Not All Diseases that Become More Common with Aging are at Increased risk from ADT: Consider Glaucoma

There is no getting around the fact that ADT has a wealth of side effects, many of which are common in men as they get older … regardless of whether they are treated for prostate cancer or are on ADT. The risk of certain cardiovascular diseases and diabetes increases with age as does the risk of gaining weight as fat and losing muscle mass. ADT increases those risks.

Given the number and severity of ADT adverse effects it is not surprising that patients worry about whether any sign or symptom of a disease that they experience may in fact be due to being on ADT. We track Internet discussions among advanced prostate cancer patients and almost daily someone asks whether this or that symptom they are experiencing might be due to the fact that they're on ADT.

Against that background, we try to track every possible ADT side effect and examine the quality of the data to support it. We're not just interested in documenting all the adverse effects; we’re also interested in cases where ADT can be excluded from being a causal factor. There is now just that sort of report for open angle glaucoma (OAG).

Glaucoma is common disease due to increased pressure in the eye that can lead to blindness. Glaucoma comes in various forms, but the most common form is open angle glaucoma, and it is more common in people as they age. There is now a report out of Taiwan, which compared the incidents of OAG for 1791 prostate cancer patients on ADT match with 1791 patients not on ADT. The study also had a separate control group of 3582 men not diagnosed with prostate cancer nor on ADT.

The incidence of OAG was the same in the control group and the prostate cancer patients not receiving ADT. That means that prostate cancer itself neither elevates nor decreases the risk of OAG. However, the men receiving ADT showed a significantly lower risk of OAG compared to the two other groups.

This is good news, and it follows a somewhat similar study from Korea, which also showed a significantly lower incidence of OAG in Korean prostate cancer patients treated with ADT compared to patients not on the ADT.

It remains to be seen whether this positive association holds up for men of a non-Asian background.

References:

Yang, P. J., Lin, C. W., Lee, C. Y., Huang, J. Y., Hsieh, M. J., & Yang, S. F. (2023). The Use of Androgen Deprivation Therapy for Prostate Cancer Lead to Similar Rate of Following Open Angle Glaucoma: A Population-Based Cohort Study. Cancers, 15(11), 2915.

Who Regrets Most Going on ADT, and Why?

Over the years we have talked to hundreds of prostate cancer patients, who have previously been on ADT, about how bothered they were by ADT side effects. The responses covered the spectrum. Some patients felt they had no side effects at all. Others swore they would never go back on ADT because they found the side effects so intolerable.

We didn’t ask though whether those who were on ADT short term to improve the effectiveness of radiotherapy used to treat localized disease, had such significant regret that they would decline going back on it, if they experienced “biochemical failure” (i.e., a rising PSA indicative of disease progression).

Concern about ADT regret negatively influencing patients’ willingness to go back on ADT led a group of researchers in Australia to search for factors that influence ADT regret (Booth et al. 2023). The researchers hypothesized that the more bothered a patient was from ADT side effects, the more regret they would have. So, they surveyed 234 patients about the side effects they experienced and how bothersome they were. Next, they asked the patients who had significant regret, what sort of survival benefit they would want to be willing to go on ADT a second time if they experienced disease progression.

The side effects that the patients found most bothersome were the common ones reported from many other studies, e.g., hot flashes, fatigue, and sexual problems. But despite the side effects, the level of regret was over all quite low. Although a third of the men with regret said that they would hope for a >10% survival benefit to be willing to go on ADT again, we don’t know if that would remain true if they were experiencing pain from advancing disease.

In a search for factors that correlate with ADT regret, such as patients’ age, time since treatment, and comorbidities, the one variable that stood out strongly was biochemical failure post-radiotherapy administered with curative intent along with adjuvant ADT. This is hardly surprising. If a patient undergoes any cancer treatment with the hope that it will be curative and it is not, they may view the treatment as a waste of time, with no benefit, just side effects.

