By: Dan Sperling, MD

The meeting of the American Urological Association in New Orleans (May 15-19, 2015) is the largest annual urology brain trust in the U.S. Tens of thousands of attendees from our own nation and the international community attend peer-reviewed presentations on all things urological, including prostate cancer. Especially stimulating, at times provocative, are panel discussions in which experts debate a subject.

One such debate as this year’s AUA opened included four authorities offering their respective viewpoints on the topic entitled “Focal Therapy for Prostate Cancer – Hope or Hype?”[i] On the side of hope were Prof. Mark Emberton (University College Hospitals London) and Dr. Aaron Katz (Urology Chair, Winthrop University Hospital, Garden City NY). Representing the hype viewpoint were Dr. Mark Gonzalgo (Brady Urological Institute, Johns Hopkins) and Dr. Eric Klein (Glickman Urological and Kidney Institute, Cleveland Clinic). The discussion was moderated by Dr. Peter Scardino (Chair, Dept. of Surgery, Memorial Sloan Kettering).

Dr. Scardino opened the session with a definition of focal therapy as “any ablative procedure that targets one lesion within the prostate that is the dominant or most clinically significant, leaving most of the prostate unmolested.” He pointed out that focal therapy reduces side effects, does not burn treatment bridges, and lowers patient anxiety over having been diagnosed with prostate cancer. He also enumerated focal therapy downsides, including pathology evidence of multifocal disease, lack of universal treatment and follow up criteria, and the difficulty of replicating the precise tumor location.

On the hope side, Dr. Emberton led off by establishing focal therapy within the context of global shifts in prostate cancer management algorithms. He cited research by Panebianco et al.[ii] that illustrates the new role of multiparametric MRI (mpMRI) in qualifying men for targeted treatment. An open question regarding the safety of a focal approach concerns the natural history of prostate cancer cells, and he referred to molecular studies suggesting that high-risk prostate cancer has a different metastatic capacity and process than low-risk lesions. He described a case in which mpMRI detected a Gleason 3+4 cancer, and the patient’s PSA was 6.7 ng/mL. A focal treatment was delivered with electroporation and its success was verified by follow up mpMRI. The PSA level fell to 1.7 ng/mL. All healthy structures were preserved, and the patient’s urinary and sexual functions held at pre-treatment baseline. He concluded with the observation that quality of life after focal therapy is equivalent to that of active surveillance (in which the cancer is still present) but that time would tell if that remains the case.

Dr. Klein, representing the opposing view, challenged the idea that imaging has high accuracy in detecting biologically significant lesions. While accepting that MRI is more likely to identify significant rather than insignificant lesions, he referenced two studies (Sonn et al., 2013; Pinto et al., 2015) demonstrating that over 30% of all cancers were missed by MRI—though that includes cancers that some would define as insignificant—and 25-20% of Gleason 7 cancers were missed. He stated that overall MRI misses 15% of intermediate to high-risk cancers. He shared the view that no one fully knows how safe it is to ignore Gleason 6 disease, and that no all low-risk disease proves to be indolent or nonrecurrent. His case example was that of a patient whose multifocal cancer was treated with radical prostatectomy. However, he eventually died of metastatic disease, which had the same pattern of genetic mutations as those found in the Gleason 6 lesions identified in post-surgery histopathology. Today, genomic profiling of tumors can identify those low-risk tumors (often missed by MRI) into recurrent vs. non-recurrent disease, so it can’t be assumed that patients with low-risk disease are candidates for focal therapy. Finally, be brought up a recent study of apparently normal prostate tissue in which healthy cells harbored mutations found in a patient’s tumor, suggesting that focal therapy in such a case would be inadequate. Thus, Dr. Klein stated that focal therapy is “not ready for primetime.”

The next speaker, Dr. Katz, returned to the pro-focal position. He pointed to new diagnostic tools such as genomics and biomarkers which, together with mpMRI and the clinical factors of PSA, PSA density and tumor volume, can stratify unifocal vs. multifocal PCa. Patients with aggressive tumor markers, and the score from the OncoTypeDX® test, can be excluded as candidates for focal treatment. Dr. Katz described the advantages to patients in terms of the very low risk of urinary and sexual side effects, and that studies using post-focal treatment biopsy have low rates of residual cancer (3-12.5%). By pulling in the patient viewpoint, Dr. Katz implied the effect that patient demand has on influencing a trend in the direction of increased focal treatment, though he never explicitly referred to this in what was intended to be strictly a clinical debate.

The anti-focal position was then presented by Dr. Gonzalgo, who began with the point that multifocality is present in 90% of prostate cancer patients. By citing pathology evidence of genetic heterogeneity of multiple lesions within the same gland, he argued that targeting only the significant lesion may never be safe because metastatic disease can arise from secondary disease foci. He also discounted the analogy to breast lumpectomy in which cases the dominant lesion is not only surgically removed but adjuvant radiation and/or chemotherapy can be used prophylactically after surgery, which is not the case with prostate cancer. Not only did he conclude by saying that MRI and PSA are insufficient to identify recurrence, with future treatment costs unknown, but questioned the value of a focal treatment when surveillance alone results in 99% metastasis-free survival without added cost or the rare side effects of targeted treatment.

It is up to the reader to decide if the pro or con side “won” the debate. However, by understanding the various areas of concern that go into the issue, every thoughtful reader is provided with pathways along which to pursue personal reading toward an informed position on the matter. In that sense, everyone wins.

[i] http://www.urotoday.com/index.php?option=com_content&view=article&id=80694:aua15-focal-therapy-for-prostate-cancer-hope-or-hype-session-highlights&catid=1655:aua-2015-prostate-cancer&Itemid=2460&utm_source=newsletter_2676&utm_medium=email&utm_campaign=uroalerts-prostate-cancer-daily

[ii] Panebianco V, Barchetti F, Sciarra A et al. Multiparametric magnetic resonance imaging vs. standard care in men being evaluated for prostate cancer: a randomized study. Urol Oncol. 2015 Jan;33(1):17.e1-7. doi: 10.1016/j.urolonc.2014.09.013.