Experts Disagree Over Focal Therapy for Prostate Cancer

Janis C. Kelly

October 30, 2015

Arguments over the use of focal therapy for prostate cancer, which uses ultrasound to treat only the index lesion in the prostate, have heated up. The October issue of the Journal of Urology carries a pro and con couplet of articles. The point of view in favor of focal therapy is from Mark Emberton, MD, who argues that focal therapy is "a legitimate and necessary response to a changing world." The opposing view is from Mark L. Gonzalgo, MD, PhD, who counters that focal therapy "aims to kill cancer while minimizing side effects" but that, on the basis of current data, "the hype...outweighs the hope."

This face-off occurred in the wake of the FDA's decision to approve the first high-intensity focused ultrasound (HIFU) device for ablation of prostate tissue. Although HIFU was previously turned down twice by the FDA's Gastroenterology-Urology Devices Panel for prostate cancer treatment, it is widely used for that purpose outside the United States.

Dr Emberton, who is from the Division of Surgery and Interventional Science, University College London, United Kingdom, and has been using HIFU for about 8 years, argued that advances in imaging and biopsy techniques have permitted more accurate stratification of patients. "An appropriate response to this is to broaden the spectrum of care for patients so that we can maximize the risk-benefit ratio for each patient ― as we do in all other solid organ cancer," he told Medscape Medical News.

Dr Gonzalgo, who is professor and chief of urology at the University of Miami Hospital and associate director for clinical affairs, Sylvester Comprehensive Cancer Center, at the University of Miami Miller School of Medicine, in Florida, objected that focal therapy may not be optimal because prostate cancer is a multifocal disease and that the idea that treating the index lesion is as good as treating the whole prostate is not supported by strong scientific evidence. Drawing analogies between prostate cancer and breast or renal cancer is not scientifically valid, he argued, and the tools currently available for imaging prostate cancer may not be accurate enough for localizing and treating all clinically significant disease.

Dr Emberton point out that most cancer is multifocal, even lung cancer. "The interesting observation is that most small foci appear not to progress," Dr Emberton said. "The multifocal arguments in prostate cancer are becoming more and more insecure as the evidence shows that modern Gleason pattern 3 exhibits a nonmetastatic phenotype. If pattern 3 goes the way of patterns 1 and 2, we no longer have multifocal disease."

Dr Emberton added, "It is hard to argue the case that the tiny foci matter with data from the PIVOT [Prostate cancer Intervention Versus Observation Trial] study available. If whole-gland treatment vs no treatment (or very little treatment) failed to provide survival benefits in a large random controlled trial [of men with low-risk prostate cancer], it closes the argument, as all the men that were treated conservatively had large and small foci, presumably.

"We need long-term studies and outcomes on patients who have undergone focal therapy compared to patients who have undergone surgery or radiation therapy," Dr Gonzalgo told Medscape Medical News.

Dr Gonzalgo said in an interview that he agrees that there is a need for more selective treatment and for improved risk stratification of patients who have prostate cancer. However, he had concerns over the HIFU approach, which include the characterization of disease within the prostate gland. Dr Gonzalgo suggested that improved imaging technology, molecular/functional imaging, or the use of newer molecular tests for prostate cancer might help stratify patients in terms of prostate cancer risk.

"One potential danger of focal therapy is undertreatment of clinically significant disease that could negatively impact patient outcomes," Dr Gonzalgo said. "Furthermore, options for salvage treatment following focal therapy may be limited."

According to Dr Emberton, the big story is whether focal therapy is a better tissue-preserving approach in that it allows men with higher-risk disease to entertain a strategy that allows them to keep their prostate and therefore their function. How this is to be done is the lesser story but is still important, he added.

Dr Emberton's group has been using HIFU in a tissue-preserving manner for about 8 years now and finds it to be versatile and reliable. He warned, "It does need the operator to be skilled (just like surgery), and some users have found it hard to gain the competencies required."

Looking ahead, Dr Gonzalgo would like to see studies on the durability/effectiveness of long-term cancer control using focal therapy in comparison with radical prostatectomy or radiation therapy. He also called for studies of potential complications, options for salvage therapy, and cost efficacy.

Dr Emberton said that there are two big unanswered questions about focal therapy for prostate cancer. One concerns the impact of multifocality. The other pertains to the risk of developing secondary lesions.

"Interestingly, the only way you can study it is to do focal therapy and watch the men closely," Dr Emberton said. "All tissue-preserving cancer surgeries (colectomy, partial nephrectomy, liver resection, bladder resection, mastectomy [the other breast is usually preserved]) have surveillance strategies to try and identify new tumors if they arise. MRI will probably serve this role. The question is, who is at risk, and what is the risk? In these other tumors, which are associated with mortality rates much higher than prostate cancer, the risk of secondary tumors is seen to be acceptably small."

The authors report no relevant financial relationships.

J Urol. 2015;194:875-876, 876–877. Article 1 abstract, article 2 abstract

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