Intermittent Hormonal Therapy Proves to be Viable in Prostate Cancer

Laura Panjwani

With no significant difference between intermittent and continuous androgen-deprivation therapy, patients with prostate cancer may experience an improvement in their quality of life with the former.

Androgen-deprivation therapy may be an effective treatment in prostate cancer, though its side effects may result in a loss of quality of life for patients. 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.

"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," said Leonard G. Gomella, MD, in an interview with Targeted Oncology.

"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."

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

Despite these advancements, Gomella, 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, says updated data from both CHAARTED and STAMPEDE may negatively impact intermittent hormonal therapy.

"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," he said.

"That is now going to become the standard of care for patients with metastatic disease. We may need to investigate that."

Gomella stressed the success or failure of a patient undergoing intermittent hormonal therapy is reliant on the proper stratification, adding that if a does not achieve a low PSA after 7 or 8 months of hormonal therapy, medical professionals should revert to continuous hormonal therapy.

"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," he said. "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."

With the potential downsides to intermittent hormonal therapy, as well as the need to monitor patients to make sure they benefit from this treatment, Gomella says the risk are fairly low and most major organizations treating patients with prostate cancer endorse the treatment strategy as an option.

"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," he said.

"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."