Hemi-gland Ablation Research Articles

Treatment Planning Strategies for Interstitial Ultrasound Ablation of Prostate Cancer.

To develop patient-specific 3D models using Finite-Difference Time-Domain (FDTD) simulations and pre-treatment planning tools for the selective thermal ablation of prostate cancer with interstitial ultrasound. This involves the integration with a FDA 510(k) cleared catheter-based ultrasound interstitial applicators and delivery system. A 3D generalized "prostate" model was developed to generate temperature and thermal dose profiles for different applicator operating parameters and anticipated perfusion ranges. A priori planning, based upon these pre-calculated lethal thermal dose and iso-temperature clouds, was devised for iterative device selection and positioning. Full 3D patient-specific anatomic modeling of actual placement of single or multiple applicators to conformally ablate target regions can be applied, with optional integrated pilot-point temperature-based feedback control and urethral/rectum cooling. These numerical models were verified against previously reported ex-vivo experimental results obtained in soft tissues. For generic prostate tissue, 360 treatment schemes were simulated based on the number of transducers (1-4), applied power (8-20 W/cm2), heating time (5, 7.5, 10 min), and blood perfusion (0, 2.5, 5 kg/m3/s) using forward treatment modelling. Selectable ablation zones ranged from 0.8-3.0 cm and 0.8-5.3 cm in radial and axial directions, respectively. 3D patient-specific thermal treatment modeling for 12 Cases of T2/T3 prostate disease demonstrate applicability of workflow and technique for focal, quadrant and hemi-gland ablation. A temperature threshold (e.g., Tthres = 52 °C) at the treatment margin, emulating placement of invasive temperature sensing, can be applied for pilot-point feedback control to improve conformality of thermal ablation. Also, binary power control (e.g., Treg = 45 °C) can be applied which will regulate the applied power level to maintain the surrounding temperature to a safe limit or maximum threshold until the set heating time. Prostate-specific simulations of interstitial ultrasound applicators were used to generate a library of thermal-dose distributions to visually optimize and set applicator positioning and directivity during a priori treatment planning pre-procedure. Anatomic 3D forward treatment planning in patient-specific models, along with optional temperature-based feedback control, demonstrated single and multi-applicator implant strategies to effectively ablate focal disease while affording protection of normal tissues.

Defining the index lesion for potential salvage partial or hemi-gland ablation after radiation therapy for localized prostate cancer

BackgroundSalvage partial gland ablation (sPGA) has been proposed to treat some localized radiorecurrent prostate cancer. The role of prostate biopsy and magnetic resonance imaging (MRI) characteristics to identify patients eligible for sPGA is unknown. ObjectiveTo evaluate the ability of MRI and prostate biopsy characteristics to identify an index lesion suitable for sPGA and validate this selection using detailed tumor maps created from whole-mount slides from salvage radical prostatectomy (sRP) specimens. Design, setting, and participantsMen who underwent sRP for recurrent prostate cancer following primary radiotherapy with external beam radiotherapy (EBRT) and/or brachytherapy between 2000 and 2014 at a single high-volume cancer center were eligible. Those with tumor maps, MRI and biopsy data were included in analysis. Outcome measurements and statistical analysisPrimary outcome was the ability of clinicopathologic and imaging criteria to identify patients who may be eligible for sPGA based on detailed tumor map from whole-mount sRP slides. Results and limitationsOf 216 men who underwent sRP following whole gland radiotherapy, tumor maps, MRI, and biopsy data were available for 77. Of these, 15 (19%) were determined to be eligible for sPGA based on biopsy-proven unilateral disease in contiguous sextant segments, a dominant lesion on MRI concordant with biopsy location or no focal region of interest, and no imaging evidence of extraprostatic disease. Review of tumor maps identified 6 additional men who would have met criteria for sPGA, resulting in sensitivity of 71% (95% C.I. 48%–89%) and specificity of 100% (lower bound of 95% C.I. 94%). None of the 15 men who met the criteria for sPGA on clinical data were identified incorrectly on tumor maps to require full gland surgery (upper bound of 95% C.I. 22%). Median tumor volume of the index lesion was 0.4 cc and recurrent cancer was noted in the apex, mid-gland, and base in 81%, 100%, and 29% of men. ConclusionsIn men with recurrent prostate cancer after radiotherapy, biopsy findings and MRI can be used to select index lesions potentially amenable for sPGA and can guide patient evaluation for inclusion in clinical trials of sPGA following radiation failure. Larger, prospective studies are required to evaluate both the role of MRI and clinical criteria in guiding focal salvage therapy and the effectiveness of this modality for radiorecurrent prostate cancer.

