SAN ANTONIOIncreasing the radiation dose from 70 Gy to 78 Gy favorably affects outcome in some patients with locally confined prostate cancer, according to preliminary results of a randomized dose escalation study reported at the 41st Annual Meeting of the American Society for Therapeutic Radiology and Oncology (ASTRO).
The study showed significantly improved freedom from failure rates and freedom from distant metastases in patients with a PSA greater than 10 ng/mL. Its these patients that drove what appears to be an emerging statistical significance for the entire group. And this is the group that should be targeted for future clinical trials, particularly those who are at intermediate risk, such as those with T1 and T2 disease, said Alan Pollack, MD, PhD, professor of radiation oncology, the University of Texas M.D. Anderson Cancer Center.
The primary endpoint of the trial, started in 1993, was relapse or a rise in PSA, defined as three consecutive rises on follow-up. A secondary endpoint was to determine the rate of biopsy positivity 2 years after treatment for those who remained disease free. Eligible patients had stage T1 to T3 disease. Only two patients had a lymph node dissection and were N0, the rest were NX. The patients had no history of pelvic radiotherapy, radical prostatectomy, or androgen ablation.
Patients were stratified by pretreatment PSA into three groups: PSA less than or equal to 4 ng/mL, PSA between 4.1 and 10 ng/mL, and PSA greater than 10 ng/mL. Mean pretreatment PSA was 9.1 to 9.8 ng/mL (median, 7.5 to 7.8 ng/mL).
The 70 Gy group received treatment using four-field conventional radiotherapy throughout. The 78 Gy dose was delivered using a six-field conformal boost technique. Of 301 evaluable patients, 150 were in the 70 Gy group; 151 in the 78 Gy group. Median follow-up is 40 months.
The overall freedom from failure rate at 5 years was 79% in the 78 Gy group and 69% in the 70 Gy group. With a P value of .057, this is of borderline significance, Dr. Pollack said.
The researchers looked at subgroups, because we felt that this would be important for future trials, in trying to determine which patients would be optimal for dose escalation studies in prostate cancer, Dr. Pollack said.
In a subgroup analysis of T1 and T2 patients, 87% of patients in the higher-dose group were free of failure at 5 years vs 77% in the lower-dose group (P = .1). For patients with Gleason scores less than or equal to 6, freedom from failure at 5 years was 93% in the higher-dose group vs 75% in the lower-dose group, a significant difference. However, there was no significant difference between arms for patients with Gleason scores greater than 6 (about 65% in both arms).
There was no significant difference in freedom from failure based on pretreatment PSA less than 10 ng/mL (about 80% for both groups). The largest difference was in terms of pretreatment PSA greater than 10, said Dr. Pollack. In the higher-dose group, 75% of these patients were free of failure at 5 years vs 48% in the 70 Gy group.
Further analysis showed that patients with intermediate-risk features seemed to benefit the most from dose escalation, in particular, patients with T1 and T2 disease and PSA greater than 10, he said.
In terms of freedom from distant metastases at 5 years, there was no significant difference between the two groups. It was about 97% overall, Dr. Pollack said, but when we looked at the patients with pretreatment PSA greater than 10 ng/mL, we did see the development of statistical significance between the two groups (P = .05), with 98% free of distant metastases in the 78 Gy group vs 87% in the 70 Gy group.
Biopsies were performed on 150 patients who were failure free at 2 years, 79 in the lower-dose group and 71 in the higher-dose group. The biopsies were divided into four groups. Two groups were considered to be biopsy negative: those with no tumor in the specimen and those with atypical or suspicious cells that were not diagnostic of carcinoma. Two groups were considered to be biopsy positive: those who had carcinoma with therapy effect and those with frank carcinoma.
The total rate of biopsy positivity was 31%, with no significant difference between the two arms, Dr. Pollack reported, but when you look at the four categories, you find that there were more patients in the 78 Gy group who had no tumor in the specimen and, also, more who had therapy effect. I think we need longer follow-up and repeat biopsies at longer periods of time to see if any of these patients convert to negative.
Regarding outcome, patients who were biopsy negative had an 87% freedom from failure rate at 5 years vs 64% for those with evidence of carcinoma in the specimen, regardless of whether there was treatment effect.
Dr. Pollack said that even with only 40 months of follow-up, there is a suggestion from these data that the effect on biochemical failure may eventually translate into a stronger effect on freedom from distant metastases.