I offer intermittent therapy to men who have a reasonably long doubling time. For a patient with a less than 3-month PSADT, it’s difficult to administer intermittent therapy. They don’t enjoy as long of a break. But for men with a PSADT of more than 3 months, I’ll consider a break and see how that break goes, and future treatment decisions will be made depending on that first break.

In the metastatic setting, the only men to whom I would offer intermittent therapy are those with minimal disease who’ve had an excellent response to hormonal therapy and who have side effects from hormonal therapy from which they would like to take a break. I would have a discussion with the patients informing them that intermittent therapy may not be as effective as continuous therapy.

If I were to initiate ADT for a patient with PSA-only relapse, I would generally use continuous administration.

I use intermittent hormonal therapy for patients with PSA-only recurrence probably less than 25% of the time. I would not use intermittent hormonal therapy for patients with metastatic prostate cancer.

If I were to initiate ADT for a patient with PSA-only relapse, I would generally use continuous administration. I will use continuous administration for pretty much all patients with PSA-only disease in the relapsed setting. Intermittent administration is still something that is not standard in northern Europe.

For a patient with hormone-naïve metastatic disease, I would use continuous therapy if I were going to treat with ADT.

Knowing that the data are unclear, for almost all these patients we use intermittent therapy because we do not have convincing data that, for PSA-only recurrence, intermittent therapy is harmful in any way. It may give patients the benefit of hormone holidays and make them feel psychologically better. So, for almost all the patients, we use intermittent therapy and certainly monitor their testosterone levels.

We tend to use intermittent therapy in a lot of patients with hormone-naïve metastatic prostate cancer, knowing that this is extraordinarily controversial, despite all our recent studies. I don’t believe we have definitive data indicating that for patients with PSA-only recurrence it’s a problem to administer intermittent ADT.

The most important factor that I take into consideration is the PSADT. However, if patients want treatment regardless of what the doubling time is — and many do — then I’ll go ahead and offer them treatment. I would administer intermittent therapy.

There are all kinds of guidelines in this setting, but the problem is that there’s no Level 1, evidence-based data to tell us what to do. The reason people go with PSADTs is that natural history data show what happens to those patients who do or don’t receive hormonal therapy when the PSADT is rapid. I don’t necessarily look at the Gleason score.

I don’t believe we have a good long-term prospective study that’s evaluated whether immediate treatment is better than delayed treatment in this setting. A few patients don’t want to do anything because of the side effects. The preponderance of patients prefer to have their PSA levels under control.

In my practice, I use intermittent hormonal therapy almost 100% of the time. If I have the occasional one in 500 patients who does not want to cycle off therapy at the end of 9 months, I usually treat.

In terms of patients with metastatic prostate cancer, I use intermittent hormonal therapy under the circumstances that the patient has a good prognosis, based on whatever the patient’s PSA level is at 7 months of therapy. This is based on the SWOG data. So if the patient falls under the good-risk group, has significant symptoms due to hormone therapy and understands that some data suggest that intermittent therapy might not be as good as continuous therapy, I will still offer that patient intermittent therapy for quality-of-life reasons. I would do this probably about 60% to 80% of the time.

When I initiate ADT for a patient with PSA-only relapse, I generally use intermittent administration. I would say that I use intermittent administration 90% of the time. I do not use it all the time.

In the setting of metastatic prostate cancer, I would consider intermittent therapy for a patient with a profound response, if his PSA went to a low level and stayed there for a couple of years. In this situation, I would consider intermittent therapy.

There’s no evidence that starting treatment immediately is beneficial. Generally, I recommend treatment immediately for a patient with a PSADT of less than 3 months because those patients will soon have a positive scan, which would be the next trigger for treatment. So it’s always a discussion with the patient and what his tolerance level is. But if a patient asks what I would do, if the doubling time were 3 months or less I would start treatment.

I’m not a big fan of intermittent therapy. This is our institutional philosophy after a lot of discussion with all the practitioners involved in treatment and the medical oncologists. Patients who are potential candidates for intermittent therapy are also potential candidates for observation alone. So generally I recommend observation. The rare patient who goes on intermittent therapy would be the one who insists that he can’t tolerate the PSA anxiety and then wants to receive treatment. But generally I do not offer intermittent therapy for patients with PSA-only relapse and for patients with metastatic disease.

If I’m going to “pull the trigger” for a patient with PSA-only relapse who has disease with a PSADT of less than 3 months, I’m probably going to administer continuous hormonal therapy.

If the PSADT is 6 or 12 months and they want to start therapy, then in that scenario I would use intermittent administration.

I would use intermittent administration in pretty much everybody. For a patient with metastatic prostate cancer, I rarely use intermittent therapy. Tolerability is an issue. However, in this situation I believe the SWOG-9346 data, which show a 7-month advantage to continuous therapy.

I believe the controversy regarding the use of intermittent versus continuous ADT is because of the results of the Laurence Klotz study, which included patients with PSA-only disease. However, the problem with the Klotz data is that doubling times were not used to select patients. So the question is whether some of these patients should have received hormonal therapy in the first place. The paradox about the Klotz data is the issue about attaining nadir testosterone on continuous blockade, which was recently published in a 2015 issue of the Journal of Clinical Oncology. Those patients on continuous blockade therapy who attain a nadir testosterone of ≤0.7 nmol/L are the ones who are going to fare better. They have a longer time to castration resistance, and they have a better outcome. There is some contradiction in the findings of the study, but I believe it shows us that we need to understand more about the biology of the disease.

Based on the Klotz results and Hussain’s data, for a patient with rising PSA-only disease I will offer intermittent androgen blockade because I believe that the survival is similar for both, but there may be a quality-of-life benefit.

For patients with metastatic disease, unless they are having debilitating symptoms I rarely, if ever, offer intermittent blockade because the intermediate-risk group from Maha Hussain’s analysis basically showed that those patients don’t fare as well on intermittent therapy. So there’s a rationale for it.

In terms of using intermittent therapy, I go by what the SWOG protocol did, which is 7 months on and then stop. My restart points are a little nebulous. For a patient with a PSA level of 5-10 ng/mL or a rapid PSADT, I’ll restart therapy.

If I initiate ADT for a patient with PSA-only relapse, I generally use intermittent administration. For a patient with metastatic prostate cancer, I use intermittent hormonal therapy 10% of the time.

The important factors I consider include the patient’s age, anxiety level, performance status and comorbidities. For instance, ADT makes diabetes more difficult to control. So the presence or absence of diabetes fits into the equation a little. However, my treatment decision is mostly based on the patient’s preference. I find it difficult to be dogmatic when the data we have don’t allow me to do so.

If somebody is pushing to be treated, I am fine with that and I would administer intermittent therapy. I use the intermittent approach typically with 6 months of therapy. Then I’ll see how the patients respond. If they have relatively benign disease and they have a great response, I may not treat again for 2 or 3 years.

I would use intermittent administration when I initiate ADT for a patient with PSA-only relapse. I use intermittent administration therapy for patients with PSA-only recurrence at least 80% of the time.

I tend to use continuous therapy for a patient with metastatic prostate cancer. Occasionally I’ll go to intermittent therapy in some of my elderly patients who are having toxicity issues or other issues that I’m concerned about. So for anybody who has a reasonably strong performance status and longevity of 5 years or more, I’ll use continuous administration unless the patient has a tolerability or toxicity issue. For my elderly patients, my threshold is even lower for instituting intermittent administration in the setting of metastatic disease.