Performance of multiparametric magnetic resonance imaging in the evaluation and management of clinically low-risk prostate cancer

ObjectiveThe purpose of this article is to review the multiparametric magnetic resonance imaging (mMRI) of the prostate and MR-guided prostate biopsy, and their role in the evaluation and management of men with low-risk prostate cancer.MethodsWe performed a literature review based on the MEDLINE database search for publications on the role of mMRI (a) in detection and localization of prostate cancer, prediction of tumor aggressiveness and progression and (b) in guiding targeted prostate biopsy.ResultsThe mMRI, particularly diffusion-weighted imaging with T2-weighted imaging, is a useful tool for tumor localization in low-risk prostate cancer as it can detect lesions that are more likely missed on extended biopsy schemes and can identify clinically significant disease requiring definitive treatment. The MR-guided biopsy of the most suspicious lesions enables more accurate and safer approach to guide enrollment into the active surveillance program. However, the MR-guided biopsy is complex. The fusion of MRI data with transrectal ultrasound for the purpose of biopsy provides a more feasible technique with documented accurate sampling.ConclusionAlthough the mMRI is not routinely used for risk stratification and prognostic assessment in prostate cancer, it can provide valuable information to guide management of men with low-risk disease. Incorporation of mMRI into the workup and monitoring of patients with low-risk prostate cancer can help discriminate clinically significant disease from indolent disease. Targeted biopsy of MR-suspicious lesions enables accurate sampling of potentially aggressive tumors that may affect outcomes.     

Multiparametric magnetic resonance imaging: Current role in prostate cancer management

Digital rectal examination, serum prostate‐specific antigen screening and transrectal ultrasound‐guided biopsy are conventionally used as screening, diagnostic and surveillance tools for prostate cancer. However, they have limited sensitivity and specificity. In recent years, the role of multiparametric magnetic resonance imaging has steadily grown, and is now part of the standard clinical management in many institutions. In multiparametric magnetic resonance imaging, the morphological assessment of T2‐weighted imaging is correlated with diffusion‐weighted imaging, dynamic contrast‐enhanced imaging perfusion and/or magnetic resonance spectroscopic imaging. Multiparametric magnetic resonance imaging is currently regarded as the most sensitive and specific imaging technique for the evaluation of prostate cancer, including detection, staging, localization and aggressiveness evaluation. This article presents an overview of multiparametric magnetic resonance imaging, and discusses the current role of multiparametric magnetic resonance imaging in the different fields of prostate cancer management.     

Value of Multiparametric MRI in the Work-up of Prostate Cancer

The role of magnetic resonance imaging (MRI) in prostate cancer evaluation is controversial and likely underestimated. Technological advances over the past 5 years have demonstrated that multiparametric MRI, including diffusion-weighted imaging (DWI) and dynamic contrast-enhanced MRI, can evaluate the actual tumor burden of a newly diagnosed prostate cancer more accurately than sextant biopsy protocols. Tumor risk, defined by the D’Amico criteria, hence can be re-evaluated by multiparametric MRI. As a result, there is increasing evidence that MRI before repeat or even initial biopsy can accurately select patients who require immediate biopsies and those in whom biopsy could be deferred. Also, a relationship between apparent diffusion coefficient (ADC), calculated from DWI, and Gleason score was found. Thus, MRI before biopsy helps to detect high-grade tumors to target biopsies within areas of low ADC values. To achieve good targeting accuracy, transrectal ultrasound (TRUS)-MRI image registration is necessary. Three-dimensional deformable registration is sufficiently accurate to match TRUS and MRI volumes with a topographic precision of 1 mm. Real-time MRI-guided biopsy is another technique under evaluation. Both approaches will allow for increasing acceptance of focal therapies, should these techniques be validated in the future.     

