When given a choice, only 14% of men on ADT ≥1 year chose having an orchiectomy every though they are candidates for life long ADT. Quality of life outcomes showed no difference between orchiectomy and continuing standard ADT. Notably, decision regret was low among patients who chose the orchiectomy.

Reference: 

Lazarovich, A., Stadler, W. M., Eggener, S., Tremblay, S., Page, A., Diaz, H., ... & Reizine, N. (2025, September). The comeback of orchiectomy in advanced prostate cancer-is that feasible?. In Urologic Oncology: Seminars and Original Investigations. Elsevier.

Though not specific to ADT, long-term green space exposure is linked to lower mortality in prostate cancer survivors. QED: If you have a choice, go for a walk in the woods!

Reference:

Ji, J. S., Wang, H., Song, J., Iyer, H., Xu, M., Zhang, Y., ... & Ping, H. (2025). Long-term green space exposure associate with lower mortality in prostate cancer survivors: a retrospective cohort study using SEER from 1995 to 2019. Environment International, 109812.

Huge N> 60K) long term (data over 30 years) out of Sweden shows that for men diagnosed with Prostate Cancer have overall prolonged survival—“even those with very high-risk cancer, were twice as likely to die of other causes than from Prostate Cancer.”

Reference:

Scilipoti, P., Bratt, O., Garmo, H., Orrason, A. W., Gedeborg, R., Stattin, P., & Westerberg, M. (2025). Long-Term Outcomes After Guideline-Recommended Treatment of Men With Prostate Cancer. Journal of the National Comprehensive Cancer Network, 23(7), e257022. Retrieved Jul 18, 2025, from https://doi.org/10.6004/jnccn.2025.7022

Prostate Cancer Patients Benefit Greatly From Exercise, but For Many it is Difficult to Commit to Exercising in The Long Term

This will be a short blog entry. That’s because the main story is told in the title of the paper by Houben et al. cited below.

That paper focuses on 78 patients on ADT who participated in a 20-week supervised resistance exercise training program. The program worked in that the patients had more muscle mass and more strength at the end of 20 weeks compared to when they started in the program.

The researchers, however, also looked at whether the benefit of the exercise was retained one year after it started. That was more than a half year after the research program had ended and the men were on their own. The authors are very honest about the fact that the benefits of exercise at 20 weeks were largely NOT sustained when the patients were re-assessed at the one-year mark.

When we pair that paper with the other paper listed below (i.e., Western et al. 2024), we get some insights into factors that lead to cancer patients not staying with exercise even after they have started it. Western et al. looked at dropout rates during exercise research studies while still underway. It is important to note that that the Western et al. study was not specific to prostate cancer. The majority of participants were in fact women with breast cancer. However, it was a large study with over 300 participants treated for male genitourinary cancers, which would have been predominantly prostate cancer.

Of those 300+ participants, just over 10% dropped out.

Being overweight or obese was the major correlated to men dropping out of the study. They were also more likely to drop out if part of the exercise program was not strictly supervised. Lastly, individuals with a low to medium level of education were more likely to drop out than individuals with higher levels of education.  

The author conclude that more effort needs to be taken to retain cancer patients in exercise programs, who fit the profile outlined above whether in a formal research study or on their own. To that we add that patients are more likely to stay with exercise if they start early…and preferrable before they are challenged by the side effects of their cancer treatments. That surely fits for patients treated with ADT.

References:

Western B, Ivarsson A, Vistad I, Demmelmaier I, Aaronson NK, Radcliffe G, … & Buffart LM. Dropout from exercise trials among cancer survivors-An individual patient data meta-analysis from the POLARIS study. Scand J Med Sci Sports. 2024 Feb;34(2):e14575. doi: 10.1111/sms.14575. PMID: 38339809.

Houben, L. H., Overkamp, M., Senden, J. M., van Roermund, J. G., de Vries, P., de Laet, K., ... & Beijer, S. (2024). Benefits of resistance training are not preserved after cessation of supervised training in prostate cancer patients on androgen deprivation therapy. European Journal of Sport Science, 24(1), 116-126.

Yet Again, We Explore the Topic of the Impact of ADT on Cognitive Function

When it comes to the quality of life of patients on ADT one major area of research is the impact of ADT on cognition. Patients usually discuss this in terms of brain fog, problems with memory, or just problems in finding common things around their home. Despite a huge number of studies on the topic, there's not been a solid consensus about how ADT, either alone or combined with ARTAs, impacts patients’ cognitive abilities.

We now have a new comprehensive review and meta-analysis of the research that is more rigorous than any so far. Twenty studies are included in the systematic review built upon data from 1440 patients. Fifteen of those 20 had enough data to be used in a meta-analysis.

