Original Article

Suicide In Patients With Pancreatic Cancer Kiran K. Turaga, MD, MPH1; Mokenge P. Malafa, MD1; Paul B. Jacobsen, PhD2; Michael J. Schell, PhD3; and Michael G. Sarr, MD4

BACKGROUND: Depression is highly prevalent in patients with pancreatic cancer and can result in fatal outcomes from suicides. The authors report suicide rates among patients with pancreatic cancer in the United States and identify factors associated with greater suicide rates. METHODS: The current study reviewed data in the SEER database for patients diagnosed with pancreatic adenocarcinoma from 1995-2005. Logistic regression models were used to perform multivariate modeling for factors associated with suicide, while Kaplan-Meier analysis was used to assess factors affecting survival. RESULTS: Among 36,221 patients followed for 22,145 person-years, the suicide rate was 135.4 per 100,000 person-years. The corresponding rate in the US population aged 65-74 years was 12.5 per 100,000 person-years, with a Standardized Mortality Ratio (SMR) of 10.8 (95% CI, 9.2-12.7). Greater suicide rates were noted in males (Odds Ratio (OR) 13.5 [95% CI, 3.2-56.9, P < .001]) and, among males, in patients undergoing an operative intervention (OR 2.5 [95% CI, 1.0-6.5, P ¼ .05]). Married men had a lesser risk of committing suicide (OR 0.3 [95% CI, 0.1-0.6, P ¼ .002]). Median survival among patients undergoing operative intervention was 2 months for those who committed suicide compared with 10 months for those who did not commit suicide. CONCLUSIONS: Male patients with pancreatic adenocarcinoma have a risk of suicide nearly 11 times that of the general population. Patients who undergo an operative intervention are more likely to commit suicide, generally in the early postoperative period. C 2010 American Cancer Society. Cancer 2011;117:642–7. V KEYWORDS: depression, pancreatic cancer, suicide, psychologic intervention.

Suicide, a feared and often preventable consequence of untreated depression, is being recognized increasingly among cancer patients1-9; yet, the magnitude of this problem in patients with pancreatic cancer is unknown. This topic is of considerable importance, because patients with adenocarcinoma of the pancreas have a 33%-76% prevalence of depression,10,11 and pancreatic cancer is the fourth leading cause of cancer death.12 A strong association between depression and pancreatic cancer has been established since the 1930s; indeed, depression in patients with pancreatic cancer has been shown to have a stronger association than for other advanced intra-abdominal malignancies, such as gastric and colon cancer.13,14 A recent report by the Institute of Medicine15 identified the need for greater efforts to decrease psychosocial distress among cancer patients. Patients with pancreatic cancer can be considered at increased risk of depression and suicide, and should be targeted for intervention, but data on which to base such initiatives are lacking. The aim of our study was to identify the suicide rate among patients with pancreatic cancer, using population-based data to identify patient, disease, and therapy characteristics associated with commission of suicide. MATERIALS AND METHODS This study was approved and exempted from Institutional Review Board review at the University of South Florida, which participates in research activities at the H. Lee Moffitt Cancer Center and Research Institute. Data Sources Patients with pancreatic adenocarcinoma were identified from the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute. The SEER program is a network of population-based, incident tumor registries Corresponding author: Kiran K. Turaga, MD, MPH, H. Lee Moffitt Cancer Center and Research Institute, 12902 USF Magnolia Drive, SRB 24016, Tampa, FL 33612; Fax: (813) 745-4064; [email protected] 1 Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida; 2Department of Health Outcomes and Behavior, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida; 3Behavioral Sciences and Biostatistics Core, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida; 4Division of Gastroenterological and General Surgery, Mayo Clinic, Rochester, Minnesota

The authors of this article contributed as follows: Kiran Turaga: inception, collection of data, analysis of data, critical revision of manuscript; Mokenge Malafa: analysis of data, critical revision of manuscript; Paul Jacobsen: analysis of data, critical revision of manuscript; Michael Schell: analysis of data, critical revision of manuscript; Michael Sarr: analysis of data, critical revision of manuscript. See editorial on pages 446-8, this issue. DOI: 10.1002/cncr.25428, Received: November 28, 2009; Revised: February 9, 2010; Accepted: February 9, 2010, Published online September 7, 2010 in Wiley Online Library (wileyonlinelibrary.com)

