A Multi-Institutional Study of Magnetic Resonance/Ultrasound Fusion-Guided Nanoparticle-Directed Focal Therapy for Prostate Ablation.

PURPOSE: Focal therapy aims to provide a durable oncologic treatment option for men with prostate cancer (PCa), while preserving their quality of life. Most focal therapy modalities rely on the direct tissue effect, resulting in a possible nontargeted approach to ablation. Here, we report the results of the first human feasibility trial utilizing nanoparticle-directed focal photothermal ablation for PCa. MATERIALS AND METHODS: A prospective, open-label, single-arm, multicenter study of men with localized PCa in Gleason Grade Group 1 to 3 was conducted. Men received a single infusion of gold nanoparticles (AuroShells), followed by magnetic resonance (MR)/ultrasound (US) fusion-guided laser excitation of the target tissue to induce photothermal ablation. MRI was used to assess the effectiveness of prostate tissue ablation at 48 to 96 hours, 3 months, and 12 months post treatment. At 3 months, a targeted fusion biopsy of the lesion(s) was conducted. At 12 months, a targeted fusion biopsy and standard templated biopsy were performed. Treatment success was determined based on a negative MR/US fusion biopsy outcome within the treated area. RESULTS: Forty-six men were enrolled in the study, and 44 men with 45 lesions completed nanoparticle infusion and laser treatment. The mean PSA level at baseline was 9.5 ng/mL, which decreased to 5.9 ng/mL at 3 months and to 4.7 ng/mL at 12 months (P < .0001). The oncologic success rates at 3 and 12 months resulted in 29 (66%) and 32 (73%) of 44 patients, respectively, being successfully treated, confirmed with negative MR/US fusion biopsies within the ablation zone. Among Gleason Grade Group, maximum lesion diameter on MRI, prostate volume, and Prostate Imaging Reporting and Data System scoring, the maximum lesion diameter was significantly associated with the odds of treatment failure at 12 months (P = .046). CONCLUSIONS: Nanoparticle-directed focal laser ablation of neoplastic prostate tissue resulted in 73% of patients with successful treatment at 12 months post treatment, confirmed by negative MR/US fusion biopsy of the treated lesion and a systematic biopsy. CLINICAL TRIAL REGISTRATION NO.: 02680535.

A comprehensive comparison between mpMRI of the prostate, MR-US fusion biopsy and whole mount histopathology.

OBJECTIVES: To compare multiparametric magnetic resonance imaging (mpMRI) findings, US-MR fusion prostate biopsy results and whole-mount thin-section histopathology after radical prostatectomy. PATIENTS AND METHODS: Overall 259 patients, who had undergone mpMRI with lesions reported as PI-RADS 3-5, underwent a MR-US fusion biopsy between 2018 and 2020. Overall 186 biopsies yielded prostate cancer and 104 patients subsequently underwent endoscopic extraperitoneal radical prostatectomy. Histopathology of biopsies was compared to the final histopathology in whole mount thin sections after radical prostatectomy by means of descriptive statistics, and further, the lesions from mpMRT were compared to whole mount histology. RESULTS: Prostate cancer was diagnosed in 186 (71.8%) of 259 patients (median age 69.2 y, range 42-82 y, median PSA 7.8 ng/ml, range 2.1-31.3 ng/ml). Of those, 95 (51,1%) underwent radical endoscopic prostatectomy, and 80 (43%) chose radiotherapy or active surveillance. In 52/95 (54,7%) with RPE additional lesions were found in the final histological whole mount sections not described at mpMRI. 22/95 (23,2%) of RPE patients had ≥ 1 additional Gleason score ≥ 7 lesions, 23 /259 (8,4%) of biopsies, respectively. The Gleason score after surgery was upgraded in 37/95 (38,9%) and downgraded in 18/95 (18,9%) patients. CONCLUSION: If we compare all 259 performed biopsies with the final histological whole mount sections which showed additional lesions with Gleason ≥ 7 (23,2%), it can be assumed that up to 10% of clinical significant carcinomas are missed during primary assessment via mpMRI. The majority of additional findings after RP were intermediate/high risk tumors. Upgrades from low-risk to intermediate or high-risk occurred.

A comparative study of transperineal software-assisted magnetic resonance/ultrasound fusion biopsy and transrectal cognitive fusion biopsy of the prostate.

