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Finding Minimal Extraprostatic Disease: Who Cares?
EURURO-6340; No. of Pages 2 EUROPEAN UROLOGY XXX (2015) XXX–XXX
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Platinum Priority – Editorial Referring to the article published on pp. x–y of this issue
Finding Minimal Extraprostatic Disease: Who Cares? Anwar R. Padhani a,*, Giuseppe Petralia b, Francesco Sanguedolce c,d a
Paul Strickland Scanner Centre, Mount Vernon Cancer Centre, Middlesex, UK; b Division of Radiology, IEO - European Institute of Oncology, Milan, Italy;
c
Northampton General Hospital, NHS Trust, Northampton, UK; d King’s College Hospital, NHS Foundation Trust, London, UK
The radiologic quest to accurately distinguish organconfined from non–organ-confined prostate cancer (PCa) has been a prolonged and ultimately unrewarding exercise. We have to face the fact that the best of our magnetic resonance imaging (MRI) machines cannot accurately detect minimal microscopic extrascapular tumour extension (ECE). In the modern era, however, when even patients with extensive ECE undergo successful surgical resections [1], the question that should be asked is, ‘‘Who really cares about microscopic ECE?’’ In this month’s issue of European Urology, de Rooij et al presented a meta-analysis of studies undertaken in the past 15 yr on the accuracy of MRI for the local staging of PCa, focusing on stage T2 versus T3 [2]. The pooled results are familiar to working radiologists but may be less well appreciated by urologists, namely, MRI has consistently high specificity (91%; 95% confidence interval [CI], 88–93%) for ruling in ECE but has very limited and highly variability sensitivity (57%; 95% CI, 88–93%) for ruling out ECE. Consequently, if an average radiologist says that ECE is present, then he or she is very likely to be correct, and the information should be acted on accordingly; however, when a radiologist says that there is no ECE, then this result should be viewed with some doubt and acted on according to the radiologist’s expertise and the potential management plan. The clinical management aspects of the presented radiologic results require further discussion. Clearly, it is the interplay between patients’ risk profiles and potential management plans for which MRI staging accuracy matters; however, the sensitivity analysis according to patient risk profiles is not stable, with a trend towards lower sensitivity for ECE in low-risk disease, thus limiting the applicability of
the presented data to patients. The authors recommended that a ‘‘risk-tailored’’ approach should be used for MRI analysis, using ‘‘high sensitivity readings in low- and intermediate-risk disease’’ and ‘‘high specificity readings in high-risk disease’’ [2]; what this means from a management perspective is not intuitively clear. To explain, if a patient is to undergo external beam radiation therapy for intermediate-risk disease that is amenable to cure, then the presence of established ECE on MRI would point towards unfavourable disease, requiring more aggressive management including the use of nodal irradiation and a longer course of adjuvant androgen deprivation therapy (ADT) as needed [3]. In contrast, for intermediate-risk disease in the absence of established ECE on MRI, nodal irradiation may not be needed, and short-course adjuvant ADT may suffice because microscopic ECE represents a disease category with more favourable prognosis [3,4]. For similar patients undergoing curative surgery, the presence of established disease on MRI calls for a surgical approach that avoids positive surgical margins (PSMs); however, wider surgical margins at the MRI-depicted site of ECE may not be sufficient to reduce PSM rates, even when more extensive surgery is undertaken at the location of suspected ECE, as shown by a recent randomised control trial [5]. Indeed, it seems that the most effective way to reduce PSMs is to undertake intraoperative frozen section (IFS) analysis at the location of the index prostatic lesion depicted by MRI and to perform as many secondary resections as necessary until negative margins are achieved. Using this combined MRI–IFS approach, Petralia et al were able to half the PSM rate of IFS-assisted radical robotic prostatectomy [6]. For those patients with no detected ECE on MRI, the threat of microscopic ECE remains sufficiently
DOI of original article: http://dx.doi.org/10.1016/j.eururo.2015.07.029. * Corresponding author. Paul Strickland Scanner Centre, Mount Vernon Cancer Centre, Rickmansworth Road, Northwood, Middlesex HA6 2RN, UK. Tel. +44 0 1923 844751; Fax: +44 0 1923 844600. E-mail address: [email protected] (A.R. Padhani). http://dx.doi.org/10.1016/j.eururo.2015.07.045 0302-2838/# 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.
