Carey J. Myers, MD, PhD

Patients with cancer are at increased risk for both suicidal ideation and completed suicide due to a combination of biological and psychological factors that must be addressed to increase quality of life. More research is needed to determine the best methods of screening, evaluation, and treatment for suicidal thoughts and actions in this population.

- Cancers with the highest suicide risk include head and neck, lung, and pancreas.

- Health care providers do not feel adequately prepared to assess patients for suicidality.

- Increased risk is associated with older age, male gender, increased paid, lack of social supports, preexisting mood disorders, hopelessness; iatrogenic and biological factors must be assessed and addressed.

Cancer has plagued humanity since the beginning of recorded history. The first mention of cancer in the literature appeared in the Edwin Smith papyrus, dated ~3000BC. Surviving documents from ancient Greek and Roman physicians detail attempts at diagnosing and curing and give us the language we use today (oncos and cancer, respectively).

Although the overall prevalence of mortality due to cancer has been decreasing, it is still the second leading cause of death in the United States, responsible for 599,108 (21.3% of total) deaths in 2017.

 In comparison, suicide ranks 10th in this list, with 47,173 (1.7% of total) deaths. The most common cancers worldwide are lung, breast, 

, prostate, skin, and stomach; lung, colorectal, stomach, liver, and breast cancers account for the most deaths.

Changing attitudes toward suicide has altered the recorded prevalence over time, but it has always been a factor in human death. The desire to control, to some extent, the timing and manner of one’s death has always been a human temptation, and this draw increases when physical or emotional distress are present. Although estimates vary, patients with cancer are, at minimum, twice as likely to die by suicide. Moreover, having psychiatric care pre-diagnosis may not mitigate this increased risk.

Table 1. Suicide Rates in Different Cancers

Table 2. Factors Associated With Increased Suicide Risk in Cancer

Suicide risk is not the same for all types of cancer, nor is it consistent over the disease course (

).Several studies have found that suicide risk is at least twice that of the general population and is highest immediately after diagnosis.

Among cancers with the highest suicide risk are those affecting the head and neck, lung, pancreas, and larynx/pharynx. Prostate cancer has a higher suicide rate in the first year after diagnosis, but lower overall unless metastatic disease is found, with additional increased risk when treatment is defined but not received. Unique to cancer is that the risk of suicide persists more than 15 years past diagnosis.

In addition to increased suicide risk, patients with head and neck cancers have higher depression scores than the general population even before a cancer diagnosis, leading to the question whether this subset of patients are struggling with a biological cause in addition to diagnosis-related symptoms.

 Complicating these cases is the well-known association of many head and neck cancers with tobacco, alcohol, and other substance use, leading to the question of whether the pre-existing mood disorders lead to substance use that increases the risk of cancer. The relative increase in number of cases linked to human papillomavirus instead of substance use may alter this picture.

Regarding lung cancer, although the risk of suicide has been decreasing, Rahouma and colleagues6 found that these patients are at a higher risk than those with the more prevalent breast, prostate, or colorectal cancer. Furthermore, a large proportion of suicides may occur in patients with possibly non-fatal disease.

The risk in patients with breast cancer has been relatively stable over the last 4 decades and may be linked to whether the patient has undergone surgery. Findings from Simpson and colleagues

 indicate that penile cancer patients have one of the lowest suicide rates and, in their study, all patients who died by suicide had undergone surgical intervention. The link between surgical intervention and suicide risk may be linked to cosmetic effects, particularly as they affect sexual organs and can potentially alter patients’ view of their desirability and sexual roles.

In colorectal cancer, risk differs depending on the site of the lesion. Distally located disease is linked to a higher rate of suicide. This effect may be due to the more severe effects of distal disease on quality of life. Suicide risk in patients with stomach cancer was 

 with diarrhea, which can have a significant impact on lifestyle.

 It is not surprising that patients with terminal cancers report significantly more suicidal ideation.

One of the challenges in suicide prevention is determining the most effective ways to assess risk and screen for suicidal thoughts and intentions. Very little information has been collected regarding formal suicide risk assessment in cancer patients 

 found that health care providers did not feel adequately prepared to ask about suicidality or provide support and resources to patients.