BACKGROUND: The advantages and disadvantages of transperineal and transrectal biopsies remain controversial in the era of prostate targeted biopsy. In this study, we compared the cancer detection and complication rates of transperineal magnetic resonance/ultrasound (MR/US) fusion biopsy and transrectal cognitive fusion biopsy of the prostate. METHODS: This was a comparative study of two prospectively collected cohorts. Men with clinically suspected prostate cancer and prostate imaging reporting and data system (PI-RADS) score ≥ 3 lesions on multi-parametric magnetic resonance imaging (mpMRI) were enrolled. They underwent either transperineal software fusion biopsy or transrectal cognitive fusion biopsy and systematic biopsy. The detection rates of any prostate cancer and clinically significant prostate cancer (csPC, defined as Gleason score ≥ 3 + 4) and the complication rates between both groups were analysed. RESULTS: Ninety-two and 85 patients underwent transperineal software fusion and transrectal cognitive fusion biopsies, respectively. The detection rate for any prostate cancer was similar between both groups (60.8% vs. 56.4%, p = 0.659). In terms of csPC detection, transperineal fusion biopsy outperformed transrectal fusion biopsy (52.2% vs. 36.5%, p = 0.036). In multivariate regression analysis, age, PI-RADS score > 3, and transperineal route were significant predictors of csPC. Meanwhile, transperineal biopsy resulted in a higher rate of urinary retention than transrectal biopsy (18.5% vs. 4.7%, p = 0.009). No serious infectious complications were noted, although a patient developed sepsis after transrectal biopsy. CONCLUSIONS: Transperineal software fusion biopsy provided a higher csPC detection rate than transrectal cognitive fusion biopsy and carried minimal risk for infectious complications in patients with MRI-visible prostate lesions.

Spatial Tracking of Targeted Prostate Biopsy Locations: Moving Towards Effective Focal Partial Prostate Gland Ablation with Improved Treatment Planning.

The ability to selectively characterize, localize, and predict the specific areas of the prostate gland which harbor the worst biologic behavior is requisite for optimal prostate cancer therapy, especially in the emerging field of partial prostate gland ablation (focal therapy). In this manuscript, we highlight contemporary techniques in target tracking for focal therapy planning. Multiparametric magnetic resonance imaging has emerged as a dominant strategy to localize biopsy sites most likely to contain high-grade lesions. In-bore MRI biopsy and MR/US fusion biopsy using cognitive or software-enhanced co-registration have also become the most common strategy to accomplish this technical challenge. Such advances have led to growing optimism in the field of focal therapy for prostate cancer.

MR/US Fusion Technology: What Makes It Tick?

MR/US fusion biopsy has emerged as a significant refinement of traditional prostate cancer diagnostic techniques. Utilizing not only quantitative imaging suspicion information from mpMRI but also the spatial accuracy and three-dimensional localization allows such strategies to specifically sample areas of concern with the gland. As such, diagnostic certainty is markedly improved. In this manuscript, we aim to highlight the multidisciplinary approach (amongst urologists, radiologists, pathologists, imaging technologists, nursing staff, and patients) which is required to launch and maintain a successful prostate imaging program.

Robotic-assisted laparoscopic radical prostatectomy for treatment of a newly identified lesion revealed no viable cells in the previously treated area with microwave focal therapy.

Introduction: Histological outcome of the targeted focal therapy is in principle confirmed by targeted needle biopsy from the treated area in clinical trial. Herein, we report a rare case in which the MFT was followed by RARP. Case presentation: A 68-year-old man with PSA 9.6 ng/mL and PI-RADS 4 lesion in the right transition zone on multi-parametric MRI underwent MR/ultrasound fusion-guided targeted biopsy, which revealed grade-group 1 cancer. Targeted focal therapy with microwave ablation was performed, resulting in disappearance of the PI-RADS 4 lesion at post-operative 4 months. However, PSA rose to 11.5 ng/mL, and a new PI-RADS 4 lesion, was identified in the left peripheral zone. RARP was performed to reveal new grade-group 3 cancer, and no viable cells in the previously treated area with MFT. Conclusion: RARP was safely performed even after MFT and proved the pathological complete response of microwave ablation.

Predictors of disparity between targeted and in-zone systematic cores during transrectal MR/US-fusion prostate biopsy.