What the researchers didn’t consider is how well informed the patients were about ADT side effects beforethey started on ADT. Although Booth et al. (2023) doesn’t cite Wibowo et al. (2020), where we show that educating patients ahead of time about ADT side effects—and ways to manage those side effects—reduce bother from that treatment. Indeed, pre-emptive education increases patients’ self-efficacy in managing ADT side effects.

Whereas education about ADT before starting on the drugs can significantly reduce side effect, neither Booth et al. (2023) nor Wibowo et al. (2000) investigated whether knowing what to expect influences patient willingness to go back on ADT, if they experience biochemical failure after early treatment. Hopefully, Booth et al. or others will follow-up on that.

References:

Booth, V., Eade, T., Hruby, G., Lieng, H., Brown, C., Guo, L., ... & Kneebone, A. (2023). Decision regret and bother with the addition of androgen deprivation therapy to definitive radiation treatment for localised prostate cancer. Practical Radiation Oncology (in press).

Wibowo, E., Wassersug, R. J., Robinson, J. W., Santos-Iglesias, P., Matthew, A., McLeod, D. L., & Walker, L. M. (2020). An Educational Program to Help Patients Manage Androgen Deprivation Therapy Side Effects: Feasibility, Acceptability, and Preliminary Outcomes. American journal of men's health, 14(1), 1557988319898991. https://doi.org/10.1177/1557988319898991

What are the Pros and Cons of Adding a Second Generation Anti-androgen to Standard ADT … and is One Anti-androgen Really Better than the Others in that Regard?

There has been a slew of studies in the last decade showing that intensifying standard ADT with a second generation anti-anti-androgen (AA), such as darolutamide (Nubeqa), enzalutamide (Xtandi) or apalutamide (Erleada), can extend life for prostate cancer patients facing disease progression when curative treatments are no longer an option. As a result, it has become standard protocol to offer one of these three drugs along with ADT to patients experiencing biochemical progression (i.e., a rising PSA) after localized treatment for prostate cancer.

But all drug treatments come with side effects. In that regard, we now have a comprehensive review and a meta-analysis by Nowakowska et al. (2023) of “functional toxic effects” of the AAs when used along with standard ADT. These are the serious side effects that can directly affect how patients feel and function in everyday life.

The meta-analysis involved 12 randomized trials comprised of over 13,500 patients. The median age of the men across the studies was ~70 years and the relevant studies had follow-up from just over a year to four years.

The meta-analysis documented significant increases in fatigue with the addition of AAs to ADT. The authors also “found a 2-fold increased risk of cognitive toxic effects with the AAs.” In addition, they reported that the “AAs conferred an 87% increased relative risk of a fall compared to controls [i.e., men on ADT alone].”

Those are serious side effects. As such, any patient being offered an AA on top of ADT might reasonably want to know, how the three AAs compare in terms of both cancer control and the risk of such “functional toxic effects. 

At the recent 2023 American Society of Clinical Oncology meeting, an abstract was presented by Morgans et al. (2023) that ranked darolutamide as somewhat better than its two competitors in slowing the time prostate cancer takes to progress to metastatic castration-resistant disease. But, what about those serious side effects? That brings us back to the recent metanalysis of functional toxic effects. There, the authors reviewed a 2020 paper by Fizazi et al. showing that the risk of “fatigue, mental impairment disorders, [and] falls” are all increased when ADT is intensified with darolutamide. Nowakowska et al. (2023) define “mental impairment disorders” as including “disturbances in attention.” That links up the three adverse effects. If “cognitive toxic effects” means a patient, who is not paying attention to where he places his feet when walking, and as also suffering fatigue, he is at increased risk of tripping and having a serious fall.

The authors, to their credit, recognize as a key point of their review that there is a need for physicians to “prevent, identify, and intervene on cognitive and functional toxic effects” in patients receiving AAs for prostate cancer. A preventive action that patients can take on their own is to be physically active before they start on the drugs and to maintain a good exercise program while on the drugs.

