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Re: Accuracy of Multiparametric Magnetic Resonance Imaging in Confirming Eligibility for Active Surveillance for Men with Prostate Cancer
IMAGING
1113
Re: Determination of Optimal Drug Dose and Light Dose Index to Achieve Minimally Invasive Focal Ablation of Localized Prostate Cancer Using WST11-Vascular Targeted Photodynamic (VTP) Therapy C. M. Moore, A. R. Azzouzi, E. Barret, A. Villers, G. Muir, N. Barber, J. Trachtenberg, N. Arumainayagam, B. Gaillac, C. Allen, A. Schertz and M. Emberton Division of Surgery and Interventional Science, University College London, London, United Kingdom BJU Int 2014; Epub ahead of print.
Abstract available at http://jurology.com/ Editorial Comment: This study of photodynamic therapy for focal treatment of prostate cancer reflects the findings in men treated in a phase I/II dose escalation study of a vascular targeted photodynamic therapy using an agent, WST11, which largely remains in the vascular space. The drug, when exposed to a specific wavelength of light, causes vascular thrombosis and tissue necrosis. In this study men with unilateral cancer on biopsy were subjected to gland hemiablation by vascular targeted photodynamic therapy. At increasing doses of drug, laser energy and number of laser fibers an optimal combination of drug dose and light energy was defined. At this dose confluent necrosis of the desired treatment volume was achieved in the majority of men treated. A previous version of the drug, WST09, was associated with considerable toxicity, resulting in cessation of its clinical development. None of the previous toxicity was observed with the current drug. A number of men in this and subsequent studies had residual cancer on biopsy, typically in untreated regions of the prostate. This finding illustrates the importance of 2 separate issues in evaluating the efficacy of focal therapy. First, the best method for candidate selection and cancer localization must be determined. This study falls short in addressing that issue. Systematic biopsy is clearly inadequate. The other concern, ie how to achieve confluent, complete zonal necrosis, is well addressed in this subset evaluation. Samir S. Taneja, MD
Suggested Reading Chevalier S, Cury FL, Scarlata E et al: Endoscopic vascular targeted photodynamic therapy with the photosensitizer WST11 for benign prostatic hyperplasia in the preclinical dog model. J Urol 2013; 190: 1946. Chevalier S, Anidjar M, Scarlata E et al: Preclinical study of the novel vascular occluding agent, WST11, for photodynamic therapy of the canine prostate. J Urol 2011; 186: 302.
Imaging Re: Accuracy of Multiparametric Magnetic Resonance Imaging in Confirming Eligibility for Active Surveillance for Men with Prostate Cancer L. Stamatakis, M. M. Siddiqui, J. W. Nix, J. Logan, S. Rais-Bahrami, A. Walton-Diaz, A. N. Hoang, S. Vourganti, H. Truong, B. Shuch, H. L. Parnes, B. Turkbey, P. L. Choyke, B. J. Wood, R. M. Simon and P. A. Pinto Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland Cancer 2013; 119: 3359e3366.
