EDITORIAL URRENT C OPINION
Focal therapy of prostate cancer: making steady progress toward a first-line image-guided treatment modality Thomas J. Polascik
Although there were only a few reports in the literature regarding the concept of focal therapy for prostate cancer prior to 2006, a group of thought leaders at that time had the vision to formalize the foundational work for image-guided therapy and partial gland ablation. The original meeting hosted at Duke in Durham, North Carolina, in 2008 was essentially an international workshop for investigators, clinicians, and scientists interested in further exploring the concept of focal therapy. Since that landmark meeting, this year will mark the 8th International Symposium on Focal Therapy and Imaging in Prostate and Kidney Cancer hosted in the Netherlands in June 2015. Much has changed since that time. In this journal dedicated to the topic of Focal Therapy of Prostate Cancer, I have selected several new topics that are germaine to the further development of focal therapy. Active surveillance is an integral component of focal therapy, as the untreated areas of the prostate have to be monitored for de-novo tumors. The evaluation of a patient as a candidate for focal therapy is often said to be more detailed than that for whole gland therapy, requiring tumor volume, spatial location, and an understanding of tumor biology. Tay et al. (pp. 185–190) make the argument that contemporary active surveillance protocols similarly need to be modernized to gain a better appreciation of what cancer(s) resides in the prostate and what the malignant potential may be. These authors make a plea to modernize active surveillance protocols by incorporating multiparametric MRI (mpMRI) and molecular markers to better and more confidently select men for active surveillance strategies. In 2015, there has been great acceptance of mpMRI for the characterization of prostate cancer, but the argument has always been that due to the higher costs and still limited access to expert MRI centers, transrectal ultrasound (TRUS) is a more readily available and useful tool to the practicing urologist, particularly in the outpatient office setting. Postema et al. (pp. 191–197) discuss the possibilities
of the development of multiparametric TRUS, an imaging tool that would have similar functionality to mpMRI. Similar to mpMRI, quantification techniques are being developed for ultrasound that better differentiate cancer from normal parenchyma. Both contrast-enhanced ultrasound quantification and shear wave elastography allow for improved prostate cancer detection. This is an exciting new technical leap that should allow urologists to have at their fingertips a number of different functional parameters when scanning the prostate with realtime ultrasonography in the office setting that can be done in one single session. Ouzzane et al. (pp. 198–204) report on the pathological implications of mpMRI for focal therapy planning. This group has had a wealth of experience in both pathologic mapping of the prostate and mpMRI correlation with histology. The question arises regarding how accurate the location and volume of tumor detected on mpMRI compares with histopathology and is a current active area of research. The authors discuss current thought on the pathologic implications of mpMRI and how its application to focal therapy may provide an adequate safe margin of ablation. These authors believe the actual boundary of the tumor lies beyond the visible edge of the MRI-detected lesion, and this finding must be taken into account when performing focal therapy to achieve complete ablation of the cancer. Although MRI-TRUS fusion systems are becoming more commonly utilized to guide intervention because of their lower cost and portability, in-bore MRI remains the original imaging platform. Ghai and Trachtenberg (pp. 205–211) discuss the benefits of using in-bore MRI for both diagnosis and focal Duke Cancer Institute, Durham, North Carolina, USA Correspondence to Thomas J. Polascik, MD, FACS, Professor of Surgery, Duke Cancer Institute, Durham, NC 27710, USA. E-mail: [email protected] Curr Opin Urol 2015, 25:183–184 DOI:10.1097/MOU.0000000000000171
0963-0643 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.co-urology.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Focal therapy of prostate cancer
treatment of prostate cancer. Although in-bore interventions have inherent challenges and require a level of expertise, the main advantage of this technique is the real-time thermal monitoring of the treatment and ability to image immediately after the therapy. These authors describe a number of devices (laser, focused ultrasound, and cryoablation) utilizing this method and the various approaches (transperineal, transrectal, and transurethral) to target the tumor. Patient selection remains one of the critical elements to the successful focal treatment of a prostate tumor. Orczyk et al. (pp. 212–219) provide a contemporary viewpoint and discuss what types of cancers we should be treating with focal therapy in 2015. In the earliest days of focal therapy, the majority of treating physicians tended to focus on localized low-risk tumors. However with the further adoption of active surveillance, particularly for the low-risk patient, focal therapy has shifted to target intermediate-risk disease. These authors provide the current evidence for such an approach and also stress the importance of tumor localization within the