The Columbia Suicide Severity Rating Scale (C-SSRS) is widely used for assessing suicidal intent, acts of furtherance, and suicide attempts. It has been studied and validated, and it is available in a variety of languages. It is free and designed to be used by anyone, including people without prior mental health care experience; there are versions specifically for people with cognitive impairments and children. However, it does not provide guidance as to full assessments or further steps once the screening is positive.

The Beck Hopelessness Scale asks true/false questions about future orientation, motivation, and expectations in order to assess negative feelings about the future. It can be used as an indirect evaluation of suicidal thoughts but does not address it directly. The detailed interpretation report can be very useful in assessing changes over time, but although the questions can be asked by anyone, the interpretation requires a trained professional.

The Hamilton Depression Scale (HAM-D) is a relatively brief questionnaire that asks about a variety of symptoms of depression; suicide is mentioned in 1 of the 17 questions, which are on a graded scale. It does not ask about atypical symptoms and, while it has relatively high sensitivity, specificity is low.

The Patient Health Questionnaire-9 (PHQ-9) is a brief set of questions designed to be asked and reviewed by any health care professional, with recommendations of when to advise further assessment by a mental health professional. It has shown to be reliable and valid in multiple studies. Like the HAM-D, it has relatively high sensitivity and low specificity.

Multiple studies have shown cancer as an independent risk factor for completed and attempted suicide. Spoletini and colleagues

 contrasted suicide in the general population, which they attributed to “genetic and psychological vulnerability to stress,” to suicide in cancer patients, which involved the “intrinsic bio-psychological vulnerability to distress” linked to changes in the immune system associated with cancer. Thus far, research has not identified consistent risk factors that enable the jump from suicidal ideation to suicide attempts. Underlying factors such as mood disorders may increase risk but require “additional precipitating events or conditions.”

Hopelessness and rumination are primary cognitive predictors; and hopelessness may be associated with recurrent self-harm. Depression is a major risk factor, as it is in the general population, but the cancer population is at higher baseline risk for depression, which has been linked to immunological changes.

 Identification and treatment of depression in cancer patients has been shown to decrease morbidity and mortality.

An important component of identifying at-risk patients is to determine the characteristics of those who historically have higher rates of suicide. As in the general population, the overall suicide rate in patients with cancer is linked to male gender, white race, lack of a partner and/or other social supports, and preexisting emotional or anxiety disorders as significant risk factors.

 In addition, older age, pain, advanced, disease, and poor prognosis are variables specific to this population that increase the risk of both suicidal ideations and suicide. Physical illnesses in general, particularly those associated with physical pain with consequent lifestyle limitations, are consistent risk factors that play a role in at least 25% of suicides, and the correlation increases with age.

 Patients with significant uncontrolled pain are at higher risk—thus a key component of cancer treatment must be adequate pain control. Minimal information has been collected on how substance use as reaction to a cancer diagnosis contributes to the risk of suicide. This may prove to be an important factor (

Although few thorough examinations of the methods typically used for suicide have been conducted, the National Cancer Institute 

 that overdose with painkillers and sedatives is the most common method of suicide used by cancer patients, and most of these occur at home.

 Despite this, screening for other methods of suicide (particularly firearms) should not be neglected.

A general understanding of suicidal ideation and behaviors involves alterations in the serotonin and HPA systems. The effects of a disease like cancer that alters immune system function can also alter these axes, which may result in increased risk of suicide. Independently of co-occurring cancer, the immune system is altered in depression (changes in cytokine and cell mediated immunity, changes in HPA axis) and may contribute to the development of depression in a reciprocal manner.

Depression secondary to medical causes should be ruled out in cancer patients. This typically includes an evaluation of B12 and folate levels, anemia, thyroid hormone imbalance, and adrenal hormone imbalance. The utility of assessing electrolyte abnormalities, including sodium, potassium, and magnesium remains unclear, although there is considerable interest in the effect of imbalances on mental health.

To further complicate this picture, several medications used to treat cancer have been linked to depression, such as corticosteroids, L-asparaginase, interferon-alpha, and amphotericin B.

Careful review of medication regimens and treatment alternatives may offer options for minimizing the effect of cancer therapy on mental health.

The “escape model” of suicidal drive may come into play, particularly in patients with a terminal diagnosis. This model postulates that the desire to escape from intolerable distress, combined with increased awareness of the factors contributing to that distress, leads to suicide.