Sokolova and Graff (2023) provide an accompanying editorial to the Nowakowska et al. (2023) paper, that acknowledge the trade-off between extending life and maintaining a good quality of life. As they succinctly state “men must determine whether the potential benefits of treatment are worth the influence on their quality of life.” That is an all-to-often tough trade-off in the world of cancer. When facing it, prostate cancer patients shouldn’t face it alone but talk it over with those close to them, for their decision will influence not just themselves, but also their loved ones.

References:

Morgans, A., Shore, N., Khan N., Constantinovici, N., Khan, J., Chen, G., Xu, J., Ortiz, J., & George, D. Comparative real-world (RW) evidence on darolutamide (Daro), enzalutamide (Enza), and apalutamide (Apa) for patients (Pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC) in the United States: DEAR. Journal of Clinical Oncology, 21(16\_suppl, 5097. https://doi.org/10.1200/JCO.2023.41.16\_suppl.5097

Nowakowska, M., Ortega, R., Wehner, M., & Nead, K. (2023). Association of Second-generation Antiandrogens With Cognitive and Functional Toxic Effects in Randomized Clinical Trials: A Systematic Review and Meta-analysis. JAMA oncology, e230998. https://doi.org/10.1001/jamaoncol.2023.0998

Sokolova, A., & Graff, J. (2023). Balancing Treatment Benefits of Androgen-Receptor Signal Inhibitors and Quality of Life in Patients With Prostate Cancer. JAMA oncology, 10.1001/jamaoncol.2023.0982. https://doi.org/10.1001/jamaoncol.2023.0982

Fizazi, K., Shore, N., Tammela, T., Ulys, A., Vjaters, E., Polyakov, S., Jievaltas, M., Luz, M., Alekseev, B., Kuss, I., Le Berre, M., Petrenciuc, O., Snapir, A., Sarapohja, T., Smith, M., & ARAMIS Investigators. (2020). Nonmetastatic, Castration-Resistant Prostate Cancer and Survival with Darolutamide. The New England journal of medicine, 383(11), 1040–1049. https://doi.org/10.1056/NEJMoa2001342

The Better the Survival, The More we Need to Focus on Quality of Life

A slew of studies in the last half decade or so have compared treating patients, who have metastatic prostate cancer, with ADT alone, or ADT in combination with other agents, notably either abiraterone and prednisone or a second-generation anti-androgens. These combinations have come to be known as “doublet therapy.” If one adds in a chemotherapy agent like, docetaxel, that is now referred to as “triplet therapy.” Collectively these studies have pointed to better survival for these advanced patients when ADT is combined with at least one of the newer agents.

As patients survive longer on these intensified treatment protocols, it becomes important to look at not just their survival, but their health-related quality of life (HR-QoL). Inspired by that concern, an international group of uro-oncologists reviewed six important studies that have shown the benefit for prostate cancer treatment intensifications. Here the researchers focused specifically on patients’ HR-QoL.

As a general conclusion, the authors found that either enzalutamide or abiraterone, when combined with ADT, increased overall HR-QoL compared to ADT alone.

The authors flagged though a major problem in comparing these studies; i.e., they used a wide variety of measures of HR-QoL making it difficult to compare the studies. For example, two studies focussed on the time to “clinically meaningful deterioration.” Another looked at “patient reported deterioration.” Some looked at “progression;” others looked at “physical symptoms.” They may sound similar, but they are not.

The authors found in general that the combinations did not improve sexual function and the authors believed that was simply because the ADT alone would have greatly suppressed sexual function.

Patients were more likely to report loss of appetite, if they were taking enzalutamide and ADT rather than just ADT. The combination of darolutimide, ADT, and docetaxel led to a longer time to pain progression compared to ADT alone.

