With advances in medical technology, cancer patients are living longer, but their risk of non-cancer death is increasing due to the increasing incidence of mental illness(Zaorsky et al. 2017). Among numerous cancers, mental illness is more prevalent in pancreatic cancer patients, therefore, it is necessary to explore the risk of non-caner death in them. In this study, 5,996,478 pancreatic cancer patients and other cancer patients were extracted from the 1975–2016 SEER 18-REGISTRY dataset to elaborate on the risk of suicide/accidental death between pancreatic cancer patients and the general population/other cancer patients. The research results demonstrate that pancreatic cancer patients had a significantly higher risk of suicide and accidental death than the general population. To account for the baseline differences between the general population and cancer patients, we also compared pancreatic cancer patients to other cancer patients and observed that pancreatic cancer patients had a higher risk of suicide and accidental death. Finally, after adjusting for patient characteristics, we conclude that the suicide risk factors include male, white, unmarried, and patients who had not received surgery, while accidental death's risk factors include those 65 and older, male, unmarried, and those who had priority surgery or radiation therapy, as well as those who had not received surgery.
In 2011, K. K. Turaga et al.(Turaga et al. 2011) utilized the SEER dataset to extract data for almost 10 years (from 1995 to 2005) to report on the risk of suicide in pancreatic cancer patients. The findings revealed that males and unmarried were risk factors for suicide in pancreatic cancer patients, which matched our findings. Furthermore, their findings indicated that the risk of suicide in males with pancreatic cancer was around 11 times greater than in the general population, but our findings revealed that the risk of suicide in men with pancreatic cancer was only 5 to 6 times higher. Besides, we also observed that surgery and race had a role in the suicide of pancreatic cancer patients. These discrepancies are most likely attributable to methodological variances and sample inclusion and exclusion criteria. In comparison to the study by k. K. Turaga et al., this study included more samples and considered more confounding factors, resulting in more credible results. Besides that, we also discuss pancreatic cancer patients' accidental deaths, elaborating on pancreatic cancer patients’ non-cancer death risk in more detail.
As shown in Table 2 and Table 3, pancreatic cancer patients whose age ≥ 40 have a higher risk of suicide/accidental death than those whose age < 40. Among patients age ≥ 40, particularly those whose age between 40–64, the risk of suicide is 5 times more than the general population and 3 times more than other cancer patients. Cox regression analysis showed that age was not an influencing factor for suicide but accidental death, which may be because pancreatic cancer spreads quickly and early diagnosis is difficult, most individuals are diagnosed after they reach old age. (As can be seen from Table 1, pancreatic cancer patients under 40 years old account for only 1.5% of the total population, while those over 65 years old account for 64.2%). Those old patients are more likely to have problems concentrating, organ damage, mobility difficulties, and other medical complications, all of which are associated with an increased risk of accidental injury(Yang et al. 2020); at the same time, few of them have access to the Internet, which means they are less likely to have access to adequate information about pancreatic cancer on the Internet, which could lead them to ineffective or even harmful decisions(Bass et al. 2006) and may increase their risk of accidental death. Therefore, it is suggested to initiate voluntary activities or establish support groups to regularly enhance knowledge related to pancreatic cancer for these patients, so that they can have a correct and objective understanding of their disease, reduce the needless stress generated by a lack of background information about the illness, and boost their confidence in their ability to overcome it.
Race is the influencing factor of suicide, which may be linked to the socioeconomic situation, social background, educational attainment, and other factors(Ivey-Stephenson et al. 2017). Priority treatment, particularly priority radiation therapy, is a substantial risk factor for pancreatic cancer patients' accidental death, which may be connected to radiation therapy's adverse effects. In patients with head and neck cancer, radiation treatment has been proven to cause cognitive impairment, which may raise the chance of death by accident(Yang et al. 2020).
Table 4 shows that gender and marital statuses are shared influencing factors of suicide and accidental death in pancreatic cancer patients. Male with pancreatic cancer had a greater risk of suicide and accidental death than females, while a study of suicide and accidental death among bone tumors patients found a similar difference(Yu et al. 2021). However, we think the fundamental reasons for gender variations in the risk of suicide and accidental death are due to undiscovered confoundings factors (such as income, lifestyle, and family structure). Marital status has an important influence on a person’s psychological status: the research by Noquez revealed that widower, single, and divorced pancreatic cancer patients had a higher burden of symptoms, such as pain, exhaustion, sadness, anxiety, and soma(Noquez 2008). Studies have also shown that emotional support from a spouse reduces the risk of accidental death(Cubbin, LeClere, and Smith 2000), illustrating the importance of a partner for pancreatic cancer patients. In addition to providing emotional and spiritual support, a partner of a pancreatic cancer patient can also serve as the patient's caregiver by helping the patient accept medical advice, informing family members about the disease promptly, and communicating with experts about treatment options.
