Minimally Invasive Ablative Therapies for the Treatment of Prostate Cancer

Prostate Cancer

9c_RIU0520_04-13.qxd 4/21/11 1:47 PM Page 61 LITERATURE REVIEWS News and Views From the Literature Prostate Cancer Minimally Invasive Ablative Therapies for the Treatment of Prostate Cancer Herbert Lepor, MD New York University School of Medicine, New York, NY [Rev Urol. 2011;13(1):61-62 doi: 10.3909/riu0520] © 2011 MedReviews ®, LLC Six Years’ Experience With High-Intensity Focused Ultrasonography for Prostate Cancer: Oncological Outcomes Using the New ‘Stuttgart’ Definition for Biochemical Failure Ripert T, Azémar MD, Ménard J, et al. BJU Int. doi: 10.1111/j.1464-410X.2010.09710.x. Published online November 17, 2010. he three widely accepted options for managing localized prostate cancer include radical prostatectomy, radiation therapy, and active surveillance. Over the past decade, there has been increasing interest in minimally invasive ablative therapies (MIAT) for the treatment of prostate cancer. MIAT has been investigated as salvage treatment following failed radiation therapy, wholegland ablation for primary treatment of clinically localized disease, and targeted or focal ablation for regions of the prostate known to harbor the disease. Today, there is a fairly robust amount of published literature for whole- T gland ablation of prostate cancer for primary and salvage treatment indications. As our ability to define the site, extent, and aggressiveness of the disease improves attributable to advances in prostate imaging, biopsy tissue sampling, and molecular risk stratification, it is my prediction that focal therapy will emerge as a widely accepted indication for MIAT. Worldwide, the most commonly used approaches for MIAT of the prostate are high-intensity focused ultrasound (HIFU) and cryotherapy. There are two systems available for HIFU (Sonablate® 500 [US HIFU LLC, Charlotte, NC] and Ablatherm® HIFU [EDAP TMS, Vaulx-en-Velin, France]). Because these devices have inherent differences in the delivery of focused ultrasound energy and only the Sonablate 500 has the ability for monitoring tissue destruction in real time, clinical outcomes from one device cannot be extrapolated to the other. An article recently published by Ripert and colleagues reported on the experience of two French urologists using the Ablatherm HIFU device. This article received a great deal of attention, and commentary on it posted on Medscape1 questioned the role of HIFU for primary treatment of localized prostate cancer on the basis of this single experience. There have been many articles published in the peer-reviewed literature addressing oncological and quality-of-life outcomes following HIFU for prostate cancer. Common sense dictates that the role of HIFU, or any treatment for prostate cancer, cannot be judged solely on the basis of a single clinical experience especially when there are different energy delivery systems available. Because this article has been in the spotlight, I feel compelled to critically review the strengths and limitations of its study design, and interpret the results in context with the totality of the literature reporting experiences with HIFU as a treatment for prostate cancer. VOL. 13 NO. 1 2011 REVIEWS IN UROLOGY 61 RiU_Apr2011_p61-64.qxd 4/13/11 10:54 AM Page 62 Prostate Cancer continued The study by Ripert and colleagues was based on a twoman experience of 86 prostate cancer cases treated with HIFU. If one focuses only on the 53 evaluable men who underwent “adequate” HIFU treatment of primary disease, 62% were treatment failures based on prostate-specific antigen (PSA) recurrence using the Stuttgart definition of biochemical recurrence. As an isolated observation, this high failure rate is disconcerting and warrants an explanation if HIFU is to be considered a legitimate option for primary treatment of clinically localized prostate cancer. There are many glaring deficiencies in the Ripert study design. First, only 86 HIFU procedures were performed over a 6-year interval by two urologists using the Ablatherm device. Of these 86 procedures, 12 were performed following failed radiation therapy and 9 were retreatment. Only 65 procedures were performed as initial primary treatment of clinically localized prostate cancer. Therefore, on average, these two urologists performed approximately five procedures per year which, in my opinion, is far too low to gain proficiency with the technology. This will become evident when examining the poor posttreatment PSA nadir levels achieved by these French urologists, which is why, in my opinion, their poor surgical technique is the primary explanation for their poor