Despite increasing interest among some clinicians and researchers in the idea of focal therapy for clinically localized prostate cancer, the approach is still in its infancy and should be regarded as experimental, say the authors of an essay published in the May 1 issue of the Journal of Clinical Oncology.
Focal therapy homes in on the index malignant lesion in the prostate gland and involves removal of only the affected part, not the whole gland as in prostatectomy; for that reason, it has been likened to a "male lumpectomy." The index malignant lesion is ablated with high-intensity focal ultrasound (HIFU), which has been used in Europe but is not approved in the United States.
Many questions remain unanswered and some might never be answered, write Gianluca Giannarini, MD, from the Department of Urology at the University of Bern in Switzerland.
An American expert approached for comment agrees.
"Focal therapy should be considered experimental as we await long-term outcomes," said Chandan Guha, MD, MBBS, PhD, vice chair of the Department of Radiation Oncology at the Montefiore Medical Center and Albert Einstein College of Medicine in Bronx, New York.
"There is a lot of interest, mainly among urologists, to do focal therapy, but the whole scientific paradigm is questionable," Dr. Guha told Medscape Medical News.
Questions and Controversies
Dr. Giannarini and colleagues say that "several misconceptions and intrinsic limitations" related to focal therapy could prevent its development as a treatment option for men with clinically localized prostate cancer.
The index lesion is generally defined as the largest-volume lesion with the highest grade. "However, some disagreement exists regarding this definition. For example, whether a lesion of higher volume and lower grade or a concomitant lesion of lower volume and higher grade represent the index lesion in a given patient is currently under debate," Dr. Giannarini and colleagues note.
Whichever it is, the theory is that the index lesion dictates the biologic behavior of the tumor and, ultimately, how lethal it is, and that selectively destroying it will prevent cancer progression. "However, there is no definitive proof for this assumption," the authors write.
If an index lesion does exist, it should have 2 main prerequisites: limited volume and unilateral location. However, prostate cancer is a multifocal disease. "The idea that treating the index lesion (whichever it may be) is equal to treating the whole gland still needs to be scientifically proven," they explain.
In their view, one key issue with focal therapy for localized prostate cancer is identifying the optimal candidate for this approach. "Unfortunately, to date there are no standardized inclusion or exclusion criteria. Some investigators argue that focal therapy is an alternative to active surveillance for men with low-risk disease, while others claim that focal therapy should be an alternative to radical therapy for those men likely to benefit from active treatment," Dr. Giannarini and colleagues point out.
They note that in published series to date, most patients who underwent focal therapy had low-risk prostate cancer with a Gleason score of 6 or lower. "These are exactly the patients who should not yet receive any treatment," the authors say.
Some physicians consider focal therapy to be an alternative to active surveillance in anxious low-risk patients who specifically request active treatment. "However, we believe that treating patient anxiety with any kind of unnecessary cancer therapy does not represent good medical practice," they note.
Time to Throw in the Towel?
Dr. Guha agrees. "You can't treat just to treat the anxiety of the patient," he told Medscape Medical News. "That could be overtreatment because some low-risk patients might qualify for active surveillance. At the same time, treating part of the prostate to temporarily reduce PSA might be inadequate because of the multifocal nature of prostate cancer," he explained.
Another unknown is how the success of focal therapy should be defined. "There are no standardized criteria to define tumor persistence or progression and no standardized tools or follow-up schedules to monitor patients after focal therapy," Dr. Giannarini and colleagues point out.
Other open questions are whether focal therapy is truly free of complications and whether it is cost-effective. Many of these questions will likely remain unanswered, the authors report.
They think the time has come to "acknowledge that not all concepts and principles of organ preservation, common to several malignancies, can be translated to prostate cancer. Ignoring this simple fact may lead to inadequate management of this highly heterogeneous disease entity." The authors declined a request for an interview.
Dr. Guha, who reviewed the commentary for Medscape Medical News, said he thinks it is "reasonably balanced."
"I personally think that some elements of focal therapy could be beneficial if combined with standard radiation therapy, especially for aggressive disease," Dr. Guha said, noting that he and his colleagues are planning trials to assess this approach.
Potential candidates would be patients with a dominant lesion within the prostate, seen on imaging, that would be difficult to cure with radiation. "In this situation, the large or dominant tumor can be ablated with HIFU, and whole-prostate radiation can be used for microscopic disease and lymph node disease where HIFU can not be given," Dr. Guha explained.
The US Food and Drug Administration has not approved HIFU yet. "At Montefiore, our goal is to have a combination trial where focal ablative therapy for a dominant lesion can be combined with standard-of-care radiation therapy," Dr. Guha told Medscape Medical News.
Dr. Giannarini and Dr. Guha have disclosed no relevant financial relationships.J Clin Oncol. 2014;32:1299-1301.