According to the results shown in Table 2 and Table 3, we found an interesting trend: the SMR of suicide and accidental death is 8.52 and 2.75 respectively in pancreatic cancer patients within the first three months after diagnosis, significantly higher than another period. Similarly, A cohort study from Japan also found a significant increase in the risk of suicide and accidental death in the first six months after cancer diagnosis, especially in the first month(Harashima et al. 2021). This might be because the stage of cancer diagnosis is a significant stressor that has a direct influence on the likelihood of patients’ behavior of suicide or accidental death. At the same time, such stressors will also place a huge emotional burden on patients, which will lead to patients no longer actively receiving treatment, such as not following the treatment advice of experts, increasing difficulties in communicating with health workers, etc, which will lead to an increased risk of suicide and accidental death in patients with pancreatic cancer. Therefore, we urge physicians to focus on the psychological status of patients within three months of diagnosis of pancreatic cancer, and oncologists also need to enhance the frequency of communication with these patients, which has been shown to play an indispensable role in suicide prevention(Trevino et al. 2014).
Another interesting finding is according to the ‘cancer-directed surgery’ variable, the variable was classified as ‘performed’, ‘not recommended’, and ‘recommended but not performed’. Among patients who did not undergo surgery, patients classified as ‘recommended but not performed’ have the highest risk of suicide, followed by ‘not recommended’. To validate the results, we also plotted Kaplan–Meier cumulative risk curve of suicide/accidental death in a certain period (monthly count), which was classified according to 'cancer-directed surgery' for pancreatic cancer patients' variable, with results consistent with previous: patients classified as ‘recommended but not performed’ have the highest risk of suicide (Log-rank test, p < 0.01). The above conclusion tells us should attach importance to those who can accept surgery, especially in part because of the subjective reason they refused surgery patients (referred to as ‘recommended but not performed’). In reality, more than one-third of pancreatic cancer patients are unable to accept radical surgery owing to the fast advancement of the disease, if we can successfully persuade ‘recommended but not performed’ patients, according to our results, will significantly reduce pancreatic cancer patients’ risk of suicide in overall. Therefore, we propose the following treatment suggestions for the medical worker: First, General Practitioners (GPs) and emergency physicians should maintain regular contact with patients who reject their doctors' surgery recommendations. The weeks leading up to a suicide attempt are a critical time for patients who are suicidal to communicate with their primary care physician and the emergency room, according to research(Laanani et al. 2020). Through frequent communication, medical staff can learn more about these patients, which may help to find out why they reject surgical recommendations. Second, seek the help of a clinical psychologist. A study from SEER-Medicine showed that pancreatic cancer patients with a history of depression were 22 percent less likely to have cancer-guided surgery(Paredes et al. 2021). This shows that these patients have more psychological troubles, and clinical psychology can timely help these patients relieve the psychological and spiritual pressure. Increased collaboration between clinical psychologists and pancreatic cancer professionals is expected to improve patients' emotional and physical well-being. Clinical practice guidelines also offer a similar view: end-of-life psychological therapies may greatly enhance patients' moods and help them to better regulate their bodily functions to deal with the ensuing changes(Kaya et al. 2003). Third, health care workers should always pay attention to the use of psychotropic drugs in this group of patients. If the psychotropic drug utilization rate is high, it can be regarded as a sign that the burden of psychological symptoms of patients is heavy and in urgent need of relief. A pancreatic cancer cohort study from Denmark also revealed that patients who did not receive surgery were more likely to begin using antidepressants(Dengsø et al. 2020).
