Biocompatible gold nanoparticles designed to absorb light at wave-lengths of high tissue transparency have been of particular interest for biomedical applications. The ability of such nanoparticles ...to convert absorbed near-infrared light to heat and induce highly localized hyperthermia has been shown to be highly effective for photothermal cancer therapy, resulting in cell death and tumor remission in a multitude of preclinical animal models. Here we report the initial results of a clinical trial in which laser-excited gold-silica nanoshells (GSNs) were used in combination with magnetic resonance–ultrasound fusion imaging to focally ablate low-intermediate-grade tumors within the prostate. The overall goal is to provide highly localized regional control of prostate cancer that also results in greatly reduced patient morbidity and improved functional outcomes. This pilot device study reports feasibility and safety data from 16 cases of patients diagnosed with low- or intermediate-risk localized prostate cancer. After GSN infusion and high-precision laser ablation, patients underwent multiparametric MRI of the prostate at 48 to 72 h, followed by postprocedure mpMRI/ultrasound targeted fusion biopsies at 3 and 12 mo, as well as a standard 12-core systematic biopsy at 12 mo. GSN-mediated focal laser ablation was successfully achieved in 94% (15/16) of patients, with no significant difference in International Prostate Symptom Score or Sexual Health Inventory for Men observed after treatment. This treatment protocol appears to be feasible and safe in men with low- or intermediate-risk localized prostate cancer without serious complications or deleterious changes in genitourinary function.
Purpose Prostate Imaging Reporting and Data System version 2 was developed to standardize the interpretation and reporting of multiparametric prostate magnetic resonance imaging and provide ...guidelines for biopsy of multiparametric magnetic resonance imaging findings. We prospectively evaluated the cancer detection rate at each overall PI-RADSv2 score. Materials and Methods This prospective study included 62 consecutive patients with 116 lesions who underwent multiparametric prostate magnetic resonance imaging at 3T with PI-RADSv2 evaluation and subsequent targeted magnetic resonance imaging/ transrectal ultrasound fusion guided biopsy and concurrent 12-core systematic prostate biopsy between May and September 2015. Median patient age and prostate specific antigen values were 65.5 years (range 50.3 to 76.6) and 7.10 ng/ml (range 0.47 to 863.0), respectively. Mean lesion size was 12.7 mm overall. Lesion based cancer detection rates for all tumors and for Gleason 3+4 or greater tumors at each PI-RADSv2 score were calculated. Univariate analysis was performed to assess differences in the cancer detection rate among PI-RADSv2 scores. Results A total of 116 lesions in 62 patients were evaluated prospectively (0 PI-RADS 1, 18 PI-RADS 2, 19 PI-RADS 3, 47 PI-RADS 4, 32 PI-RADS 5), and the patients underwent magnetic resonance/transrectal ultrasound fusion guided biopsy and systematic biopsy. Histopathology revealed 55 of 116 (47.4%) cancers (17 Gleason 3+3, 16 Gleason 3+4, 6 Gleason 4+3, 12 Gleason 4+4, 3 Gleason 4+5 and 1 Gleason 5+4). Based on targeted biopsy on a per lesion basis, the overall cancer detection rates of PI-RADS 2, 3, 4 and 5 scores for all tumors was 22.2%, 15.8%, 29.8% and 78.1%, respectively. The cancer detection rate of PI-RADS 2, 3, 4, and 5 scores for Gleason 3+4 or greater tumors was 5.6%, 0%, 21.3% and 75%, respectively. Differences in the cancer detection rate between overall PI-RADS 4 and 5 scores were significant (p <0.001 for Gleason greater than 3+3 and Gleason 3+4 or greater cancers). Conclusions A PI-RADS score of 5 had the highest prospective cancer detection rate (78%). A PI-RADS score of 4 had only a 30% cancer detection rate, which is lower than expected. Surprisingly, no or few significant cancers were detected at a PI-RADS score of 3 (16%). These early prospective data suggest that current criteria result in a high false-positive rate that lowers the cancer detection rate. Therefore, stricter criteria may be needed in the future to decrease false-positives and increase the cancer detection rate for PI-RADS scores of 3, 4 and 5.