The studies were inconsistent in terms of what they reported on in terms of “emotional well-being” and “social and family well being.” None of the studies looked at the well-being of the intimate partners and caregivers of the patients.

In their key last paragraph, the authors write “We plea for a standardization of measurements to allow quantitative comparisons across future studies.” We would add to this that future studies should also look at the HR-QoL and welfare of the partners and caregivers of the patient’s since it has been known for a long time that ADT not only burdens prostate cancer patients directly, but indirectly also their loved ones.

Reference:

Afferi, L., Longoni, M., Moschini, M., Gandaglia, G., Morgans, A., Cathomas, R., Mattei, A., Breda, A., Scarpa, R. M., Papalia, R., de Nunzio, C., & Esperto, F. (2023). Health-related quality of life in patients with metastatic hormone-sensitive prostate cancer treated with androgen receptor signaling inhibitors: the role of combination treatment therapy. Prostate cancer and prostatic diseases, 10.1038/s41391-023-00668-0. Advance online publication. https://doi.org/10.1038/s41391-023-00668-0

Let's Talk about Prostate Cancer and Depression

There is a lot you can learn from the massive datasets acquired in the countries that keep national health registries. The National Prostate Cancer Registry of Sweden, for example, has data on almost 200,000 men diagnosed with prostate cancer between 1998 and 2017. With samples that size, one can look at slew of factors that can influence serious, but rare outcomes of a cancer diagnosis and its treatment. A good example is the risk of depression and suicide for men with prostate cancer. And we now have a registry study from Sweden that looked at exactly that.

The authors of this new study found that men diagnosed with high-risk PCa have substantially higher rates of major depression and suicide relative to men without PCa. These risks remain high >10 years post diagnosis. In contrast, men with low or intermediate risk PCa have modestly higher rates of major depression and slightly elevated risk of suicide, but this is only seen in the first year after their diagnosis.

Other factors that came into play in terms of an elevated risk of depression are having lower education, lower income, and also having had a previous history of depression before the prostate cancer diagnosis.

What also stands out for us, and it is relevant to readers of this blog now, is ADT was a contributory factor for depression in the advanced patients.

One of the strengths of this study was that the researchers could compare all the prostate cancer patients to other men in the health registry that were matched with the cancer patients in terms of the age and any comorbidities that they had.

A diagnosis of prostate cancer itself can raise the risk of depression. But when the cancer is of low risk and patients realize that they can have many years of life, the risk of depression declines within a year or so. Patients, however, who are diagnosed with more advanced disease are in a different and more challenging situation; they are more likely to go on ADT and if the disease progresses, the risk of depression goes up. Here both treatment with ADT and disease progression, or the fear of it, exacerbate pre-existing depression.

What we believe the major take home message from this study is not that ADT causes men to become suicidal, for the number was extremely low in this population; i.e, just one in 500 of the advanced patients. However, the incidents of major depression were about 8% of the men in this study. That led the authors to push for men diagnosed with prostate cancer to be screened for depression. Our take on that is that it's important that patients, who have had episodes of major depression and are starting an ADT, to be aware of the risk and to inform their clinicians of their history. We agree with the authors as well, that along with monitoring the status of the patients’ cancer, their mental health should also be assessed, particularly if they go on ADT.

Reference:

Crump, C., Stattin, P., Brooks, J. D., Sundquist, J., Bill-Axelson, A., Edwards, A. C., Sundquist, K., & Sieh, W. (2023). Long-term Risks of Depression and Suicide Among Men with Prostate Cancer: A National Cohort Study. European urology, S0302-2838(23)02787-2. Advance online publication. https://doi.org/10.1016/j.eururo.2023.04.026

Should the Presence of Visceral Metastases Make a Difference in Treating Patients with Advanced Prostate Cancer?

Typically, when prostate cancer spreads beyond the prostate gland, the metastases show up in the skeleton system. However, with improved imaging, such as with PSMA diagnostic scans, oncologists are increasingly finding prostate cancer in the viscera as well.

