Editorial
Multiparametric MRI for Prostate Cancer Seeing Is Believing Christopher A. Warlick, MD, PhD
In this issue of Cancer, Salami et al present a study examining the ability of multiparametric magnetic resonance imaging (MP-MRI) with subsequent MRI/transrectal ultrasound (TRUS) fusion biopsy (fusion biopsy) and the Prostate Cancer Prevention Trial High-Grade (PCPTHG) nomogram to predict the presence of clinically significant prostate cancer in a largely referral-based population.1 Theirs is another article in a growing chorus suggesting improvement in our ability to identify clinically significant disease through the use of MP-MRI and image-guided biopsies. The authors report on 175 men who underwent MP-MRI for an elevated prostate-specific antigen (PSA) level or an abnormal digital rectal examination (DRE). If a suspicious lesion was identified on MP-MRI, then the men underwent fusion biopsy followed by a standard 12-core biopsy after the fusion system was turned off in an effort to blind the urologist obtaining the biopsy. The majority of men had previously undergone TRUS-guided prostate biopsy. It is noteworthy that a large fraction of men who had suspicious lesions identified did not undergo the protocol biopsy and, instead, underwent biopsy by their primary urologists and were not included in the analysis. The men who underwent MP-MRI but who had no suspicious lesions identified also did not undergo a protocol biopsy. The outcome of any biopsies these men may have undergone is not reported. These limitations aside, the authors noted an overall cancer detection rate of 64.6%, and 47.4% of men had Gleason scores 7. The cancer detection rate was similar among men who had undergone previous biopsy and those who had not. The area under the receiver operating characteristic curve (AUC) for MP-MRI and fusion biopsy in predicting clinically significant disease, as defined by the presence of a Gleason score 7, was 0.769 compared with 0.676 for the PCPTHG, which did not reflect a statistically significant difference. MP-MRI and fusion biopsy performed statistically better than the PCPTHG when the definition of clinically significant disease was changed according to the Epstein criteria (0.812 vs 0.676, respectively), an outcome the PCPTHG was not designed to predict. The authors conclude that MP-MRI and fusion biopsy perform better than the PCPTHG in predicting the presence of clinically significant disease. Salami and colleagues correctly state that the PCPTHG nomogram was developed in the placebo arm of the PCPT, which comprised men different from the relatively high-risk men in the current study who were referred for evaluation because of an elevated PSA (and likely rising PSA in many cases) or an abnormal DRE. The majority of these men had already undergone a previous biopsy. Given these differences, it is perhaps less surprising that the nomogram did not perform terribly well in this population of men. Application of a nomogram to a different patient than for whom it was intended may result in a vastly different performance of the nomogram, and the validity of the prediction may be compromised. The study was also limited by 2 types of potential bias. Selection bias may be involved, because there was the loss of a large fraction of men who qualified for the study but did not undergo the protocol biopsy. It is unknown whether the characteristics of these men were the same as those who stayed in the study. It is possible that some of these men were not referred back for protocol biopsy because the lesions noted on MRI were so obvious that the primary urologist felt confident that they could biopsy the suspicious areas either with or without MRI guidance, potentially removing a population of men who likely would have been positive by TRUS-guided biopsy and would not benefit from fusion biopsy. In addition, there was a lack of follow-up biopsies in men who had negative scans; thus, it is not clear how many cancers were not diagnosed by MRI or what was the nature of those cancers. Furthermore, the lack of independent verification of
Corresponding author: Christopher Warlick, MD, PhD, 420 Delaware Street SE, Mayo Mail Code 394, Minneapolis, Minneapolis, MN 55455; Fax: (612) 626-0428; [email protected] Department of Urology, University of Minnesota, Minneapolis, Minnesota See referenced original article on pages 2876-82, this issue. DOI: 10.1002/cncr.28787, Received: April 8, 2014; Accepted: April 21, 2014, Published online June 10, 2014 in Wiley Online Library (wileyonlinelibrary.com)
2806
Cancer
September 15, 2014
MP-MRI: Seeing is Believing/Warlick
