We finally appear to have mid-term follow-up data from a sizeable series of North American patients with low- and intermediate-risk prostate cancer treated with first-line, high-intensity focused ultrasound (HIFU). The follow-up is limited to a median of 2 years, however, which allows projection of outcomes at 4 years.
Pinthus et al. report data collected prospectively from men at a single Canadian center, all treated with “third-generation” HIFU technology. (The abstract of the paper is not specific, but the use of the term “third-generation” suggests to us that these patients were treated with Ablatherm as opposed to Sonablate technology.)
All outcomes data are reported after a single HIFU session, and none of the patients were given a TURP prior to their HIFU. The authors claim that this is the largest, prospective cohort of North American men with prostate cancer treated with primary HIFU for whom mid-term oncological outcome data have been reported, and we also believe this to be the case.
Here are the key data about the patient series and the assessment of their outcomes:
- 447 consecutive patients received a single session of HIFU between May 2005 and December 2010.
- Follow-up included PSA assays every 3 months during the first year and every 6 months thereafter.
- Patients who had previously received any form of radiation, androgen deprivation therapy (ADT), or HIFU were excluded from the analysis, as were patients with fewer than two consecutive PSA assays.
- Biochemical progression-free survival (bPFS) was reported based on two definitions
- The Stuttgart definition (PSA nadir + 1.2 ng/ml and rising)
- The Horwitz definition (two consecutive increases of at least 0.5 ng/ml)
Here is a summary of the study results:
- 402/447 patients met the study’s inclusion criteria.
- The average (median) follow-up was 24 months (range, 6 to 48 months).
- 183/402 men (45.5 percent) had D’Amico low-risk prostate cancer.
- 219/402 men (54.5 percent) had D’Amico intermediate-risk prostate cacner.
- Absolute, post-treatment nadir PSA levels (achieved within a median of 3 months after treatment) were
- Mean — 0.36 ± 0.69 ng/ml
- Median — 0.1 ng/ml
- Overall estimated average (mean) rates of bPFS at 4 years were
- 68 percent (range, 61 to 75 percent) based on the Stuttgart definition
- 72 percent (range, 68 to 77 percent) based on the Horwitz definition
- Overall estimated average (mean) rates of bPFS at 4 years were significantly higher for a men with a PSA nadir ≤ 0.5 ng/ml
- 79 percent (range, 72 to 86 percent) vs. 25 percent (range, 13 to 38 percent) based on the Stuttgart definition
- 82 percent (range, 77 to 87 percent) vs. 33 percent (range, 21 to 44 percent) based on the Horowitz definition
- Overall estimated average (mean) rates of bPFS at 4 years were also significantly higher for a men with a prostate volume ≤ 30 ml (post-treatment)
- 72 percent (range, 64 to 79 percent) vs. 56 percent (range, 42 to 69 percent) based on the Stuttgart definition
- 75 percent (range, 69 to 80 percent) vs. 63 percent (range, 53 to 74 percent) based on the Horowitz definition
- Pre-treatment PSA levels and PSA nadir levels of > 0.5 ng/ml were predictors of bPFS using both definitions.
The authors conclude that first-line HIFU appears to have “promising” rates of bPFS at 4 years of follow-up among patients with low- and intermediate-risk prostate cancer who achieve PSA nadir levels < 0.5 ng/ml and that prostate volume < 30 ml post-treatment is associated with PSA nadir levels of < 0.5 ng/ml, suggesting the potential for combining pre-HIFU reduction of the volume of the prostate (medically or surgically) with HIFU for men with larger prostates.
Alas, this paper appears to offer us no data whatsoever on the side effects associated with HIFU treatment in this series of men. It should also be noted that these rates of bPFS are lower than those that would normally be expected by a skilled surgeon (or probably a skilled radiation oncologist or brachytherapist) in a similar series of patients treated in the same time frame — although such comparisons always need to be made with caution.