When it Comes to ADT, some Patient Reported Outcomes (PROs) Miss the Mark

It is increasingly popular for researchers to use patient reported outcome measures (PROMs) to capture data on the Quality of Life (QoL) of cancer patients. For many of us, who are patients, when one hears of “patient reported outcomes”, we envision a doctor or nurse asking us about how we're feeling, what side effects we're experiencing, and what is the greatest concern to us. In the clinical setting, however, PROMs tend to be captured using questionnaires that patients fill in rather than information gathered through direct conversation with healthcare providers.

In the world of prostate cancer, one of the most popular and commonly used PROMs is the Expanded Prostate Cancer Index Composite; i.e., the EPIC. The EPIC has been around for over 20 years and has been used in over 700 studies. As more researchers use the EPIC, more may assume it’s use is appropriate. However, from our perspective the EPIC has serious limitations when used to assess the QoL of men on ADT.

The EPIC has several separate domains. One is labelled “sexual function.” The questions there don’t actually ask about sexual function, but rather about “how big a problem,” the patient perceives to be having related to their sexual desire, ability to have erections, and ability to reach orgasm over the past 4 weeks.

ADT limits men’s ability to have erections and to reach orgasms, but it also affects sexual desire.

Patients, who are sexually active at the time they start ADT, may either find ways to continue to be sexually active … or they may abandon having sexual activity altogether. Reasons for this differ but may include expectations about the kind of the sexual activity they have, or their partner’s interest in sex. The loss of erections and orgasm may be greatly bothersome, not only to the patient but also the partner if they both have high desire for sex. Alternatively, the same changes may be of little bother for either of them, yet they may have a good, strong, co-supportive, dyadic bond built upon other factors than sex. Aging may also contribute to changes in sexual activity and interest. 

The EPIC questionnaire fails to sort this out. This is because the sexual domain in the questionnaire asks about bother, not function. Both patients and partners may have no sexual function, but also little or no bother from that because they have little sexual desire. Or they may be greatly bothered. There’s no way of telling based on the wording in the EPIC.

What concerns us here is a new study by Movsas et al. (2023), which used the EPIC questionnaire to look at QoL for prostate cancer patients with intermediate risk disease, who either used androgen deprivation therapy short term to support radiotherapy (RT) or got RT without ADT. The participants were surveyed with the EPIC at baseline, at the end of their RT treatments, six months later, a year later, and then five years later.

The EPIC revealed that the patients were greatly bothered by the impact of ADT on their sexual desire, erections, and ability to have orgasms at the end of their RT sessions. However, as time went by, the overall EPIC score for the sexual domain improved in the ADT group. The scores became less extreme and less clinically meaningful.

Had the patients returned to baseline and recovered from the ADT’s impact in the sexual domain? Or had they adapted to (or resigned to) a sex-free life without erections and orgasms secondary to reduced sexual desire? The paper doesn’t say. Furthermore, the researchers did not survey the partners to find out how they were doing. Nothing is said about sexual interests or bother for the partners of the men who had been on ADT.

The paper also reports on another EPIC QoL domain that collected data on whether the patients have experienced in the last four weeks hot flashes, loss of body hair, depression, a lack of energy, and any change in body weight. The results showed major changes in most of these variables at the six-month mark, but less so at the year mark.

Often hot flashes simply diminish overtime, loss of body hair typically occurs within six months and doesn’t change after that. Changes in body weight may be substantial in the first six months, but patients may be taking action to stabilize that so they’re no longer experiencing changes in their weight after months to a few years go by. Once again, one cannot tell whether these QoL features have returned to baseline or stabilized overtime.

This study involved approximately 400 patients. It is not clear though what to make of the authors statement that “PRO differences were relatively short-lived, with no clinically meaningful differences between patients getting ADT or not with RT, by one year after initiating treatment.” That could easily be interpreted to mean that ADT effects are transient and disappear after one year. The paper concludes by saying that instruments like the EPIC “provide added value to help individuals make fully informed decisions among the treatment options.”

When patients are offered ADT, they might like to know what changes might occur that can be easily reversed, and which ones are more permanent. As sexual function impacts both the partner and the patient, to help them make “fully informed decisions among treatment options,” they should both be informed about the changes they’re going to experience that may be difficult to reverse upon completion of short-term ADT. This can include the health and stability of their intimate partnership.

Reference:

Movsas, B., Rodgers, J., Elshaikh, M., Martinez, A., Morton, G. , Krauss, D., Yan, D., Citrin, D., Hershatter, B., Michalski, J., Ellis, R., Kavadi, V., Gore, E., Gustafson, G., Schulz, C., Velker, V., Olson, A., Cury, F., Papagikos, M., Karrison, T., Sandler, H., and Bruner, D. (2023). Dose-Escalated Radiation Alone or in Combination With Short-Term Total Androgen Suppression for Intermediate-Risk Prostate Cancer: Patient-Reported Outcomes From NRG/Radiation Therapy Oncology Group 0815 Randomized Trial. Journal of clinical oncology: official journal of the American Society of Clinical Oncology, 41(17), 3217–3224. https://doi.org/10.1200/JCO.22.02389