the tested result, for instance, by pathology after prostatectomy, raises the possibility of verification bias playing a role to some degree in the observed results. The above noted limitations are not unique to this study and have become common in the literature as we strive to provide the best evidence we can generate that a particular approach or technology works within the confines of practicality, time, and available resources. Despite these limitations, the study does suggest that MP-MRI and guided biopsies likely perform better than the PCPTHG in predicting men with some definitions of clinically significant disease. The use of MP-MRI is expanding and has indeed demonstrated significant promise in the ability to detect prostate cancer, including high-grade lesions, particularly in men with previous negative TRUS biopsies. Several studies have produced a cancer detection rate of between 38% and 59% in this population.2-6 Currently, it remains to be determined whether MP-MRI would work as a primary screening tool in men at lower risk of prostate cancer, such as men with normal PSA and DRE findings. Alternatively, perhaps MP-MRI–based screening would perform better among men at higher risk of prostate cancer, such as men of African American descent or men with a family history of prostate cancer, even before they present with elevated PSA or abnormal DRE. Given the significant disparities in outcomes suffered by African American men, it appears that an improved screening regimen for these men beyond PSA warrants investigation. Another application of MP-MRI has been in the selection of men for active surveillance. MP-MRI and MRI-guided biopsies have demonstrated a significant negative predictive value for the detection of clinically significant disease, thus causing some to advocate for its use in selecting men for active surveillance.7-10 However, it is becoming increasingly apparent that perhaps the definitions of clinically significant disease, and specifically criteria to be used for selecting patients for active surveillance, need to be revisited in the context of MP-MRI and guided biopsies. The Epstein criteria originally were developed when 6-core biopsies were the standard and, commonly interpreted in the context of 12-core to 16-core TRUS biopsies, may not be applicable to MRIguided biopsies. Recent re-evaluation of the Epstein criteria indicate that, although they are still useful, many men may be misclassified as having indolent disease by virtue of the finding that the more aggressive disease is missed on TRUS biopsy because of its anterior location. This problem may be addressed by the use of MP-MRI Cancer
September 15, 2014
and MRI-guided biopsies, because the anterior prostate can be more easily targeted. This appears to be more problematic in African American men than Caucasians.11 Furthermore, MRI-guided biopsies on average tend to have a greater percentage of the core involved with cancer than TRUS biopsies.5 It is somewhat unclear exactly how to interpret the findings of positive biopsies generated in this way in the context of the Epstein criteria; simply because we are able to sample a lesion better does not necessarily change the intrinsic volume or aggressiveness of the lesion. It would likely be overkill to exclude a man from active surveillance because of the finding of an increased volume of cancer on a particular core of tissue obtained by MRIguided biopsy if they otherwise would have qualified based on a TRUS biopsy, because the majority of these men do well. Furthermore, if 2 biopsies are obtained from 2 different areas of the same suspicious lesion on fusion or MRI-guided biopsy, then should that count as 2 cores or just 1 core in application of the Epstein criteria or other active surveillance selection criteria that include the number of cores of tissue positive for cancer? Consensus will need to be reached on such issues as long as we continue to use these criteria to determine the presence of insignificant disease and to select men for active surveillance. On the basis of these concerns, it seems that 1 natural next step is the incorporation of new molecular-based risk stratification tools, such as Oncotype DX for prostate marketed by Genomic Health (Redwood City, Calif) or the Prolaris assay marketed by Myriad Genetics (Salt Lake City, Utah), into a model that includes clinical and pathologic information. To the degree that these tests are subject to sampling error inherent in TRUS biopsies, MRI-guided biopsies are likely to provide more relevant information from what we believe to be the most clinically significant lesions in the prostate and avoid information obtained from accidently discovered clinically insignificant lesions obtained through TRUS biopsies. Ultimately, we hope to develop imaging biomarkers of aggressiveness that would eventually obviate the need for biopsy in most cases and allow us to make clinical decisions based solely on imaging characteristics. The advent of MRI/ultrasound fusion technology combines the advantages of MP-MRI with the convenience of in-office ultrasound. At least 6 MRI/ultrasound fusion systems have been developed worldwide.12 Three systems are readily commercially available in the United States, including the UroNav sold by InVivo (Gainesville, Fla), which uses a rigid coregistration system; the Urostation sold by Koelis (La Tronche, France), which employs an elastic coregistration system; and the Atemis system 2807
