EAU PCa 2018: Focal Therapy in 2018: Still Experimental?

Milan, Italy (UroToday.com) Dr. Emberton gave an eloquent talk on the role of focal therapy for prostate cancer in the current era. According to Dr. Emberton, focal therapy is a heuristic that describes an attempt to reduce the rate of positive margins, to individualize treatment, to improve the therapeutic ratio, to create oncological consistency, and to uphold a long-standing urological tradition.

Dr. Emberton believes that the following are established factors associated with focal therapy: First, men place high utility on genitourinary function. Second, men recruit quickly to focal therapy clinical trials, which shows their extensive interest in such a therapeutic option. Third, urologists are best placed to drive the research and development of the focal therapy agenda. Focal therapy is currently ready for prime time, as it is aimed to treat patients with clinically significant cancer that is limited to a distinct zone of the prostate. Furthermore, we have the technology that can identify these men, and the energy sources that can ablate a given volume of tissue in a reliable way. Lastly, we also have the ability to measure the responses to such therapies.

There are a range of technologies that are capable of destroying tissues in a predictable and reliable manner. These technologies use extremes of temperature, either in a direct or indirect way. These technologies also include high voltage current, high dose radiotherapy, laser light, and toxic direct injection. The applicability of these energy sources is limited by their physical attributes. For example, for electricity – tissue impedance is a major factor, there is a ‘heat-sink” effect limiting technologies based on heat, for radiotherapy-based treatments, the characteristics of the used beam is critical, and lastly, technologies which are based on sound, are affected by attenuation.

What patients are eligible for focal therapy was the next topic discussed by Dr. Emberton. Ideally, these are patients with a discrete lesion on MRI, harboring clinically significant cancer, with an option to a apply a safety margin of 5 mm. These patients have a high utility to preserve genitourinary function and are completely aware of the present uncertainties of this treatment and the possibility of salvage treatment and its consequences.

Published date show that focal therapy is overall very safe, preserves genitourinary function in the majority of men, has an oncological control (freedom from disease) in over 80% of men, and can achieve a 5-year oncological control in more than 80% of men. Most studies on focal therapy show its significant high safety and low rate of complications, with 0.5% of patients experiencing grade 4 complications, less than 10% having grade 3 complications, and 20-40% of patients having grade 1-2 complications. When assessing the overall IIEF erectile function scores and change over time following treatment, it is clear that despite an increase use of approximately 30% in PDE-5 inhibitors, within 12 months there is return to baseline.

However, there still some considerable residual uncertainties associated with focal therapy. These include the justification for repeat therapy, the opportunity of salvage therapies, the long-term outcomes of in-field status and out of field status, and lastly, the cost-effectiveness on a life-time cost model.

In summary, focal therapy has emerged as a new class of therapy which now commands legitimacy, in regard to patient acceptance, academic acceptance and use, harm reduction, health related quality of life, and economic aspects. Focal therapy has forced an order of precision in terms of risk stratification that was missing so far. The out of field status after a long follow-up period, the long term results of focal therapy (at least 15 years), and the direction of the regulatory pathway, still need to be researched and studied.

To start a focal therapy program, the most stringent quality control measures need to be embraced. Exceptional imaging is mandatory, a true partnership with radiology is required, near perfect risk stratification needs to be performed, expert management of energy sources is needed, and physicians must have a commitment to long-term follow-up and upholding of registries.

Speaker: Mark Emberton, London, Great Britain 

Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, Twitter:@GoldbergHanan at the 2nd EAU Update on Prostate Cancer (PCa18)– September 14-15, 2018 – Milan, Italy

Reference:

1. Yap T et al. Eur Urol 2015