In patients with metastatic disease, the standard treatment is not just ADT, but ADT combined with either abiraterone and prednisone or one of the newer anti-androgens, such as enzalutamide.  

A group of researchers asked a simple question: Does the presence of visceral mets make a difference in terms of what is the best treatment for the patient? To find the answer, the authors reviewed data from six, relatively recent, phase III trials that included almost 5400 patients. Out of that sample, just over 15% of the patients had visceral metastasis. Based on the study the authors reviewed, some patients were treated with a newer anti-androgen while others received abiraterone acetate and prednisone.

The winner here was the abiraterone and prednisone. For patients with visceral mets, abiraterone and prednisone combined with ADT improved overall survival better than anti-androgens and ADT.

This confirms how important it is to have good imaging when dealing with a rising PSA after treatment for localized disease. Knowing where the disease is in the body helps physicians to come up with the best personalized treatment.

Reference:

Yekedüz, E., McKay, R. R., Gillessen, S., Choueiri, T. K., & Ürün, Y. (2023). Visceral Metastasis Predicts Response to New Hormonal Agents in Metastatic Castration-Sensitive Prostate Cancer. The oncologist, oyad102. Advance online publication. https://doi.org/10.1093/oncolo/oyad102

So, is the cardiovascular disease risk really lower for patients with an LHRH antagonist then an LHRH agonist for ADT?

Both LHRH agonists and LHRH antagonists can be used for androgen deprivation therapy. A commonly used LHRH antagonist is the drug Firmagon (degarelix) and is administered as a monthly depot injection. Compared to the LHRH agonist drugs, such as Lupron (Leuprorelin) or Zoladex (goserelin), degarelix suppresses testosterone faster and supposedly carries lower risk of cardiovascular disease (CVD). However, it requires two injections when patients start on it and the depot injections last only a single month. It is not uncommon that patients, who have a high PSA at diagnosis, start on degarelix and then shift over to an LHRH agonist drug, where injection can last three months or more. All these drugs are equally effective in suppressing testosterone.

Early on there was some data suggesting that the risk of a serious CVD in the form of a myocardial infarct (MI; what we commonly call a heart attack) was lower for the antagonist than the agonist. But does this hold up for all major CVDs? This includes MIs, strokes, ischemic heart disease (IHD; where the heart muscle is not getting enough oxygen leading to pain that often radiated to the left shoulder), arrythmia, and heart failure.

We finally have a comprehensive review that looks at the specific risk factors for these various CVDs for patients on LHRH agonists versus LHRH antagonist and the results are intriguing. The antagonist is indeed associated with less risk of heart failure, particularly for patients, who have had prior CVD when starting on ADT. There is a different story though for men with no prior history of CVD. For them, the antagonist was associated with a decreased risk ischemic heart disease, but an increased risk of arrhythmia.

All of this points towards a need for a rigorous cardiovascular assessment for patients starting on ADT. The best drug for each patient depends on their cardiac status, history, and the need for rapid androgen suppression.

Reference:

Dragomir, A., Touma, N., Hu, J., Perreault, S., & Aprikian, A. G. (2023). Androgen Deprivation Therapy and Risk of Cardiovascular Disease in Patients With Prostate Cancer Based on Existence of Cardiovascular Risk. Journal of the National Comprehensive Cancer Network : JNCCN, 21(2), 163–171.

https://pubmed.ncbi.nlm.nih.gov/36791755/

Is There Still a Context for using Bicalutamide (Casodex) as Monotherapy for ADT?

Although it is not used this way in North America, there are places where the first generation oral antiandrogen, bicalutamide (Casodex), is used as a monotherapy for ADT. Because this drug blocks the receptors for androgens, the serum testosterone levels for patients on bicalutamide monotherapy remain high.