Editorial
sold by Eigen (Grass Valley, Calif), which uses elastic coregistration. The development of MRI/ultrasound fusion platforms is an important technological advance for urologists, because, before their development, prostate biopsy was in jeopardy of becoming the purview of radiologists able to perform MRI-guided biopsies in the MRI suite to the exclusion of the urologist. Fusion technology will likely accelerate the adoption of MP-MRI in the routine management of patients being considered for prostate biopsy. However, as noted in the current article by Salami et al, the results achieved in their study and in other similarly published series represent a best-case scenario using state-of-the-art MRI techniques, including a 3T magnet with surface as well as endorectal coils, and images interpreted by a panel of 3 radiologists with extensive experience reading prostate MRIs. It is not clear that the results would be similar outside of the context of a similarly experienced center. There is no doubt a learning curve exists for both radiologists and urologists in reading prostate MRIs and performing MRI-guided interventions. It is likely that, during the anticipated expansion phase over the next few years, many groups may experience results that do not mirror the literature until enough experience is collectively gained that the majority of urologists and radiologists become adequately familiar with the techniques and principles, similar to how most urologists currently are comfortable with TRUS, whereas, in the past, this was not the case. Another likely unanticipated consequence of an expansion of fusion biopsy techniques is that, in the short term, the number of cores of tissue removed during biopsies will likely go up before they go down as practitioners perform standard 12-core to 14-core biopsies (and as they biopsy more borderline suspicious lesions) in addition to the biopsy of significantly MRI-suspicious lesions initially, until enough experience is gained that lesions can be confidently excluded without biopsy. Ultimately, as more evidence accrues, hopefully we will be able to biopsy only the MRI-suspicious lesions, thus limiting the number of cores men undergo and excluding some men completely from biopsy. In the current environment of growing cost concerns, the other important determinant of how widespread and rapidly MP-MRI and guided biopsies expand is cost. MP-MRI obtained in preparation of a fusion biopsy adds an additional cost of approximately $1500 to $2000 onto the costs of a TRUS-guided biopsy. Although the performance of a fusion biopsy itself is only slightly more expensive than that of a standard TRUS biopsy, a substantial initial capital investment is 2808
required to purchase a fusion system (approximately $200,000). Before the complete adoption of MP-MRI into routine diagnostic practice, it will probably be necessary to demonstrate a cost savings downstream of the use of MRI. This is only likely to happen if it is demonstrated conclusively that MP-MRI can safely exclude substantial numbers of men from biopsy and possible diagnosis and treatment of disease unlikely to affect a man’s life span. A recent article by Pokorny et al,13 who compared TRUS biopsy results with MRIguided biopsy results in biopsy-naive men who were referred to biopsy for an elevated PSA, demonstrated that TRUS biopsies detected cancer in 56.5% of men, 37.3% of which were considered low-risk cancers; whereas MRI-guided biopsy detected cancer in 69.7% of men, and only 6.1% were considered low risk. The MRI-guided biopsy pathway reduced the need for biopsy by 51% and reduced the risk of diagnosis of lowrisk prostate cancer by 89.4% while increasing the diagnosis of intermediate-risk and high-risk disease by 17.7% suggesting the possibility of a cost savings while improving care. Information provided by studies such as these as well as the study by Salami et al in the current issue take us 1 step further in that direction. If a picture is worth a thousand words, how many biopsies is the absence of an MRI-suspicious lesion worth? FUNDING SUPPORT No specific funding was disclosed.
