Adding ADT to RT Also Best in Milder Prostate Cancer?

Kate Johnson

April 14, 2014

VIENNA, Austria — The addition of 6 months of androgen deprivation therapy (ADT) to radiation in men with localized prostate cancer, mostly intermediate-risk patients, significantly improves recurrence rates, according to new results from a European Organization for Research and Treatment of Cancer (EORTC) study (EORTC 22991). However, longer follow-up is needed to determine whether the benefits will translate to improved survival.

At present, patients with intermediate-risk prostate cancer are treated with radiotherapy alone, but researchers presenting the new data here at the European Society for Radiotherapy and Oncology (ESTRO) 33 annual conference suggested that this practice needs changing.

"These findings need to be taken into account in daily clinical practice," lead investigator Michel Bolla, MD, professor of radiation oncology at Grenoble University Hospital, France, commented in a statement.

"They show that three-dimensional conformal radiotherapy, whether intensity modulated or not, and regardless of the dose level, has to be combined with short-term androgen deprivation therapy in order to obtain a significant decrease in the risk of relapse," he said.

"The results of this trial are important and practice-changing," said the president of ESTRO, professor Vincenzo Valentini, a radiation oncologist at the Policlinico Universitario A. Gemelli, Rome, Italy, in a written statement. "It is clear that an additional 6 months of hormone treatment in addition to radiotherapy improves the outcome for men with localised prostate cancer. This option should now be considered for all men with prostate cancer that is at risk of growing and spreading."

However, another expert suggested that survival data are needed before clinical practice changes.

"If this does prove to increase prostate cancer–specific survival in the intermediate-risk group specifically, it will be a game changer in the clinic," said Robert Bristow, MD, PhD, a senior scientist at the Ontario Cancer Institute and professor of medical biophysics at the University of Toronto, Ontario, Canada, who acted as discussant for the paper.

"Right now these patients are treated with radiotherapy alone in most North American centers," he told Medscape Medical News. "We will see in time if this combined modality with the addition of 6 months of hormone therapy shows cure for these patients or whether it has just delayed progression."

Adding to ADT to radiotherapy is already standard of care for high-risk prostate cancer, and 10-year results from the Trans-Tasman Radiation Oncology Group (TROG) 96.01 trial show that neoadjuvant ADT cut the prostate cancer–specific mortality rate in half compared with radiation treatment alone (11% vs 22%).

Study Found "Amazing Difference"

The EORTC 22991, conducted across 12 European countries, randomly assigned 819 patients (mean age, 70 years) with localized intermediate- or high-risk cancer to irradiation alone or irradiation plus ADT for the primary endpoint of 5-year biochemical progression-free survival.

Most of the patients (74.8%) were classified as intermediate risk, with the remaining 24.8% classified as high risk.

For irradiation dose, centers opted for 1 of 3 doses: 70 Gy, 74 Gy, or 78 Gy.

ADT was delivered with 2 injections of a luteinizing hormone–releasing hormone analogue: the first on day 1 of radiation and the second 3 months later. To prevent flare, the oral antiandrogen agent bicalutamide (50 mg daily) was started 15 days before the first injection.

There was "an amazing difference" between the groups in 5-year progression-free survival (PFS), said Dr. Bolla, "and this was true whatever the level of radiation dose."

After a mean follow-up of 7.2 years, the 5-year biochemical PFS rate was 82.5% in the ADT group vs 69.3% in the radiotherapy-only group (hazard ratio [HR], 0.53; P < .001). The 5-year clinical PFS rate was 88.7% vs 80.8%, respectively (HR, 0.63; P < .001), and the 5-year locoregional failure rate was 2.1% vs 6.6%, respectively (HR, 0.37; P = .001).

The 5-year distant metastasis rate showed a similar trend (2% vs 6%; HR, 0.57; P = .0053), but "we need more time to assess overall survival (91.5% vs 87.7%; HR, 0.82; P = .22) since there were only 25 deaths due to prostate cancer," he said.

Late grade 3 or 4 gastrointestinal toxicity did not differ between the groups (2% in the radiotherapy-only group and 1.2% in the combination therapy group), but late grade 3 or 4 genitourinary toxicity was increased in the combined therapy group (6.1% vs 3.6%), as was the rate of severely impaired sexual function (27% vs 19.4%).

"While the trial may not be adequately powered for overall survival," noted Dr. Bristow in his discussion, "the early data are encouraging, and the overall toxicity was reasonable."

The increased toxicity of ADT with respect to sexual function "is not surprising. The question is whether some of these patients will be permanently hypogonadal — in other words, castrate for the rest of their life — and will this change in terms of quality of life as time goes on, with respect to not only their overall well-being but also issues pertaining to bone loss as well as metabolic syndrome?"

Additionally, Dr. Bristow pointed out that the trial assessed local control by digital-rectal examination (DRE), and "there can be a bias against the radiotherapy arm when you use the DRE relative to an arm that has had androgen deprivation therapy…It would be nice to have postradiotherapy biopsies because understanding the reason for local failure is important."

The trial was supported by the European Organization for Research and Treatment of Cancer (EORTC), the EORTC Foundation, and AstraZeneca. Dr. Bolla, Dr. Bristow, and Dr. Valentini have disclosed no relevant financial relationships.

European Society for Radiotherapy and Oncology (ESTRO) 33. Abstract OC-0522. Presented April 7, 2014.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.