Revisión sistemática de los métodos para incrementar la eficacia de la resonancia magnética en el diagnóstico precoz de cáncer de próstata clínicamente significativo

Background and ObjectiveProstate cancer (PC) is the malignant neoplasm with the highest incidence after lung cancer worldwide. The objective of this study is to review the literature on the methods that improve the efficacy of the current strategy for the early diagnosis of clinically significant PC (csPC), based on the performance of magnetic resonance imaging (RM) and targeted biopsies when suspicious lesions are detected, in addition to systematic biopsy.Evidence acquisitionA systematic literature review was performed in PubMed, Web of Science and Cochrane according to the PRISMA criteria (Preferred Reporting Items for Systematic Reviews and Meta-Analyses), using the search terms: multiparametric magnetic resonance imaging, biparametric magnetic resonance imaging, biomarkers in prostate cancer, prostate cancer y early diagnosis. A total of 297 references were identified and, using the PICO selection criteria, 21 publications were finally selected to synthesize the evidence.Evidence synthesisWith the consolidation of MRI as the test of choice for the diagnosis of prostate cancer, the role of PSA density (PSAD) becomes relevant as a predictive tool included in prediction nomograms, without added cost. PSAD and diagnostic markers, combined with MRI, offer a high diagnostic power with an area under curve (AUC) above 0,7. Only the SHTLM3 model integrates markers in the creation of a nomogram. Prediction models also offer consistent efficacy with an AUC greater than 0,8 when associating MRI.ConclusionsThe efficacy of MRI in clinically significant prostate cancer detection can be improved with different parameters in order to generate predictive models that support decision making.     

Targeted prostate biopsy： value of multiparametric magnetic resonance imaging in detection of localized cancer

Prostate cancer is the second most common cancer in men, with 1.1 million new cases worldwide reported by the World Health Organization in one recent year. Transrectal ultrasound （TRUS）-guided biopsy has been used for the diagnosis of prostate cancer for over 2 decades, but the technique is usually blind to cancer location. Moreover, the false negative rate of TRUS biopsy has been reported to be as high as 47%. Multiparametric magnetic resonance imaging （mp-MRI） includes T1- and T2-weighted imaging as well as dynamic contrast-enhanced （DCE） and diffusion-weighted imaging （DWI）. mp-MRI is a major advance in the imaging of prostate cancer, enabling targeted biopsy of suspicious lesions. Evolving targeted biopsy techniquesmincluding direct in-bore biopsy, cognitive fusion and software-based MRI-ultrasound （MRI-US） fusion--have led to a several-fold improvement in cancer detection compared to the earlier method. Importantly, the detection of clinically significant cancers has been greatly facilitated by targeting, compared to systematic biopsy alone. Targeted biopsy via MRI-US fusion may dramatically alter the way prostate cancer is diagnosed and managed.     

Target detection: Magnetic resonance imaging-ultrasound fusion–guided prostate biopsy

Recent advances in multiparametric magnetic resonance imaging (MRI) have enabled image-guided detection of prostate cancer. Fusion of MRI with real-time ultrasound (US) allows the information from MRI to be used to direct biopsy needles under US guidance in an office-based procedure. Fusion can be performed either cognitively or electronically, using a fusion device. Fusion devices allow superimposition (coregistration) of stored MRI images on real-time US images; areas of suspicion found on MRI can then serve as targets during US-guided biopsy. Currently available fusion devices use a variety of technologies to perform coregistration: robotic tracking via a mechanical arm with built-in encoders (Artemis/Eigen, BioJet/Geoscan); electromagnetic tracking (UroNav/Philips-Invivo, Hi-RVS/Hitachi); or tracking with a 3D US probe (Urostation/Koelis). Targeted fusion biopsy has been shown to identify more clinically significant cancers and fewer insignificant cancers than conventional biopsy. Fusion biopsy appears to be a major advancement over conventional biopsy because it allows (1) direct targeting of suspicious areas not seen on US and (2) follow-up biopsy of specific cancerous sites in men undergoing active surveillance.     

