicide

Short abstract

There is significant decrease in suicide mortality among NSCLC patients in US over past decades. Older age, male sex, unmarried status, surgery were risk factors of committing suicide.

1. INTRODUCTION

Suicide is one of major causes of non‐cancer‐related death, which took up 1.4% of all deaths worldwide in 2015.1 Several studies have also demonstrated that the suicide rate of cancer patients is twice that of general population.2, 3, 4, 5, 6 Notably, when considering different anatomic cancer sites, patients diagnosed with lung cancer had a higher suicide rate than those with other cancer, with a standardized mortality ratio of 5.74.2 Factors associated with increased suicide risk among lung cancer patients were Asians, men, older, widowed, small cell lung carcinoma, metastatic, and refusing treatment.7

Lung cancer is second most common cancer, and 85% of them are non‐small cell lung carcinoma (NSCLC).8 Although several researchers have observed a high risk of suicide among lung cancer patients (being discussed as a single cancer entity), further examinations of patients with the most common subtype of lung cancer (NSCLC) are required, because of totally different distribution, treatment strategy and prognosis between subtypes.2, 7, 9 However, to our knowledge, a comprehensive study about the suicide issues among NSCLC patients has not been specifically published. Given that potential suicide prevention, knowing the trend of suicide rate and the high‐risk patient is of great importance. Therefore, we conducted this study using a large population‐based database to estimate the trend of suicide rate and identify the high‐risk group of NSCLC patients. In addition, we also performed a sub‐analysis of patients diagnosed from 2004 to 2013 to depict recent issues.

2. MATERIAL AND METHODS

National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database is an authoritative source of information on cancer incidence and survival in the United States. SEER database encompasses about 28% of United State population and collect cases diagnosed between 1973 and 2013.

We extracted data of patients diagnosed with primary NSCLC from SEER database(1973‐2013) using the SEER*Stat software (v8.3.4, Cancer Statistic Branch, NCI, Calverton), using International Classification of Disease for Oncology, Third Edition (ICD‐O‐3), morphology codes: 8012/3, 8046/3, 8070/3, 8140/3, 8240/3, 8250/3, 8560/3 and 9053/3; and site codes: C33.9, C34.0, C34.1, C34.2, C34.3, C34.8 and C34.9.10, 11 Patients with unknown follow‐up, diagnosed below 18 and recognized by autopsy and death certificate were excluded.

Patients whose cause of death variable coded as “Suicide and self‐inflicted injury” were identified. We obtained the demographic and clinicopathological data from the SEER database, including age, sex, race, marital status, year at diagnosis, state, tumor site, grade, histologic type, stage, surgery, cause of death, survival time, vital status and radiation. Patients were divided into 3 groups according to age at diagnosis (younger than 60 years, 60‐74 years, and older than 75 years). Race were sorted by white, black and others. We classified patients as married or unmarried. Year of diagnosis were separated into 3 groups (before 1993, 1994‐2003, after 2004). We classified the tumor site as upper lung, middle lung, lower lung, and bronchus/others. Grade of tumor were categorized into I/II, III/IV, and unknown groups. Surgery and radiation were both classified as performed, not performed, and unknown. Disease stage for the analysis was coded based on the variable “SEER Historic Stage A.” We give a value of 0.5 months to those who didn't survive for a full month after diagnosis, because SEER record their survival time in months.

Univariate analysis using chi‐square test was used to compare patients committed suicide with those died from other causes. Multivariable logistic regression was employed to find out independent risk factors for suicide. All statistical analyses were performed using R version 3.4.2 software (Institute for Statistics and Mathematics, Vienna, Austria; http://www.r-project.org). Statistical significance was set at two‐sided < .05.

3. RESULTS

3.1. Patient cohort characteristics

In total, 495 889 patients diagnosed with nonsmall‐cell lung cancer were extracted. Among all patients, 694 (0.14%) of them died from suicide. Among all patients, 207 306 (41.8%) of them are female while 288 583 (58.2%) of them are male. Among those patients committed suicide, 77 (11.1%) of them are female, and 617 (88.9%) of them are male. In total, 403 288 (81.3%) of them are white, 59 005 (11.9%) of them are black, and 33 596 (6.8%) of them are unknown and other races. As for those suicided patients, 634 (91.4%) of them are white, 25 (3.6%) of them are black, and 35 (5.0%) of them are unknown or other races. In all, 138 210 (27.9%) of them were diagnosed below 60, 237 648 (47.9%) of them were diagnosed between 60 to 75, and 120 031 (24.2%) of them were diagnosed over 75.

