Jonathan Bloom

Follow-up of negative MRI-targeted prostate biopsies: when are we missing cancer?

IntroductionMultiparametric magnetic resonance imaging (mpMRI) has improved clinicians’ ability to detect clinically significant prostate cancer (csPCa). Combining or fusing these images with the real-time imaging of transrectal ultrasound (TRUS) allows urologists to better sample lesions with a targeted biopsy (Tbx) leading to the detection of greater rates of csPCa and decreased rates of low-risk PCa. In this review, we evaluate the technical aspects of the mpMRI-guided Tbx procedure to identify possible sources of error and provide clinical context to a negative Tbx.MethodsA literature search was conducted of possible reasons for false-negative TBx. This includes discussion on false-positive mpMRI findings, termed “PCa mimics,” that may incorrectly suggest high likelihood of csPCa as well as errors during Tbx resulting in inexact image fusion or biopsy needle placement.ResultsDespite the strong negative predictive value associated with Tbx, concerns of missed disease often remain, especially with MR-visible lesions. This raises questions about what to do next after a negative Tbx result. Potential sources of error can arise from each step in the targeted biopsy process ranging from “PCa mimics” or technical errors during mpMRI acquisition to failure to properly register MRI and TRUS images on a fusion biopsy platform to technical or anatomic limits on needle placement accuracy.ConclusionsA better understanding of these potential pitfalls in the mpMRI-guided Tbx procedure will aid interpretation of a negative Tbx, identify areas for improving technical proficiency, and improve both physician understanding of negative Tbx and patient-management options.

Predicting Gleason Group Progression for Men on Prostate Cancer Active Surveillance: The Role of a Negative Confirmatory MRI-US Fusion Biopsy

Purpose: Active surveillance has gained acceptance as an alternative to definitive therapy in many men with prostate cancer. Confirmatory biopsies to assess the appropriateness of active surveillance are routinely performed and negative biopsies are regarded as a favorable prognostic indicator. We sought to determine the prognostic implications of negative multiparametric magnetic resonance imaging-transrectal ultrasound guided fusion biopsy consisting of extended sextant, systematic biopsy plus multiparametric magnetic resonance imaging guided targeted biopsy of suspicious lesions on magnetic resonance imaging. Materials and Methods: All patients referred with Gleason Grade Group 1 or 2 prostate cancer based on systematic biopsy performed elsewhere underwent confirmatory fusion biopsy. Patients who continued on active surveillance after a positive or a negative fusion biopsy were followed. The baseline characteristics of the biopsy negative and positive cases were compared. Cox regression analysis was used to determine the prognostic significance of a negative fusion biopsy. Kaplan-Meier survival curves were used to estimate Grade Group progression with time. Results: Of the 542 patients referred with Grade Group 1 (466) or Grade Group 2 (76) cancer 111 (20.5%) had a negative fusion biopsy. A total of 60 vs 122 patients with a negative vs a positive fusion biopsy were followed on active surveillance with a median time to Grade Group progression of 74.3 and 44.6 months, respectively (p <0.01). Negative fusion biopsy was associated with a reduced risk of Grade Group progression (HR 0.41, 95% CI 0.22-0.77, p <0.01). Conclusions: A negative confirmatory fusion biopsy confers a favorable prognosis for Grade Group progression. These results can be used when counseling patients about the risk of progression and for planning future followup and biopsies in patients on active surveillance.PURPOSEnActive surveillance has gained acceptance as an alternative to definitive therapy in many men with prostate cancer. Confirmatory biopsies to assess the appropriateness of active surveillance are routinely performed and negative biopsies are regarded as a favorable prognostic indicator. We sought to determine the prognostic implications of negative multiparametric magnetic resonance imaging-transrectal ultrasound guided fusion biopsy consisting of extended sextant, systematic biopsy plus multiparametric magnetic resonance imaging guided targeted biopsy of suspicious lesions on magnetic resonance imaging.nnnMATERIALS AND METHODSnAll patients referred with Gleason Grade Group 1 or 2 prostate cancer based on systematic biopsy performed elsewhere underwent confirmatory fusion biopsy. Patients who continued on active surveillance after a positive or a negative fusion biopsy were followed. The baseline characteristics of the biopsy negative and positive cases were compared. Cox regression analysis was used to determine the prognostic significance of a negative fusion biopsy. Kaplan-Meier survival curves were used to estimate Grade Group progression with time.nnnRESULTSnOf the 542 patients referred with Grade Group 1 (466) or Grade Group 2 (76) cancer 111 (20.5%) had a negative fusion biopsy. A total of 60 vs 122 patients with a negative vs a positive fusion biopsy were followed on active surveillance with a median time to Grade Group progression of 74.3 and 44.6 months, respectively (p <0.01). Negative fusion biopsy was associated with a reduced risk of Grade Group progression (HR 0.41, 95% CI 0.22-0.77, p <0.01).nnnCONCLUSIONSnA negative confirmatory fusion biopsy confers a favorable prognosis for Grade Group progression. These results can be used when counseling patients about the risk of progression and for planning future followup and biopsies in patients on active surveillance.