CONFLICT OF INTEREST DISCLOSURES Dr. Warlick reports personal fees from Dendreon Corporation outside the submitted work.
REFERENCES 1. Salami SS, Vira MA, Turkbey B, et al. Multiparametric magnetic resonance imaging outperforms the Prostate Cancer Prevention Trial risk calculator in predicting clinically significant prostate cancer. Cancer. 2014;120:2876-2882. 2. Vourganti S, Rastinehad A, Yerram NK, et al. Multiparametric magnetic resonance imaging and ultrasound fusion biopsy detect prostate cancer in patients with prior negative transrectal ultrasound biopsies. J Urol. 2012;188:2152-2157. 3. Hambrock T, Somford DM, Hoeks C, et al. Magnetic resonance imaging guided prostate biopsy in men with repeat negative biopsies and increased prostate specific antigen. J Urol. 2010;183:520527. 4. Roethke M, Anastasiadis AG, Lichy M, et al. MRI-guided prostate biopsy detects clinically significant cancer: analysis of a cohort of 100 patients after previous negative TRUS biopsy. World J Urol. 2012;30:213-218. 5. Pinto PA, Chung PH, Rastinehad AR, et al. Magnetic resonance imaging/ultrasound fusion guided prostate biopsy improves cancer detection following transrectal ultrasound biopsy and correlates with multiparametric magnetic resonance imaging. J Urol. 2011;186:1281-1285. 6. Franiel T, Stephan C, Erbersdobler A, et al. Areas suspicious for prostate cancer: MR-guided biopsy in patients with at least 1 transrectal
Cancer
September 15, 2014
MP-MRI: Seeing is Believing/Warlick
7.
8. 9.
10.
US-guided biopsy with a negative finding—multiparametric MR imaging for detection and biopsy planning. Radiology. 2011;259: 162-172. Haffner J, Lemaitre L, Puech P, et al. Role of magnetic resonance imaging before initial biopsy: comparison of magnetic resonance imaging-targeted and systematic biopsy for significant prostate cancer detection. BJU Int. 2011;108:171-178. Fradet V, Kurhanewicz J, Cowan JE, et al. Prostate cancer managed with active surveillance: role of anatomic MR imaging and MR spectroscopic imaging. Radiology. 2010;256:176-183. Margel D, Yap SA, Lawrentschuk N, et al. Impact of multiparametric endorectal coil prostate magnetic resonance imaging on disease reclassification among active surveillance candidates: a prospective cohort study. J Urol. 2012;187:1247-1252. Hoeks CM, Somford DM, van Oort IM, et al. Value of 3-T multiparametric magnetic resonance imaging and magnetic resonance-
Cancer
September 15, 2014
guided biopsy for early risk restratification in active surveillance of low-risk prostate cancer: a prospective multicenter cohort study. Invest Radiol. 2014;49:165-172. 11. Kryvenko ON, Carter HB, Trock BJ, Epstein JI. Biopsy criteria for determining appropriateness for active surveillance in the modern era. Urology. 2014;83:869-874. 12. Logan JK, Rais-Bahrami S, Turkbey B, et al. Current status of MRI and ultrasound fusion software platforms for guidance of prostate biopsies [published online ahead of print December 3, 2013]. BJU Int. doi: 10.1111/bju.12593. 13. Pokorny MR, de Rooij M, Duncan E, et al. Prospective study of diagnostic accuracy comparing prostate cancer detection by transrectal ultrasound-guided biopsy versus magnetic resonance (MR) imaging with subsequent MR-guided biopsy in men without previous prostate biopsies [published online ahead of print March 14, 2014]. Eur Urol. doi: 10.1016/j.eururo.2014.03.002.