3.2. Differences in rates of suicide mortality by decade and state

The suicide mortality rates between all 3 time intervals were significantly different (before 1993: 0.21%, 1994‐2003: 0.16%, after 2004: 0.09%, overall: 0.14%, < .001) (Table 1). Patients from Kentucky, Louisiana, New Jersey were not recorded before 1993. When considering differences among different time intervals, California (before 1993: 0.25%, 1994‐2003: 0.18%, after 2004: 0.10%, < .001), Michigan (before 1993: 0.19%, 1994‐2003: 0.12%, after 2004: 0.07%, = .001), Washington (before 1993: 0.27%, 1994‐2003:0.19%, after 2004: 0.11%, = .010) show significant drop of suicide mortality rate.

Table 1.

Suicide mortality rates by states and time of diagnosis

State Before 1993 SMR (%) 1994‐2003 SMR (%) After 2004 SMR (%) Total SMR (%) P
All states 246 0.21 227 0.16 221 0.09 694 0.14 <.001
California 66 0.25 92 0.18 84 0.10 242 0.15 <.001
Connecticut 12 0.11 9 0.08 5 0.04 26 0.08 .004
Georgia 24 0.28 31 0.22 32 0.11 87 0.17 .015
Hawaii 6 0.14 6 0.20 5 0.12 17 0.15 .100
Iowa 25 0.15 16 0.17 11 0.10 52 0.14 <.001
Kentucky 6 0.09 15 0.07 21 0.08 .058
Louisiana 5 0.07 14 0.09 19 0.08 .048
Michigan 48 0.19 17 0.12 10 0.07 75 0.14 <.001
New Jersey 7 0.06 16 0.06 23 0.06 .068
New Mexico 10 0.20 13 0.37 9 0.21 32 0.25 .017
Utah 13 0.42 6 0.29 6 0.22 25 0.32 .014
Washington 42 0.27 19 0.19 14 0.11 75 0.20 <.001

SMR, Suicide mortality rate.

3.3. Risk factors of suicide mortality in the entire cohort

Univariate analysis showed that suicide mortality was significantly higher in male patient (< .001), white (P < .001), diagnosed between 60 and 75 (= .034), squamous cell carcinoma (= .006), surgery (< .001) and without radiation therapy (= .018) (Table 2).

Table 2.

Results of univariate analysis and multivariable logistic regression for the entire cohort

Characteristics Overall Suicide SMR (%) P a OR 95% CI P b
n 495 889 694 0.14
Sex
Female 207 306 77 0.04 <.001 1.00
Male 288 583 617 0.21 6.22 4.92‐7.98 <.001
Race
Black 59 005 25 0.04 <.001 1.00
Unknown/others 33 596 35 0.10 2.75 1.65‐4.66 <.001
White 403 288 634 0.16 3.89 2.66‐5.97 <.001
Marital
Unmarried 223 335 299 0.13 .319 1.43 1.22‐1.67 <.001
Married 272 554 395 0.14 1.00
Year at diagnosis
2004‐ 236 391 221 0.09 <.001 1.00
‐1993 116 202 246 0.21 1.83 1.43‐2.34 <.001
1994‐2003 143 296 227 0.16 1.61 1.34‐1.95 <.001
Age at diagnosis
<60 138 210 164 0.12 .034 1.00
60‐75 237 648 360 0.15 1.24 1.03‐1.50 .024
>75 120 031 170 0.14 1.31 1.05‐1.63 .018
Site
Upper 250 535 347 0.14 .495
Bronchus/other 107 101 144 0.13
Middle 20 688 24 0.12
Lower 117 565 179 0.15
Grade
I/II 100 566 144 0.14 .175
III/IV 178 591 270 0.15
Unknown 216 732 280 0.13
Histology
BAC 16 275 19 0.12 .006 1.00
LCC 33 119 48 0.14 1.12 0.66‐1.96 .679
Others 70 826 71 0.10 1.18 0.72‐2.03 .533
S 149 388 245 0.16 1.21 0.77‐2.01 .431
AC 218 088 296 0.14 1.35 0.87‐2.24 .206
ASC 8193 15 0.18 1.45 0.72‐2.85 .286
Stage
Distant 224 941 246 0.11 <.001 1.00
Localized 73 293 111 0.15 1.15 0.89‐1.48 .284
Regional 109 710 149 0.14 1.05 0.84‐1.30 .684
Unstaged 87 945 188 0.21 1.17 0.91‐1.52 .219
Surgery
No 364 393 444 0.12 <.001 1.00
Unknown 1081 1 0.09 0.78 0.04‐3.45 .801
Yes 130 415 249 0.19 1.44 1.19‐1.73 <.001
Months
≥6 years 46 144 68 0.15 .762
1 year 310 902 436 0.14
2 years 74 528 111 0.15
3 years 33 462 38 0.11
4 years 18 465 26 0.14
5 years 12 388 15 0.12
Radiation
No 265 814 397 0.15 .018 1.00
Unknown 2932 8 0.27 1.66 0.75‐3.13 .158
Yes 227 143 289 0.13 0.88 0.74‐1.03 .109