three-dimensional space of the prostate and appropriate risk stratification. The most current approach in focal therapy is to target and treat the dominant lesion in an intermediate-risk group population, allowing for surveillance of small volume clinically insignificant secondary tumors. These authors provide the rationale for this approach based on small clinical trials, consensus panels, and correlative science. Dr J. Coleman (pp. 220–224) discusses the functional outcomes of partial prostate ablation and tackles the question if we are adequately managing patient expectations of a bar set too high. In seeking nontraditional therapies for prostate cancer, many patients today present with a very low tolerance for any adverse functional side-effects while expecting the cancer to simultaneously be eliminated. Dr Coleman also advocates for patient disclosure regarding the current limitations of focal therapy. Although some men may present requesting focal
184
www.co-urology.com
therapy with high expectations for a full functional recovery to baseline, setting realistic expectations upfront will provide greater balance with perceived and actual outcomes. Finally, we take a look at the landscape for focal therapy in the East. Much of the early work has been done in Europe and North America. Kimura et al. (pp. 225–229) discuss the Opportunities of Targeted Focal Treatment in Japan. These authors examine the current trends in screening, detection, and the evolving environment of treatment options. Prostate-specific antigen screening is expected to rise dramatically, especially in developed Asian countries. Enhanced screening, employment of mpMRI-fusion biopsies, and an aging population predict an increased need for the treatment. Active surveillance has not gained widespread acceptance of yet, perhaps in part due to cultural influence. Focal therapy using high intensity ultrasound and brachytherapy has been utilized; however, it may take some time for focal therapy to gain greater traction in this region. Prostate focal therapy is a noble but nascent concept and remains on the threshold of entering contemporary, mainstream urology. This issue distills the progress and challenges in the journey of focal therapy, nested in the framework of continuing rapid developments in the realm of prostate oncology, and that of imaging and ablative technology. We hope that this review of the contemporary scientific basis of focal therapy engenders the reader to embark on this exciting adventure. Acknowledgements None. Financial support and sponsorship None. Conflicts of interest Angiodynamics – clinical trial; Endocare – consultant, investment interest.
Volume 25 Number 3 May 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Focal therapy of prostate cancer: making steady progress toward a first-line image-guided treatment modality Thomas J. Polascik
Although there were only a few reports in the literature regarding the concept of focal therapy for prostate cancer prior to 2006, a group of thought leaders at that time had the vision to formalize the foundational work for image-guided therapy and partial gland ablation. The original meeting hosted at Duke in Durham, North Carolina, in 2008 was essentially an international workshop for investigators, clinicians, and scientists interested in further exploring the concept of focal therapy. Since that landmark meeting, this year will mark the 8th International Symposium on Focal Therapy and Imaging in Prostate and Kidney Cancer hosted in the Netherlands in June 2015. Much has changed since that time. In this journal dedicated to the topic of Focal Therapy of Prostate Cancer, I have selected several new topics that are germaine to the further development of focal therapy. Active surveillance is an integral component of focal therapy, as the untreated areas of the prostate have to be monitored for de-novo tumors. The evaluation of a patient as a candidate for focal therapy is often said to be more detailed than that for whole gland therapy, requiring tumor volume, spatial location, and an understanding of tumor biology. Tay et al. (pp. 185–190) make the argument that contemporary active surveillance protocols similarly need to be modernized to gain a better appreciation of what cancer(s) resides in the prostate and what the malignant potential may be. These authors make a plea to modernize active surveillance protocols by incorporating multiparametric MRI (mpMRI) and molecular markers to better and more confidently select men for active surveillance strategies. In 2015, there has been great acceptance of mpMRI for the characterization of prostate cancer, but the argument has always been that due to the higher costs and still limited access to expert MRI centers, transrectal ultrasound (TRUS) is a more readily available and useful tool to the practicing urologist, particularly in the outpatient office setting. Postema et al. (pp. 191–197) discuss the possibilities
