A. Villers

Image-Guided Prostate Biopsy Using Magnetic Resonance Imaging–Derived Targets: A Systematic Review

CONTEXTnTechnical improvements in prostate magnetic resonance imaging (MRI) have resulted in the use of MRI to target prostate biopsies.nnnOBJECTIVEnTo systematically review the literature to compare the accuracy of MRI-targeted biopsy with standard transrectal biopsy in the detection of clinically significant prostate cancer.nnnEVIDENCE ACQUISITIONnThe PubMed, Embase, and Cochrane databases were searched from inception until December 3, 2011, using the search criteria prostate OR prostate cancer AND magnetic resonance imaging OR MRI AND biopsy OR target. Four reviewers independently assessed 4222 records; 222 records required full review. Fifty unique records (corresponding to 16 discrete patient populations) directly compared an MRI-targeted with a standard transrectal approach.nnnEVIDENCE SYNTHESISnEvidence synthesis was used to address specific questions. Where MRI was applied to all biopsy-naive men, 62% (374 of 599) had MRI abnormalities. When subjected to a targeted biopsy, 66% (248 of 374) had prostate cancer detected. Both targeted and standard biopsy detected clinically significant cancer in 43% (236 or 237 of 555, respectively). Missed clinically significant cancers occurred in 13 men using targeted biopsy and 12 using a standard approach. Targeted biopsy was more efficient. A third fewer men were biopsied overall. Those who had biopsy required a mean of 3.8 targeted cores compared with 12 standard cores. A targeted approach avoided the diagnosis of clinically insignificant cancer in 53 of 555 (10%) of the presenting population.nnnCONCLUSIONSnMRI-guided biopsy detects clinically significant prostate cancer in an equivalent number of men versus standard biopsy. This is achieved using fewer biopsies in fewer men, with a reduction in the diagnosis of clinically insignificant cancer. Variability in study methodology limits the strength of recommendation that can be made. There is a need for a robust multicentre trial of targeted biopsies.

Standards of Reporting for MRI-targeted Biopsy Studies (START) of the Prostate: Recommendations from an International Working Group.

BACKGROUNDnA systematic literature review of magnetic resonance imaging (MRI)-targeted prostate biopsy demonstrates poor adherence to the Standards for the Reporting of Diagnostic Accuracy (STARD) recommendations for the full and transparent reporting of diagnostic studies.nnnOBJECTIVEnTo define and recommend Standards of Reporting for MRI-targeted Biopsy Studies (START).nnnDESIGN, SETTING, AND PARTICIPANTSnEach member of a panel of 23 experts in urology, radiology, histopathology, and methodology used the RAND/UCLA appropriateness methodology to score a 258-statement premeeting questionnaire. The collated responses were presented at a face-to-face meeting, and each statement was rescored after group discussion.nnnOUTCOME MEASUREMENTS AND STATISTICAL ANALYSISnMeasures of agreement and consensus were calculated for each statement. The most important statements, based on group median score, the degree of group consensus, and the content of the group discussion, were used to create a checklist of reporting criteria (the START checklist).nnnRESULTS AND LIMITATIONSnThe strongest recommendations were to report histologic results of standard and targeted cores separately using Gleason score and maximum cancer core length. A table comparing detection rates of clinically significant and clinically insignificant disease by targeted and standard approaches should also be used. It was recommended to report the recruitment criteria for MRI-targeted biopsy, prior biopsy status of the population, a brief description of the MRI sequences, MRI reporting method, radiologist experience, and image registration technique. There was uncertainty about which histologic criteria constitute clinically significant cancer when the prostate is sampled using MRI-targeted biopsy, and it was agreed that a new definition of clinical significance in this setting needed to be derived in future studies.nnnCONCLUSIONSnUse of the START checklist would improve the quality of reporting in MRI-targeted biopsy studies and facilitate a comparison between standard and MRI-targeted approaches.

MRI-Targeted or Standard Biopsy for Prostate-Cancer Diagnosis

Background Multiparametric magnetic resonance imaging (MRI), with or without targeted biopsy, is an alternative to standard transrectal ultrasonography–guided biopsy for prostate‐cancer detection in men with a raised prostate‐specific antigen level who have not undergone biopsy. However, comparative evidence is limited. Methods In a multicenter, randomized, noninferiority trial, we assigned men with a clinical suspicion of prostate cancer who had not undergone biopsy previously to undergo MRI, with or without targeted biopsy, or standard transrectal ultrasonography–guided biopsy. Men in the MRI‐targeted biopsy group underwent a targeted biopsy (without standard biopsy cores) if the MRI was suggestive of prostate cancer; men whose MRI results were not suggestive of prostate cancer were not offered biopsy. Standard biopsy was a 10‐to‐12–core, transrectal ultrasonography–guided biopsy. The primary outcome was the proportion of men who received a diagnosis of clinically significant cancer. Secondary outcomes included the proportion of men who received a diagnosis of clinically insignificant cancer. Results A total of 500 men underwent randomization. In the MRI‐targeted biopsy group, 71 of 252 men (28%) had MRI results that were not suggestive of prostate cancer, so they did not undergo biopsy. Clinically significant cancer was detected in 95 men (38%) in the MRI‐targeted biopsy group, as compared with 64 of 248 (26%) in the standard‐biopsy group (adjusted difference, 12 percentage points; 95% confidence interval [CI], 4 to 20; P=0.005). MRI, with or without targeted biopsy, was noninferior to standard biopsy, and the 95% confidence interval indicated the superiority of this strategy over standard biopsy. Fewer men in the MRI‐targeted biopsy group than in the standard‐biopsy group received a diagnosis of clinically insignificant cancer (adjusted difference, ‐13 percentage points; 95% CI, ‐19 to ‐7; P<0.001). Conclusions The use of risk assessment with MRI before biopsy and MRI‐targeted biopsy was superior to standard transrectal ultrasonography–guided biopsy in men at clinical risk for prostate cancer who had not undergone biopsy previously. (Funded by the National Institute for Health Research and the European Association of Urology Research Foundation; PRECISION ClinicalTrials.gov number, NCT02380027.)