2809
Multiparametric MRI for Prostate Cancer Seeing Is Believing Christopher A. Warlick, MD, PhD
In this issue of Cancer, Salami et al present a study examining the ability of multiparametric magnetic resonance imaging (MP-MRI) with subsequent MRI/transrectal ultrasound (TRUS) fusion biopsy (fusion biopsy) and the Prostate Cancer Prevention Trial High-Grade (PCPTHG) nomogram to predict the presence of clinically significant prostate cancer in a largely referral-based population.1 Theirs is another article in a growing chorus suggesting improvement in our ability to identify clinically significant disease through the use of MP-MRI and image-guided biopsies. The authors report on 175 men who underwent MP-MRI for an elevated prostate-specific antigen (PSA) level or an abnormal digital rectal examination (DRE). If a suspicious lesion was identified on MP-MRI, then the men underwent fusion biopsy followed by a standard 12-core biopsy after the fusion system was turned off in an effort to blind the urologist obtaining the biopsy. The majority of men had previously undergone TRUS-guided prostate biopsy. It is noteworthy that a large fraction of men who had suspicious lesions identified did not undergo the protocol biopsy and, instead, underwent biopsy by their primary urologists and were not included in the analysis. The men who underwent MP-MRI but who had no suspicious lesions identified also did not undergo a protocol biopsy. The outcome of any biopsies these men may have undergone is not reported. These limitations aside, the authors noted an overall cancer detection rate of 64.6%, and 47.4% of men had Gleason scores 7. The cancer detection rate was similar among men who had undergone previous biopsy and those who had not. The area under the receiver operating characteristic curve (AUC) for MP-MRI and fusion biopsy in predicting clinically significant disease, as defined by the presence of a Gleason score 7, was 0.769 compared with 0.676 for the PCPTHG, which did not reflect a statistically significant difference. MP-MRI and fusion biopsy performed statistically better than the PCPTHG when the definition of clinically significant disease was changed according to the Epstein criteria (0.812 vs 0.676, respectively), an outcome the PCPTHG was not designed to predict. The authors conclude that MP-MRI and fusion biopsy perform better than the PCPTHG in predicting the presence of clinically significant disease. Salami and colleagues correctly state that the PCPTHG nomogram was developed in the placebo arm of the PCPT, which comprised men different from the relatively high-risk men in the current study who were referred for evaluation because of an elevated PSA (and likely rising PSA in many cases) or an abnormal DRE. The majority of these men had already undergone a previous biopsy. Given these differences, it is perhaps less surprising that the nomogram did not perform terribly well in this population of men. Application of a nomogram to a different patient than for whom it was intended may result in a vastly different performance of the nomogram, and the validity of the prediction may be compromised. The study was also limited by 2 types of potential bias. Selection bias may be involved, because there was the loss of a large fraction of men who qualified for the study but did not undergo the protocol biopsy. It is unknown whether the characteristics of these men were the same as those who stayed in the study. It is possible that some of these men were not referred back for protocol biopsy because the lesions noted on MRI were so obvious that the primary urologist felt confident that they could biopsy the suspicious areas either with or without MRI guidance, potentially removing a population of men who likely would have been positive by TRUS-guided biopsy and would not benefit from fusion biopsy. In addition, there was a lack of follow-up biopsies in men who had negative scans; thus, it is not clear how many cancers were not diagnosed by MRI or what was the nature of those cancers. Furthermore, the lack of independent verification of
Corresponding author: Christopher Warlick, MD, PhD, 420 Delaware Street SE, Mayo Mail Code 394, Minneapolis, Minneapolis, MN 55455; Fax: (612) 626-0428; [email protected] Department of Urology, University of Minnesota, Minneapolis, Minnesota See referenced original article on pages 2876-82, this issue. DOI: 10.1002/cncr.28787, Received: April 8, 2014; Accepted: April 21, 2014, Published online June 10, 2014 in Wiley Online Library (wileyonlinelibrary.com)
2806
Cancer
September 15, 2014
MP-MRI: Seeing is Believing/Warlick