of the development of multiparametric TRUS, an imaging tool that would have similar functionality to mpMRI. Similar to mpMRI, quantification techniques are being developed for ultrasound that better differentiate cancer from normal parenchyma. Both contrast-enhanced ultrasound quantification and shear wave elastography allow for improved prostate cancer detection. This is an exciting new technical leap that should allow urologists to have at their fingertips a number of different functional parameters when scanning the prostate with realtime ultrasonography in the office setting that can be done in one single session. Ouzzane et al. (pp. 198–204) report on the pathological implications of mpMRI for focal therapy planning. This group has had a wealth of experience in both pathologic mapping of the prostate and mpMRI correlation with histology. The question arises regarding how accurate the location and volume of tumor detected on mpMRI compares with histopathology and is a current active area of research. The authors discuss current thought on the pathologic implications of mpMRI and how its application to focal therapy may provide an adequate safe margin of ablation. These authors believe the actual boundary of the tumor lies beyond the visible edge of the MRI-detected lesion, and this finding must be taken into account when performing focal therapy to achieve complete ablation of the cancer. Although MRI-TRUS fusion systems are becoming more commonly utilized to guide intervention because of their lower cost and portability, in-bore MRI remains the original imaging platform. Ghai and Trachtenberg (pp. 205–211) discuss the benefits of using in-bore MRI for both diagnosis and focal Duke Cancer Institute, Durham, North Carolina, USA Correspondence to Thomas J. Polascik, MD, FACS, Professor of Surgery, Duke Cancer Institute, Durham, NC 27710, USA. E-mail: [email protected] Curr Opin Urol 2015, 25:183–184 DOI:10.1097/MOU.0000000000000171
0963-0643 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.co-urology.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Focal therapy of prostate cancer
treatment of prostate cancer. Although in-bore interventions have inherent challenges and require a level of expertise, the main advantage of this technique is the real-time thermal monitoring of the treatment and ability to image immediately after the therapy. These authors describe a number of devices (laser, focused ultrasound, and cryoablation) utilizing this method and the various approaches (transperineal, transrectal, and transurethral) to target the tumor. Patient selection remains one of the critical elements to the successful focal treatment of a prostate tumor. Orczyk et al. (pp. 212–219) provide a contemporary viewpoint and discuss what types of cancers we should be treating with focal therapy in 2015. In the earliest days of focal therapy, the majority of treating physicians tended to focus on localized low-risk tumors. However with the further adoption of active surveillance, particularly for the low-risk patient, focal therapy has shifted to target intermediate-risk disease. These authors provide the current evidence for such an approach and also stress the importance of tumor localization within the three-dimensional space of the prostate and appropriate risk stratification. The most current approach in focal therapy is to target and treat the dominant lesion in an intermediate-risk group population, allowing for surveillance of small volume clinically insignificant secondary tumors. These authors provide the rationale for this approach based on small clinical trials, consensus panels, and correlative science. Dr J. Coleman (pp. 220–224) discusses the functional outcomes of partial prostate ablation and tackles the question if we are adequately managing patient expectations of a bar set too high. In seeking nontraditional therapies for prostate cancer, many patients today present with a very low tolerance for any adverse functional side-effects while expecting the cancer to simultaneously be eliminated. Dr Coleman also advocates for patient disclosure regarding the current limitations of focal therapy. Although some men may present requesting focal
184
www.co-urology.com
therapy with high expectations for a full functional recovery to baseline, setting realistic expectations upfront will provide greater balance with perceived and actual outcomes. Finally, we take a look at the landscape for focal therapy in the East. Much of the early work has been done in Europe and North America. Kimura et al. (pp. 225–229) discuss the Opportunities of Targeted Focal Treatment in Japan. These authors examine the current trends in screening, detection, and the evolving environment of treatment options. Prostate-specific antigen screening is expected to rise dramatically, especially in developed Asian countries. Enhanced screening, employment of mpMRI-fusion biopsies, and an aging population predict an increased need for the treatment. Active surveillance has not gained widespread acceptance of yet, perhaps in part due to cultural influence. Focal therapy using high intensity ultrasound and brachytherapy has been utilized; however, it may take some time for focal therapy to gain greater traction in this region. Prostate focal therapy is a noble but nascent concept and remains on the threshold of entering contemporary, mainstream urology. This issue distills the progress and challenges in the journey of focal therapy, nested in the framework of continuing rapid developments in the realm of prostate oncology, and that of imaging and ablative technology. We hope that this review of the contemporary scientific basis of focal therapy engenders the reader to embark on this exciting adventure. Acknowledgements None. Financial support and sponsorship None. Conflicts of interest Angiodynamics – clinical trial; Endocare – consultant, investment interest.
Volume 25 Number 3 May 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
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