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Suicide In Pancreatic Cancer Patients/Turaga et al

capturing about 26% of the United States population. We used data available for public use from 1995-2005 for our analysis in an attempt to minimize temporal bias. Study Population and Study Variables We included all patients classified as ICD-3 code 8140/3, adenocarcinoma not otherwise specified (NOS), which refers to pancreatic adenocarcinoma and excludes other malignant neoplasms such as neuroendocrine malignancies and premalignant neoplasms. We used age at diagnosis, sex, SEER summary stage grouping (localized, regional, distant, and unstaged), survival, operative intervention or not (and, if not, if recommended or not), radiation therapy, and marital status at diagnosis as covariates. Marital status was coded as married, single, divorced, separated, widowed, or unknown. For this analysis, we combined patients into 2 groups, married or single, with the single group categorized as divorced, separated, and widowed. Patients with missing data were excluded from the results, although a sensitivity analysis was performed to check the effect on the covariates. Data on concomitant preexisting illnesses, such as depression or other psychiatric conditions, were not available. Patients were considered to have committed suicide if the cause of death variable was coded as ‘‘suicide and selfinflicted injury (50220).’’ Patients with other cause of death values, including ‘‘accidents and adverse effects (50210),’’ ‘‘homicide and legal intervention (50230),’’ and ‘‘other cause of death (50300),’’ were not classified as suicides. Surgical intervention is coded in the SEER database as a separate variable that indicates if an operation was performed and if it was recommended or not. The actual surgical procedure directed at the primary site is coded as a separate variable. No record of chemotherapy appears in this database. We assigned a nonzero value (0.5 months) to patients who did not survive a full month after diagnosis, because the SEER database records survival in months. This is consistent with epidemiologic convention.16 Statistical Analysis The Student t test and the chi-square test with Fisher exact modification were used for patients who committed suicide. Standardized mortality was calculated via the ratio of obtained mortality with expected mortality from a standardized US population in 2005.17 We used the suicide rates available for ages 65-74, the age distribution of 69% of our study population. Sex-specific rates were available and therefore used for analysis. Confidence intervals were calculated with Fisher mid-P exact confidence intervals from

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web-based software available at http://www.sph.emory.edu/
cdckms/exact-midP-SMR.html. Logistic regression was used to determine the association of pancreatic adenocarcinoma and patients who committed suicide. Survival characteristics were assessed using Kaplan-Meier analysis and the log-rank test. Multivariate modeling was performed using the Cox proportional hazards model. Cause-specific mortality—with suicide counted as a failure—was performed in addition to all-cause mortality. Given the small number of events, we did not use the competing risks model. Multivariate modeling was performed for both sexes, but we present data only for the males given the high univariate odds, which made multivariate models unstable in the presence of such a strong covariate. Post-model estimates were tested for validity of the model, and the Hosmer-Lemeshow test was used to assess goodness-of-fit. A P-value of .05 or less was considered statistically significant. All analyses were performed using SEER Stat version 6.4.4 (2008) and Stata/SE Version 9.0 (StataCorp LP, College Station, TX).

RESULTS A total of 36,221 patients with pancreatic adenocarcinoma were identified, of whom 30 committed suicide over an observed 22,248 person-years. The incidence rate among patients with pancreatic adenocarcinoma was 135.5 per 100,000 person-years. The corresponding suicide rate in the United States in the year 2005 for people 65-74 years of age was 12.5 per 100,000 years.18 This calculation yields a standardized mortality ratio (SMR) of 10.8 (95% CI, 9.2-12.7). Patient and Disease Characteristics The average age at diagnosis of pancreatic adenocarcinoma was 68.5 years (interquartile range, 60-77 years), and 50.8% (N ¼ 18,420) of the population were male. Caucasians were the predominant race in the distribution (N ¼ 29,599 [81.9%]), whereas African Americans (N ¼ 4068 [11.2%]) and Asian/Pacific Islanders (N ¼ 2291 [6.3%]) composed the majority of the remaining races. More patients were included in the SEER database after the year 2000 (N ¼ 26,308 [72%]) compared with 1995-2000 (N ¼ 9913 [27%]). The majority of the patients were married (N ¼ 20,611 [58.8%]), whereas 3155 (8.7%) were divorced and 3812 (10.5%) were single and never married. Characteristics of Therapy Overall, 30,042 (83.5%) patients did not undergo any form of operative intervention, whereas 5923 (16.5%) underwent operative treatment. Operative intervention was not recommended to the majority of patients with

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Original Article Table 1. Suicide Rates and Standardized Mortality Ratios

Variable

No. of Suicides

Person Years

Suicide Rate per 100,000 Person Years

SMR Compared to US Population Aged 65-74 y

95% CI

Age 60 y Age