Prebiopsy magnetic resonance spectroscopy and imaging in the diagnosis of prostate cancer

Introduction: Existing screening investigations for the diagnosis of early prostate cancer lack specificity, resulting in a high negative biopsy rate. There is increasing interest in the use of various magnetic resonance methods for improving the yield of transrectal ultrasound‐guided biopsies of the prostate in men suspected to have prostate cancer. We review the existing status of such investigations. Methods: A literature search was carried out using the Pubmed database to identify articles related to magnetic resonance methods for diagnosing prostate cancer. References from these articles were also extracted and reviewed. Results: Recent studies have focused on prebiopsy magnetic resonance investigations using conventional magnetic resonance imaging, dynamic contrast enhanced magnetic resonance imaging, diffusion weighted magnetic resonance imaging, magnetization transfer imaging and magnetic resonance spectroscopy of the prostate. This marks a shift from the earlier strategy of carrying out postbiopsy magnetic resonance investigations. Prebiopsy magnetic resonance investigations has been useful in identifying patients who are more likely to have a biopsy positive for malignancy. Conclusions: Prebiopsy magnetic resonance investigations has a potential role in increasing specificity of screening for early prostate cancer. It has a role in the targeting of biopsy sites, avoiding unnecessary biopsies and predicting the outcome of biopsies.     

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

Background

The current diagnosis of prostate cancer (PCa) uses transrectal ultrasound–guided biopsy (TRUSGB). TRUSGB leads to sampling errors causing delayed diagnosis, overdetection of indolent PCa, and misclassification. Advances in multiparametric magnetic resonance imaging (mpMRI) suggest that imaging and selective magnetic resonance (MR)–guided biopsy (MRGB) may be superior to TRUSGB.

Objective

To compare the diagnostic efficacy of the magnetic resonance imaging (MRI) pathway with TRUSGB.

Design, setting, and participants

A total of 223 consecutive biopsy-naive men referred to a urologist with elevated prostate-specific antigen participated in a single-institution, prospective, investigator-blinded, diagnostic study from July 2012 through January 2013.

Intervention

All participants had mpMRI and TRUSGB. Men with equivocal or suspicious lesions on mpMRI also underwent MRGB.

Outcome measurements and statistical analysis

The primary outcome was PCa detection. Secondary outcomes were histopathologic details of biopsy and radical prostatectomy specimens, adverse events, and MRI reader performance. Sensitivity, specificity, negative predictive values (NPVs), and positive predictive values were estimated and basic statistics presented by number (percentage) or median (interquartile range).

Results and limitations

Of 223 men, 142 (63.7%) had PCa. TRUSGB detected 126 cases of PCa in 223 men (56.5%) including 47 (37.3%) classed as low risk. MRGB detected 99 cases of PCa in 142 men (69.7%) with equivocal or suspicious mpMRI, of which 6 (6.1%) were low risk. The MRGB pathway reduced the need for biopsy by 51%, decreased the diagnosis of low-risk PCa by 89.4%, and increased the detection of intermediate/high-risk PCa by 17.7%. The estimated NPVs of TRUSGB and MRGB for intermediate/high-risk disease were 71.9% and 96.9%, respectively. The main limitation is the lack of long follow-up.

Conclusions

We found that mpMRI/MRGB reduces the detection of low-risk PCa and reduces the number of men requiring biopsy while improving the overall rate of detection of intermediate/high-risk PCa.

Patient summary

We compared the results of standard prostate biopsies with a magnetic resonance (MR) image–based targeted biopsy diagnostic pathway in men with elevated prostate-specific antigen. Our results suggest patient benefits of the MR pathway. Follow-up of negative investigations is required.     