AC, Adenocarcinoma; ASC, Adenosquamous carcinoma; BAC, Bronchioloalveolar; CI, confidence interval; LCC, Large cell carcinoma; S, Squamous; SMR, Suicide mortality rate.

a

P value on univariate analysis.

b

P value on logistic regression.

Multivariate logistic regression was then performed including factors significant on univariate analysis. In terms of demographic factors, sex (male vs female: OR 6.22, 95% CI : 4.96‐7.98, < .001), race (white vs black: OR 3.89, 95% CI: 2.66‐5.97, < .001, unknown/others vs black: OR 2.75, 95%CI: 1.65‐4.66, < .001), marital status (unmarried vs married: OR 1.43, 95% CI: 1.22‐1.67, < .001), year at diagnosis (‐1993 vs 2004+: OR 1.83, 95% CI: 1.43‐2.34, < .001,1994‐2003 vs 2004+: OR 1.61, 95% CI: 1.34‐1.95, < .001), age at diagnosis (60‐74 vs <60: OR 1.24, 95% CI: 1.03‐1.50, = .022, >75 vs <60: OR 1.32, 95% CI: 1.06‐1.64, = .014) were independently associated with higher risk of suicide mortality. As for clinical factors, surgery (Yes vs No: OR: 1.44, 95% CI: 1.19‐1.73, < .001) was relative to higher risk of suicide (Table 2).

3.4. Sub‐analysis of patients diagnosed from 2004 to 2013

This subgroup of patients can better represent the demographic and clinicopathological character of recent patients. So we do the sub‐analysis of patients diagnosed from 2004 to 2013.

Univariate analysis displayed that higher suicide mortality rate was associated with male patients (< .001), white patients (< .001), and patients didn't have radiation therapy (= .115). Concerning the time after diagnosis, the highest suicide mortality rate was found to be the first year after diagnosis (= .008).

Multivariate logistic regression was operated considering factors significant on univariate analysis. In respect of demographic factors, sex (male vs female: OR 7.12, 95% CI: 4.77‐11.12, < .001), race (white vs black: OR 4.76, 95% CI: 2.41‐11.23, < .001, unknown/others vs black: OR 2.46, 95% CI: 0.94‐6.82, = .069), marital status (unmarried vs married: OR 1.41, 95% CI:1.08‐1.85, = .012) were independently correlated to higher risk of suicide mortality. As for clinical factors, radiation (Yes vs No: OR:0.74, 95% CI: 0.55‐0.99, = .046) were relative to higher risk of suicide. Finally, time elapsed from cancer diagnosis was also relative with higher rate of suicide mortality (= .008), with the first year of diagnosis taking the highest rate (OR 4.79, 95% CI: 1.93‐15.97, = .003), followed by the second year (OR 4.31, 95% CI: 1.68‐14.60, = .007) (Table 3).

Table 3.

