What Prostate Cancer Patients Treated with ADT Recall About It Is Worse Than We Thought

Buried within a retrospective study about what prostate cancer patients in Australia recall about their cancer treatments are some disturbing data on hormone (aka androgen deprivation) therapy. The study ran from 2009 to 2019. The data of particular interest are from 221 respondents, who were asked about their treatment history and provided enough information that their recollections could be compared with their actual medical records.

The men were on average 76 years old and had been treated on average six years earlier (range 0 to 18 years). Their recall of their treatment history was overall pretty good, ranging from a high of 96% (for chemo) to a low 66% (for ADT). Notably, this low recall accuracy for ADT means that a third of the respondents could not recall correctly whether they had or had not been on ADT. In fact, over a quarter asserted that they had not had ADT when their medical records showed they had. The patients who recalled accurately being on ADT were overall: 1) younger, 2) had been on ADT more recently, and 3) had been treated solely by ADT.

The author suggested that overall poor recall about ADT may be because the patients viewed ADT as a minor “passive treatment” and they did not consider it (or were not informed about it) being a major part of the effort to control their cancer.

The authors conclude their paper saying because “recall is indicative of patient understanding [of treatment and side effect management], our results suggest that there is an opportunity for further improvement particularly in the areas of hormonal treatment….“ We couldn’t agree more. The ability of patients and those around them to maintain a good quality of life when the patients are on ADT is predicated on the fact that the patients know they on that treatment! It is hard to help patients recognize and adapt to ADT, if they do not even know they are getting that treatment.

It’s hard to imagine anything more discouraging about the concept of informed consent, when there are patients on certain treatments, who do not even know they are getting that treatment. Hopefully the situation, in terms of educating patients about treatment options, side effects, and outcomes, has improved in Australia and elsewhere since the time when the men in this study where getting their cancer treatments.

To read the full paper, see: https://www.sciencedirect.com/science/article/pii/S2405632422000427

Reference:

Brown, A., Tan, A., Anable, L., Callander, E., Lourenco, R. D. A., & Pain, T. (2022). Perceptions and Recall of Treatment for Prostate Cancer: A Survey of Two Populations. Technical Innovations & Patient Support in Radiation Oncology.

Yet another obscure side effect of ADT? Not really.

In order to help PCa patients manage adverse effects of ADT, we need to know all the ways that ADT affects the body. As such, we try to track all the literature suggesting ADT side effects no matter how obscure those side effects might be.

A new paper out of Turkey looked at the effect of ADT on various aspects of the eyes of 57 patients. This included high resolution CAT scans, which allowed the researchers to assess details, such as: the size of small muscles that move our eyes to redirect our gaze, the fat around the eyes, and the thickness of the optic nerve. The researchers found that 12 months or more of ADT caused a decrease in the size of the muscles that move the eye and an increase in the fat around and behind the eye. This extra fat pushed the eye forward slightly stretching and thinning the optic nerve.

At first glance, this sounds scary. Thus, it is important to point out the authors found no evidence of clinical changes in vision. They noted that these changes were “remarkably lower” than what would be considered clinically significant.

The change in fat was approximately 12% over baseline. Researchers pointed out this was in the range of what is commonly reported as overall weight gain for men on ADT for a year or more. The change in muscle mass was similarly consistent with what is average for men on ADT long term. Typically, though, when we think about changes in fat and muscle with prolonged use of ADT, we think about weight gain around the abdomen and weaker legs from loss of muscle mass in the extremities

It is not surprising that the same changes happen on a much smaller scale for the tiny muscles and fat around the eyes. Indeed, these results are what we would have predicted from what we know about ADT’s effects on the body in general. It is good to note that although the sample size was not large, there is no indication that these changes around the eye affect vision in any significant way

Reference:

Sonmez H, K, Sonmez G, Doğan S, Horozoglu F, Demirtas A, Evereklioglu C (2022) Effects of Androgen Deprivation Therapy on the Extraocular Muscles, Retrobulbar Orbital Fat and the Optic Nerve in Patients with Prostate Cancer. Ophthalmic Res. doi: 10.1159/000527387

A Few Comments on the Surgical Option for ADT

The original form of androgen deprivation therapy, which won Charles Huggins, MD, the Nobel prize, was surgical castration. Although that may seem like excessive treatment compared to the injectable LHRH agonist and antagonist drugs now used for ADT, it remains as effective for PCa control and less expensive in the long term. In poverty-stricken parts of the world, surgical castration is still offered to patients who cannot afford the more expensive LHRH agonist and antagonist drugs.

