When prostate cancer (PCa) patients are considering treatment options, they frequently ask their doctors how one treatment compares with another. In particular, patients who are qualified for focal treatment (minimally invasive application of thermal energy to destroy just the tumor while sparing healthy tissue) are asking about the “trifecta”: cancer control, urinary continence, and sexual function. These are hard questions to answer because apples-to-apples comparisons don’t yet exist. As of this writing, there are no randomized comparison studies involving two matched prostate cancer patient groups, both qualified for focal therapy, one of which receives one type of focal treatment and the other receives a different one.
However, two published reports, each involving a small sample, provide information that can be assembled into a rough comparison. Lee et al. (2014)[i] published FLA data on 21 patients, 13 of whom completed the 12-month study protocol at the time of publication; Feijoo et al (2016)[ii] reported on 71 focal HIFU patients treated with hemiablation, 67 of whom completed the 12-month protocol at the time of publication. (It should be noted that hemiablation, while considered a focal treatment, actually destroys the half of the prostate that contains the identified tumor, whereas FLA destroys just the tumor plus a margin of safety up to 10mm beyond the tumor edges.) Both studies used multiparametric MRI and TRUS biopsies to identify tumors amenable to focal ablation (destruction). Likewise, both studies involved control biopsies at 12 months post-treatment to evaluate cancer control, and intermittent validated questionnaires to assess patient experience of urinary control and sexual function.
Taking into account that these studies were not designed using strictly comparable variables, here are the factors that lend themselves to side-by-side observations:
|Continence at 3 months||100%||100%|
|Return to baseline potency at 3 months||No significant change from baseline for all patients (100%)||No significant change from baseline for 11/21 patients (52%)|
|Negative biopsy at 12 months (n=number who completed 12-month follow-up at time of study)||n=13
12 had negative biopsy (92%)
56 had negative biopsy (84%)
Although the sample size is small, especially in the FLA report, it appears that FLA has less impact on sexual function than HIFU hemiablation. This might be explained in terms of a larger ablation zone for HIFU, since hemiablation can affect the neurovascular bundle on the treated side of the gland, thereby possibly diminishing potency. This has been observed in robotic-assisted radical prostatectomy cases in which the nerve bundle is preserved on one side in an effort to preserve potency, but return to potency is not guaranteed. In this sense, it’s a skewed FLA/HIFU comparison, since the FLA cases in this study were true targeted treatments that did not affect the nerve bundles on either side of the gland.
In addition to different ablation approaches (targeted vs. hemiablation) the control biopsy method also differed between the two papers. In the FLA group, at 12 months patients underwent an MRI-guided targeted sampling of the ablation zone as well as a computer-generated random TRUS biopsy of the whole gland. The HIFU study involved a random TRUS sampling only of the treated side of the gland. Thus, it is difficult to explain the difference in the rate of cancer control at 12 months (92% for FLA vs. 84% for HIFU) because the biopsy methods were not truly comparable.
Focal therapy for prostate cancer lacks long term study with large populations. In addition, randomized prospective comparisons do not exist between FLA and HIFU – or any focal treatments, for that matter. Given the lack of mature, meaningful data, comparisons must be based on reviewing published studies. Ongoing collegial processes to define standards that should be built in to the design of all focal treatment studies are in the works, and would be a huge contribution to identifying differences in side effects and cancer control.
This is what patients are asking for, and it is up to researchers to deliver the results.
[i] Lee T, Mendhiratta N, Sperling D, Lepor H. Focal laser ablation for localized prostate cancer: principles, clinical trials, and our initial experience. Rev Urol. 2014;16(2):55-65.
[ii] Feijoo ER, Sivaraman A, Barret E, Sanchez-Salas R et al. Focal high-intensity focused ultrasound targeted hemiablation for unilateral prostate cancer: a prospective evaluation of oncologic and functional outcomes. Eur Urol. 2016 Feb;69(2):214-20.