NEWS & VIEWS PROSTATE CANCER
Depression and prostate cancer —why do they show up together? David R. H. Christie and Christopher F. Sharpley
Patients with prostate cancer are known to be affected by higher levels of depression than their peers. Patients with this combination are less likely to undergo definitive treatment and have lower rates of survival. A new study has investigated the likelihood of a diagnosis of depression prior to prostate cancer. Christie, D. R. H. & Sharpley, C. F. Nat. Rev. Urol. advance online publication 26 August 2014; doi:10.1038/nrurol.2014.226
This year, an article by Prasad and colleagues 1 was published in the Journal of Clinical Oncology describing an investigation into the rate of diagnosis of depression in men 2 years before receiving a diagnosis of prostate cancer. Important new findings were revealed, principally that men with pre-existing diagnosed depression form a distinct population among patients with prostate cancer, and have specific outcomes. Compared with patients with prostate cancer who were not diagnosed with depression before their prostate cancer diagnosis, men with a previous diagnosis of depression were older, displayed higher rates of comorbid ity, were less likely to be married and had lower household incomes. After receiving their prostate cancer diagnosis, patients with prior depression were also less likely to undergo definitive treatment by either radiotherapy or prostatectomy and had a lower overall survival rate. Even though the length of fo llow-up duration in this study was relatively short (with a maximum of only
6 years), the difference in survival was easily identifiable, and was particularly noticeable in men with low-risk prostate cancers with and without a prior diagnosis of depression, who had an absolute difference in survival of ≈10% at 5 years after prostate cancer treatment. Although causes of death were not described, it is unlikely that many of these extra deaths would be the direct result of their prostate cancer, but might be related to their depression and comorbidities.
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…the impact of each condition on the treatment of the other warrants consideration
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Prasad et al.1 noted that the proportion of patients with a diagnosis of prostate cancer who had received a diagnosis of depression within the preceding 2 years was 4.6%, but the real rate of depression in this population could be even higher. Over half of the men diagnosed with prostate cancer in the database during the chosen time interval were excluded from the analysis. Many of these excluded patients might be expected to have higher rates of prior depression, which could affect the figure of 4.6%. Men younger than 67 years, with metastatic disease or anxiety and patients who had died within 6 months of being diagnosed with prostate cancer were excluded from the study. Also, patients were not screened for depression using standard clinical interviews or screening scales, but were only considered to have depression if International Classification of Diseases‑9 codes were recorded in their
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file from a previous medical diagnosis. For these reasons, and others, it is possible that the rate of depression in men who went on to receive a diagnosis of prostate cancer within 2 years could be substantially higher than the reported 4.6%. Studies reporting the association between depression and prostate cancer usually examine depression after a diagnosis of prostate cancer. High rates of depression have been reported in men following a diagnosis of prostate cancer, at around 10–30% of patients.2 This rate is much higher than for the general Australian population which is ≈3%. The association between depression and prostate cancer is one that is steadily gaining attention, and potential causes for this link have been proposed. As well as the emotional impact of the diagnosis and treatment of prostate cancer, there are also some common putative physiological aetio logies, which include neuroendocrine and immunological dysfunction.3,4 For example it has been shown that patients with depression have activation of the hypothalamicpituitary-adrenal axis which might impair immune responses and contribute to the development of cancer.4 This study raises the possibility that, although prostate cancer patients are more likely to be diagnosed with depression than people in the general population, patients with depression might also be more likely to be diagnosed with prostate cancer. The contributory effect of depression on compliance with treatment and on the mortality of patients with cancer has been previously reported, and has led to calls for better application of existing screening methods for depression among these patients.5,6 Common aetiologies between depression and prostate cancer seem to suggest that those with depression could also be candidates for prostate cancer screening, for example by digital rectal examination or serum PSA measurement. The subtype of depression that commonly affects men with prostate cancer is strongly anhedonic, meaning that they tend to withdraw from their social and other daily activities.7 As screening for prostate cancer is often encouraged by the patient’s social contacts, as well as others, withdrawal from social activities by patients with depression could reduce the rate of screening for ADVANCE ONLINE PUBLICATION | 1
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NEWS & VIEWS prostate cancer in these people, and, therefore, elevate mortality from this disease. By simply asking male patients with depression if they would like to be screened for prostate cancer in general practice, prostate cancers might be detected at an earlier and more treatable stage.