Assessment of magnetic resonance imaging (MRI)-fusion prostate biopsy with concurrent standard systematic ultrasound-guided biopsy among men requiring repeat biopsy

IntroductionThe role of magnetic resonance imaging (MRI)-fusion biopsy (FB) remains unclear in men with prior negative prostate biopsies. This study aimed to compare the diagnostic accuracy of FB with concurrent systematic biopsy (SB) in patients requiring repeat prostate biopsies.MethodsPatients with previous negative prostate biopsies requiring repeat biopsies were included. Those without suspicious lesions (≥Prostate Imaging-Reporting and Data System [PI-RADS] 3) on MRI were excluded. All patients underwent FB followed by SB. The primary outcome was the sensitivity for clinically significant prostate cancer (Gleason score ≥7). The secondary objective was identification of potential predictive factors of biopsy performance.ResultsA total of 53 patients were included; 41 (77%) patients were found to have clinically significant prostate cancer. FB had a higher detection rate of significant cancer compared to SB (85% vs. 76%, respectively, p=0.20) and lower diagnosis of indolent (Gleason score 3+3=6) cancer (10% vs. 27%, respectively, p=0.05). FB alone missed six (15%) clinically significant cancers, compared to 10 (24%) with SB. SB performance was significantly impaired in patients with anterior lesions and high prostate volumes (p<0.05). There was high degree of pathological discordance between the two approaches, with concordance seen in only 34% of patients.ConclusionsIn patients with prior negative biopsies and ongoing suspicion for prostate cancer, a combined approach of FB with SB is needed for optimal detection and risk classification of clinically significant disease. Anterior tumors and large prostates were significant predictors of poor SB performance and an MRI-fusion alone approach in these settings could be considered.     

Evaluating the performance of clinical and radiological data in predicting prostate cancer in prostate imaging reporting and data system version 2.1 category 3 lesions of the peripheral and the transition zones

International Urology and Nephrology - To define the value of clinical and radiological data, using multiparametric magnetic resonance imaging (mpMRI), to predict prostate cancer (PCa) in prostate...     

An initial negative round of targeted biopsies in men with highly suspicious multiparametric magnetic resonance findings does not exclude clinically significant prostate cancer—Preliminary experience

Background

Targeted prostate biopsies are changing the landscape of prostate cancer (PCa) diagnosis with the degree of suspicion on multiparametric magnetic resonance imaging (mpMRI) being a strong predictor of targeted biopsy outcome. Data regarding the rate and potential causes of false-negative magnetic resonance imaging-transrectal ultrasound (MRI-TRUS) fusion–targeted biopsy in patients with highly suspicious mpMRI findings are lacking.

Diagnosis of early biochemical recurrence after radical prostatectomy or radiation therapy in patients with prostate cancer: State of the art

Biochemical recurrence after primary treatment in prostate cancer is not uncommon. A rising serum prostate-specific antigen level represents a first sign of disease relapse. At this time of low disease burden, imaging and particularly magnetic resonance imaging and positron emission tomography/computed tomography (PET/CT) are essential to determine the localization of the recurrence, which may be local, in lymph nodes, and/or metastatic. Imaging results allow best determine modalities of salvage treatment, which can be local by using radiotherapy or other focal treatments or systemic using hormonotherapy. Current evidence suggests that multiparametric magnetic resonance imaging, PET/CT with prostate specific membrane antigen and lympho-magnetic resonance imaging are effective and complementary to detect local recurrences and distant metastases.     

La resonancia magnética como herramienta para el diagnóstico del cáncer de próstata: nuevas evidencias y posicionamiento de la ESUT (EAU Section of Uro-Technology)

Prostate cancer (PCa) is the second leading cause of cancer-related mortality and the most frequently diagnosed male malignant disease among men. The manifestation of PCa ranges from indolent to highly aggressive disease and due to this high variation in PCa progression, the diagnosis and subsequent treatment planning can be challenging. The current diagnostic approach with PSA testing and digital rectal examination followed by transrectal ultrasound biopsies lack in both sensitivity and specificity in PCa detection and offers limited information about the aggressiveness and stage of the cancer. Scientific work supports the rapidly growing use of multiparametric magnetic resonance imaging as the most sensitive and specific imaging tool for detection, lesion characterization and staging of PCa. Therefore, we carried out an updated review of magnetic resonance imaging in the diagnostic PCa reviewing the latest papers published in PubMed.     