the tested result, for instance, by pathology after prostatectomy, raises the possibility of verification bias playing a role to some degree in the observed results. The above noted limitations are not unique to this study and have become common in the literature as we strive to provide the best evidence we can generate that a particular approach or technology works within the confines of practicality, time, and available resources. Despite these limitations, the study does suggest that MP-MRI and guided biopsies likely perform better than the PCPTHG in predicting men with some definitions of clinically significant disease. The use of MP-MRI is expanding and has indeed demonstrated significant promise in the ability to detect prostate cancer, including high-grade lesions, particularly in men with previous negative TRUS biopsies. Several studies have produced a cancer detection rate of between 38% and 59% in this population.2-6 Currently, it remains to be determined whether MP-MRI would work as a primary screening tool in men at lower risk of prostate cancer, such as men with normal PSA and DRE findings. Alternatively, perhaps MP-MRI–based screening would perform better among men at higher risk of prostate cancer, such as men of African American descent or men with a family history of prostate cancer, even before they present with elevated PSA or abnormal DRE. Given the significant disparities in outcomes suffered by African American men, it appears that an improved screening regimen for these men beyond PSA warrants investigation. Another application of MP-MRI has been in the selection of men for active surveillance. MP-MRI and MRI-guided biopsies have demonstrated a significant negative predictive value for the detection of clinically significant disease, thus causing some to advocate for its use in selecting men for active surveillance.7-10 However, it is becoming increasingly apparent that perhaps the definitions of clinically significant disease, and specifically criteria to be used for selecting patients for active surveillance, need to be revisited in the context of MP-MRI and guided biopsies. The Epstein criteria originally were developed when 6-core biopsies were the standard and, commonly interpreted in the context of 12-core to 16-core TRUS biopsies, may not be applicable to MRIguided biopsies. Recent re-evaluation of the Epstein criteria indicate that, although they are still useful, many men may be misclassified as having indolent disease by virtue of the finding that the more aggressive disease is missed on TRUS biopsy because of its anterior location. This problem may be addressed by the use of MP-MRI Cancer
September 15, 2014
and MRI-guided biopsies, because the anterior prostate can be more easily targeted. This appears to be more problematic in African American men than Caucasians.11 Furthermore, MRI-guided biopsies on average tend to have a greater percentage of the core involved with cancer than TRUS biopsies.5 It is somewhat unclear exactly how to interpret the findings of positive biopsies generated in this way in the context of the Epstein criteria; simply because we are able to sample a lesion better does not necessarily change the intrinsic volume or aggressiveness of the lesion. It would likely be overkill to exclude a man from active surveillance because of the finding of an increased volume of cancer on a particular core of tissue obtained by MRIguided biopsy if they otherwise would have qualified based on a TRUS biopsy, because the majority of these men do well. Furthermore, if 2 biopsies are obtained from 2 different areas of the same suspicious lesion on fusion or MRI-guided biopsy, then should that count as 2 cores or just 1 core in application of the Epstein criteria or other active surveillance selection criteria that include the number of cores of tissue positive for cancer? Consensus will need to be reached on such issues as long as we continue to use these criteria to determine the presence of insignificant disease and to select men for active surveillance. On the basis of these concerns, it seems that 1 natural next step is the incorporation of new molecular-based risk stratification tools, such as Oncotype DX for prostate marketed by Genomic Health (Redwood City, Calif) or the Prolaris assay marketed by Myriad Genetics (Salt Lake City, Utah), into a model that includes clinical and pathologic information. To the degree that these tests are subject to sampling error inherent in TRUS biopsies, MRI-guided biopsies are likely to provide more relevant information from what we believe to be the most clinically significant lesions in the prostate and avoid information obtained from accidently discovered clinically insignificant lesions obtained through TRUS biopsies. Ultimately, we hope to develop imaging biomarkers of aggressiveness that would eventually obviate the need for biopsy in most cases and allow us to make clinical decisions based solely on imaging characteristics. The advent of MRI/ultrasound fusion technology combines the advantages of MP-MRI with the convenience of in-office ultrasound. At least 6 MRI/ultrasound fusion systems have been developed worldwide.12 Three systems are readily commercially available in the United States, including the UroNav sold by InVivo (Gainesville, Fla), which uses a rigid coregistration system; the Urostation sold by Koelis (La Tronche, France), which employs an elastic coregistration system; and the Atemis system 2807