Added Value of Multiparametric Magnetic Resonance Imaging to Clinical Nomograms for Predicting Adverse Pathology in Prostate Cancer

Purpose We examined the additional value of preoperative prostate multiparametric magnetic resonance imaging and transrectal ultrasound/multiparametric magnetic resonance imaging fusion guided targeted biopsy when performed in combination with clinical nomograms to predict adverse pathology at radical prostatectomy. Materials and Methods We identified all patients who underwent 3 Tesla multiparametric magnetic resonance imaging prior to fusion biopsy and radical prostatectomy. The Partin and the MSKCC (Memorial Sloan Kettering Cancer Center) preradical prostatectomy nomograms were applied to estimate the probability of organ confined disease, extraprostatic extension, seminal vesicle invasion and lymph node involvement using transrectal ultrasound guided systematic biopsy and transrectal ultrasound/multiparametric magnetic resonance imaging fusion guided targeted biopsy Gleason scores. With radical prostatectomy pathology as the gold standard we developed multivariable logistic regression models based on these nomograms before and after adding multiparametric magnetic resonance imaging to assess any additional predictive ability. Results A total of 532 patients were included in study. When multiparametric magnetic resonance imaging findings were added to the systematic biopsy based MSKCC nomogram, the AUC increased by 0.10 for organ confined disease (p <0.001), 0.10 for extraprostatic extension (p = 0.003), 0.09 for seminal vesicle invasion (p = 0.011) and 0.06 for lymph node involvement (p = 0.120). Using Gleason scores derived from targeted biopsy compared to systematic biopsy provided an additional predictive value of organ confined disease (&Dgr; AUC 0.07, p = 0.003) and extraprostatic extension (&Dgr; AUC 0.07, p = 0.048) at radical prostatectomy with the MSKCC nomogram. Similar results were obtained using the Partin nomogram. Conclusions Magnetic resonance imaging alone or in addition to standard clinical nomograms provides significant additional predictive ability of adverse pathology at the time of radical prostatectomy. This information can be greatly beneficial to urologists for preoperative planning and for counseling patients regarding the risks of future therapy.

Comparison of Elastic and Rigid Registration during Magnetic Resonance Imaging/Ultrasound Fusion-Guided Prostate Biopsy: A Multi-Operator Phantom Study

Purpose The relative value of rigid or elastic registration during magnetic resonance imaging/ultrasound fusion guided prostate biopsy has been poorly studied. We compared registration errors (the distance between a region of interest and fiducial markers) between rigid and elastic registration during fusion guided prostate biopsy using a prostate phantom model. Materials and Methods Four gold fiducial markers visible on magnetic resonance imaging and ultrasound were placed throughout 1 phantom prostate model. The phantom underwent magnetic resonance imaging and the fiducial markers were labeled as regions of interest. An experienced user and a novice user of fusion guided prostate biopsy targeted regions of interest and then the corresponding fiducial markers on ultrasound after rigid and then elastic registration. Registration errors were compared. Results A total of 224 registration error measurements were recorded. Overall elastic registration did not provide significantly improved registration error over rigid registration (mean ± SD 4.87 ± 3.50 vs 4.11 ± 2.09 mm, p = 0.05). However, lesions near the edge of the phantom showed increased registration errors when using elastic registration (5.70 ± 3.43 vs 3.23 ± 1.68 mm, p = 0.03). Compared to the novice user the experienced user reported decreased registration error with rigid registration (3.25 ± 1.49 vs 4.98 ± 2.10 mm, p <0.01) and elastic registration (3.94 ± 2.61 vs 6.07 ± 4.16 mm, p <0.01). Conclusions We found no difference in registration errors between rigid and elastic registration overall but rigid registration decreased the registration error of targets near the prostate edge. Additionally, operator experience reduced registration errors regardless of the registration method. Therefore, elastic registration algorithms cannot serve as a replacement for attention to detail during the registration process and anatomical landmarks indicating accurate registration when beginning the procedure and before targeting each region of interest.