Stress during cancer diagnostic workup

Receiving a cancer diagnosis is an extremely stressful life event. Cancer patients have been reported to experience an excessive risk of stress-related health outcomes including suicide. The time period between the first suspicion of a potential cancer and cancer diagnosis or start of primary cancer treatment is commonly defined as “cancer diagnostic workup”. This critical time window is especially stressful, mainly due to the uncertainty about the final diagnosis. Such diagnostic process and its health consequences may also apply to a larger group of population who are evaluated for but never receive a cancer diagnosis. Till now, less attention has been devoted to the health impact of a cancer diagnostic workup. This thesis aims to assess the risk of different stress-related health outcomes during a cancer diagnostic workup, taken into account various diagnostic processes, individuals with or without a final diagnosis of cancer, and different reasons of workup initiation. We also investigated effect of a potential treatment in modulating the excessive risk of stress-related health outcomes following a cancer diagnosis.

In study I, we examined the risk of iatrogenic and non-iatrogenic injuries during weeks before and after diagnosis among all patients with cancer. To eliminate impact of shared risk factors between cancer and injuries, we compared the risk from 16 weeks before to 16 weeks after cancer diagnosis, to the same period one year earlier, of the same patient. We found that cancer patients had an increased rate of both iatrogenic and non-iatrogenic injuries requiring inpatient care shortly before and after cancer diagnosis, compared to one year before. Our findings shed further light on the total burden of medical complications and call for prevention of intentional and unintentional injuries during the diagnostic process of a cancer. In study II, we assessed the risk of injuries that required inpatient care in relation to the diagnostic workup of cervical cancer and its precursor lesions, among all women that participated screening for cervical cancer. Women diagnosed with invasive cervical cancer and its precursors lesions were identified from the National Cervical Screening Register as exposed to a diagnostic workup. Women who had a normal result in Pap smear were classified as referece group. Inpatient care of either iatrogenic injuries or non-iatrogenic injuries was extremely rare during the diagnostic procedures of cervical cancer and its precursor lesions. Although with a small number of outcomes, we still found that women with invasive cervical cancer had an increased rate of non-iatrogenic injuries in relation to receiving a diagnosis of cervical cancer. In study III, we investigated the risk of psychiatric disorders and cardiovascular diseases during the diagnostic workup of potential breast cancer. All women diagnosed with a breast cancer, a benign tumor in breast, or unspecified lump in breast, were identified and considered as exposed to a diagnostic workup of potential breast cancer. We compared the risks of psychiatric disorders and cardiovascular diseases during the six weeks before diagnosis of the exposed women to the risks among the unexposed women. We found that women with benign tumor and breast cancer had an increased rate of psychiatric disorders and cardiovascular diseases while waiting for the final diagnosis. In study IV, we aimed to assess the use of low-dose aspirin and non-aspirin NSAIDs in relation to the risk of unnatural death due to suicide or accidents among patients after receiving a cancer diagnosis. Cancer patients with aspirin or non-aspirin NSAIDs dispensed after diagnosis were considered to be medicated. We compared the risk of unnatural death during on-medication period with the risk during off-medication period. We found that aspirin intake was associated with a lower risk of unnatural death after a cancer diagnosis. We did however not find a statistically significant association between use of non-aspirin NSAIDs and risk of unnatural death.

In conclusion, a cancer diagnostic workup is associated with increased risks of a spectrum of stress-related health outcomes. Such increased risks of health outcomes, including injuries, psychiatric disorders and cardiovascular diseases, are noted for a large group of individuals being evaluated for a potential cancer, regardless of the final diagnosis. It represents therefore a great disease burden for the society. Interventions, such as low-dose aspirin intake, might be effective in reducing such risks (e.g. risk of unnatural death), after cancer diagnosis.

List of scientific papers

I. Shen Q*, Lu D*, Schelin MEC, Jöud A, Cao Y, Adami HO, Cnattingius S, Fall K, Valdimarsdóttir U, Fang F. Injuries before and after diagnosis of cancer: nationwide register based study. BMJ. 2016; 354:i4218. *Equal contribution.
https://doi.org/10.1136/bmj.i4218

II. Shen Q, Lu D, Andrae B, Schelin MEC, Sjölander A, Cao Y, Sparén P, Fang F. Injuries in relation to the diagnostic procedures of cervical cancer and its precursor lesions: a nationwide cohort study in Sweden. [Submitted]

III. Shen Q, Jöud A, Schelin MEC, Sjölander A, Cao Y, Sparén P, Fall K, Czene K, Valdimarsdóttir U, Fang F. Psychiatric disorders and cardiovascular diseases during the diagnostic workup of potential breast cancer: a population-based cohort study in Skåne, Sweden. Breast Cancer Research. 2019; 21:139.
https://doi.org/10.1186/s13058-019-1232-y

IV. Shen Q, Sjölander A, Sloan E, Walker A, Fall K, Valdimarsdóttir U, Smedby KE, Fang F. NSAID use and unnatural deaths after cancer diagnosis: a nationwide cohort study in Sweden. [Manuscript]