As mentioned earlier, only a subset of pancreatic cancer patients have conditions that allow them to undergo radical surgery. For most patients with pancreatic cancer who cannot receive radical treatment, the best choice of treatment for them is radiotherapy, chemotherapy, and targeted therapy combined with palliative treatment. Palliative care can manage patients' symptoms well, whereas patients with pancreatic cancer often have a symptom burden involving multiple organs due to the anatomical position of the pancreas. A randomized controlled trial study on pancreatic cancer also showed that a combination of palliative care is critical for improving the prognosis of patients with pancreatic cancer(Woo et al. 2019). The main symptoms of pancreatic cancer patients are pain and depression. The incidence of pain is about 70–80%, manifested as severe upper abdominal pain, but also extends to the back, patients can not lie flat and normal eating, only curled up. Besides damage to physical function and psychological integrity, pain is also associated with overall survival and quality of life in pancreatic cancer patients. Therefore, controlling pain is essential for reducing the risk of suicide/accidental death for pancreatic cancer patients. Palliative treatment is one of the most effective treatments for controlling pain, it has been reported that palliative radiotherapy has a good regulation effect on the symptom burden of pancreatic cancer patients, and most pancreatic cancer patients can get great relief of pain after palliative treatment(Ebrahimi, Rasch, and van Tienhoven 2018). The American Society of Clinical Oncology (AASC) clinical practice guidelines also recommend that patients with metastatic pancreatic cancer receive palliative care as early as possible to relieve symptoms of pain, preferably at the time of diagnosis(Sohal et al. 2018). At present, pain relief methods mainly include drugs and surgery. When it comes to drug treatment, the World Health Organization (WHO) recommends that patients take these three actions to alleviate pain("World Health Organization. WHO’s cancer pain ladder for adults. 2014"): first, take non-opioid drugs (such as aspirin and paracetamol) by mouth immediately, and if no relief is achieved, then take mild opioids (such as codeine), or try a strong opioid (such as morphine) if it still does not meet expectations; In surgical therapy, The most effective procedure so far is celiac plexus release, which relieves approximately 70 to 90 percent of the pain in patients with pancreatic cancer(Wyse et al. 2011).
Depression is another major symptom of pancreatic cancer patients. Nearly half of pancreatic cancer patients are reported to experience psychiatric symptoms (depression, anxiety, etc.) before diagnosis(Fras, Litin, and Pearson 1967; Green and Austin 1993). This suggests that there may be some biological mechanism between depression and pancreatic cancer, Andrew D. Boyd et al(Boyd and Riba 2007) reviewed the studies on the biological mechanism between pancreatic cancer and depression, but no conclusion has been reached so far. Whether there is any mechanism between pancreatic cancer and depression, it is a fact the prevalence of depression in pancreatic cancer patients is significantly higher than that in other cancer patients(Massie 2004; Fras, Litin, and Pearson 1967; Holland et al. 1986). Meanwhile, depression is the shared risk factor for suicide and accidental death, we think it plays a non-negligible role in reducing the risk of suicide/accidental death in pancreatic cancer patients. One of the most direct ways to reduce depression is taking antidepressants, which have been shown to improve symptoms and quality of life in patients with pancreatic(Purohit et al. 1978). Among the many antidepressants, selective serotonin reuptake inhibitors (SSRIs) are recommended because they are well tolerated and have few side effects, including fluoxetine, fluvoxamine, and citalopram. In addition to antidepressants, psychological interventions such as meditation, yoga, and acupuncture are also effective in alleviating depression in pancreatic cancer patients(Luo et al. 2014). In practice, health care workers can also refer to the treatment of depression in pancreatic cancer patients proposed by Walker and Sharpe(Walker and Sharpe 2009), who provide practical treatment measures from multiple aspects of education, medication, and behavior.
Although our study has revealed several important findings related to the risk of suicide and accidental death in patients with pancreatic cancer, limitations remain. To begin with, it is difficult to make an accurate distinction between suicide and accidental death when registering causes of death, especially in the case of poisoning or gunshot wounds, different coroners who see such scenes are more likely to have different judgments on the classification of cause of death; Additionally, the SEER database lacks records related to patients' mental disorders and quality of life, which may confound the real association between pancreatic cancer patients and risk of suicide/accidental death.
The study showed that pancreatic cancer patients had a higher risk of suicide and accidental death than not only the general population but also other cancer patients. Notably, we also found the first three months after diagnosis is a critical period for medical workers takes action to reduce the risk of suicide/accidental death in pancreatic cancer patients. Among the pancreatic cancer patients who had not performed surgery, we noticed ‘recommended but not performed’ patients have a higher risk of suicide/accidental death than ‘not recommended’ patients. Therefore, we suggest that for patients diagnosed within three months or classified as 'recommended but not performed', specialists need to work with cancer psychologists, and frequently pay attention to their psychological status.