Purpose To characterize clinically important prostate cancers missed at multiparametric (MP) magnetic resonance (MR) imaging. Materials and Methods The local institutional review board approved this ...HIPAA-compliant retrospective single-center study, which included 100 consecutive patients who had undergone MP MR imaging and subsequent radical prostatectomy. A genitourinary pathologist blinded to MP MR findings outlined prostate cancers on whole-mount pathology slices. Two readers correlated mapped lesions with reports of prospectively read MP MR images. Readers were blinded to histopathology results during prospective reading. At histopathologic examination, 80 clinically unimportant lesions (<5 mm; Gleason score, 3+3) were excluded. The same two readers, who were not blinded to histopathologic findings, retrospectively reviewed cancers missed at MP MR imaging and assigned a Prostate Imaging Reporting and Data System (PI-RADS) version 2 score to better understand false-negative lesion characteristics. Descriptive statistics were used to define patient characteristics, including age, prostate-specific antigen (PSA) level, PSA density, race, digital rectal examination results, and biopsy results before MR imaging. Student t test was used to determine any demographic differences between patients with false-negative MP MR imaging findings and those with correct prospective identification of all lesions. Results Of the 162 lesions, 136 (84%) were correctly identified with MP MR imaging. Size of eight lesions was underestimated. Among the 26 (16%) lesions missed at MP MR imaging, Gleason score was 3+4 in 17 (65%), 4+3 in one (4%), 4+4 in seven (27%), and 4+5 in one (4%). Retrospective PI-RADS version 2 scores were assigned (PI-RADS 1, n = 8; PI-RADS 2, n = 7; PI-RADS 3, n = 6; and PI-RADS 4, n = 5). On a per-patient basis, MP MR imaging depicted clinically important prostate cancer in 99 of 100 patients. At least one clinically important tumor was missed in 26 (26%) patients, and lesion size was underestimated in eight (8%). Conclusion Clinically important lesions can be missed or their size can be underestimated at MP MR imaging. Of missed lesions, 58% were not seen or were characterized as benign findings at second-look analysis. Recognition of the limitations of MP MR imaging is important, and new approaches to reduce this false-negative rate are needed.
RSNA, 2017 Online supplemental material is available for this article.
Objective To, first, propose a novel scoring system to standardize reporting for percutaneous nephrolithotomy because the instruments currently available to predict the percutaneous nephrolithotomy ...outcomes are cumbersome, not validated, and of limited clinical utility; and, second, assess and predict the stone-free rates and perioperative parameters applying S.T.O.N.E. nephrolithometry. Materials and Methods Five reproducible variables available from preoperative noncontrast-enhanced computed tomography were measured: stone size (S), tract length (T), obstruction (O), number of involved calices (N), and essence or stone density (E). Results A total of 117 patients were included. The mean score was 7.7 (range 4-11). The stone-free rate after the first procedure was 80%. There were 18 complications (21%). The most frequent complications were postoperative sepsis and bleeding. The S.T.O.N.E. score correlated with the postoperative stone-free status ( P = .001). The patients rendered stone free had statistically significant lower scores than the patients with residual stones (6.8 vs 9.7, P = .002). Additionally, the score correlated with the estimated blood loss ( P = .005), operative time ( P = .001), and length of hospital stay ( P = .001). Conclusion The novel scoring system we have presented was found to predict treatment success and the risk of perioperative complications after percutaneous nephrolithotomy. Reproducible, standardized parameters obtained from computed tomography imaging can be used for preoperative patient counseling, surgical planning, and evaluation of surgical outcomes across institutions and within medical studies.
Purpose
Multiparametric MRI (mpMRI) improves the detection of clinically significant prostate cancer, but is limited by interobserver variation. The second version of theProstate Imaging Reporting ...and Data System (PIRADSv2) was recently proposed as a standard for interpreting mpMRI. To assess the performance and interobserver agreement of PIRADSv2 we performed a multi‐reader study with five radiologists of varying experience.
Materials and Methods
Five radiologists (n = 2 prostate dedicated, n = 3 general body) blinded to clinicopathologic results detected and scored lesions on prostate mpMRI using PIRADSv2. The endorectal coil 3 Tesla MRI included T2W, diffusion‐weighted imaging (apparent diffusion coefficient, b2000), and dynamic contrast enhancement. Thirty‐four consecutive patients were included. Results were correlated with radical prostatectomy whole‐mount histopathology produced with patient‐specific three‐dimensional molds. An index lesion was defined on pathology as the lesion with highest Gleason score or largest volume if equivalent grades. Average sensitivity and positive predictive values (PPVs) for all lesions and index lesions were determined using generalized estimating equations. Interobserver agreement was evaluated using index of specific agreement.
Results
Average sensitivity was 91% for detecting index lesions and 63% for all lesions across all readers. PPV was 85% for PIRADS ≥ 3 and 90% for PIRADS ≥ 4. Specialists performed better only for PIRADS ≥ 4 with sensitivity 90% versus 79% (P = 0.01) for index lesions. Index of specific agreement among readers was 93% for the detection of index lesions, 74% for the detection of all lesions, and 85% for scoring index lesions, and 58% for scoring all lesions.
