ORLANDO -- Men with node-negative high-risk prostate cancer lived just as long with a 50% shorter duration of androgen deprivation therapy (ADT) compared with standard duration therapy, results of a randomized clinical trial showed.
After a median follow-up of 6.5 years, 76.2% of patients who were treated with pelvic radiotherapy and androgen blockade remained alive after 18 months of ADT versus 77% of the men whose hormonal treatment continued twice as long, reported Abdenour Nabid, MD, of Sherbrooke University Hospital in Quebec.
The treatment groups also did not differ with respect to 5- and 10-year overall and disease-specific survival (DSS), said Nabid during a press briefing prior to the Genitourinary Cancers Symposium.
"In localized high-risk prostate cancer treated with radiotherapy and androgen blockade, androgen blockade duration can be safely reduced from 36 to 18 months." he explained. "Eighteen months of androgen blockade could represent the threshold effect, with no further benefit for our patients. For these patients, side-effect duration and treatment costs of androgen blockade are significantly reduced."
"My hope is that the shorter duration can become the standard," he added.
Noting that physicians will be eager to see the published results, press briefing moderator Bruce Roth, MD, of Washington University in St. Louis, agreed that 18 months of ADT could become a new standard.
The addition of ADT to radiation therapy has been shown to improve survival in men with high-risk prostate cancer. However, the optimal duration of ADT has yet to be determined.
The current standard of 24 to 36 months demonstrated superiority over 6 months of ADT. Treatment duration beyond 6 months, but less than 24 months, had not been compared with standard-duration ADT in a large randomized trial, Roth pointed out.
The issue of ADT duration has both medical and quality-of-life implications. The longer that patients are exposed to ADT, the more likely they are to encounter treatment-related adverse effects, Nabid said. Potential effects of ADT include bone pain, nausea and vomiting, acute renal insufficiency, back pain, mental confusion, bronchopulmonary complications, sweating, fever, cardiac arrhythmias, and swings in blood glucose levels.
Perhaps the most common effects of ADT are a constellation of symptoms and conditions known as "castration syndrome," which includes loss of libido and sexual interest, erectile dysfunction, and impotence, as well as fatigue and weakness, cognitive dysfunction, mood swings, and decreased muscle mass and increased abdominal fat. Decreased physical activity and vitality and osteoporosis may also occur.
Nabid and colleagues conducted a phase III trial to compare 18 months versus 36 months of combined androgen blockade with bicalutamide (50 mg for 1 month) and goserelin (10.8 mg every 3 months). They enrolled 630 patients with newly diagnosed prostate cancer associated with one or more high-risk features: PSA level >20 ng/mL, Gleason score >7, or stage T3-4 disease.
Randomized therapy began 4 months before definitive radiation therapy, continued during radiation therapy and for the specified duration of the treatment group. The primary endpoint was overall survival (OS).
In addition to the lack of statistical difference in OS, the treatment groups did not differ significantly with respect to biochemical failure rate, need for a second course of ADT, pelvic node metastasis, bone metastasis, or cause of death. The most common causes of death were second cancers (7.3%), prostate cancer (4.9%), and cardiovascular disease (4.4%).
The 5-year OS and DSS were 92.1% and 97.6%, respectively, with 36 months of ADT versus 86.8% and 96.4% with short-course ADT. Results at 10 years also did not differ significantly between treatment groups. OS was 63.6% with standard-course ADT and 63.2% with 18 months. DSS was 87.2% in both groups.
By multivariate analysis, only patient age predicted the risk of death.
On the basis of the results, Roth said he would be willing to change his own practice and adopt 18 months of ADT as a standard. The results add to an accumulation of evidence pointing to a higher risk of diabetes and cardiovascular disease with increasing duration of ADT.
"If anything over the last couple of years, the information we have gotten about the long-term consequences of androgen deprivation is more striking than the positive aspects of prolonging therapy," Roth said. "I think probably the most important thing is the chance of getting testosterone back at end of therapy."
"I think you can imagine if you are cured of high-risk prostate cancer and have several decades more to live, but have lowered your testosterone essentially to castrate levels permanently, I think there is a price to pay for that and not something we can answer in a couple of years of follow-up," he said.
Whether ADT duration can be shortened even more remains to be seen, he added.
The Genitourinary Cancers Symposium is co-sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.
The study was supported by AstraZeneca.
Nabid and colleagues, as well as Roth, reported no conflicts of interest.
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