Prostate zonal anatomy correlates with the detection of prostate cancer on multiparametric magnetic resonance imaging/ultrasound fusion–targeted biopsy in patients with a solitary PI-RADS v2–scored lesion

PurposeTo evaluate the positive predictive value (PPV) of the Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) assessment method in patients with a single suspicious finding on prostate multiparametric magnetic resonance imaging (mpMRI).Patients and methodsA total of 176 patients underwent MRI/ultrasound fusion–targeted prostate biopsy after the detection of a single suspicious finding on mpMRI. The PPV for cancer detection was determined based on PI-RADS v2 assessment score and location.ResultsFusion biopsy detected prostate cancer in 60.2% of patients. Of these patients, 69.8% had Gleason score (GS) ≥7 prostate cancer. Targeted biopsy detected 90.5% of all GS≥7 prostate cancer. The PPV for GS≥7 detection of PI-RADS v2 category 5 (P5) and category 4 (P4) lesions was 70.2% and 37.7%, respectively. This increased to 88% and 38.5% for P5 and P4 lesions in the peripheral zone (PZ), respectively. Targeted biopsy did not miss GS≥7 disease compared with systematic biopsy in P5 lesions in the PZ and transition zone.ConclusionThe PPV of PI-RADS v2 for prostate cancer in patients with a single lesion on mpMRI is dependent on PI-RADS assessment category and location. The highest PPV was for a P5 lesion in the PZ.     

Value of Targeted Prostate Biopsy Using Magnetic Resonance–Ultrasound Fusion in Men with Prior Negative Biopsy and Elevated Prostate-specific Antigen

BackgroundConventional biopsy fails to detect the presence of some prostate cancers (PCas). Men with a prior negative biopsy but persistently elevated prostate-specific antigen (PSA) pose a diagnostic dilemma, as some harbor elusive cancer.ObjectiveTo determine whether use of magnetic resonance–ultrasound (MR-US) fusion biopsy results in improved detection of PCa compared to repeat conventional biopsy.Design, setting, and participantsIn a consecutive-case series, 105 subjects with prior negative biopsy and elevated PSA values underwent multiparametric magnetic resonance imaging (MRI) and fusion biopsy in an outpatient setting.InterventionSuspicious areas on multiparametric MRI were delineated and graded by a radiologist; MR–US fusion biopsy was performed by a urologist using the Artemis device; targeted and systematic biopsies were obtained regardless of MRI result.Outcome measurements and statistical analysisDetection rates of all PCa and clinically significant PCa (Gleason ≥3 + 4 or Gleason 6 with maximal cancer core length ≥4 mm) were determined. The yield of targeted biopsy was compared to systematic biopsy. The ability of an MRI grading system to predict clinically significant cancer was investigated. Stepwise multivariate logistic regression analysis was performed to determine predictors of significant cancer on biopsy.Results and limitationsFusion biopsy revealed PCa in 36 of 105 men (34%; 95% confidence interval [CI], 25–45). Seventy-two percent of men with PCa had clinically significant disease; 21 of 23 men (91%) with PCa on targeted biopsy had significant cancer compared to 15 of 28 (54%) with systematic biopsy. Degree of suspicion on MRI was the most powerful predictor of significant cancer on multivariate analysis. Twelve of 14 (86%) subjects with a highly suspicious MRI target were diagnosed with clinically significant cancer.ConclusionsMR–US fusion biopsy provides improved detection of PCa in men with prior negative biopsies and elevated PSA values. Most cancers found were clinically significant.     

mp-MRI Prostate Characterised PIRADS 3 Lesions are Associated with a Low Risk of Clinically Significant Prostate Cancer - A Retrospective Review of 92 Biopsied PIRADS 3 Lesions

Objective

To determine whether prostate image reporting and data system (PIRADS) 3 lesions as assessed by a 3T multiparametric magnetic resonance imaging (MRI) represent clinically significant prostate cancer.