BACKGROUND: The combination of targeted and systematic biopsies during MR/US-fusion prostate biopsy improves cancer detection over either modality alone. OBJECTIVE: To identify factors associated with disparity in detection of prostate cancer between systematic and targeted biopsies in magnetic resonance imaging positive zones. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively analyzed 171 men receiving initial MR/US fusion biopsy at our institution from 2015 to 2018. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Disparity was defined as positive targeted but negative systematic biopsy within an magnetic resonance imaging-positive zone (PIRADS 3+), or vice versa. Multivariable logistic regression was used to identify factors associated with disparity in detection of cancer on a per lesion basis. RESULTS AND LIMITATION: Three hundred and fifty-five lesions were targeted. For any cancer and clinically significant prostate cancer (csPCa), 37 (10%) and 24 (7%) lesions were target positive/systematic negative, respectively, while 30 (8%) and 23 (6%) lesions were target negative/systematic positive. In multivariable analysis, anterior location (OR 4.1, 95% CI 1.5-11.4, P = 0.007) was associated with csPCa target positive/systematic negative disparity, while higher prostate volume (OR 1.14, 95% CI 1.0-1.29, P = 0.04) was associated with csPCa target negative/systematic positive disparity. Shorter distance from apex (OR 1.02, 95% CI 1.01-1.04, P = 0.02) was associated with target positive/systematic negative disparity for any cancer. Limitations included relatively limited sample size and lack of prostatectomy specimen as a gold standard. CONCLUSIONS: Anterior or apical lesion location favors better disease capture on targeted biopsies. When doing systematic-only biopsies, surgeons may consider sampling the anterior zone separately.

Comparison of biopsy strategies for prostate biopsy according to lesion size and PSA density in MRI-directed biopsy pathway.

PURPOSE: To investigate whether the detection of clinically significant prostate cancer (csPCa) and the added value of focal saturation biopsy and systematic biopsy (SBx) differ according to index lesion size, and to compare the current guidelines for csPCa detection. METHODS: This retrospective study included consecutive men who underwent MRI and subsequent SBx and MRI-targeted biopsy (TBx) for a suspicious lesion between April 2019 and February 2020. Lesion visibility on transrectal ultrasound (US) and added value of focal saturation biopsy and SBx were compared according to index lesion size using chi-square and McNemar tests. csPCa detection rates and the proportion of biopsy-indicated men were compared among four biopsy strategies based on current guidelines. RESULTS: Of 313 men evaluated (median age, 65; interquartile range 60‒71), csPCa was detected in 110 (35%). In lesions < 10 mm, greater US invisibility (42.7% of lesions < 10 mm versus 20.0% of lesions ≥ 10 mm; p < 0.001) and higher added value of focal saturation biopsy and SBx (11.1% and 17.1% in lesions < 10 mm versus 4.2% and 6.3% in lesions ≥ 10 mm) were observed, compared with lesions ≥ 10 mm. Consideration of prostate-specific antigen (PSA) density > 0.15 ng/mL/mL as a cutoff in unsuspicious MRI led to a 14% reduction (44/313) in men who needed biopsy. CONCLUSION: Determination of the biopsy strategy in terms of the need for focal saturation biopsy or SBx should be made considering lesion size. The use of PSA density in non-suspicious MRI can lead to a reduction in biopsy-indicated men.

Magnetic Resonance and Ultrasound Fusion Imaging to Characterise Ovarian Masses: A Feasibility Study.

BACKGROUND/AIM: Magnetic resonance (MR) and ultrasound (US) fusion imaging (MR-US fusion) is already used to guide prostate biopsies and has been proven accurate for diagnosing cervical cancer. In this study, we aimed to evaluate the feasibility and performance of MR-US fusion for characterizing adnexal masses. PATIENTS AND METHODS: A retrospective study was conducted between 2014 and 2018 including women referred to our Gynaecological Oncology Department for characterization of an adnexal mass (n=106). Performance of MR-US fusion was evaluated in a subgroup of patients who underwent surgery (n=26). Two readers, blinded to final histology, performed and rated US findings according to the International Ovarian Tumor Analysis simple rules score, MR according to Ovarian-Adnexal Reporting Data System Magnetic score, and MR-US fusion through a tailored score. The reference outcome was the final pathology. RESULTS: MR-US fusion had a sensitivity of 100% (95%CI=80-100), specificity of 89% (95%CI=52-99), positive likelihood ratio of 9 (95%CI=1.4-57), and accuracy of 96% (95%CI=80-99). CONCLUSION: MR-US fusion is feasible for characterizing adnexal masses to predict ovarian cancer.

Cribriform pattern and perineural invasion on MR/US fusion biopsy predict failure of selection criteria for prostatic hemigland ablation.