Conclusion
By using PIRADSv2, general body radiologists and prostate specialists can detect high‐grade index prostate cancer lesions with high sensitivity and agreement.
Level of Evidence: 1
J. Magn. Reson. Imaging 2017;45:579–585.
IMPORTANCE: Targeted magnetic resonance (MR)/ultrasound fusion prostate biopsy has been shown to detect prostate cancer. The implications of targeted biopsy alone vs standard extended-sextant biopsy ...or the 2 modalities combined are not well understood. OBJECTIVE: To assess targeted vs standard biopsy and the 2 approaches combined for the diagnosis of intermediate- to high-risk prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of 1003 men undergoing both targeted and standard biopsy concurrently from 2007 through 2014 at the National Cancer Institute in the United States. Patients were referred for elevated level of prostate-specific antigen (PSA) or abnormal digital rectal examination results, often with prior negative biopsy results. Risk categorization was compared among targeted and standard biopsy and, when available, whole-gland pathology after prostatectomy as the “gold standard.” INTERVENTIONS: Patients underwent multiparametric prostate magnetic resonance imaging to identify regions of prostate cancer suspicion followed by targeted MR/ultrasound fusion biopsy and concurrent standard biopsy. MAIN OUTCOMES AND MEASURES: The primary objective was to compare targeted and standard biopsy approaches for detection of high-risk prostate cancer (Gleason score ≥4 + 3); secondary end points focused on detection of low-risk prostate cancer (Gleason score 3 + 3 or low-volume 3 + 4) and the biopsy ability to predict whole-gland pathology at prostatectomy. RESULTS: Targeted MR/ultrasound fusion biopsy diagnosed 461 prostate cancer cases, and standard biopsy diagnosed 469 cases. There was exact agreement between targeted and standard biopsy in 690 men (69%) undergoing biopsy. Targeted biopsy diagnosed 30% more high-risk cancers vs standard biopsy (173 vs 122 cases, P < .001) and 17% fewer low-risk cancers (213 vs 258 cases, P < .001). When standard biopsy cores were combined with the targeted approach, an additional 103 cases (22%) of mostly low-risk prostate cancer were diagnosed (83% low risk, 12% intermediate risk, and 5% high risk). The predictive ability of targeted biopsy for differentiating low-risk from intermediate- and high-risk disease in 170 men with whole-gland pathology after prostatectomy was greater than that of standard biopsy or the 2 approaches combined (area under the curve, 0.73, 0.59, and 0.67, respectively; P < .05 for all comparisons). CONCLUSIONS AND RELEVANCE: Among men undergoing biopsy for suspected prostate cancer, targeted MR/ultrasound fusion biopsy, compared with standard extended-sextant ultrasound-guided biopsy, was associated with increased detection of high-risk prostate cancer and decreased detection of low-risk prostate cancer. Future studies will be needed to assess the ultimate clinical implications of targeted biopsy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00102544
Purpose The clinical significance of a positive surgical margin after partial nephrectomy remains controversial. The association between positive margin and risk of disease recurrence in patients ...with clinically localized renal neoplasms undergoing partial nephrectomy was evaluated. Materials and Methods A retrospective multi-institutional review of 1,240 patients undergoing partial nephrectomy for clinically localized renal cell carcinoma between 2006 and 2013 was performed. Recurrence-free survival was estimated using the Kaplan-Meier method and evaluated as a function of positive surgical margin with the log rank test and Cox models adjusting for tumor size, grade, histology, pathological stage, focality and laterality. The relationship between positive margin and risk of relapse was evaluated independently for pathological high risk (pT2-3a or Fuhrman grades III-IV) and low risk (pT1 and Fuhrman grades I-II) groups. Results A positive surgical margin was encountered in 97 (7.8%) patients. Recurrence developed in 69 (5.6%) patients during a median followup of 33 months, including 37 (10.3%) with high risk disease (eg pT2-pT3a or Fuhrman grade III-IV). A positive margin was associated with an increased risk of relapse on multivariable analysis (HR 2.08, 95% CI 1.09–3.97, p=0.03) but not with site of recurrence. In a stratified analysis based on pathological features, a positive surgical margin was significantly associated with a higher risk of recurrence in cases considered high risk (HR 7.48, 95% CI 2.75–20.34, p <0.001) but not low risk (HR 0.62, 95% CI 0.08–4.75, p=0.647). Conclusions Positive surgical margins after partial nephrectomy increase the risk of disease recurrence, primarily in patients with adverse pathological features.