Excess testosterone is naturally converted to estrogen. As a result, men on this treatment regime are less likely to experience hot flashes, osteoporosis, and a total loss of their sex drive, which are all due to loss of estrogen in men on LHRH drugs. However, estrogens cause breast development and discomfort in the breast is a common side effect of bicalutimide as monotherapy.

Because of some toxicity and limited survival benefit, bicalutimide monotherapy is now not a common ADT protocol in Europe, although it is still approved there to treat prostate cancer. The patients best served by this ADT protocol are those who find the side effects of the LHRH drugs particularly difficult to tolerate yet need androgen blockade to control their prostate cancer.

Against this background, we have a new paper, which seems to us as anachronistic. The paper addresses a way to avoid breast discomfort for patients on bicalutimide monotherapy. This is to provide the patients with prophylactic radiation to the breasts. To be clear, this protocol has been around for decades, but is used less commonly in recent years. Now, bicalutimide is typically used short term in order to prevent testosterone flares when patients start on LHRH agonist drugs. The breast problems are reduced by using the bicalutimide short term. This avoids a need for any prophylactic radiation, and avoids the risk of cardio-toxicity from the radiation and the risk of a secondary, radiation-induced cancers.

The authors describe gynecomastia for prostate cancer patients as “a frequent disabling side effect of antiandrogen therapy….[and along with breast pain]… can significantly affect a patient's quality of life.” They do not provide a reference for this, but other research that they do not cite suggests that the distressed from these breast symptoms are highly variable among men who are on ADT treatments that promote breast development. Admittedly, some men find the breast symptoms very distressing while but others find them of little bother.

What is most odd about this paper is why the patients were on any drugs at all. Out of the sample of 76 men (with the mean age of 74 years), who were then followed for one to five years, 2/3 of the men had a Gleason scores of six or lower. Similarly, over 2/3 of the men had a PSA value of less than 10.

As noted in the title of paper, these men had a low to intermediate risk of prostate cancer mortality. Increasingly these men would be advised to go on active surveillance without any prostate cancer treatments. As such, they would not need any additional treatments to mitigate the side effect of the drugs.

So, why are these patients being put on bicalutamide monotherapy? According to the authors, some of the men were too frail and had too many comorbidities to be good candidates for surgery. Others were reluctant to give consent for external beam radiation or found this treatment took too long. Others evidently feared radiation-related morbidities. On that last point, it would seem better that the men simply delayed active treatment rather than go on bicalutimide monotherapy.

By both current North American and European guidelines, the majority of men in this study did not warrant starting on ADT of any form.

Reference:

Chernomordikov, E., Rouvinov, K., Mermershtain, W., & Lavrenkov, K. (2023). Prophylactic Breast Irradiation for Prevention of Bicalutamide-induced Painful Gynecomastia in Patients with Low- and Intermediate-risk Prostate Cancer. The Israel Medical Association journal: IMAJ, 25(3), 205–209.

Hormone Intensification—If Two Drugs are Good are Three Drugs Better?

In the last few years there have been a slew of studies involving standard ADT (i.e., with LHRH agonists or antagonists) combined with other drugs to treat various prostate cancer populations. These populations include both patients whose cancer is hormone sensitive as well as those who are castrate resistant. 

The drugs that are being combined with ADT included both taxane chemotherapy and various androgen receptor targeting agents (ARTAs; i.e., the second generation anti-androgens and abiraterone plus prednisone). The studies are so numerous now that it is hard to keep them all straight. Thus, it is a joy to see a pros and cons discussion of the merits of the various drug combinations in ESMO-OPEN, a journal of the European Society for Medical Oncology.

The patient population addressed in the in the ESMO-Open paper are men with metastatic prostate cancer that can still be controlled with hormonal therapy. The relatively new standard of care for these patients is ADT plus an ARTA. That would be a form of doublet therapy. Another doublet therapy though would be ADT combined with chemotherapy.