Method

A retrospective review was performed on a series of consecutive patients who underwent MRI guided biopsy of the prostate for clinical suspicion of prostate cancer between January 2013 and March 2014. Demographic, clinical, MRI and biopsy data were reviewed and compared. The same 3T MRI without the use of an endo-rectal coil was employed to assess each patient, obtaining high resolution T2 weighted images, diffusion weighted imaging and dynamic contrast enhancement. The MRI data was sent to Dynacad software for analysis. A single experienced radiologist reported all the studies from this series using a modified PIRADS scoring system. Subsequently, all the lesions marked PIRADS 3 or above were targeted with 18G core biopsy using DynaTrim in-gantry MRI guidance system. Needle position targeting the lesion was recorded prior to each biopsy. All core biopsy samples were sent to one of two pathology laboratories where they were processed and reported as per the International Society of Urological Pathology protocols.

Results

One hundred and eighteen patients comprising a total of 215 lesions were reviewed. Amongst this cohort, 92 PIRADS 3 lesions were identified and biopsied. The mean age of patients in this cohort was 62.6 years. Median prostate specific antigen (PSA) was 6.5 ng/ml and median prostate size was 78.4 ml. Eightysix (93.5%) of biopsied PIRADS 3 lesions were benign and 6 (6.5%) lesions were found to be malignant. Of these 6 malignant lesions, 4 (66%) were Gleason score 6 (3 + 3) and 2 (33%) were Gleason score 7 (3 + 4). Of the 86 non-malignant lesions, 1 (1.2%) represented high-grade prostate intraepithelial neoplasia and 2 (2.4%) represented atypical small acinar proliferation. PIRADS 3 lesions within the peripheral zone were more likely to be associated with malignant disease compared with lesions identified within the transition zone (10.8 vs. 3.8%). Those with malignant disease had a higher median PSA (8.1 vs. 6.4 ng/ml) and higher median PSA density (0.12 vs. 0.08) than those without malignant disease. Those with benign pathology had a higher prevalence of inflammation (31.4 vs. 16.7%). As per Epstein''s criteria, 4 (4.3%) of the biopsied lesions represented clinically significant disease.

Conclusion

We have demonstrated in our series, that prostate lesions characterized on a 3T multiparametric MRI examination of the prostate as PIRADS 3, according to the current prevalent scoring systems, are associated with a low likelihood of the presence of clinically significant prostate cancer.Key Words: Image guided biopsy, Prostate neoplasms, Prostate risk assessment, Magnetic resonance imaging     

Unilateral lesion detected on preoperative multiparametric magnetic resonance imaging and MRI/US fusion-guided prostate biopsy is not an appropriate indication for focal therapy in prostate cancer

PurposeThis study aimed to investigate if preoperative assessments of multiparametric magnetic resonance imaging (mpMRI) and Magnetic resonance imaging /ultrasound (MRI/US) fusion-guided prostate biopsy could be used to guide focal therapy for prostate cancer.Materials and MethodsA total of 101 prostate cancer patients undergoing radical prostatectomy were included. Preoperative findings included mpMRI and MRI/US fusion-guided prostate biopsy, while postoperative whole mount pathology was based on surgical specimen.ResultsOf the 101 patients preoperatively diagnosed with a unilateral tumor, postoperative whole mount pathology showed 73.27% were bilateral tumors, and 71.62% of bilateral lesions were clinically significant. Comparison between preoperative and postoperative findings, the correct rate of preoperative mpMRI on the lesion side (left or right) was only 20.79%. As for the Gleason score, the correct rate of preoperative MRI/US fusion-guided prostate pathology was 67.33%. Judging from postoperative whole mount pathology, 47.52% of patients had a unilateral clinically significant tumor, which is an indication for focal therapy.ConclusionPreoperative examinations of mpMRI and MRI/US fusion-guided prostate biopsy cannot be used to guide focal therapy for prostate cancer.     