A biopsy simulation study to assess the accuracy of several transrectal ultrasonography (TRUS)‐biopsy strategies compared with template prostate mapping biopsies in patients who have undergone radical prostatectomy

Study Type – Diagnostic (validating cohort)

Understanding the pathological features of focality, grade and tumour volume of early‐stage prostate cancer as a foundation for parenchyma‐sparing prostate cancer therapies: active surveillance and focal targeted therapy

Whats known on the subject? and What does the study add?

Focal therapy of prostate cancer: energies and procedures.

PURPOSEnOver the last years, focal therapy has emerged as an intermediate management technique between radical approaches (radical prostatectomy, external beam radiation, and brachytherapy) and watchful waiting to manage some early stage prostate cancers (CaP). Different energy modalities are being developed. The aim of this study is to review these energy modalities and their indications.nnnMATERIALS AND METHODSnWe reviewed the literature to concentrate on the practical aspects of focal therapy for CaP with the following key words: photodynamic therapy, high intensity focused ultrasound (HIFU), cryotherapy, focal laser ablation, electroporation, radio frequency, external beam radiation, organ-sparing approach, focal therapy, CaP, and then by cross-referencing from previously identified studies.nnnRESULTSnProstatic tumor ablation can be achieved with different energies: freezing effect for cryotherapy, thermal effect using focalized ultrasound for HIFU, and using thermal effect of light for focal laser ablation (FLA) and activation of a photosensitizer by light for PDT, among others. Radio frequency and microwave therapy have been tested in this field and demonstrated their usefulness. Electroporation is currently being developed on preclinical models. External beam radiation with microboost on neoplastic foci is under evaluation. HIFU and cryotherapy require the use of sophisticated and expensive machines and, consequently, the procedure is expensive. Laser techniques seem to be less onerous, with the added advantage of size.nnnCONCLUSIONSnSeveral energy modalities are being developed to achieve the trifecta of continence, potency, and oncologic efficiency. Those techniques come with low morbidity but clinical experience is limited regarding to oncologic outcome. Comparison of the different focal approaches is complex owing to important heterogeneity of the trials. In the future, it seems likely that each technique will have its own selective indications.

A Critical Analysis of the Current Knowledge of Surgical Anatomy of the Prostate Related to Optimisation of Cancer Control and Preservation of Continence and Erection in Candidates for Radical Prostatectomy: An Update

CONTEXTnIn 2010, we published a review summarising the available literature on surgical anatomy of the prostate and adjacent structures involved in cancer control and the functional outcome of prostatectomy.nnnOBJECTIVEnTo provide an update based on new literature to help the surgeon improve oncologic and surgical outcomes of radical prostatectomy (RP).nnnEVIDENCE ACQUISITIONnWe searched the PubMed database using the keywords radical prostatectomy, anatomy, neurovascular bundle, nerve, fascia, pelvis, sphincter, urethra, urinary continence, and erectile function. Relevant articles and textbook chapters published since the last review were critically reviewed, analysed, and summarised. Moreover, we integrated aspects that were not addressed in the last review into this update.nnnEVIDENCE SYNTHESISnWe found new evidence for several topics. Up to 40% of the cross-sectional surface area of the urethral sphincter tissue is laterally overlapped by the dorsal vascular complex and might be injured during en bloc ligation. Denonvilliers fascia is fused with the base of the prostate in a horizontal fashion dorsally/caudally of the seminal vesicles, requiring sharp detachment when preserved. During extended pelvic lymph node dissection, the erectile nerves are at risk in the presacral and internal iliac area. Dissection planes for nerve sparing can be graded according to the amount of tissue left on the prostate as a safety margin against positive surgical margins. Vascular structures can serve as landmarks. The urethral sphincter and its length after RP are influenced by the shape of the apex. Taking this shape into account allows preservation of additional sphincter length with improved postoperative continence.nnnCONCLUSIONSnThis update provides additional, detailed information about the surgical anatomy of the prostate and adjacent tissues involved in RP. This anatomy remains complex and widely variable. These details facilitate surgical orientation and dissection during RP and ideally should translate into improved outcomes.nnnPATIENT SUMMARYnBased on recent anatomic findings regarding the prostate and its surrounding tissue, the urologist can individualise the dissection during RP according to cancer and patient characteristics to improve oncologic and functional results at the same time.

