Trial Affirms Benefit of Adjuvant RT for T3 Prostate Ca

DENVER, Colorado-In patients who undergo prostatectomy for stage T3 prostate cancer, adjuvant radiation therapy improves biochemical and clinical disease-free survival and eliminates or delays the need for salvage hormonal therapy, according to a phase III randomized trial presented at the 47th Annual Meeting of the American Society for Therapeutic Radiology and Oncology (abstract 1).

"In the mid-1980s, it was recognized that men with adverse findings at surgery had a high risk of local recurrence. It was also recognized, at least by radiation oncologists, that radiation can improve that local control," said Gregory P. Swanson, MD, associate professor of radiation oncology, The University of Texas Health Science Center at San Antonio. "The long-term benefit was uncertain. In fact, some said that radiation was not likely to help because the systemic risk is so high."

Men were eligible for the trial (SWOG 8794) if they had clinical stage A or B disease and pathologic stage C disease (T3N0M0) with at least one of three high-risk features-extracapsular extension, positive margins, and seminal vesicle involvement. Patients were stratified by these features and by receipt of neoadjuvant hormonal therapy. Within 16 weeks of prostatectomy, they were assigned to immediate radiation therapy with 60 to 64 Gy to the prostate fossa or to observation alone. Prostate-specific antigen (PSA) levels were measured to assess biochemical relapse, defined as a value of 0.4 ng/mL or greater.

Analyses were based on 425 patients with a median duration of follow-up of 10 years. About two-thirds of the patients were white, and about one-fifth were black, Dr. Swanson said. Their median age was 65 years. The majority (68%) had extracapsular extension with or without positive margins, while a minority had seminal vesicle involvement alone (10%) or both features (20%). The Gleason score was 6 in about 50% of patients, 7 in 35%, and 8 to 10 in 15%. Before surgery, about half of the patients had a PSA level greater than 10 ng/mL, and before radiation therapy, about half had a detectable PSA level.

In Kaplan-Meier analyses, metastasis-free survival (the trial's primary endpoint) did not differ between the radiation therapy and observation groups at 5 years (86% vs 84%) or at 10 years (71% vs 63%), although the time to metastatic failure was about a year longer with radiation. However, biochemical relapse-free survival was significantly better in the radiation therapy group than in the observation group at 5 years (71% vs 44%) and at 10 years (52% vs 26%); the median time to biochemical failure was 10.3 years with radiation and 3.1 years with observation. Similarly, clinical relapse-free survival differed significantly in favor of radiation therapy at 5 years (84% vs 69%) and 10 years (68% vs 49%), with median times to clinical failure by group of 13.8 and 10 years.

Overall survival was statistically indistinguishable between groups, although patients lived roughly a year longer with radiation.

Follow-up is limited for assessment of salvage hormonal therapy, Dr. Swanson acknowledged, but at 5 years, a significantly smaller proportion of patients in the radiation therapy group than in the observation group had received this therapy (9% vs 20%). In addition, one- third of patients in the observation group eventually received radiation therapy for their disease.

Patterns of Failure

Patterns of failure provided some of the trial's most informative results, Dr. Swanson commented. "We have been told for a long time that the primary route of failure in these high-risk patients is going to be systemic," he said. "These data clearly show this is not the case." Specifically, in most patients in the observation group who experienced a failure, it was a local one, and radiation therapy reduced this type of failure. Of note, he added, the dose of radiation used in the trial was lower than doses used today, suggesting that contemporary doses may yield an even greater benefit.

Not unexpectedly, Dr. Swanson said, at 6 weeks of follow-up, patients in the radiation therapy group (who were in the midst of that therapy) had higher incidences of urinary and bowel problems, and poorer overall quality of life relative to their counterparts in the observation group. At 2 years, rates of urinary and bowel symptoms still differed between groups, but quality of life no longer did. And by 5 years, there were no significant differences.

Rates of complications were generally low, Dr. Swanson noted, but patients in the radiation therapy group experienced somewhat higher rates of stricture, incontinence, and proctitis.

Summing up the study findings, Dr. Swanson said, "This is the first and only adjuvant treatment proven in this group of patients with this degree of improvement; therefore, adjuvant radiation is the confirmed standard."
Trials in prostate cancer, he asserted, should now include an adjuvant radiation therapy group.

"Patients have the right to be informed of the radiation findings before participating in any protocol of any other, unproven therapy, and we as patient advocates need to make sure that happens," he concluded.