Because rates of infection were similar in men with and without prophylaxis in this trial population, the authors concluded that omission of antibiotic prophylaxis might be reasonable. Furthermore, a ...necessary feature of non-inferiority studies is that the non-inferiority limit cannot exceed the smallest effect size of an active treatment that would be expected compared with a placebo control.3 Given the low infection rates without antibiotic prophylaxis post-transperineal biopsy in the literature (0·1–0·5%),2 selection of a margin of 4% for demonstration of non-inferiority with antibiotic prophylaxis in this setting is further invalidated and leaves the current study substantially underpowered. ...although the authors use Pearson's χ2 test for testing non-inferiority of two proportions, the recommended statistical test in this scenario is the Farrington-Manning test,4 which further subjects the study to sample size underestimation.
Multiparametric magnetic resonance imaging and fusion biopsy detect more high risk prostate cancer and less low risk prostate cancer than systematic biopsy. However, there remains a small subset of ...patients in whom systematic biopsy captures higher grade disease than fusion biopsy. We sought to identify potential mechanisms of the failure of fusion biopsy in the detection of clinically significant prostate cancer.
We reviewed a prospectively maintained database of patients who underwent multiparametric magnetic resonance imaging followed by fusion biopsy and systematic biopsy from 2007 to 2014. In patients in whom disease was upgraded to clinically significant disease (Gleason 7 or greater) by systematic biopsy over fusion biopsy, independent re-review of magnetic resonance imaging, archived biopsy imaging and whole mount pathology as well as needle coordinate mapping were performed. Multivariate logistic regression analysis was done to determine predictors of upgrading by systematic biopsy.
Disease was upgraded based on systematic biopsy over fusion biopsy in 135 of 1,003 patients (13.5%), of whom only 62 (6.2%) were upgraded to intermediate (Gleason 7) and high risk (Gleason 8 or greater) prostate cancer (51 or 5.1% and 11 or 1.1%, respectively). On multivariate analysis lower prostate specific antigen (p <0.001), higher magnetic resonance imaging prostate volume (p <0.001) and a lower number of target cores (p = 0.001) were predictors of upgrading by systematic biopsy. Main mechanisms of under grading by fusion biopsy included multiparametric magnetic resonance imaging reader oversight, presence of magnetic resonance imaging invisible cancer, fusion biopsy technique error and intralesion Gleason heterogeneity.
Magnetic resonance imaging and fusion biopsy rarely missed clinically significant prostate cancer as only 62 of 1,003 cases (6.2%) were upgraded to clinically significant disease by systematic biopsy. Imaging and biopsy techniques are continually refined. Further studies will help clarify mechanisms of fusion biopsy failure and the patient populations that benefit from systematic biopsy in addition to fusion biopsy.
Focal therapy (FT) and partial gland ablation (PGA) are quickly adopted by urologists and radiologists as an option for the management of localized prostate cancer.
To find consensus on a ...standardized nomenclature and to define a follow-up guideline after FT and PGA for localized prostate cancer in clinical practice.
A review of the literature identified controversial topics in the field of FT. Online questionnaires were distributed to experts during three rounds, with the goal to achieve consensus on debated topics. The consensus project was concluded with a face-to-face meeting in which final conclusions were formulated.
Controlled feedback of responses of previous rounds were summarized and returned to the participants allowing them to re-evaluate their decisions. The level of agreement to achieve consensus on a topic was set at 80%.
Sixty-five experts participated in this interdisciplinary consensus study (72% urologists; 28% radiologists). The experts propose the use of the herein standardized nomenclature for ablative procedures. After FT/PGA, the following tests should be performed to assess treatment outcomes: prostate-specific antigen (PSA), imaging, biopsies, and functional outcome assessment. Although not a reliable marker for treatment failure, PSA should be measured every 3 mo in the 1st year and every 6 mo thereafter. Magnetic resonance imaging is the preferred image modality and should be performed at 6 and 18 mo after treatment. A systematic 12-core transrectal ultrasound-guided biopsy combined with a targeted biopsy of the treated area should be performed 6–12 mo after treatment. Functional outcomes should be obtained 3–6 mo after treatment for the first time and until stability is attained.
The panel recommends the use of the proposed nomenclature and follow-up protocols to generate reliable data supporting a broader implementation of FT as a standard of care for select patients with localized prostate cancer.
In this report, we present expert opinion on the use of a standardized nomenclature, and surveillance methodologies after focal therapy and partial gland ablation for localized prostate cancer.
In this report, we present expert opinion on the use of a standardized nomenclature and surveillance methodologies after focal therapy and partial gland ablation for localized prostate cancer. The panel recommends the use of the proposed nomenclature and follow-up protocols to generate reliable data supporting a broader implementation of focal therapy as a standard of care for select patients with localized prostate cancer.
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