Brachytherapy Sows Seeds of Prostate Cancer Survival

NEW YORK, Feb.1 -- Brachytherapy, done properly, can produce long-term disease-free survival in men with early-stage prostate cancer, investigators in an 11-center study reported.

Among more than 2,600 men who received permanent brachytherapy implants for stage T1 or T2 disease, 93% of those who received doses of at least 130 Gray to more than 90% of the prostate had an eight-year PSA-relapse-free survival, reported Michael J. Zelefsky, M.D., of Memorial Sloan-Kettering Cancer Center, and colleagues.

This success rate compared with 76% of men who received lower doses, Dr. Zelefsky and colleagues reported in the Feb. 1 issue of the International Journal for Radiation Oncology Biology Physics.

The quality of the initial implantation of radioactive seeds was the only controllable factor determining survival, the investigators wrote.

"This study is exciting because it shows that brachytherapy alone without additional surgery, radiation or drugs can be effective at curing early-stage prostate cancer," said Dr. Zelefsky and colleagues. "These results also confirm other findings that the quality of the seed implant is a critical ingredient for achieving a better outcome."

The investigators evaluated long-term outcomes, measured by prostate-specific antigen (PSA) values, in 2,693 men treated in one of 11 centers with permanent interstitial brachytherapy monotherapy for T1-T2 disease.

In all, 1,831 men (68%) were treated with iodine-125, at a median dose of 144 Gy, and 862 (32%) were treated with palladium-103, at a median dose of 130 Gy.

Men were included in the study if they had available pre-brachytherapy PSA readings, brachytherapy performed more than five years prior to data submission, had the implant procedure in the period from 1988 to 1998, and did not receive androgen deprivation therapy prior to PSA failure.

PSA relapse was defined as three successive PSA rises after a post-treatment nadir according to American Society for Therapeutic Radiology and Oncology (ASTRO) criteria, or as an absolute PSA nadir plus 2 ng/mL dated at the event.

Median follow-up was for slightly more than five years (63 months), with longest follow-up to 15 years.

They authors found that in those who had received an I-125 dose to 90% of the prostate (D90) that was greater than 130 Gy, the eight-year PSA relapse-free survival according to the ASTRO criteria was 93%. In contrast, eight-year PSA relapse-free survival among those men with D90 dose levels < 130 Gy was 76% (P < 0.001). They saw similar differences in relapse-free survival when the alternative definition of PSA relapse (nadir plus 2) was applied.

Among patients who received Pd-103-emitting implants, the five-year PSA relapse-free survival (ASTRO criteria) was 92% for those who received D90 doses of 115 Gy or more, compared with 83% for those who received doses less than 115 Gy (P=0.01). There were no significant differences between Pd-103 doses when the alternative criteria were applied, however.

In multivariate analysis, the authors identified several pre-treatment and treatment variables that were significantly associated with PSA relapse-free survival, including tumor stage (P=0.002), Gleason score (P<0.001), pre-treatment PSA level (P<0.001), treatment year (P=0.001), and the isotope used (P=0.004).

When post-implantation dosimetry was taken into account, however, the isotope used was no longer an independent predictor of relapse-free survival, they authors noted.

"We also found that the PSA nadir level was predictive of long-term biochemical outcome, which corroborated previous findings of combined implantation with external radiotherapy," the investigators wrote. "A substantial number of patients achieved low PSA nadir levels after permanent interstitial implantation, and among patients who were free of biochemical relapse at eight years, the median nadir level was 0.1 ng/mL."

Because the PSA nadir is time-dependent, the authors used a landmark analysis method, and found that that lower nadir values at three years after brachytherapy were associated with improved long-term biochemical outcomes.

The authors cautioned that their data should not be used for indirect comparison of results with other brachytherapy, external radiotherapy, or prostatectomy studies.

"Many technical, dose prescription, and target volume delineation differences existed between, and likely within, the participating institutions during this decade-long experience," they noted. "Indeed, approaches changed during the time span during which the implants were performed, as new information came to light. Postimplantation dosimetric information was not routinely available in a significant number of these patients, and central review was not performed to reduce inconsistencies."

With those caveats in mind, however, they pointed to their results as support for better quality control measures for brachytherapy, especially when it comes to assessing post-implantation dosimetry.

"In the present study, a suboptimal D90 dose conferred an approximate 2.5-fold increase for biochemical relapse to the patient. Supplemental radiation may be warranted if a suboptimal dose was delivered to the prostate, based on post-implantation dosimetric data," they wrote.