Editorial
sold by Eigen (Grass Valley, Calif), which uses elastic coregistration. The development of MRI/ultrasound fusion platforms is an important technological advance for urologists, because, before their development, prostate biopsy was in jeopardy of becoming the purview of radiologists able to perform MRI-guided biopsies in the MRI suite to the exclusion of the urologist. Fusion technology will likely accelerate the adoption of MP-MRI in the routine management of patients being considered for prostate biopsy. However, as noted in the current article by Salami et al, the results achieved in their study and in other similarly published series represent a best-case scenario using state-of-the-art MRI techniques, including a 3T magnet with surface as well as endorectal coils, and images interpreted by a panel of 3 radiologists with extensive experience reading prostate MRIs. It is not clear that the results would be similar outside of the context of a similarly experienced center. There is no doubt a learning curve exists for both radiologists and urologists in reading prostate MRIs and performing MRI-guided interventions. It is likely that, during the anticipated expansion phase over the next few years, many groups may experience results that do not mirror the literature until enough experience is collectively gained that the majority of urologists and radiologists become adequately familiar with the techniques and principles, similar to how most urologists currently are comfortable with TRUS, whereas, in the past, this was not the case. Another likely unanticipated consequence of an expansion of fusion biopsy techniques is that, in the short term, the number of cores of tissue removed during biopsies will likely go up before they go down as practitioners perform standard 12-core to 14-core biopsies (and as they biopsy more borderline suspicious lesions) in addition to the biopsy of significantly MRI-suspicious lesions initially, until enough experience is gained that lesions can be confidently excluded without biopsy. Ultimately, as more evidence accrues, hopefully we will be able to biopsy only the MRI-suspicious lesions, thus limiting the number of cores men undergo and excluding some men completely from biopsy. In the current environment of growing cost concerns, the other important determinant of how widespread and rapidly MP-MRI and guided biopsies expand is cost. MP-MRI obtained in preparation of a fusion biopsy adds an additional cost of approximately $1500 to $2000 onto the costs of a TRUS-guided biopsy. Although the performance of a fusion biopsy itself is only slightly more expensive than that of a standard TRUS biopsy, a substantial initial capital investment is 2808
required to purchase a fusion system (approximately $200,000). Before the complete adoption of MP-MRI into routine diagnostic practice, it will probably be necessary to demonstrate a cost savings downstream of the use of MRI. This is only likely to happen if it is demonstrated conclusively that MP-MRI can safely exclude substantial numbers of men from biopsy and possible diagnosis and treatment of disease unlikely to affect a man’s life span. A recent article by Pokorny et al,13 who compared TRUS biopsy results with MRIguided biopsy results in biopsy-naive men who were referred to biopsy for an elevated PSA, demonstrated that TRUS biopsies detected cancer in 56.5% of men, 37.3% of which were considered low-risk cancers; whereas MRI-guided biopsy detected cancer in 69.7% of men, and only 6.1% were considered low risk. The MRI-guided biopsy pathway reduced the need for biopsy by 51% and reduced the risk of diagnosis of lowrisk prostate cancer by 89.4% while increasing the diagnosis of intermediate-risk and high-risk disease by 17.7% suggesting the possibility of a cost savings while improving care. Information provided by studies such as these as well as the study by Salami et al in the current issue take us 1 step further in that direction. If a picture is worth a thousand words, how many biopsies is the absence of an MRI-suspicious lesion worth? FUNDING SUPPORT No specific funding was disclosed.