Results of univariate analysis and multivariable logistic regression for patients diagnosed 2004‐2013

Characteristics Overall Suicide SMR (%) P a OR 95% CI P b
n 236 391 221 0.09
Sex
Male 128 081 196 0.15 <.001 7.12 4.77‐11.12 <.001
Female 108 310 25 0.02 1.00
Race (%)
Black 28 908 7 0.02 <.001 1.00
Unknown/others 18 072 10 0.06 2.46 0.94‐6.82 .069
White 189 411 204 0.11 4.76 2.41‐11.23 <.001
Marital
Unmarried 115 326 109 0.09 .927 1.41 1.08‐1.85 .012
Married 121 065 112 0.09 1.00
Age at diagnosis
<60 61 248 48 0.08 .221 1.00
60‐75 109 508 102 0.09 1.08 0.77‐1.54 .676
>75 65 635 71 0.11 1.22 0.84‐1.79 .295
Site
Upper 121 665 108 0.09 .328 1.00
Bronchus/other 45 091 39 0.09 0.92 0.62‐1.33 .66
Middle 10 070 7 0.07 0.84 0.35‐1.67 .653
Lower 59 565 67 0.11 1.24 0.91‐1.68 .163
Grade
I/II 50 487 41 0.08 .468 1.00
III/IV 72 850 75 0.10 1.22 0.83‐1.82 .316
Unknown 113 054 105 0.09 1.22 0.82‐1.83 .338
Histology
BAC 5805 1 0.02 .292
LCC 6269 6 0.10
Others 49 618 43 0.09
S 61 110 58 0.09
AC 110 006 107 0.10
ASC 3583 6 0.17
Stage
Distant 132 310 122 0.09 .977 1.00
Localized 41 332 40 0.10 1.24 0.8‐1.89 .321
Regional 56 549 54 0.10 1.10 0.76‐1.56 .608
Unstaged 6200 5 0.08 0.86 0.3‐1.92 .751
Surgery
No 184 415 170 0.09 .761 1.00
Unknown 560 1 0.18 2.06 0.12‐9.27 .475
Yes 51 416 50 0.10 1.34 0.88‐2.04 .168
Months
≥6 years 15 970 4 0.03 .008 1.00
1 year 147 889 159 0.11 4.79 1.93‐15.97 .003
2 years 37 135 35 0.09 4.31 1.68‐14.6 .007
3 years 18 001 13 0.07 3.24 1.14‐11.58 .041
4 years 10 353 8 0.08 3.32 1.04‐12.46 .051
5 years 7043 2 0.03 1.18 0.16‐6.06 .848
Radiation
No 136 621 143 0.10 .115 1.00
Unknown 1329 1 0.08 0.63 0.04‐2.83 .65
Yes 98 441 77 0.08 0.74 0.55‐0.99 .046

AC: Adenocarcinoma; ASC: Adenosquamous carcinoma; BAC: Bronchioloalveolar; CI: confidence interval; LCC: Large cell carcinoma; S: Squamous; SMR: Suicide mortality rate.

a

P value on univariate analysis.

b

P value on logistic regression.

4. DISCUSSION

Our study observed significant improvement in suicide prevention among NSCLC patients in US over past decades. Urban et al9 found that suicide has not changed significantly decreased in lung cancer over time. However, in contrast to rising suicide rate of US general population, the suicide mortality rate of NSCLC patients has decreased considerably over past decades, which is consistent with previous study about suicide trend among cancer patients.12, 13, 14 This result may be associated with relatively better prognosis of NSCLC, because of early screening test for lung cancer and significant advances in treatment, such as chemotherapy and targeted therapy.15, 16, 17

Demographic characteristics associated with an increased rate of suicide in the NSCLC patients, such as older age, male sex, race were similar to those in general population.18 Earlier research showed that older people tend to commit complete suicide among general population.19, 20 Older patients with cancer are also high‐risk group, which is consistent with our research.21, 22, 23 Older patients usually encountered with greater disease burden, and social psychological pressure. Higher suicide rate of older NSCLC patients may be related to pressure and depression.20 Another possible reason is that, they hold the rational will of ending their life at the right time.24 Male sex is a risk factor of suicide in NSCLC patients, and it is accordant with trends in general population and those with other cancer.2, 25 Although depression seemed to be higher in female patients with NSCLC, male patients are more likely to succeed in ending their own life.26, 27 However, the incidence of female suicidal behavior in NSCLC patients may be underrepresented, because failed suicide attempts were not recorded in the SEER database.22 Race has a significant impact on suicidal ideation. The risk of dying from suicide was more than double for the white NSCLC patients than for the black patients.28 The reason is for higher suicide rate in white patients with NSCLC is still unknown, and hopelessness in those patients is likely to associate with suicidal behavior.29 In addition, unmarried NSCLC patients are easier exposed to suicide attempts. Married patients have a greater socioeconomic status than unmarried.30, 31 Many cancer research studies have reported a poor prognosis in unmarried patients.32, 33, 34

