Studies: High-intensity focused ultrasound yields strong 5-year PSA-free survival

September 1, 2009

Two of several studies presented by the same international team suggest that high-intensity focused ultrasound provides good biochemical-free survival at 5 years in patients treated in the absence of hormone therapy.

Chicago-Two of several studies presented at the AUA annual meeting by the same international team suggest that high-intensity focused ultrasound (HIFU) provides good biochemical-free survival (BFS) at 5 years in pa-tients treated in the absence of hormone therapy. Data from the study also indicate that criteria unique to the technology are more reliable for predicting outcomes than criteria established for other procedures, such as radiation therapy.

Study co-author John F. Ward, MD, assistant professor of urology at the M.D. Anderson Cancer Center, Houston, said that the two studies were conducted to establish criteria that would allow accurate evaluation of HIFU outcomes. The technology is not approved in the United States, but its use is growing in Canada, the United Kingdom, and several countries in Europe and Asia.

The first of the two studies looked at men treated for prostate cancer using HIFU, but without previous hormone therapy.

The researchers used data from the Ablatherm Treatment Registry (also known as the "@-Registry") to identify 468 patients who met the study's inclusion criteria: localized disease (T1-2), no interventions for prostate cancer other than HIFU, and treatment with curative intent with a minimum of 2-year follow-up. The patients were stratified according to D'Amico risk categories.

The median pre-treatment PSA was 6.9 ± 25.8 months. The median PSA nadir following treatment was 0.1 ng/mL and was reached 16 ± 12.3 weeks following the procedure.

88% achieve BFS at 5 years

The BFS rates for the patients were evaluated according to two risk measures. The first was the Phoenix definition of biochemical failure (nadir + 2.0 ng/mL PSA rise). The second was the Stuttgart definition of biochemical failure (nadir +1.2 ng/mL PSA rise). This latter definition was designed specifically to evaluate patients receiving HIFU.

Under the Phoenix definition, 86% of the low-risk and 88% of moderate-risk patients achieved BFS at 5 years. Under the Stuttgart definition, 79% of the low-risk and 71% of moderate-risk patients achieved BFS at 5 years. There were too few high-risk patients to allow for reliable evaluation.

"HIFU appears to have intermediate outcomes comparable to other treatment modalities for low- and moderate-risk patients, but this will have to be studied at a longer follow-up," said Dr. Ward. He added that PSA measures should not be the sole factors for determining interventions such as salvage therapy; PSA kinetics, biopsy results, co-morbidities, age, and clinical experience should be considered as well.

Stuttgart definition found predictive

The Stuttgart definition of biochemical failure was evaluated in the second study. Researchers evaluated 285 patients from the @-Registry who had HIFU, received at least 2 years of follow-up, and had at least four PSA measurements. Clinical failure was defined as a positive post-treatment biopsy, initiation of a secondary prostate cancer treatment, evidence of metastases, or death from the cancer.

Outcomes were plotted against the predictive values of the American Society for Therapeutic Radiology and Oncology (ASTRO) and Phoenix definitions of failure and were compared to a range of definitions unique to HIFU. One of these was the Stuttgart definition, which was found to have a sensitivity of 77.5%, a specificity of 79%, a positive predictive value (PPV) of 55%, and a negative predictive value (NPV) of 91.5%.

These findings were compared to the ASTRO definition, which had a sensitivity of 51%, a specificity of 78%, a PPV of 31%, and an NPV of 88%, as well as the Phoenix, which had a sensitivity of 60%, a specificity of 78%, a PPV of 36%, and an NPV of 92%.

The researchers concluded that clinically significant recurrence of prostate cancer following HIFU is best predicted by the Stuttgart definition.

"This is an important step forward. Early studies have been criticized because HIFU and cryoablation outcomes were reported with definitions created for other treatment modalities, namely, radiation. We can now compare apples to apples. We no longer need to measure HIFU outcomes with definitions used for radiation patients," said Dr. Ward, who served as first author for this study. Further research is needed to validate the Stuttgart definition values.

Dr. Ward declined to estimate if or when HIFU might be approved in the U.S. He did note that the FDA was requiring HIFU outcomes be compared to cryoablation outcomes, and Dr. Ward said that he did not know of any other instances in which the FDA required an emerging prostate cancer therapy to be compared to an accepted treatment modality.

Dr. Ward indicates that he conducts scientific trials for EDAP TMS.