 Accordingly, cancers with less than 5-year survival rates correlated to higher suicide risk, leading some to wonder whether the type of cancer is more important than the cancer diagnosis.

There are confusing data regarding the complicated mix of desire to speed up death, depression, hopelessness, and suicide risk. It appears that patients with baseline depression are more likely to want hastened death, expressing this desire up to 4 times as often, but Porta-Sales and colleagues

 found that simply discussing the wish for more rapid death did not cause distress, and that nearly 80% of patients felt it was an important topic for the care team to discuss.

Studies of suicidal ideation and completed suicide in adult cancer patients and survivors make up the bulk of the research in this area. As treatments and survival rates for childhood cancers improve, long-term studies of this population must include this information to more fully understand the lifelong effects of cancer treatment in children and adolescents, particularly since suicide is the top cause of death in the young adult populations of many developed countries. Gunnes and colleagues

 showed an increased risk of suicide in Norwegian patients aged 23 to 48 years who had a diagnosis of cancer before the age of 25. At exceptional risk were survivors of brain and testicular tumors, as well as leukemia. An American study did not replicate this finding but reported an increased risk of suicidal ideation compared with sibling controls.

 The average age of those who reported a first incident of suicidal ideation was 34 years, and they were, on average, 26 years past diagnosis. This is a serious example of how the sequelae of childhood cancer treatment can persist far into adulthood.

Is Refusal of Treatment a Form of Suicide?

Complicating the discussion of suicide in cancer patients is the subject of refusal of treatment. Is this considered suicide? Frenkel

 noted that “the unique patients who refuse conventional treatment are at times self-directed, confident, and active, and have thought deeply about the meaning of life and cancer and about their cancer treatment options.” What does it mean to have the ability to choose, to some extent, when we will die? This controversy has been taken all the way to the Supreme Court, with Justice Brandeis writing in Olmstead vs US that “the right to be left alone . . . the most comprehensive of rights and the right most valued by civilized men,” and Justice Burger clarifying that “nothing in this utterance suggests that Justice Brandeis thought an individual possessed their rights only as to sensible beliefs, valid thoughts, reasonable emotions.”

 Physicians are trained that the ultimate goal is to save or at least prolong life, but often neglected is the consideration of quality of life and patients’ desire to live, and die, in a manner they can, to some extent, control. Isenberg-Grzeda and colleagues

 reported on 3 patients who attempted suicide after being deemed ineligible for medical assistance in dying, further exemplifying the desire to have some say over the end of their lives.

Treatments can be quite similar to the treatment of depression in the general population, with psychotherapy and pharmacotherapy (selective serotonin reuptake inhibitors, selective serotonin-norepinephrine reuptake inhibitors, mirtazapine, trazodone) forming the basis. The most recent review of antidepressant therapy for depression in cancer patients did not show a significant improvement from placebo, but 

 noted that there were few studies from which to draw this information and noted that much more research is needed in this area.

Psychotherapy, no matter how brief, can help patients adjust to their new health circumstances and reassess their view of their life up until their diagnosis and goals going forward. In addition, special considerations such as the influence of altered immune activity and the effects of chemotherapy must also weigh into treatment decisions. Moreover, prescribers must be judicious in choosing medications that can be expected to show some positive effect within the patient’s expected lifetime, which may be significantly shortened. Stimulants may be useful in treating symptoms of fatigue and inattention that are common during cancer treatment. Close collaboration with the oncologic team can help to optimize mental health during cancer treatment.

Suicide and cancer are the top 10 causes of death in the adult population of the United States, and the world. Patients with cancer are at increased risk for both 

 and completed suicide. Factors contributing to this increase are both biological and psychological and components must be addressed in a timely fashion to increase quality of life. A refusal of treatment must not automatically be considered an instrument of suicide but viewed as a complex decision factoring in goals of care, particularly quality of life. More research is needed to determine how best to evaluate and treat oncology patients for suicidal thoughts and behaviors.

is faculty member, Department of Psychiatry, Albert Einstein Medical Center, Philadelphia, PA. The authors have nothing to disclose regarding this article.

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A literature review of suicide in cancer patients

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Patients with cancer are at increased risk for both suicidal ideation and completed suicide. The authors discuss factors contributing to this increase in both biological and psychological realms.

Carey J. Myers, MD, PhD

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