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…there are some special issues to consider when both of these common conditions occur together
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In the study by Prasad and colleagues,1 the observation of the tendency for patients with prior depression to choose noncurative forms of treatment for prostate cancer adds a new dimension to the debate about treatment choice. The role of patient concern about the adverse effects of treatment in making their treatment decisions has been assessed.8 Apart from the need to cure the cancer, the possibility of having sexual and urinary dysfunction caused by the therapy rate highly in the patient’s decision-making process. These concerns about the toxic effects of treatment could be expressed more strongly by a patient with depressive symptoms, and might steer the urologist into avoiding recommending treatments that could have permanent effects, or with which the patient is less likely to comply. Hormone therapy might be chosen owing to the expectation that the adverse effects of this treatment are reversible, but patients receiving hormone
therapy have been shown to have a higher rate of depression than those receiving other treatment modalities, and these psycho logical effects have been associated with the adverse effects of hormone therapy.9,10 Prasad et al.1 argue that hormone therapy does not seem to exacerbate prior depression, but they do so on the basis of limited data, and the role of prior depression in a patient’s decision to have adjuvant treatment such as neoadjuvant hormone therapy, prior to radiotherapy or adjuvant radiotherapy after surgery was not addressed in this study. However, Prasad and colleagues1 suggest that the emotional state of the patient might be an important factor to consider in studies into how patients make decisions. The study by Prasad et al.1 adds important new findings to the research surrounding prostate cancer and depression. Better treatments for each condition are needed, and the impact of each condition on the treatment of the other warrants consideration. Those involved in treating either of these conditions should be aware that with each condition there is a risk that the other is also present and there are some special issues to consider when both of these common conditions occur together. Genesiscare, John Flynn Hospital, Inland Drive, Tugun, Gold Coast, QLD 4224, Australia (D.R.H.C.). Brain-Behaviour Research Group, University of New England, Armidale, NSW 2351, Australia (C.F.S.). Correspondence to: D.R.H.C.
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Competing interests The authors declare no competing interests. 1.
Prasad, S. M. et al. Effect of depression on diagnosis, treatment and mortality of men with clinically localized prostate cancer. J. Clin. Oncol. 32, 2471–2478 (2014). 2. Sharpley, C. F., Bitsika, V. & Christie, D. R. H. Psychological distress among prostate cancer patients: Fact or fiction. Clin. Med. Oncol. 2, 563–572 (2008). 3. Reiche, E. M. V., Nunes, S. O. V. & Morimoto, H. K. Stress, depression, the immune system, and cancer. Lancet Oncol. 5, 617–625 (2004). 4. Kiecolt, J. K., Robles, T. F., Heffner, K. L. & Glaser, R. Psycho-oncology and cancer: psychoneuroimmunology and cancer. Ann. Oncol. 13, 165–169 (2002). 5. Di Matteo, R. M., Lepper, H. S. & Croghan, T. W. Depression is a risk factor for non-compliance with medical treatment.: Meta-analysis of the effects of anxiety and depression on patient adherence. Arch. Intern. Med. 160, 2101–2107 (2000). 6. Pinquart, M. & Duberstein, P. R. Depression and cancer mortality: a meta-analysis. Psychol. Med. 40, 11, 1797–1810 (2010). 7. Sharpley, C. F., Bitsika, V. & Christie, D. R. H. Do prostate cancer patients suffer more from depressed mood or anhedonia? Psycho-Oncol. 22, 1718–1723 (2013). 8. Berry, D. L. et al. Factors that predict treatment choice and satisfaction with the decisions in men with localized prostate cancer. Clin. Genitourin. Cancer 5, 219–226 (2006). 9. Sharpley, C. F., Christie, D. R. H. & Bitsika, V. Do hormone treatments for prostate cancer cause anxiety and depression? Int. J. Clin. Oncol. 19, 523–530 (2014). 10. Sharpley, C. F., Bitsika, V. & Christie, D. R. H. Do patient-reported androgen deprivation therapy side effects predict anxiety and depression among prostate cancer patients undergoing radiotherapy? Implications for psychosocial therapy interventions. J. Psychosoc. Oncol. 30, 185–197 (2012).
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