OBJECTIVES: To assess clinicopathologic factors on MR/US fusion biopsy that might predict failure of theoretical selection criteria for prostatic hemigland ablation (HA). SUBJECTS AND METHODS: A retrospectively maintained single institution multiparametric MRI database (n = 1667) was queried to identify 355 patients who underwent MR/US fusion biopsy, including both targeted biopsy and concurrent systematic biopsy from December 1, 2014 to June 1, 2018. Clinical, pathological, and imaging variables were assessed on fusion biopsy (Table 1) to determine who met theoretical selection criteria for HA, defined as unilateral intermediate-risk prostate cancer per NCCN criteria (Grade Group [GG] 2 or 3 with prostate-specific antigen <20) and no evidence of extraprostatic extension (EPE) on multiparametric MRI. Predictors of selection criteria failure were then assessed in patients who also underwent radical prostatectomy (RP). Failure of the theoretical HA selection criteria was defined as presence of GG ≧ 2 on the contralateral (untreated) side, or the presence of high-risk disease (any GG ≧ 4 or EPE) in the RP specimen. RESULTS: Of the 355 patients who underwent fusion biopsy, 84 patients met the theoretical selection criteria for HA. Of those patients eligible, 54 underwent RP, 37 (68.5%) of which represented unsuccessful HA selection criteria. Patients no longer met HA selection criteria on the basis of upgrading alone in 6/54 (11.1%), EPE alone in 9/54 (16.7%), bilateral GG 2 or 3 in 16/54 (29.6%) or combined EPE and bilateral GG 2 or 3 in 6/54 (11.1%) cases. In the HA selection failures due to upgrading, three also had EPE, one of whom also had missed contralateral GG ≧ 2 disease. The only factor independently associated with HA failure was any presence of cribriform pattern (HR 7.01, P = 0.021). Perineural invasion on systematic biopsyalso appeared to improve the performance of our multivariable model (HR 5.33, P = 0.052), though it was not statistically significant when using a cutoff of <0.05. Accuracy for predicting successful HA was 0.32 and improved to 0.74 if PNI or cribriform were excluded and 0.84 if both were excluded. CONCLUSIONS: In a retrospective analysis of RP patients who underwent preoperative MRI/US fusion biopsy, current selection criteria for prostatic HA based on NCCN intermediate-risk stratification failed to accurately identify appropriate candidates in 68.5% of patients. Cribriform pattern and PNI detected on biopsy reduced the failure of hemigland selection criteria to 43%. These criteria should be routinely reported on biopsy pathology and taken into consideration when selecting patients for HA in prospective clinical trials.

Visibility of prostate cancer on transrectal ultrasound during fusion with multiparametric magnetic resonance imaging for biopsy.

OBJECTIVES: To determine transrectal ultrasound (TRUS) visibility of magnetic resonance (MR) lesions. METHODS: Data from 34 patients with 56 MR lesions and prostatectomy were used. Five observers localized and determined TRUS visibility during retrospective fusion. Visibility was correlated to Prostate Imaging-Reporting and Data System (PIRADS) and Gleason scores. RESULTS: TRUS visibility occurred in 43% of all MR lesions and in 62% of PIRADS 5 lesions. Visible lesions had a significantly lower localization variability. On prostatectomy, 58% of the TRUS-visible lesions had a Gleason 4 or 5 component. CONCLUSIONS: Almost half of the MR lesions were visible on TRUS. TRUS-visible lesions were more aggressive than TRUS-invisible lesions.

MR-targeted TRUS prostate biopsy using local reference augmentation: initial experience.

PURPOSE: To evaluate MR-targeted TRUS prostate biopsy using a novel local reference augmentation method. PATIENTS AND METHODS: Tracker-based MR-TRUS fusion was applied using local reference augmentation. In contrast to conventional whole gland fusion, local reference augmentation focuses the highest registration accuracy to the region surrounding the lesion to be biopsied. Pre-acquired multi-parametric MR images (mpMRI) were evaluated using PIRADS classification. T2-weighted MR images were imported on an ultrasound machine to allow for MR-TRUS fusion. Biopsies were targeted to the most suspicious lesion area identified on mpMRI. Each target was biopsied 1-5 times. For each biopsied lesion the diameter, PIRADS and Gleason scores, visibility during fusion, and representativeness were recorded. RESULTS: Included were 23 consecutive patients with 25 MR suspicious lesions, of which 11 patients had a previous negative TRUS-guided biopsy and 12 were biopsy naïve. The cancer detection rate was 64 % (Gleason score ≥6). Biopsy was negative (i.e., no Gleason score) in seven patients confirmed by follow-up in all of them (up to 18 months). After MR-TRUS fusion, 88 % of the lesions could be visualized on TRUS. The cancer detection rate increases with increasing lesion size, being 73 % for lesions larger than 10 mm. CONCLUSION: Tracker-based MR-TRUS fusion biopsy with local reference augmentation is feasible, especially for lesions with an MR maximum diameter of at least 10 mm or PIRADS 5 lesions. If this is not the case, we recommend in-bore MR-guided biopsy.