Long-Term Postsurgical ADT May Reduce Prostate Cancer Metastasis Risk

Patients who received ADT for two years were less likely to develop metastatic disease, an expert told CURE®.

The addition of two years of androgen deprivation therapy (ADT) improved metastasis-free survival of patients with prostate cancer who received radiotherapy after surgery when compared with patients who underwent six additional months of ADT, research has shown.

“For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy,” researchers for the RADICALS-HD trial wrote in The Lancet.

As defined by the National Cancer Institute, ADT is treatment intended to suppress or block the production of or action of male hormones.

The trial enrolled 1,523 patients, with a median age of 65, between Jan. 30, 2008 and July 7, 2015 from 138 cancer centers in Canada, Denmark, Ireland and the United Kingdom. Patients had undergone radical prostatectomy (surgical removal of the prostate and some nearby tissue and lymph nodes). Patients received short-course (six months) ADT (761 patients) or long-course (24 months) ADT (762 patients) as well as postsurgical radiotherapy.

At a median follow-up of 8.9 years, researchers reported 313 metastasis-free survival events — 174 in the short-course ADT cohort and 139 in the long-course ADT cohort — with 10-year metastasis-free survival rates of 71.9% and 78.1%, respectively. Grade 3 (severe) or higher toxicity occurred in 14% and 19% of patients, respectively, and there were no treatment-related deaths, researchers stated.

RADICALS-HD chief investigator professor Chris Parker, consultant clinical oncologist at The Royal Marsden NHS Foundation Trust and professor of prostate oncology at The Institute of Cancer Research in London, spoke with CURE® via email about the role of ADT in prostate cancer treatment, the findings of the study and more.

CURE®: For patients with prostate cancer, what do you hope is the big takeaway from these findings?

Parker: Whether or not to add hormone therapy [ADT] to post-operative radiotherapy for prostate cancer has been controversial. RADICALS-HD is the first trial to compare long-term versus short term hormone therapy in men receiving post-operative radiotherapy. The trial found that, for patients with a high risk of their cancer reoccurring, long-term ADT reduced the risk of metastatic disease compared with short-term ADT. It also found that for those with a lower risk of their cancer returning, that the addition of hormone therapy had little benefit compared to radiotherapy alone. The main takeaway is that treatment for cancer should be tailored to the individual case, and that this research better informs clinicians and patients to make decisions around individual care.

Given these findings, what conversations should patients be having with their care teams regarding their duration of postoperative ADT with radiotherapy?

The adverse effects of ADT are well-known. Patients and clinicians now have information on the potential benefits of ADT in this setting so that they can weigh up whether to use ADT and, if so, for how long.

Was there anything about these findings that you found surprising? If so, what and why?

Men taking part in the trial were less likely to develop metastatic disease than we had predicted. The outcome for men receiving post-operative radiotherapy alone, without ADT, was good. Thus, there is limited scope for improvement with the addition of ADT.

What do these findings mean as far as treatment options available for patients who are unable to receive long-course ADT due to the side effect burden?

They can be reassured that the benefit of long-term versus short-term ADT is relatively modest.

What is the basic science behind ADT treatment, and how does it function in the treatment of prostate cancer?

ADT lowers testosterone levels and has been known to be an active treatment for prostate cancer for many decades. It may be particularly effective when used in combination with radiotherapy.

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