Interestingly, characteristics of NSCLC seems to be not relevant to suicide of patients, which is controversial with former analysis.9 In patients diagnosed between 1973 and 2013, clinical characteristics such as primary site, histologic type, historic stage have no significant influence on suicide. The same as those diagnosed recently. A possible reason is that multiple primary tumor may interfere with the result. In our study, patients with multiple primary tumor were excluded to prevent interference of other tumors. Another possible reason is that the prognosis of patients with advanced NSCLC is poor, they may die from the disease itself rather than other causes. Patients diagnosed between 1973 and 2013 who undergo treatment like surgery are more likely to suicide. This is also different from previous research.9 It can be explained by debility and loss of autonomy brought by the curative surgery toward NSCLC.35

When considering patients diagnosed between 1973 and 2013, Suicide mortality rate (SMR) is not significantly associated with time after diagnosed. But SMR is observed to be higher within the first year of NSCLC diagnosis among patients diagnosed between 2004 and 2013. It has been reported that cancer patients were at high risk of suicide within the first year of diagnosis and associated demographic and clinical factors were analyzed.36 The different result can be possibly explained by the improvement of life quality of long‐term survivor of NSCLC patients, and the major reason for suicidal behavior of recent NSCLC patients is possibly shock of cancer diagnosis.37, 38

While the demographic risk factors of cancer‐related suicide are focused on, psychological and social risk factors are frequently missed. Suicide is a complicated phenomenon that biological, psychological and social risk factors would interact and influence on it. Cancer diagnosis may lead to demoralization of NSCLC patients, such as hopelessness and helplessness, which can lead to suicidal ideation.39 Poor consequences of cancer treatment may bring physical and mental pain to NSCLC patients.40 It has been reported that cancer patients with low socioeconomic status and family support are more likely to suicide.41 The National Comprehensive Cancer Network provides a distress management guideline that recommends screening all patients for distress.42 Our findings may assist oncologists to effectively identify those NSCLC patients at higher risk of suicide, specifically for older, white, unmarried male patients with surgery. For those NSCLC patients with high risk of suicide, we should pay more attention, because appropriate psychosocial interventions have a positive impact on quality of life.43 To reduce cancer‐related suicide, patients’ understanding of cancer diagnosis and treatment options should be ensured.44 Besides, promoting family communication combine with encouraging self‐determination and participation in treatment can mitigate social risk of suicide.44, 45

There are some limitations in our study. Suicide is a complicated phenomenon affected by factors such as economic level and education level. These factors are not included in SEER database. Additionally, SEER database only contains data of US patients, so our study is limited to US patients, and research over the world is still needed. Moreover, details of treatment to NSCLC were not taken in, and we only know whether patients have undergone surgery and radiation or not. Details of treatment such as the time after surgery and chemotherapy may be associated with suicide of cancer patient.3 Furthermore, our study can't obtain suicide attempts data of NSCLC patients, and patients potential to suicide were likely to be underestimated.

5. CONCLUSIONS

In summary, our study observed a significant decrease in suicide mortality among NSCLC patients in US over past decades. Older age, male sex, unmarried status, and surgery were risk factors of committing suicide. Grade, stage, histologic type and primary site of NSCLC appear not relate to suicide. It can help clinicians identified these NSCLC patients for better support and suicide prevention. Further studies are still needed.

CONFLICT OF INTEREST

All of the authors have no conflicts of interested to declare.

ACKNOWLEDGMENTS

The authors acknowledge the efforts of the Surveillance, Epidemiology, and End Results (SEER) Program tumor registries in providing high quality open resources for researchers. The authors would like to thank editors and the anonymous reviewers for their valuable comments and suggestions to improve the quality of the paper.

Zhou H, Xian W, Zhang Y, et al. Trends in incidence and associated risk factors of suicide mortality in patients with non‐small cell lung cancer. Cancer Med. 2018;7:4146–4155. 10.1002/cam4.1656

Funding information

This work was supported by the National Key R&D Program of China (2016YFC0905500).

Zhou, Xian, and Zhang contributed equally to this work and should be regarded as co‐first authors.

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