CONFLICT OF INTEREST DISCLOSURES Dr. Warlick reports personal fees from Dendreon Corporation outside the submitted work.
REFERENCES 1. Salami SS, Vira MA, Turkbey B, et al. Multiparametric magnetic resonance imaging outperforms the Prostate Cancer Prevention Trial risk calculator in predicting clinically significant prostate cancer. Cancer. 2014;120:2876-2882. 2. Vourganti S, Rastinehad A, Yerram NK, et al. Multiparametric magnetic resonance imaging and ultrasound fusion biopsy detect prostate cancer in patients with prior negative transrectal ultrasound biopsies. J Urol. 2012;188:2152-2157. 3. Hambrock T, Somford DM, Hoeks C, et al. Magnetic resonance imaging guided prostate biopsy in men with repeat negative biopsies and increased prostate specific antigen. J Urol. 2010;183:520527. 4. Roethke M, Anastasiadis AG, Lichy M, et al. MRI-guided prostate biopsy detects clinically significant cancer: analysis of a cohort of 100 patients after previous negative TRUS biopsy. World J Urol. 2012;30:213-218. 5. Pinto PA, Chung PH, Rastinehad AR, et al. Magnetic resonance imaging/ultrasound fusion guided prostate biopsy improves cancer detection following transrectal ultrasound biopsy and correlates with multiparametric magnetic resonance imaging. J Urol. 2011;186:1281-1285. 6. Franiel T, Stephan C, Erbersdobler A, et al. Areas suspicious for prostate cancer: MR-guided biopsy in patients with at least 1 transrectal
Cancer
September 15, 2014
MP-MRI: Seeing is Believing/Warlick
7.
8. 9.
10.
US-guided biopsy with a negative finding—multiparametric MR imaging for detection and biopsy planning. Radiology. 2011;259: 162-172. Haffner J, Lemaitre L, Puech P, et al. Role of magnetic resonance imaging before initial biopsy: comparison of magnetic resonance imaging-targeted and systematic biopsy for significant prostate cancer detection. BJU Int. 2011;108:171-178. Fradet V, Kurhanewicz J, Cowan JE, et al. Prostate cancer managed with active surveillance: role of anatomic MR imaging and MR spectroscopic imaging. Radiology. 2010;256:176-183. Margel D, Yap SA, Lawrentschuk N, et al. Impact of multiparametric endorectal coil prostate magnetic resonance imaging on disease reclassification among active surveillance candidates: a prospective cohort study. J Urol. 2012;187:1247-1252. Hoeks CM, Somford DM, van Oort IM, et al. Value of 3-T multiparametric magnetic resonance imaging and magnetic resonance-
Cancer
September 15, 2014
guided biopsy for early risk restratification in active surveillance of low-risk prostate cancer: a prospective multicenter cohort study. Invest Radiol. 2014;49:165-172. 11. Kryvenko ON, Carter HB, Trock BJ, Epstein JI. Biopsy criteria for determining appropriateness for active surveillance in the modern era. Urology. 2014;83:869-874. 12. Logan JK, Rais-Bahrami S, Turkbey B, et al. Current status of MRI and ultrasound fusion software platforms for guidance of prostate biopsies [published online ahead of print December 3, 2013]. BJU Int. doi: 10.1111/bju.12593. 13. Pokorny MR, de Rooij M, Duncan E, et al. Prospective study of diagnostic accuracy comparing prostate cancer detection by transrectal ultrasound-guided biopsy versus magnetic resonance (MR) imaging with subsequent MR-guided biopsy in men without previous prostate biopsies [published online ahead of print March 14, 2014]. Eur Urol. doi: 10.1016/j.eururo.2014.03.002.
2809
