JAMA sub-journal: New endocrine therapy can cause depression, how to evaluate clinically?

*Only for medical professionals to read reference Prostate cancer anti-androgen treatment needs to pay attention to this! Second-generation anti-androgens have brought hope to countless prostate cancer patients at risk of treatment.
However, are second-generation anti-androgens (AAs) associated with an increased risk of depression in older men diagnosed with prostate cancer? Recently, JAMA Oncology The journal published a study on the theme of the Association of Second-generation Antiandrogens With Depression Among Patients With Prostate Cancer
.

In layman's terms, new endocrine drugs may increase the risk of depression, so how to find the optimal solution between disease treatment and depression? This study observed the relationship between depression and depression in prostate cancer patients who did not use endocrine therapy, traditional endocrine therapy, and second-generation anti-androgen therapy through a retrospective cohort study.
In contrast, prostate cancer patients treated with second-generation anti-androgen drugs had a significantly increased risk of depression
.

Let's take a closer look at the specific research content~ In order to explore the relationship between second-generation anti-androgens (AAs) and depression, researchers from MD Anderson Cancer Research Center and Baylor College of Medicine in the United States through the National Cancer Center, SEER (Surveillance, Epidemiology, and End Results) database (National Cancer Institute Surveillance, Epidemiology and End Results Database), Texas Tumor Registry and Medicare Database and other retrospective analyses from January 2011 to 2015 Clinical data of patients 66 years of age and older who were diagnosed with prostate cancer and had no second primary tumor within 12 months of December, excluding those who had received any form of endocrine therapy before the diagnosis of prostate cancer and those who were diagnosed with depression.
A total of 30,069 patients were included in the retrospective cohort
.

The retrospective cohort screening flow chart evaluated the use of adjuvant hormone therapy (HT) from the date of prostate cancer diagnosis and was divided into three groups based on whether or not second-generation anti-androgen therapy had been used, namely no use of any form of HT (no HT group), Those who had used HT but not any second-generation anti-androgen therapy (AA) were defined as the traditional HT group, and those who had used any second-generation AA but no other HT (second-generation AA group) were divided into three groups
.

Individuals exposed to endocrine therapy were divided into established groups according to a time-varying exposure variable
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And stratified according to the cumulative duration of HT use, defined as 1-6 months, 7-12 months, and over 12 months
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Results of the study showed that of 30,069 patients, 17,710 (59%) were not receiving HT, 11,311 (38%) were receiving conventional HT only, and 1,048 (3%) were using second-generation AA
.

The baseline characteristics of the different exposure groups were statistically significant for all variables without inverse probability weighting (IPTW) (Figure below)
.

All standardized differences except year of diagnosis, age, race, and marital status after IPTW adjustment were less than 10%, and the difference between the no-HT group and the second-generation AA group was approximately 20%
.

After IPTW adjustment, the second-generation AA group was older, (proportion of patients ≥81 years old: 24% in the second-generation AA group; 18% in the traditional HT group; 7% in the no-HT group) and had advanced features (eg, distant disease: 24% in the second-generation AA group; 8% in the traditional HT group; 0.
7% in the no-HT group)
.

Median follow-up after diagnosis was 3.
8 years (0.
5-7 years)
.

The second-generation AA group had the highest cumulative incidence of depression at 1 and 2 years compared with the traditional HT and no HT groups (Figure below)
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From 6 months after prostate cancer diagnosis, the cumulative incidence of depression was estimated by the competing risks method as shown in the table below
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For patients with metastatic prostate cancer (mPC) at first diagnosis, the incidence of depression was significantly higher than that of conventional HT (11.
49%; 95% CI 9.
46%-13.
73%) and no HT group (12.
65%; 95% CI 7.
40%-19.
38%) In contrast, the second-generation AA group had the highest 2-year cumulative incidence of depression (17.
20%; 95% CI 14.
20%-20.
46%)
.

IPTW multivariate-adjusted Cox proportional hazards analysis showed that both the traditional HT group and the second-generation AA group had a statistically significant increase in the risk of depression compared with the no-HT group (see table below)
.

In addition, patients receiving second-generation AA were more likely to suffer from depression than those receiving conventional HT alone (HR, 2.
26; 95% CI 1.
88-2.
73; P<0.
001)
.

Taken together, this cohort study concluded that patients with prostate cancer who received second-generation AA had a 2-fold increase in the incidence of depression compared with conventional HT or HT-naïve prostate cancer patients
.

Expert Comments The results of this study suggest that the use of second-generation AAs is associated with a clinically significant increased risk of depression compared with traditional HT alone or no HT
.

From the perspective of the included population, except for patients who had previously used endocrine therapy or were diagnosed with depression, basically all were included in this study, including prostate cancer patients with or without distant metastasis at the time of diagnosis
.

The results of the study also confirmed that in the real world, the vast majority of patients receiving endocrine therapy are still dominated by traditional endocrine therapy.
Of course, this is related to factors such as the time span of this study and the time to market of second-generation AA
.

In addition, older patients (≥81 years) were more likely to be treated with second-generation endocrine drugs
.

As clinicians, we should not only pay attention to the "live long" of prostate cancer patients, but also pay attention to the "live well" of patients
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Endocrine therapy is an important part of prostate cancer treatment, and it is the long-term treatment method used by the vast majority of prostate cancer patients
.

Nowadays, new endocrine drugs have been recommended by major guidelines because of their superior curative effect, prolonging the time of recurrence and progression, enabling patients to obtain "long survival" and the availability of medical insurance
.

For the application of new endocrine drugs, the depression caused by them may be a problem that is often overlooked in clinical diagnosis and treatment
.

The implication of this study is that early depression screening and aggressive treatment are feasible interventions for clinicians that can greatly improve patients' quality of life and clinical outcomes
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In addition, in terms of communication, the possible increased risk of depression with the use of second-generation AA should be discussed with patients, and depression screening should be considered for all HT recipients, especially those receiving second-generation AA
.

Therefore, further prospective studies are warranted to determine the impact of depression on clinical outcomes in prostate cancer and the ability of interventions to prevent, recognize, and treat depression in this patient population
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In addition, the present study was a retrospective study of older men over 66 years of age who were more likely to have advanced disease in men treated with second-generation AA and to receive second-line therapy after failure of first-line therapy
.

Therefore, the second-generation AA group may be more likely to experience depression and poor treatment course secondary to prostate cancer severity
.

In addition, the current "MDT diagnosis and treatment model" of prostate cancer, especially advanced prostate cancer, appropriately adding mental and psychological experts is also beneficial for such patients
.

  Commentary expert Professor Li Xiaojiang Director, Chief Physician, Doctoral Supervisor of the Oncology Department of the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine Chairman of the Oncology Professional Committee of the Tianjin Association of Traditional Chinese Medicine Vice Chairman of the Traditional Cancer Medicine Committee of the Tianjin Anti-Cancer Association Standing Committee Member and Secretary General of the Traditional Medicine Professional Committee Deputy Secretary General and Member of the Oncology Branch of the Chinese Association of Traditional Chinese Medicine Member of the First Youth Council of the China Anti-Cancer Association References of the Standing Committee of the Oncology Committee of Integrative Medicine: [1] Nowakowska MK, Lei X, Wehner MR, Corn PG, Giordano SH, Nead KT.
Association of Second-generation Antiandrogens With Depression Among Patients With Prostate Cancer.
JAMA Netw Open.
2021 Dec 1;4(12):e2140803.
doi: 10.
1001/jamanetworkopen.
2021.
40803.