The authors present the cases, both for and against going with triplet therapy in the form of ADT + an ARTA + chemo for this patient population. With overall survival as a primary outcome, the authors conclude that this “up front triplet combination …will become a new standard of care for fit men with de novo metastatic hormone sensitive prostate cancer”.

However, when discussing the case against triplet therapy, the authors point out that in much of the world these men will have been previously treated for localized disease and they should be distinguished from those who are first diagnosed with metastatic, but still castrate sensitive, disease. The men, who have been pretreated for localized disease, are likely being followed closely with PSA tests and may have a relatively low tumor burden when diagnosed with metastatic disease. The authors argue this should be taken into consideration when deciding to move from doublet to triplet therapy. Given the heightened adverse side effect risk in tripled therapy, these patients may be better off staying on a doublet therapy protocol. All of these treatments have substantial side effects burdens and thus the overall health of the individual patient, such as the risks of hypertension and liver toxicity, should be taken into consideration when moving from doublet to a triplet therapy.

We are optimistic that there will be substantial refinements in the next few years about when it is best to use hormone intensified treatments and which treatments will be best for specific patient populations. A driving factor here is the availability of higher quality imaging of tumors and improvements in tumor targeted treatments. Treatment protocols are also likely to change as we learn more about the genetics behind metastatic prostate cancer and get a better sense of when to start a patient on triplet therapies given their genetic profile and comorbidities.

Reference:

Oing, C., & Bristow, R. (2023). Systemic treatment of metastatic hormone-sensitive prostate cancer-upfront triplet versus doublet combination therapy. ESMO open, 8(2), 101194.

https://doi.org/10.1016/j.esmoop.2023.101194

Are the Side Effects from ADT Different for Men of Asian Versus African or European Ethnicity?

In general men from Asian ethnic groups are less likely to die of prostate cancer compared to men from European or African ethnic groups. Studies from individual Asian countries have established that generally, Asian men have a better baseline metabolic profile compared to Caucasian prostate cancer patients. Several studies have shown, for example, that Asian men are less likely to have severe cardiac events on ADT and may be able to tolerate multiple rounds of chemotherapy with less toxicity than those of Caucasian background.

Note though that in the last paragraph we mention studies from individual Asian countries. How broad reaching are these ethnic generalizations?

There's a new study that looks at the adverse metabolic responses to ADT for men from several Asian countries. The study followed 589 patients for a year or more from Hong Kong, the People's Republic of China, Taiwan, and Malaysia. The average age of the men was 72 years.

Within six months, the men showed significant increases in fasting glucose levels and in hemoglobin A1c indicative of increased risk of diabetes. Similarly, their triglyceride levels were elevated and on average they gained 1 kilogram in weight within a year and a half of starting on ADT. These are common signs of metabolic syndrome seen in men on ADT from European and African ethnic groups.

The Asian patients thus show similar metabolic shifts to those seen in men from other continents and ethnicities, although not quite as severe. The Asian men in general are not as likely to be overweight as, say, North American prostate cancer patients and that may account substantially for the Asian men doing better on ADT.

Large population studies of health and ethnicity, like this one, will be increasingly important as we learn more about the genetics of prostate cancer progression. Studies like this can help us find genetic biomarkers of disease development and hopefully identify treatments that are most effective for men of diverse genetic backgrounds.

Reference:

Wong, C., Xu, N., Lim, J., Feng, K., Chan, W., Chan, M., Leung, S., Chen, D., Lin, Y., Chiu, P., Yee, C., Teoh, J., Huang, C., Yeoh, W., Ong, T., Wei, Y., & Ng, C. (2023). Adverse metabolic consequences of androgen deprivation therapy (ADT) on Asian patients with prostate cancer: Primary results from the real-life experience of ADT in Asia (READT) study. The Prostate, 10.1002/pros.24519.

https://doi.org/10.1002/pros.24519