MUC1 drives epithelial-mesenchymal transition in renal carcinoma through Wnt/β-catenin pathway and interaction with SNAIL promoter.

MUC1 is overexpressed in human carcinomas. The transcription factor SNAIL can activate epithelial-mesenchymal transition (EMT) in cancer cells. In this study, in renal carcinoma, we demonstrate that (i) MUC1 and SNAIL were overexpressed in human sarcomatoid carcinomas, (ii) SNAIL increased indirectly MUC1 expression, (iii) MUC1 overexpression induced EMT, (iv) MUC1 C-terminal domain (MUC1-C) and β-catenin increased SNAIL transcriptional activity by interaction with its promoter and (v) blocking MUC1-C nuclear localization decreased Wnt/β-catenin signaling pathway activation and SNAIL expression. Altogether, our findings demonstrate that MUC1 is an actor in EMT and appears as a new therapeutic target.

Photodynamic therapy in urology: What can we do now and where are we heading?

BACKGROUNDnPhotodynamic therapy (PDT) is an innovative technique in oncologic urology. Its application appears increasingly realistic to all kind of cancers with technological progress made in treatment planning and light delivery associated with the emergence of novel photosensitizers. The aim of this study is to review applications of this technique in urology.nnnMATERIALS AND METHODSnWe reviewed the literature on PDT for urological malignancies with the following key words: photodynamic therapy, prostate cancer, kidney cancer, urothelial cancer, penile cancer and then by cross-referencing from previously identified studies.nnnRESULTSnFocal therapy of prostate cancer is an application of PDT. Clinical studies are ongoing to determine PDT efficacy and safety. PDT as salvage treatment after radiotherapy has been tested. Oncologic results were promising but important side effects were reported. Individual dosimetric planning is necessary to avoid toxicity. PDT was tested to treat superficial bladder carcinoma with promising oncologic results. Serious side effects have limited use of first photosensitizers generation. Second generation of photosensitizer allowed reducing morbidity. For upper urinary tract carcinoma and urethra, data are limited. Few studies described PDT application in penile oncology for conservative management of carcinoma in situ and premalignant lesions. For renal cancer, PDT was only tested on preclinical model despite of its potential application. No data is available concerning PDT application for testicular cancer.nnnCONCLUSIONnPDT clinical applications in urology have proved a kind of efficiency balanced with an important morbidity. Development of new photosensitizer generations and improvement in illumination protocols should permit to decrease side effects.

Trans-rectal ultrasound visibility of prostate lesions identified by magnetic resonance imaging increases accuracy of image-fusion targeted biopsies

AbstractPurposenTo compare the diagnostic yield of targeted prostate biopsy using image-fusion of multi-parametric magnetic resonance (mp-MR) with real-time trans-rectal ultrasound (TRUS) for clinically significant lesions that are suspicious only on mp-MR versus lesions that are suspicious on both mp-MR and TRUS.MethodsPre-biopsy MRI and TRUS were each scaled on a 3-point score: highly suspicious, likely, and unlikely for clinically significant cancer (sPCa). Using an MR-TRUS elastic image-fusion system (Koelis), a 127 consecutive patients with a suspicious clinically significant index lesion on pre-biopsy mp-MR underwent systematic biopsies and MR/US-fusion targeted biopsies (01/2010–09/2013). Biopsy histological outcomes were retrospectively compared with MR suspicion level and TRUS-visibility of the MR-suspicious lesion. sPCa was defined as biopsy Gleason scorexa0≥7 and/or maximum cancer core lengthxa0≥5xa0mm.ResultsnTargeted biopsies outperformed systematic biopsies in overall cancer detection rate (61 vs. 41xa0%; pxa0=xa00.007), sPCa detection rate (43 vs. 23xa0%; pxa0=xa00.0013), cancer core length (7.5 vs. 3.9xa0mm; pxa0=xa00.0002), and cancer rate per core (56 vs. 12xa0%; pxa0<xa00.0001), respectively. Highly suspicious lesions on mp-MR correlated with higher positive biopsy rate (pxa0<xa00.0001), higher Gleason score (pxa0=xa00.018), and greater cancer core length (pxa0<xa00.0001). Highly suspicious lesions on TRUS in corresponding to MR-suspicious lesion had a higher biopsy yield (pxa0<xa00.0001) and higher sPCa detection rate (pxa0<xa00.0001). Since majority of MR-suspicious lesions were also suspicious on TRUS, TRUS-visibility allowed selection of the specific MR-visible lesion which should be targeted from among the multiple TRUS suspicious lesions in each prostate.ConclusionsMR-TRUS fusion-image-guided biopsies outperformed systematic biopsies. TRUS-visibility of a MR-suspicious lesion facilitates image-guided biopsies, resulting in higher detection of significant cancer.