Please cite this article in press as: Padhani ADTDDIFFDR, et al. Finding Minimal Extraprostatic Disease: Who Cares? Eur Urol (2015), http://dx.doi.org/10.1016/j.eururo.2015.07.045
EURURO-6340; No. of Pages 2 2
EUROPEAN UROLOGY XXX (2015) XXX–XXX
high such that nerve-sparing surgery should again be assisted by frozen section analysis at the MRI location of lesions that are at the margins of the prostate gland. Given the high negative predictive value of multiparametric MRI (mpMRI) for lesion localisation, nerve sparing without frozen section analysis can be performed safely at sites away from the site of the index lesion to expedite the time required for surgical resections [6]. The study of de Rooij et al [2] also highlights other aspects of radiologic debate that often arise at multidisciplinary meetings. One of these concerns is the requirement of the endorectal coil for MRI. The meta-analysis shows that endorectal coil usage showed no discernible benefit for ECE detection when used on machines operating at the field strength of 3 T, although there is a measurable benefit for cancer staging at 1.5 T. There is also a slight but discernible improved sensitivity for seminal vesicle invasion detection when endorectal coils are used. Another important message is that imaging at the higher field strength of 3 T improves detection sensitivity for ECE and overall T3 staging accuracy, providing further impetus for all PCa evaluations to be undertaken at the highest field strength available, in accordance with current imaging guidelines [7]. Finally, and perhaps most intriguingly, mpMRI, which incorporates additional functional techniques, improves sensitivity for ECE detection compared with morphologic evaluations undertaken by T2-weighted images alone. The obvious question that arises is, ‘‘How do lower resolution techniques such as magnetic resonance spectroscopic imaging and diffusion weighted imaging (DWI) improve staging accuracy, which of necessity should be addressable only with high-resolution imaging techniques?’’ The answer is that mpMRI, particularly DWI, can depict the location of the majority of index prostatic lesions [8]. Because T3 disease is directly related to the index lesion size and aggressiveness [9], the ability of mpMRI to successfully depict most index lesions focuses attention on the adjacent prostatic capsule and seminal vesicle. Radiologists are trained to call T3 disease when there is broad contact length of tumour with the prostatic capsule [10], particularly when the cancer has a low apparent diffusion coefficient value on DWI and/or when the Prostate Imaging Reporting and Data System (PI-RADS) score is high [7], thus improving sensitivity. We have already noted that this improved
ability to detect index lesion location also improves surgical resections [6]. The study of de Rooij et al [2] on the average accuracy of MRI to distinguish T2 from T3 disease provides the working basis for discussions within multidisciplinary teams regarding the optimal management of PCa patients; such discussions need to take into account other factors including the clinical risk profiles of patients. Conflicts of interest: The authors have nothing to disclose.
References [1] Somford DM, Hamoen EH, Fu¨tterer JJ, et al. The predictive value of endorectal 3-Tesla multiparametric MRI for extraprostatic extension in low-, intermediate and high-risk prostate cancer patients. J Urol 2013;190:1728–34. [2] de Rooij M, Hamoen EHJ, Witjes JA, Barentsz JO, Rovers MM. Accuracy of magnetic resonance imaging for local staging of prostate cancer: a diagnostic meta-analysis. Eur Urol. In press. http://dx. doi.org/10.1016/j.eururo.2015.07.029 [3] D’Amico AV. Personalizing the management of men with intermediate-risk prostate cancer. Eur Urol 2013;64:903–4. [4] Chuang AY, Nielsen ME, Hernandez DJ, Walsh PC, Epstein JI. The significance of positive surgical margin in areas of capsular incision in otherwise organ confined disease at radical prostatectomy. J Urol 2007;178:1306–10. [5] Rud E, Baco E, Klotz D, et al. Does preoperative magnetic resonance imaging reduce the rate of positive surgical margins at radical prostatectomy in a randomised clinical trial? Eur Urol 2015;68: 487–96. [6] Petralia G, Musi G, Padhani AR, et al. Robot-assisted radical prostatectomy: multiparametric MR imaging-directed intraoperative frozen-section analysis to reduce the rate of positive surgical margins. Radiology 2015;274:434–44. [7] Barentsz JO, Richenberg J, Clements R, et al. ESUR prostate MR guidelines 2012. Eur Radiol 2012;22:746–57. [8] Rud E, Klotz D, Rennesund K, et al. Detection of the index tumour and tumour volume in prostate cancer using T2-weighted and diffusion-weighted magnetic resonance imaging (MRI) alone. BJU Int 2014;114:E32–42. [9] Karavitakis M, Ahmed HU, Abel PD, Hazell S, Winkler MH. Margin status after laparoscopic radical prostatectomy and the index lesion: implications for preoperative evaluation of tumor focality in prostate cancer. J Endourol 2012;26:503–8. [10] Baco E, Rud E, Vlatkovic L, et al. Predictive value of magnetic resonance imaging determined tumor contact length for extracapsular extension of prostate cancer. J Urol 2015;193:466–72.