But what about in a country like Turkey?

In a new study, researchers asked 217 urologists and 170 medical oncologists in Turkey, if they offered surgical castration as an ADT option to their advanced PCa patients. Only 7.5% offered this option. Surgeons were statistically more likely to offer it than medical oncologist, but that is hardly surprising since surgical castration is a surgical procedure performed by surgeons.

We have two comments on this study.

In the discussionof their findings, the authors take it as a given that patients consider surgical castration detrimental to their body image. This may be true, but the literature documenting this is very limited. There is remarkably little data on patient preference for different forms of ADT, where the patients were confirmed to be fully informed of the costs and benefits of all the treatment options. One would suppose that patient choice would be influenced by their knowledge about the effectiveness of the treatment against the side effects that might occur.

A common argument against surgical compared to pharmacological castration is that surgery is not reversable. However, this argument is not particularly relevant for older, patients with a advanced disease and do not desire to father children. Patients in that class, who start on ADT, are likely to stay on treatment for the rest of their life.

A couple of studies have found that PCa patients, who elected surgical castration for ADT, were significantly less anxious overall than patients on injectable depot LHRH medications. Now, with so many different ways to suppress testosterone’s influence on PCa cells, it might be worth exploring how much patient comfort or discomfort—with any form of treatment—is influenced by their knowledge of treatment options.

If less than 10% of physicians present all the options to their patients, it would not be surprising that patients may not be making well-informed decisions about their treatments. Are few advanced PCa patients in Turkey (or elsewhere) considering surgical castration for ADT because they feel it will negatively impact their self-image or because they are not being told about that option by their physicians?

This is more than an academic discussion. There are increasingly data showing that the effectiveness in cancer control for patients on the standard ADT drugs can be enhanced with the newer androgen receptor targeting agents (ARTAs). But ARTAs are not cheap drugs. When patient’s financial status is limited, ADT via surgical castration remains a credible option. It certainly should remain an option offered to patients, who might benefit from both standard ADT plus an ARTA, but can’t afford both.

To read the full paper, see: https://www.turkishjournalofurology.com/Content/files/sayilar/206/287-293.pdf

Reference:

Semiz, H. S., Kisa, E., Yildirim, E. C., Atag, E., Arayici, M. E., Muezzinoglu, T., & Karaoglu, A. (2022). What Is Your Choice for Androgen Deprivation Therapy in Metastatic Prostate Carcinoma: Surgical or Medical?. Turk J Urol, 48(4), 287-293.

Do men need to stay on ADT when they have advanced PCa and have started taking one of the newer antigen receptor targeting agents?

In a short theoretical paper, a group of Italian researchers question the rationale for advanced PCa patients staying on standard ADT when they start on an antigen receptor targeting agent (i.e.,the ARTAs; abiraterone, enzalutamide, apalutamide and darolutamide). Their argument is built around the idea that, if bipolar androgen therapy (BAT) helps control PCa by cycling between testosterone and androgen suppression, then it may be similarly advantageous to come off of standard ADT agents, when one is on an ARTA agent.

This is an interesting idea, but it is well ahead of the clinical research. The ARTAs were initially introduced to treat the most advanced PCa and now, justified by data from a series of on-going clinical trials, they are being introduced earlier in the treatment progression. We simply do not have enough data on the long-term efficacy of ARTA monotherapy to know whether they will work better alone, specifically in terms of both long-term survival and patient quality of life. Presumably, the patient quality of life will be better. However, we don’t know about survival. That’s because it takes many years to collect long term survival data and most of drugs have not been around long enough to answer that question.

It also needs to be recognized that BAT is still quite experimental and about 1/3 of the patients in trails so far found that the protocol accelerated their disease.

What this says to us is not only do we need more long-term data on ARTAs when used in combination with other therapies, but we also need more long-term data on the efficacy of ARTAs used alone as either continuous or intermittent therapy.

To read the full paper, see: https://doi.org/10.1007/s12020-022-03166-w

Reference:

Caramella, I., Dalla Volta, A., Bergamini, M., Cosentini, D., Valcamonico, F., & Berruti, A. (2022). Maintenance of androgen deprivation therapy or testosterone supplementation in the management of castration-resistant prostate cancer: That is the question. Endocrine, https://doi.org/10.1007/s12020-022-03166-w