Panel Reaches Consensus On Focal Therapy Trial Design

By: Dan Sperling, MD

There are many published reports the safety, effectiveness and sides effects of various focal treatment methods (cryotherapy, HIFU, photodynamic therapy and laser ablation), but they are difficult to compare side by side because they are designed differently. When patients ask me how one treatment compares with another, I try to explain it’s difficult to be specific due to the lack of uniform study design standards for how patients are selected for inclusion, how and when their treatment results are assessed, and even lack of well-defined endpoints.

It would be economically impossible for a single institution to conduct a study large enough to generate enough information to resolve the comparison problem. However, around the globe there are enough top level institutions with the means to conduct individual focal therapy trials, so achieving consensus on how to design such trials is a meaningful step toward collaboration in collecting, pooling and comparing data. To that end, an international multidisciplinary panel of 48 experts has been undergoing a process toward agreement of uniform study design. I want to share the latest report on the results.

The process they used is based on a structured communication exercise called the Delphi method (you can read more about this method at http://en.wikipedia.org/wiki/Delphi_method). This approach to gaining consensus assumes that a number of rounds of questionnaires will produce increasing agreement as participants read the results of everyone’s responses from each previous round. In this case, there were four stages of questionnaires to gather expert opinion on trial design, followed by 13 panel members meeting to discuss and clarify the results, and then to define the conclusions. Here are their focal trial design standards:

• Patient inclusion: PSA <15 ng/mL, clinical stage T1c-T2a, Gleason 3+3 or 3+4, life expectancy >10 years, and any prostate volument
• Post-treatment evaluation: TRUS biopsies taken between 6-12 months after treatment
• Primary objective: focal ablation of clinically significant disease with negative biopsies at 12 months after treatment as the primary endpoint.

Personally, I have mixed feelings about the results. Overall, I applaud this constructive step toward establishing uniform standards for conducting future focal therapy trials. It will better assure that the results among many different centers are able to be fairly and comprehensibly compared. One focal therapy can be compared with another—something which does not yet exist—or one focal therapy can be compared with a whole-gland treatment such as prostatectomy or a form of radiation.

On the other hand, I am disappointed that assessing treatment effectiveness is limited to TRUS biopsy, which is not capable of precise guidance into the zone of ablation. However, if mpMRI-ultrasound fusion guided transrectal biopsy is within the guidelines, it would at least add a measure of accuracy by incorporating pre- and post-treatment mpMRI prostate images in order to identify the exact location of treatment.

I acknowledge the fine consensus-building method used by the panel to develop uniform standards for designing future focal therapy trials. I can only hope that clinicians and researchers around the globe will soon embrace the importance of mpMRI and find a way to incorporate it into such clinical studies.

NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.