Please cite this article in press as: Padhani ADTDDIFFDR, et al. Finding Minimal Extraprostatic Disease: Who Cares? Eur Urol (2015), http://dx.doi.org/10.1016/j.eururo.2015.07.045
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Platinum Priority – Editorial Referring to the article published on pp. x–y of this issue
Finding Minimal Extraprostatic Disease: Who Cares? Anwar R. Padhani a,*, Giuseppe Petralia b, Francesco Sanguedolce c,d a
Paul Strickland Scanner Centre, Mount Vernon Cancer Centre, Middlesex, UK; b Division of Radiology, IEO - European Institute of Oncology, Milan, Italy;
c
Northampton General Hospital, NHS Trust, Northampton, UK; d King’s College Hospital, NHS Foundation Trust, London, UK
The radiologic quest to accurately distinguish organconfined from non–organ-confined prostate cancer (PCa) has been a prolonged and ultimately unrewarding exercise. We have to face the fact that the best of our magnetic resonance imaging (MRI) machines cannot accurately detect minimal microscopic extrascapular tumour extension (ECE). In the modern era, however, when even patients with extensive ECE undergo successful surgical resections [1], the question that should be asked is, ‘‘Who really cares about microscopic ECE?’’ In this month’s issue of European Urology, de Rooij et al presented a meta-analysis of studies undertaken in the past 15 yr on the accuracy of MRI for the local staging of PCa, focusing on stage T2 versus T3 [2]. The pooled results are familiar to working radiologists but may be less well appreciated by urologists, namely, MRI has consistently high specificity (91%; 95% confidence interval [CI], 88–93%) for ruling in ECE but has very limited and highly variability sensitivity (57%; 95% CI, 88–93%) for ruling out ECE. Consequently, if an average radiologist says that ECE is present, then he or she is very likely to be correct, and the information should be acted on accordingly; however, when a radiologist says that there is no ECE, then this result should be viewed with some doubt and acted on according to the radiologist’s expertise and the potential management plan. The clinical management aspects of the presented radiologic results require further discussion. Clearly, it is the interplay between patients’ risk profiles and potential management plans for which MRI staging accuracy matters; however, the sensitivity analysis according to patient risk profiles is not stable, with a trend towards lower sensitivity for ECE in low-risk disease, thus limiting the applicability of
the presented data to patients. The authors recommended that a ‘‘risk-tailored’’ approach should be used for MRI analysis, using ‘‘high sensitivity readings in low- and intermediate-risk disease’’ and ‘‘high specificity readings in high-risk disease’’ [2]; what this means from a management perspective is not intuitively clear. To explain, if a patient is to undergo external beam radiation therapy for intermediate-risk disease that is amenable to cure, then the presence of established ECE on MRI would point towards unfavourable disease, requiring more aggressive management including the use of nodal irradiation and a longer course of adjuvant androgen deprivation therapy (ADT) as needed [3]. In contrast, for intermediate-risk disease in the absence of established ECE on MRI, nodal irradiation may not be needed, and short-course adjuvant ADT may suffice because microscopic ECE represents a disease category with more favourable prognosis [3,4]. For similar patients undergoing curative surgery, the presence of established disease on MRI calls for a surgical approach that avoids positive surgical margins (PSMs); however, wider surgical margins at the MRI-depicted site of ECE may not be sufficient to reduce PSM rates, even when more extensive surgery is undertaken at the location of suspected ECE, as shown by a recent randomised control trial [5]. Indeed, it seems that the most effective way to reduce PSMs is to undertake intraoperative frozen section (IFS) analysis at the location of the index prostatic lesion depicted by MRI and to perform as many secondary resections as necessary until negative margins are achieved. Using this combined MRI–IFS approach, Petralia et al were able to half the PSM rate of IFS-assisted radical robotic prostatectomy [6]. For those patients with no detected ECE on MRI, the threat of microscopic ECE remains sufficiently
DOI of original article: http://dx.doi.org/10.1016/j.eururo.2015.07.029. * Corresponding author. Paul Strickland Scanner Centre, Mount Vernon Cancer Centre, Rickmansworth Road, Northwood, Middlesex HA6 2RN, UK. Tel. +44 0 1923 844751; Fax: +44 0 1923 844600. E-mail address: [email protected] (A.R. Padhani). http://dx.doi.org/10.1016/j.eururo.2015.07.045 0302-2838/# 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.
