A report just published on line in The Lancet Oncology provides data from a study of the use of focally directed (as opposed to whole gland) high-intensity focused ultrasound (HIFU) in the treatment of a small series of men with localized prostate cancer between 2007 and 2010. The data are interesting but follow-up to date is short.
According to this article by Ahmed et al., the research team recruited a cohort of 42 men with localized prostate cancer, all of whom met the following eligibility criteria:
- PSA level ≤ 15 ng/ml
- Gleason score ≤ 4 + 3 = 7
- Clinical stage ≤ T2
- No prior treatment for prostate cancer (including no prior androgen deprivation)
- Able to safely undergo multiparametric MRI and receive general anesthesia
All 42 patients agreed to be treated by focal HIFU, directed to all identified prostate cancer lesions (and to a margin of normal tissue) identified on multiparametric MRI, template prostate-mapping biopsies, or both. Additional information about the study design and patient eligibility is available on the ClinicalTrials.gov web site.
The results of this trial are reported as follows:
- The age range of the 42 patients enrolled was from 45 to 80 years.
- A single patient died (from pneumonia, unrelated to his treatment) 3 months after treatment; he was excluded from data analyses.
- The following short-term complications were potentially associated with treatment.
- 1 patient was hospitalized for acute urinary retention post-treatment.
- 1 patient had interventions for stricture that required hospital admission.
- 9/41 patients (22 percent) had mild to moderate, intermittent, self-resolving pain on urination (median duration, 5.0 days).
- 14/41 patients (34 percent) reported urinary debris with a median duration of 14.5 days.
- 7/41 men (17 percent) had an infection of the urinary tract.
- On average (median), International Index of Erectile Function-15 (IIEF-15) overall scores were similar at baseline (prior to treatment) and at 12 months post-treatment (p = 0.60).
- Significant reductions were observed between baseline and 12 months post-treatment for IIEF-15 erectile (p = 0.042) and orgasmic function (p = 0·003).
- 31/35 patients with good baseline function (89 percent) had erections sufficient for penetration 12 months after focal therapy.
- Median UCLA Expanded Prostate Cancer Index Composite (EPIC) urinary incontinence scores were similar at baseline and at 12 months post-treatment (p = 0.045).
- Lower urinary tract symptoms, assessed by International Prostate Symptom Score (IPSS), improved at 12 months post-treatment compared to baseline levels (p = 0·026).
- IPSS quality of life scores showed no difference between baseline and 12 months post-treatment (p = 0.655).
- All 38 men with no baseline urinary incontinence were leak-free and pad-free at 9 months post-treatment.
- All 40 men who were pad-free at baseline were pad-free again at 3 months post-treatment and remained pad-free at 12 months post-treatment.
- No histological evidence of cancer was identified in 30/39 men (77 percent) biopsied at 6 months and 36/39 men (92 percent) were free of clinically significant cancer.
- 4/41 patients (10 percent) required retreatment.
- After retreatment of the above-mentioned 4 patients, 39/41 (95 percent) had no evidence of disease on multiparametric MRI at 12 months.
The authors conclude that, “Focal therapy of individual prostate cancer lesions, whether multifocal or unifocal, leads to a low rate of genitourinary side effects and an encouraging rate of early absence of clinically significant prostate cancer.”
Now let us first state clearly that Ahmed and his colleagues are to be congratulated, once again, on the thoroughness with which they have conducted this study. The degree of detail is impressive and gives a very clear appreciation of the immediate post-treatment and the 12-month follow-up data on outcomes of all types related to this study.
However, there are a number of key points that we would make in our evaluation of this study:
- The follow-up period of just 12 months is very short. There are good reasons to believe that some of these patients may exhibit recurrence with longer follow-up (most particularly among those patients with Gleason 4 + 3 = 7 disease).
- We are not sure that we agree that this study demonstrates that focal HIFU has “a low rate of genitourinary side effects.” Erectile and orgasmic function were clearly seriously affected, and “erections sufficient for penetration” may have been meaningful for the 80-year-old man in this study by significantly less satisfactory if it also applied to the 45-year-old.
- This is a small study in a series of carefully selected and motivated patients. Such patients tend to be prejudiced to see their outcomes in a positive light.
These comments should not be seen as being “critical” of the study. Rather, they are intended to point out issues that the thoughtful reader should take into account when assessing these data.
Additional information about this study is available on the Bloomberg.com web site based on an interview with Dr. Ahmed. Dr. Ahmed is clearly excited by these results, but more study is clearly going to be needed.
The problem we continue to see with the clinical use of HIFU in the USA is that there are still no data that provide us (let alone the US Food & Drug Administration) with a comparison of outcomes after HIFU (let alone focal HIFU) to any other form of recognized first-line treatment (e.g., brachytherapy). Absent such data, it continues to be unlikely that HIFU is going to be an approved form of first-line treatment for localized prostate cancer in the USA any time in the near future.