Once men with metastatic hormone-sensitive prostate cancer start androgen deprivation therapy (ADT) and an androgen receptor pathway inhibitor (ARPI), the conventional thinking is that they stay on them indefinitely. 

But treatment comes at the cost of considerable side effects, including fatigue, hot flashes, sexual problems, weight gain, and others. Their use has also been associated with increased risks for cardiovascular disease, osteoporosis, and depression.

Giving men a break from ADT plus ARPI could improve their quality of life, and the results of the phase 2 A-DREAM study, which were reported at the American Society of Clinical Oncology (ASCO) 2026, suggest it can be safe to do so.

“Men often lose motivation and vitality on the drugs and feel weak” due to the testosterone suppression. “There’s a fair likelihood that there will be some improvement” with a treatment break, said lead investigator Atish Choudhury, MD, a genitourinary medical oncologist at the Dana-Farber Cancer Institute in Boston.

Choudhury explained what was done in the A-DREAM study and shared his experience with metastatic prostate cancer drug holidays in an interview with Medscape Medical News. His comments, where were edited for clarity, are presented in a question-and-answer format below.

What Did A-DREAM Find?

The 78 men in A-DREAM had a mix of oligometastatic and more extensive metastases on conventional imaging.

They had been on ADT — most often luteinizing hormone-releasing hormone agonists — for 18-24 months and an ARPI for at least a year. Their prostate-specific antigens (PSAs) were less than 0.2 ng/mL, and their testosterone levels were less than 50 ng/dL.

After treatment was stopped, patients were followed with PSA and testosterone levels every 3 months plus CT/MRI and bone scans at least every 6 months. Treatment was restarted if PSAs climbed back to ≥ 5 ng/mL, there was radiographic progression, or patients became symptomatic.

Eighteen months after treatment interruption, 41% of men (32/78) remained off treatment with normal testosterone levels of ≥ 150 ng/dL. At a median follow-up of 26.9 months, 38.5% were eugonadal and off treatment.

There was one prostate cancer death.

How Does Dana-Farber Handle Drug Holidays?

Treatment breaks for hormone-sensitive metastatic prostate cancer are already a common practice at Dana-Farber. When men learn they are eligible, most are eager to give it a try.

Although A-DREAM included a PSA cut point of 5 ng/mL to restart treatment, our usual triggers are new or changing metastases on prostate-specific membrane antigen-PET imaging.

A drug holiday is already a part of oligometastatic disease treatment. Surgery or, more often, radiation are used to ablate metastases, then men go onto ADT plus an ARPI, which is stopped at 2 years. We’ve followed some of these patients out 4, 5, even 7 years, and they haven’t had to resume treatment even though their testosterone recovered.

It’s not an uncommon way to treat oligometastatic disease in academic centers. My preference is that the primary tumor is treated beforehand to delay the onset of castration-resistant disease.

For men with more extensive metastases, if the primary has been treated, PSA is undetectable, and imaging shows no active disease, I do consider treatment breaks even if we didn’t treat the metastatic sites.

Is it Safe to Let Testosterone Recover?

Testosterone stimulates cancer regrowth, and there were men in A-DREAM who needed to resume treatment quickly after their testosterone normalized.

For patients to feel better, however, testosterone must be allowed to recover. By monitoring men closely and restarting treatment early, the thinking is that tumors can be brought back under control.

Restarting ADT plus ARPI worked for m ost men in A-DREAM. Of the 29 who had to restart treatment, only four no longer responded and needed other therapies. That’s not too different from what we would expect for patients in the metastatic setting over that period of time. Patients do eventually become resistant to ADT and ARPIs.

Men with high-volume disease at baseline were more likely to have to resume treatment, whereas men whose metastases were radiated were less likely.

Lessons From A-DREAM

The one prostate cancer death in the study was in a man who had lung and bone metastases. His PSA rose even before his testosterone recovered. Reinitiating treatment didn’t bring his cancer back under control.

So if you have a patient who is widely metastatic, even with a PSA less than 0.2 ng/mL, you want to have additional parameters. Perhaps PSA should be completely undetectable, and treatment should be restarted if PSA rises before testosterone recovers.

A remaining concern is that drug holidays could accelerate ADT/ARPI resistance. That didn’t seem to happen in A-DREAM, but the study didn’t answer the question definitively.

A large phase 3 European trial — De-Escalate — should provide clarity and perhaps more confidence that treatment breaks don’t compromise overall survival.

The National Cancer Institute and Veracyte funded the A-DREAM study. Among other industry ties, Choudhury reported receiving honoraria, consulting fees, research funding, and/or travel reimbursements from Astellas, Pfizer, Janssen, and Bayer, makers of ARPIs and other prostate cancer therapies.

M. Alexander Otto is a physician assistant and award-wining journalist. He is also an MIT science journalism fellow. Email: aotto@medscape.net.