Please cite this article in press as: Padhani ADTDDIFFDR, et al. Finding Minimal Extraprostatic Disease: Who Cares? Eur Urol (2015), http://dx.doi.org/10.1016/j.eururo.2015.07.045
EURURO-6340; No. of Pages 2 2
EUROPEAN UROLOGY XXX (2015) XXX–XXX
high such that nerve-sparing surgery should again be assisted by frozen section analysis at the MRI location of lesions that are at the margins of the prostate gland. Given the high negative predictive value of multiparametric MRI (mpMRI) for lesion localisation, nerve sparing without frozen section analysis can be performed safely at sites away from the site of the index lesion to expedite the time required for surgical resections [6]. The study of de Rooij et al [2] also highlights other aspects of radiologic debate that often arise at multidisciplinary meetings. One of these concerns is the requirement of the endorectal coil for MRI. The meta-analysis shows that endorectal coil usage showed no discernible benefit for ECE detection when used on machines operating at the field strength of 3 T, although there is a measurable benefit for cancer staging at 1.5 T. There is also a slight but discernible improved sensitivity for seminal vesicle invasion detection when endorectal coils are used. Another important message is that imaging at the higher field strength of 3 T improves detection sensitivity for ECE and overall T3 staging accuracy, providing further impetus for all PCa evaluations to be undertaken at the highest field strength available, in accordance with current imaging guidelines [7]. Finally, and perhaps most intriguingly, mpMRI, which incorporates additional functional techniques, improves sensitivity for ECE detection compared with morphologic evaluations undertaken by T2-weighted images alone. The obvious question that arises is, ‘‘How do lower resolution techniques such as magnetic resonance spectroscopic imaging and diffusion weighted imaging (DWI) improve staging accuracy, which of necessity should be addressable only with high-resolution imaging techniques?’’ The answer is that mpMRI, particularly DWI, can depict the location of the majority of index prostatic lesions [8]. Because T3 disease is directly related to the index lesion size and aggressiveness [9], the ability of mpMRI to successfully depict most index lesions focuses attention on the adjacent prostatic capsule and seminal vesicle. Radiologists are trained to call T3 disease when there is broad contact length of tumour with the prostatic capsule [10], particularly when the cancer has a low apparent diffusion coefficient value on DWI and/or when the Prostate Imaging Reporting and Data System (PI-RADS) score is high [7], thus improving sensitivity. We have already noted that this improved
ability to detect index lesion location also improves surgical resections [6]. The study of de Rooij et al [2] on the average accuracy of MRI to distinguish T2 from T3 disease provides the working basis for discussions within multidisciplinary teams regarding the optimal management of PCa patients; such discussions need to take into account other factors including the clinical risk profiles of patients. Conflicts of interest: The authors have nothing to disclose.
References [1] Somford DM, Hamoen EH, Fu¨tterer JJ, et al. The predictive value of endorectal 3-Tesla multiparametric MRI for extraprostatic extension in low-, intermediate and high-risk prostate cancer patients. J Urol 2013;190:1728–34. [2] de Rooij M, Hamoen EHJ, Witjes JA, Barentsz JO, Rovers MM. Accuracy of magnetic resonance imaging for local staging of prostate cancer: a diagnostic meta-analysis. Eur Urol. In press. http://dx. doi.org/10.1016/j.eururo.2015.07.029 [3] D’Amico AV. Personalizing the management of men with intermediate-risk prostate cancer. Eur Urol 2013;64:903–4. [4] Chuang AY, Nielsen ME, Hernandez DJ, Walsh PC, Epstein JI. The significance of positive surgical margin in areas of capsular incision in otherwise organ confined disease at radical prostatectomy. J Urol 2007;178:1306–10. [5] Rud E, Baco E, Klotz D, et al. Does preoperative magnetic resonance imaging reduce the rate of positive surgical margins at radical prostatectomy in a randomised clinical trial? Eur Urol 2015;68: 487–96. [6] Petralia G, Musi G, Padhani AR, et al. Robot-assisted radical prostatectomy: multiparametric MR imaging-directed intraoperative frozen-section analysis to reduce the rate of positive surgical margins. Radiology 2015;274:434–44. [7] Barentsz JO, Richenberg J, Clements R, et al. ESUR prostate MR guidelines 2012. Eur Radiol 2012;22:746–57. [8] Rud E, Klotz D, Rennesund K, et al. Detection of the index tumour and tumour volume in prostate cancer using T2-weighted and diffusion-weighted magnetic resonance imaging (MRI) alone. BJU Int 2014;114:E32–42. [9] Karavitakis M, Ahmed HU, Abel PD, Hazell S, Winkler MH. Margin status after laparoscopic radical prostatectomy and the index lesion: implications for preoperative evaluation of tumor focality in prostate cancer. J Endourol 2012;26:503–8. [10] Baco E, Rud E, Vlatkovic L, et al. Predictive value of magnetic resonance imaging determined tumor contact length for extracapsular extension of prostate cancer. J Urol 2015;193:466–72.
Please cite this article in press as: Padhani ADTDDIFFDR, et al. Finding Minimal Extraprostatic Disease: Who Cares? Eur Urol (2015), http://dx.doi.org/10.1016/j.eururo.2015.07.045