outcomes. Twelve additional cases were excluded for various reasons including recognized inadequate treatment, leaving only 53 evaluable primary disease cases. Half of these men had intermediate risk disease. Although the manufacturers of the Ablatherm device recommend excluding men with prostate volumes  40 cm3, men with prostate volumes up to 50 cm3 were included in the Ripert study. HIFU is similar to radiation therapy (RT) in that prostate tissue is ultimately destroyed and not surgically removed. Because it is virtually impossible to totally eradicate every PSA-producing cell with radiation without damaging adjacent structures, various definitions have been recommended for biochemical recurrence (BCR) assuming residual viable prostate tissue will contribute to a measureable PSA after radiation therapy. The Phoenix definition (nadir post–radiation therapy PSA  2 ng/mL), a consensus definition of BCR following RT, has also been applied to ablative technologies. The Stuttgart definition (nadir post-ablation PSA  1.2 ng/mL) has been suggested as an alternative definition of BCR following HIFU and other MIAT following whole-gland ablation with the intent to cure prostate cancer. Ripert and colleagues provide a summary of BCR rates for other reported clinical experiences using the Ablatherm device. In those studies reporting very favorable BCR rates, the median PSA nadir following HIFU treatment was 0.1 ng/mL, suggesting that HIFU successfully eradicated the overwhelming majority of the prostate gland. In those studies reporting poor outcomes, including the Ripert study, the median posttreatment PSA nadir ranged between 1.0 ng/mL 62 VOL. 13 NO. 1 2011 REVIEWS IN UROLOGY and 1.3 ng/mL. The studies consistently reporting poor outcomes following HIFU had median PSA nadir levels 10 times greater than those reporting good outcomes. These unacceptably very high posttreatment PSA nadir levels can only be explained by a totally inadequate ablation or poor selection of cases with occult metastatic disease. One cannot condemn the technology, but rather the surgeons whose poor surgical technique likely led to high failure rates. In the subset of men in the Ripert study who achieved posttreatment PSA nadirs  0.2 ng/mL—which would reflect both good surgical technique and the selection of candidates who in fact have localized disease—approximately 75% of men achieved durable (6-year) biochemical-free survival. Dr. Uchida is a highly experienced HIFU surgeon who uses the Sonablate 500 device, which I believe is superior technology due to its more precise delivery of energy and monitoring of tissue destruction compared with the Ablatherm device. Uchida and colleagues reported 5-year BCR rates of only 16% and 34% for low- and intermediate-risk disease, respectively, using the Phoenix definition of BCR.2 These are impressive outcomes and clearly rival those achieved with RT. In my opinion, these impressive outcomes reflect the advanced capabilities of Sonablate technology and the skill of the operator. There is no doubt that successful surgical outcomes are often related to clinical experience. A rigorous communitybased study of outcomes following radical prostatectomy reported severe incontinence rates of approximately 10%.3 In the community setting, the average urologist performs about five radical prostatectomies a year, similar to the number performed by Ripert and colleagues. I have personally performed over 4000 radical prostatectomies and my reported severe incontinence rate is 2%. It is, therefore, not surprising that experienced HIFU surgeons achieve superior results, no different than experienced surgeons who perform radical prostatectomy as well as any complex surgical procedure. So, in my opinion, the Ripert report is consistent with the literature. When the prostate is appropriately ablated in legitimately selected cases, low PSA nadir levels are achieved. Even Ripert achieved good outcomes when the prostate was adequately treated. The challenge, as with any new technology, is to minimize the learning curve for those who embrace this new technology. References 1. 2. 3. Chodak G. HIFU for prostate cancer: new study results disappointing. Medscape Urology. http://www.medscape.com/viewarticle/735487. Accessed March 20, 2011. Uchida T, Shoji S, Nakano M, et al. High-intensity focused ultrasound as salvage therapy for patients with recurrent prostate cancer after external beam radiation, brachytherapy or proton therapy. BJU Int. 2011;107:378-382. Penson DF, Mclerran D, Feng Z, et al. 5-year urinary and sexual outcomes after radical prostatectomy: results from the prostate cancer outcomes study. J Urol. 2005;173:1701-1705.