In the ADT book, we reference a 2014 meta-analysis, which was the most comprehensive meta-analysis previous analysis. That paper concluded that the best evidence for cognitive impairment was in the visuo-spatial domain. However, this new analysis questions that conclusion. The authors are careful to distinguish different types of trials, such as whether patients were compared to their baseline data only or whether there was a control group.

What the authors found in their new meta-analysis is that consistent evidence for objective cognitive impairment from ADT is still lacking. The authors offer some suggestions for why they got this result. For example, they noted that some 20 to 50% prostate cancer patients show some sign of objective cognitive decline even before they are exposed to ADT. This could be due to depression or anxiety directly or indirectly related to the stress of having advancing cancer.

The authors even found some evidence of cognitive improvement (!) when they compared patients tested at baseline and re-tested at a later date. They suggested that this could be the result of the participants learning how to take the tests from their previous exposure to the tests. 

What is probably the most surprising and relevant take-away for patients from this paper is that  authors found evidence of subjective cognitive decline with ADT.  Objective cognition is measured with standardized tests whereas subjective cognition is documented by simply asking the patients various questions about whether they feel like they are having a harder time thinking, remembering, and finding things, whether they are words or objects in the world they live in.

From a patient's perspective what matters most is subjective sense of cognitive decline versus the objectivemeasures. It is that subjective impression of cognitive impairment that would be associated with distress in patients. It could be tied to fatigue, insomnia, and depression, which are common in cancer patients. One study that the authors cite, for example, shows that patients reporting subjective cognitive impairment showed insomnia as a mediating factor.

In the real-world objective cognitive impairment is worth assessing and finding ways to limit it  for the safety of the patient. At the same time in the real world, it is subjective sense of brain fog and cognitive impairment that stresses out patients. If stressed out patients have poor sleep quality, that can lead to fatigue and depression. Patients in that situation may report a high level of brain fog which in turn can lead to problems with sleeping in a feedback loop fashion.

This may seem scary, but there is a somewhat positive side to the story. There are interventions that can help with sleep quality and depression, and perhaps help with the subjective sense of cognitive impairment. This can include various medications, but exercise alone has been shown to help with managing insomnia, daytime fatigue, and depression.

In contrast, it is harder to treat objective cognitive decline of the sort associated with aging.

This paper is superb not only in its thoroughness, but in pointing out that clinicians treating patients with ADT need to take seriously the patients’ concerns about brain fog and cognitive impairment…even if they’re not documented in standardized tests.

Reference:

Boué A, Joly F, Lequesne J, Lange M. Does hormone therapy impact cognition in patients with prostate cancer? A systematic review and meta-analysis. Cancer. 2024 Feb 2. doi: 10.1002/cncr.35210.

More on ADT and Depression

The incidence of depression for men over the age of 65 in the general population is about 9.5%. In contrast, various studies suggested that men diagnosed with prostate cancer have an overall incidence of depression of 10 to 40%. A new review article and meta-analysis of 38 studies by Qazi et al. (2024), which collectively included data from over 350,000 men, arrived at a pooled estimate of depression of 20.9% of men treated with ADT. That is substantial.

Another new study by Mandel et al. (2024) extracted data from a global database (i.e., TriNetX) of almost 80,000 men on ADT who were subsequently prescribed anti-depressant medication. It confirmed that ADT increases the risk of depression in men diagnosed with prostate cancer.

What particularly stands out in Mandel et al. study is the difference between the White and Black population. To quote the authors, “After starting ADT, White patients had 30% greater odds of being diagnosed with the depression, compared to Black patients.” Mandel  also found that White patients were at greater odds of getting treated with anti-depressants than the Black patients.

This is not to say that the Black population is less likely to experience depression. The data do not show that. The problem appears to be that depression is being under diagnosing for Black prostate cancer patients and subsequently inadequately treated in that population.

This is just one more example of racial disparities in healthcare for White and Black men in the USA.

References:

Mandel AL, Simhal RK, Shah YB, Wang KR, Lallas CD, Shah MS. Racial disparities in diagnosis and treatment of depression Associated with androgen deprivation therapy for prostate cancer. Urology. 2024 Feb 21:S0090-4295(24)00094-3. doi: 10.1016/j.urology.2024.01.021.

Qazi SU, Altaf Z, Zafar M, Tariq MA, Khalid A, Kaleem A, Saad E, Qazi S. Development of depression in patients using androgen deprivation therapy: A systemic review and meta-analysis. Prostate. 2024 Feb 19. doi: 10.1002/pros.24676.