BOSTON (FRONTLINE MEDICAL NEWS) – In a finding hailed as “paradigm changing,” men with favorable intermediate-risk prostate cancer may have good disease control with brachytherapy alone, with fewer late-term toxicities than with brachytherapy combined with external-beam radiation, investigators reported.

After 5 years of follow-up, there were no significant differences in rates of freedom from disease progression among patients assigned to receive combined external-beam radiation (EBRT) and transperineal interstitial permanent brachytherapy (PB) or PB alone in selected patients with intermediate-risk prostatic carcinoma.

There were no differences in acute toxicities between the treatment groups, but patients who underwent combined therapy had significantly more late grade 2 or grade 3 toxicities than those who underwent brachytherapy alone, reported Bradley R. Prestidge, MD, medical director of the Bon Secours Cancer Institute at DePaul Medical Center in Norfolk, Virginia.

“I think you’re underselling your results – I’m pretty excited about these results,” Colleen Lawton, MD, professor and vice chair of radiation oncology at the Medical College of Wisconsin in Milwaukee, told Dr. Prestidge at the annual meeting of the American Society of Radiation Oncology.

The results show that, “for the intermediate-risk group, not the worst of intermediate [risk] but the vast majority, they don’t need the toxicity of that external beam, and they don’t need the cost of it,” she said at a briefing following his presentation of the data in a plenary session.

Dr. Lawton said that, when the NRG Oncology/RTOG 0232 study was initiated (the first patients were enrolled in 2003), “there were factions that believed you could not treat intermediate-risk prostate cancer – which isn’t the best, isn’t the worse, but is somewhere in the middle – with anything but the combination, and this shows that’s not true.”

The trial was designed to test the hypothesis that patients with intermediate-risk prostate cancer treated with combined EBRT and PB would have a 10% improvement in freedom from progression (FFP), compared with men treated with PB alone.

A total of 579 patients with histologically confirmed prostate cancer, stages T1c-2b and Zubrod performance score 0 or 1 were enrolled. The patients also had Gleason score 2-6 and prostate-specific antigen (PSA) from 10 to less than 20 ng/mL; Gleason score and PSA less than 10 ng/mL; or prostate volume less than 60 cc.

In addition, androgen deprivation therapy (ADT) was not allowed on the study, and patients could not have distant metastases or radiographically suspicious nodes at the time of enrollment.

Patients were stratified by stage, Gleason score, PSA and history of ADT, and then randomized to the combined therapy, consisting of 45 Gy in a partial pelvis dose delivered in 1.8 Gy fractions for 5 weeks, followed 2-4 weeks later with brachytherapy using either a radioactive iodine (I-125) source prescribed as a 110-Gy boost dose, or palladium 103 in a 100 Gy boost dose; or brachytherapy alone (145-Gy dose with I-I25, 125-Gy dose with palladium 103). EBRT was delivered by either intensity-modulated radiation (43%) or 3D conformal radiation.

Five years after randomization, there were a total of 66 cases of treatment failure (measured as either biochemical failure according to ASTRO criteria, local progression, distant metastases, or death from any cause), 34 occurring in men treated with the combination, and 32 in men treated with brachytherapy alone. Biochemical failures accounted for 68% of events among patients on the combined modalities and 53% of those on brachytherapy alone. There were 9 deaths in the combined arm and 14 deaths in the brachytherapy-only arm, but none were prostate cancer related, Dr. Prestidge said.

In multivariate analysis adjusted for treatment type, age, race, prior hormonal therapy, Gleason/PSA, and tumor stage, the only significant predictor of FFP was Gleason 7/PSA less than 10 ng/mL, which was associated with better outcomes, compared with Gleason score less than 7/PSA 10-20 ng/mL (odds ratio, 0.5; P = .046).

There was no difference in 5-year overall survival between the groups.

As noted before, there were no significant differences in acute toxicities, but there were significantly more late grade 2 or greater toxicities among patients who underwent EBRT and PB (53% vs. 37%; P less than .0001), and more late grade 3 or greater toxicities (12% vs. 7%; P = .039).

Michael J Zelefsky, MD, professor of radiation oncology and chief of the brachytherapy service at Memorial Sloan Kettering Cancer Center in New York, the invited discussant, said that the study suggests that “combining EBRT with brachytherapy for favorable intermediate-risk disease may constitute unnecessary overkill.”

He asserted, however, that favorable intermediate-risk disease behaves clinically more like low-risk disease, whereas unfavorable intermediate-risk disease is closer to high-risk disease in its clinical behavior.

It is plausible that, for patients with unfavorable intermediate-risk disease, added dose intensification associated with combined modality therapy could result in improved FFP and local tumor control, he said.

The study was funded by the National Cancer Institute. Dr. Prestidge disclosed consulting for Varian, Elekta, and IsoRay. Dr. Zelefsky disclosed receiving honoraria from Bebig Brachytherapy, Augmenix, and as editor-in-chief of Brachytherapy. Dr. Lawton reported no relevant disclosures.