21 October 2014 by Manit Arya
?There has been considerable interest in the FDA advisory panel hearings on high intensity focused ultrasound for the treatment of prostate cancer. Whilst the Focal Therapy User group chairs recognize that these were not related to focal therapy per se and that focal therapy is modality neutral, there are a number of issues we believe need to be highlighted:
First, it is important to note that both submissions were noted by the advisory panels to be limited in terms of the US clinical trial data that both companies submitted, having been unable to recruit to the matched cohort arms of cryotherapy or brachytherapy that was required whilst also presenting only interim trial data rather than the complete trial data. The panels also struggled to agree on a clinical measure of outcome that could verify disease control meeting the legislative requirements of the stringent FDA processes especially in light of the long natural history of the disease even when clinically significant. A number of recent consensus panels have recommended criteria to define success for clinical practice in focal therapy that we have shared with you as attachments for academic interest to this email.
Second, the indications submitted to the FDA were for whole-gland HIFU for low-risk prostate cancer (Ablatherm) and whole-gland salvage HIFU for radio-recurrent prostate cancer (Sonablate). These were considerably problematic as highlighted in the advisory panel discussions.?- The Focal Therapy User group executive does not believe that whole-gland ablation has a role in prostate cancer management unless specific indications make a patient unsuitable/ineligible for whole-gland radical therapies. The toxicity is lower for whole-gland ablation compared to whole-gland radical therapy but not considerably so and therefore the difference in our mind does not justify whole-gland ablation in most men.
- The FDA advisory panel quite rightly raised strong concerns about treating low-risk primary disease. The Focal Therapy User group chairs do not advocate focal therapy for men with low risk disease that is confirmed as low volume low Gleason grade (6) on accurate risk stratification (MRI-targeted biopsies or transperineal template systematic biopsies [mapping or otherwise]). Focal therapy is NOT an alternative to active surveillance. We strongly recommend that physicians carrying out focal therapy in compliance with NICE guidance make their practice consistent with the UCL Focal Therapy programme which is consistent with the eligibility criteria in the NCRN INDEX Stage II protocol (INDEX-LITE), namely that clinically significant disease by UCL definition two or greater is most appropriate for focal therapy, at this present moment.
In stating this, we also recognize that the threshold for any treatment is likely to rise as the evidence for active surveillance builds further.
The FDA advisory panel agreed there was a real and pressing clinical need for new treatments for radio-recurrent disease. However, they were concerned about whole-gland salvage HIFU's toxicity levels being very similar to existing modalities (whole-gland cryotherapy salvage, whole-gland radical salvage prostatectomy). The Focal Therapy User group chairs do not advocate whole- gland salvage ablation in men with radio-recurrent prostate cancer. The incontinence rates are lower than whole-gland salvage prostatectomy but are still very high with similar urethral and rectal toxicity. Focal salvage ablation has been shown to carry significantly less morbidity with acceptable early disease control outcomes. We strongly recommend that physicians undertaking focal salvage ablation should ensure accurate staging is carried out (bone-scan, cross-sectional CT/MRI according to local guidelines and practice) to rule-out metastases as well as accurate high quality mpMRI conducted and reported to British Society of Uro-radiology and European Society of Uro-radiology guidelines by radiologists trained and expert in such reporting. Targeted or transperineal systematic biopsies are needed for disease localization as for primary focal ablation.
To read the full FDA panel hearing presentations and transcripts of the discussions that occurred, please see the following weblinks.
Manit Arya & Hashim U. Ahmed Focal Therapy User Group, UK Co-chairs