FPSA/TPSA、PSAD联合多参数磁共振成像PI-RADS评分在诊断PSA灰区前列腺癌中的作用

目的探讨游离前列腺特异性抗原(PSA)与总PSA的比值(FPSA/TPSA)、PSA密度(PSAD)联合多参数磁共振成像(mp-MRI)PI-RADS(前列腺影像数据与报告系统)评分在PSA灰区前列腺癌(PCa)中的诊断价值。方法选取2016年5月至2018年8月在本院就诊的PSA灰区、经前列腺穿刺活检确诊为前列腺癌或良性前列腺增生(BPH)的患者117例,统计上述患者FPSA、TPSA、多参数磁共振PI-RADS评分数据,计算FPSA/TPSA、PSAD,比较两组患者各项指标的差异,并使用受试者工作曲线(ROC)分析FPSA/TPSA、PSAD及多参数磁共振PI-RADS评分对PSA灰区前列腺癌的诊断价值。结果两组患者的年龄、FPSA、TPSA、FPSA/TPSA差异均无统计学意义(P>0.05);但两组患者PSAD、多参数磁共振PI-RADS评分差异有统计学意义(P<0.01);受试者工作曲线(ROC)分析结果显示FPSA/TPSA、PSAD联合PI-RADS评分检测对PCa及BPH患者曲线下面积AUC=0.771(P<0.01)。结论对于PSA在灰区的患者,PSAD、PI-RADS评分对诊断前列腺癌有显著价值。FPSA/TPSA、PSAD联合多参数磁共振成像PI-RADS评分在诊断PSA灰区前列腺癌方面有重要应用价值。     

Active surveillance for prostate cancer: when to recommend delayed intervention

There are no agreed upon guidelines for placing patients on active surveillance (AS). Therefore, there are no absolute criteria for taking patients off AS and when to recommend treatment. The criteria used to define progression are currently based on prostate specific antigen (PSA) kinetics, biopsy reclassification, and change in clinical stage. Multiple studies have evaluated predictors of progression such as PSA, PSA density (PSAD), prostate volume, core positivity, and visible lesion on multiparametric magnetic resonance imaging (mpMRI). Furthermore, published nomograms designed to predict indolent prostate cancer do not perform well when used to predict progression. Newer biomarkers have also not performed well to predict progression. These findings highlight that clinical and pathologic variables are not enough to identify patients that will progress while on AS. In the future, with the use of imaging, biomarkers, and gene expression assays, we should be better equipped to diagnose/stage prostate cancer and to distinguish between insignificant and significant disease.     

Molecular profiling of indolent human prostate cancer: tackling technical challenges to achieve high-fidelity genome-wide data

The contemporary problem of prostate cancer overtreatment can be partially attributed to the diagnosis of potentially indolent prostate cancers that pose low risk to aged men, and lack of sufficiently accurate risk stratification methods to reliably seek out men with indolent diseases. Since progressive acquisition and accumulation of genomic alterations, both genetic and epigenetic, is a defining feature of all human cancers at different stages of disease progression, it is hypothesized that RNA and DNA alterations characteristic of indolent prostate tumors may be different from those previously characterized in the setting of clinically significant prostate cancer. Approaches capable of detecting such alterations on a genome-wide level are the most promising. Such analysis may uncover molecular events defining early initiating stages along the natural history of prostate cancer progression, and ultimately lead to rational development of risk stratification methods for identification of men who can safely forego treatment. However, defining and characterizing indolent prostate cancer in a clinically relevant context remains a challenge, particularly when genome-wide approaches are employed to profile formalin-fixed paraffin-embedded (FFPE) tissue specimens. Here, we provide the conceptual basis underlying the importance of understanding indolent prostate cancer from molecular profiling studies, identify the key hurdles in sample acquisition and variables that affect molecular data derived from FFPE tissues, and highlight recent progresses in efforts to address these technical challenges.