Leonard G. Gomella, MD, discusses intermittent hormonal therapy for patients with prostate cancer as well as its benefits and challenges.
Leonard G. Gomella, MD
Androgen-deprivation therapy, while an effective treatment for prostate cancer, can result in side effects and a reduced quality of life. Allowing low-risk patients to take breaks between treatments—a practice known as intermittent hormonal therapy, or a “hormone holiday”—may combat these challenges without impacting survival.
A recent systematic review and meta-analysis conducted by JAMA Oncology found no significant difference between intermittent and continuous therapy for overall survival (HR, 1.02; 95% CI, 0.93-1.11; 8 trials, 5352 patients), cancer-specific survival (HR, 1.02; 95% CI, 0.87-1.19; 5 trials, 3613 patients), and progression-free survival (HR, 0.94; 95% CI, 0.84-1.05; 4 trials, 1774 patients).
The review was based on 15 trials with 6856 patients who also reported a minimal difference in quality of life between interventions and an improvement in physical and sexual functioning with intermittent therapy.1
To learn more about intermittent hormonal therapy and its benefits and challenges, OncLive spoke with Leonard G. Gomella, MD, who presented on the topic at the 26th International Prostate Cancer Update, which took place from January 20 to 23, 2016, in Denver, Colorado.
Gomella is the the Bernard W. Godwin, Jr. Professor of Prostate Cancer and chairman of the Department of Urology at Jefferson Medical College, senior director for Clinical Affairs of Jefferson Kimmel Cancer Center, and president of the Society for Urologic Oncology.Gomella: Intermittent hormonal therapy has been growing in popularity over the years. Patients who receive hormone therapy often have side effects, and giving them so-called “hormone holidays” may improve quality of life. Over the years, there has really been a lot of trials and experimental work that laid the groundwork for this going back 20 years.
Very recently, several big clinical trials have basically shown that, in general, patients who receive intermittent hormonal therapy have the same cancer-specific and overall survival as patients who receive continuous hormonal therapy. Patients can take a “hormone holiday” and perhaps improve their quality of life and, along the way, also save some money.
In addition, there has also always been a theoretical idea that intermittent hormonal therapy could potentially delay the development of castration-resistant prostate cancer.It encourages the prostate cancer to have more dependence on hormonal manipulation. When the testosterone levels are high, it encourages the development and growth of cells, which are androgen-dependent. When the hormone levels are low, it encourages the growth of cells that are androgen-independent.
By theoretically encouraging more cells to be androgen-dependent, you tend to keep them more dependent on the hormones and potentially delay the development of androgen or castration resistance. This has been effectively shown in animal models and in cell cultures, but it remains theoretical in patient use.The one thing that may have negatively impacted intermittent hormonal therapy is the updated CHAARTED and STAMPEDE data. People are now coming in with metastatic disease and receiving both chemotherapy and hormonal therapy.
The use of intermittent hormonal therapy for these patients, who are now getting hormonal therapy and chemotherapy at the presentation of metastatic prostate cancer, may actually start to go down because we don’t yet have any data at this point combining intermittent hormonal therapy with chemotherapy. That is now going to become the standard of care for patients with metastatic disease. We may need to investigate that.
I believe it will become a standard of care for people to use intermittent hormonal therapy after chemotherapy. However, we don’t know if that is going to be better or the same.The success of intermittent hormonal therapy is based on proper patient stratification. For example, if you have a patient who you are going to start hormonal therapy on who has advanced prostate cancer or recurrent cancer following local radiation or local radiation plus surgery, you put them on hormonal therapy.
After 7 or 8 months, check their PSA. If their PSA has come down to less than 4, hormonal therapy can be stopped. The patient is then followed every 3 months. When their PSA starts to increase again—especially if it goes up to 10 or 20 depending on each individual oncologist’s threshold—then you restart them on hormonal therapy.
The most important thing is patient stratification. If a patient does not get a very low PSA after 7 or 8 months of hormonal therapy, you should probably not do intermittent hormonal therapy. They should stay on continuous hormonal therapy.Basically, all of the major organizations now endorse this. The risk is really minimal. The upside is probably greater than the downside.
If you stratify patients properly, it is safe. The patients who do the best have very low PSA levels after you put them on hormone therapy. If a patient does not have a low PSA following therapy, they should not go on intermittent hormonal therapy.
One analysis showed if you have patients with really aggressive cancer, like those who have a high Gleason score, you probably should leave them on continuous hormonal therapy. There is a small risk that you might compromise a patient’s survival if you don’t follow the stratification and correctly identify those who are going to be the best responders but, overall, it is not considered to be that hazardous.One thing an oncologist should do is try to identify metastatic disease early. That is where imaging may come into play. We have a tendency to image people less often in urology, even though medical oncologists are aggressive about imaging patients. The take-home message is that we should try to image patients more often to identify early metastatic disease, and start them on treatment at the earliest time of metastasis.
Magnan S, Zarychanski R, Pilote L, et al. Intermittent vs continuous androgen deprivation therapy for prostate cancer: a systematic review and meta-analysis. JAMA. 2015;1(9):1261-1269.