Abstract available at http://jurology.com/ Editorial Comment: Candidates had to meet study criteria of prostate specific antigen density 0.15 or less, 2 or fewer positive cores, less than 50% tumor in any core, Gleason score 6 or less and stage T1c disease. All patients underwent multiparametric magnetic resonance (MR) imaging,
1114
TESTIS CANCER AND ADVANCES IN ONCOLOGIC THERAPY
which included transrectal 3 T imaging with T1 and T2-weighted dynamic contrast enhancement, diffusion and MR spectroscopy. The MR imaging protocol used is clearly state of the art. Some imaging centers do not use 3 T endorectal imaging, some do not perform spectroscopy and many do not do either. MR scans were reviewed, and number of lesions, diameter, total volume and density (total lesion volume/prostate volume) were assessed. Lesions were assigned a suspicion score. If a targetable lesion was identified on MR imaging, the patient underwent transrectal ultrasound (US) guided biopsy with MR/US fusion, a technique that is important, especially in small lesions, but not universally available. The goal with prostate cancer is to balance the value of active surveillance in patients with clinically insignificant, small volume disease vs the risk of disease progression with clinically significant prostate cancer that could advance during the active surveillance period. These authors found that multiparametric MR imaging contributed to the decision making process. Three specific factors, ie number of lesions, score for suspected cancer and lesion density, were associated with confirmatory biopsy and reclassification out of active surveillance. The study has some modest limitations. The multiparametric MR/US fusion technique has not been widely validated. The fusion system may contain registration or tracking errors. Furthermore, the scoring system used by these radiologists to classify benign and malignant tumors is not standardized. However, despite these limitations, the MR technique and the MR/US fusion make this a critically important study to add to the armamentarium for men considering active surveillance. Cary Siegel, MD
Urological Oncology: Testis Cancer and Advances in Oncologic Therapy Re: Solid Tumors after Chemotherapy or Surgery for Testicular Nonseminoma: A Population-Based Study C. Fung, S. D. Fossa, M. T. Milano, J. Oldenburg and L. B. Travis University of Rochester Medical Center, Rochester, New York, and Norwegian Radium Hospital, Oslo, Norway J Clin Oncol 2013; 31: 3807e3814.
Abstract available at http://jurology.com/ Editorial Comment: There is compelling evidence for the role of radiation therapy in the development of solid cancers after treatment for testicular cancer. However, the extent to which modern cisplatin based chemotherapy contributes to excess risk is less clear. The authors used SEER (Surveillance, Epidemiology and End Results) data from 1980 to 2008 to identify 6,000 patients with testis tumor treated initially with chemotherapy and 6,600 treated with surgery without radiation therapy. A total of 210 second solid cancers were observed. There was no increase in standard incidence ratios for patients following surgery, with a standardized incidence ratio of 0.93. However, after chemotherapy the standardized incidence ratio was 1.43, with a 40% excess risk of solid cancers. The median latency period was 12.5 years but some cancers occurred more than 20 years after treatment. There was a threefold to sevenfold increased risk of cancers of the kidney, thyroid and soft tissue. This study represents the first large population based series demonstrating a significant increase in solid cancers after modern cisplatin based chemotherapy. Jerome P. Richie, MD
1113
Re: Determination of Optimal Drug Dose and Light Dose Index to Achieve Minimally Invasive Focal Ablation of Localized Prostate Cancer Using WST11-Vascular Targeted Photodynamic (VTP) Therapy C. M. Moore, A. R. Azzouzi, E. Barret, A. Villers, G. Muir, N. Barber, J. Trachtenberg, N. Arumainayagam, B. Gaillac, C. Allen, A. Schertz and M. Emberton Division of Surgery and Interventional Science, University College London, London, United Kingdom BJU Int 2014; Epub ahead of print.
Abstract available at http://jurology.com/ Editorial Comment: This study of photodynamic therapy for focal treatment of prostate cancer reflects the findings in men treated in a phase I/II dose escalation study of a vascular targeted photodynamic therapy using an agent, WST11, which largely remains in the vascular space. The drug, when exposed to a specific wavelength of light, causes vascular thrombosis and tissue necrosis. In this study men with unilateral cancer on biopsy were subjected to gland hemiablation by vascular targeted photodynamic therapy. At increasing doses of drug, laser energy and number of laser fibers an optimal combination of drug dose and light energy was defined. At this dose confluent necrosis of the desired treatment volume was achieved in the majority of men treated. A previous version of the drug, WST09, was associated with considerable toxicity, resulting in cessation of its clinical development. None of the previous toxicity was observed with the current drug. A number of men in this and subsequent studies had residual cancer on biopsy, typically in untreated regions of the prostate. This finding illustrates the importance of 2 separate issues in evaluating the efficacy of focal therapy. First, the best method for candidate selection and cancer localization must be determined. This study falls short in addressing that issue. Systematic biopsy is clearly inadequate. The other concern, ie how to achieve confluent, complete zonal necrosis, is well addressed in this subset evaluation. Samir S. Taneja, MD
Suggested Reading Chevalier S, Cury FL, Scarlata E et al: Endoscopic vascular targeted photodynamic therapy with the photosensitizer WST11 for benign prostatic hyperplasia in the preclinical dog model. J Urol 2013; 190: 1946. Chevalier S, Anidjar M, Scarlata E et al: Preclinical study of the novel vascular occluding agent, WST11, for photodynamic therapy of the canine prostate. J Urol 2011; 186: 302.
