A recent study by researchers from Harvard, MD Anderson and Weill Cornell, published in the Journal of Clinical Oncology, showed an association between a common treatment for locally advanced prostate cancer and clinical depression. These results are part of a broader conversation about how prostate cancer is treated and could impact the way that clinicians treat and monitor prostate cancer patients.

Worried senior man

Locally advanced prostate cancer is cancer that has grown outside of the prostate gland and may have spread to nearby tissues. Men with locally advanced prostate cancer may be treated with androgen deprivation therapy, or ADT, along with radiation or removal of the prostate. The goal of ADT is to lower the level of testosterone in the patient’s body. Testosterone activates a protein in the prostate called the androgen receptor that drives growth of the cancer. However, in addition to causing tumor regression, ADT has a number of unpleasant side effects, such as erectile dysfunction and enlarged breast tissue, as well as cardiovascular, musculoskeletal and metabolic effects.

Previous studies of the association between depression and ADT showed inconsistent results, possibly due to small sample sizes or varying definitions of depression. All the data from this latest study, led by Paul Nguyen, were gathered from over 70,000 patients using the Surveillance, Epidemiology and End Results (SEER)-Medicare database, which links cancer epidemiology data found in SEER with Medicare claims records, and allowed the researchers to define the stage of disease,treatment method, and the presence of a diagnosis of depression or the use of psychiatric services.

The researchers found that men treated with ADT were more likely to be diagnosed with depression and were more likely to use psychiatric services than men not treated with ADT. Furthermore, the longer those men were on ADT, the more likely they were to experience depression.

ADT causes physiological changes in sites outside the prostate because shutting off the androgen receptor in these tissues affects a myriad of genetic programs. ADT also depletes the supply of testosterone that gets converted to estrogen, which is important for cardiovascular and bone health. There is evidence that neurotransmitters can be influenced by testosterone levels and that dramatic decreases in testosterone, like those seen with ADT, can lead to an imbalance of neurotransmitters that could cause depression.

This study contributes to a larger discussion of how prostate cancer is treated. While the patients on this study were classified as having high-risk cancer, most men diagnosed with prostate cancer do not have disease that will threaten their lives, and treatment can significantly reduce quality of life without any clear life-extending benefit. One of the hot topics in prostate cancer research is distinguishing those who have lethal disease and should be treated from those who have less aggressive disease and should be carefully monitored by their physicians without an immediate medical intervention. The researchers recommend that doctors include depression as a side effect of therapy when discussing ADT with patients. They also recommend withholding ADT from patients who will not experience a significant benefit from their treatment and proactively identifying patients at risk for depression to make countermeasures available to them.


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