Imaging Re: Accuracy of Multiparametric Magnetic Resonance Imaging in Confirming Eligibility for Active Surveillance for Men with Prostate Cancer L. Stamatakis, M. M. Siddiqui, J. W. Nix, J. Logan, S. Rais-Bahrami, A. Walton-Diaz, A. N. Hoang, S. Vourganti, H. Truong, B. Shuch, H. L. Parnes, B. Turkbey, P. L. Choyke, B. J. Wood, R. M. Simon and P. A. Pinto Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland Cancer 2013; 119: 3359e3366.
Abstract available at http://jurology.com/ Editorial Comment: Candidates had to meet study criteria of prostate specific antigen density 0.15 or less, 2 or fewer positive cores, less than 50% tumor in any core, Gleason score 6 or less and stage T1c disease. All patients underwent multiparametric magnetic resonance (MR) imaging,
1114
TESTIS CANCER AND ADVANCES IN ONCOLOGIC THERAPY
which included transrectal 3 T imaging with T1 and T2-weighted dynamic contrast enhancement, diffusion and MR spectroscopy. The MR imaging protocol used is clearly state of the art. Some imaging centers do not use 3 T endorectal imaging, some do not perform spectroscopy and many do not do either. MR scans were reviewed, and number of lesions, diameter, total volume and density (total lesion volume/prostate volume) were assessed. Lesions were assigned a suspicion score. If a targetable lesion was identified on MR imaging, the patient underwent transrectal ultrasound (US) guided biopsy with MR/US fusion, a technique that is important, especially in small lesions, but not universally available. The goal with prostate cancer is to balance the value of active surveillance in patients with clinically insignificant, small volume disease vs the risk of disease progression with clinically significant prostate cancer that could advance during the active surveillance period. These authors found that multiparametric MR imaging contributed to the decision making process. Three specific factors, ie number of lesions, score for suspected cancer and lesion density, were associated with confirmatory biopsy and reclassification out of active surveillance. The study has some modest limitations. The multiparametric MR/US fusion technique has not been widely validated. The fusion system may contain registration or tracking errors. Furthermore, the scoring system used by these radiologists to classify benign and malignant tumors is not standardized. However, despite these limitations, the MR technique and the MR/US fusion make this a critically important study to add to the armamentarium for men considering active surveillance. Cary Siegel, MD
Urological Oncology: Testis Cancer and Advances in Oncologic Therapy Re: Solid Tumors after Chemotherapy or Surgery for Testicular Nonseminoma: A Population-Based Study C. Fung, S. D. Fossa, M. T. Milano, J. Oldenburg and L. B. Travis University of Rochester Medical Center, Rochester, New York, and Norwegian Radium Hospital, Oslo, Norway J Clin Oncol 2013; 31: 3807e3814.
Abstract available at http://jurology.com/ Editorial Comment: There is compelling evidence for the role of radiation therapy in the development of solid cancers after treatment for testicular cancer. However, the extent to which modern cisplatin based chemotherapy contributes to excess risk is less clear. The authors used SEER (Surveillance, Epidemiology and End Results) data from 1980 to 2008 to identify 6,000 patients with testis tumor treated initially with chemotherapy and 6,600 treated with surgery without radiation therapy. A total of 210 second solid cancers were observed. There was no increase in standard incidence ratios for patients following surgery, with a standardized incidence ratio of 0.93. However, after chemotherapy the standardized incidence ratio was 1.43, with a 40% excess risk of solid cancers. The median latency period was 12.5 years but some cancers occurred more than 20 years after treatment. There was a threefold to sevenfold increased risk of cancers of the kidney, thyroid and soft tissue. This study represents the first large population based series demonstrating a significant increase in solid cancers after modern cisplatin based chemotherapy. Jerome P. Richie, MD