Re: High Intensity Focused Ultrasound Hemigland Ablation for Prostate Cancer. Initial Outcomes of a United States Series

Re: High Intensity Focused Ultrasound Hemigland Ablation for Prostate Cancer. Initial Outcomes of a United States Series

Characteristics of Cancer Progression on Serial Biopsy in Men on Active Surveillance for Early-stage Prostate Cancer: Implications for Focal Therapy

BackgroundActive surveillance (AS) is a safe and accepted option for managing men with low-risk prostate cancer. Nevertheless, some patients lack confidence in or access to AS. Focal therapy (FT) is a possible alternative to radical treatment for such patients. ObjectiveWe evaluated dominant tumor (DT) progression across serial biopsies to determine whether men on AS could be reasonable candidates for FT. Design, setting, and participantsMen enrolled in AS at University of California, San Francisco between 1996 and 2017 with low/intermediate risk were included. Outcome measurements and statistical analysisChanges in biopsy grade, volume, and focality of the DT over time were assessed. Focality (good or poor for FT) was defined by the number of cores, laterality, and contiguity of prostate sites containing tumor (based on pathology reports). Candidates (either for targeted/quadrant ablation or for hemigland ablation) were defined based on good focality, grade group (GG) ≤2, and low-volume disease. Patients were classified as favorable (GG ≤ 2 with good focality and concordant multiparametric magnetic resonance imaging [mpMRI]) or unfavorable (poor focality or high-volume disease or discordant mpMRI) for FT at surveillance biopsies. Results and limitationsA total of 1057 men met the inclusion criteria. The median number of biopsies per patient was three (interquartile range 2–4), and 196 patients (18.5%) underwent five or more biopsies. At confirmatory biopsy, 43% remained candidates for FT (67% for targeted/quadrant ablation and 33% for hemigland ablation) and 20% had a negative biopsy. Of the candidates for FT at initial biopsy, 11% had less favorable characteristics at confirmatory biopsy. Among candidates for FT based on both initial and confirmatory biopsies, 70% remained favorable for hemigland ablation at subsequent biopsies. Limitations include retrospective design and mpMRI information only at surveillance biopsy. ConclusionsSerial biopsy findings in men with early-stage cancer on AS show that tumor location remains relatively stable and significant changes in grade and/or volume occur largely in the DT. Combined diagnostic and confirmatory biopsy findings help better select patients for FT than the use of the diagnostic biopsy alone. Patient summaryIn a large cohort of patients on active surveillance for prostate cancer, we evaluated changes across serial biopsies to identify potential candidates for focal therapy (FT). Our findings showed that the dominant tumor remained stable over time and the majority of men were favorable candidates for FT.

High Intensity Focused Ultrasound Hemigland Ablation for Prostate Cancer: Initial Outcomes of a United States Series.

We report outcomes of hemigland high intensity focused ultrasound ablation as primary treatment for localized prostate cancer in the United States. A total of 100 consecutive men underwent hemigland high intensity focused ultrasound (December 2015 to December 2019). Primary end point was treatment failure, defined as Grade Group 2 or greater on followup prostate biopsy, radical treatment, systemic therapy, metastases or prostate cancer specific mortality. IIEF (International Index of Erectile Function), I-PSS (International Prostate Symptom Score) and 90-day complications were reported. At study entry patients had very low (8%), low (20%), intermediate favorable (50%), intermediate unfavorable (17%) and high (5%) risk prostate cancer. Median followup was 20 months. The 2-year survival free from treatment failure, Grade Group 2 or greater recurrence, repeat focal high intensity focused ultrasound and radical treatment was 73%, 76%, 90% and 91%, respectively. Bilateral prostate cancer at diagnosis was the sole predictor for Grade Group 2 or greater recurrence (p=0.03). Of men who underwent posttreatment biopsy (58), 10 had in-field and 8 out-of-field Grade Group 2 or greater positive biopsy. Continence (zero pad) was maintained in 100% of patients. Median IIEF-5 and I-PSS scores before vs after hemigland high intensity focused ultrasound were 22 vs 21 (p=0.99) and 9 vs 6 (p=0.005), respectively. Minor and major complications occurred in 13% and 0% of patients. No patient had rectal fistula or died. Short-term results of focal high intensity focused ultrasound indicate safety, excellent potency and continence preservation, and adequate short-term prostate cancer control. Radical treatment was avoided in 91% of men at 2 years. Men with bilateral prostate cancer at diagnosis have increased risk for Grade Group 2 or greater recurrence. To our knowledge, this is the initial and largest United States series of focal high intensity focused ultrasound as primary treatment for prostate cancer.

Using spatial tracking with magnetic resonance imaging/ultrasound-guided biopsy to identify unilateral prostate cancer.

To create reliable predictive metrics of unilateral disease using spatial tracking from a fusion device, thereby improving patient selection for hemi-gland ablation of prostate cancer. We identified patients who received magnetic resonance imaging (MRI)/ultrasound-guided biopsy and radical prostatectomy at a single institution between 2011 and 2018. In addition to standard clinical features, we extracted quantitative features related to biopsy core and MRI target locations predictive of tumour unilaterality. Classification and Regression Tree (CART) analysis was used to create a decision tree (DT) for identifying cancer laterality. We evaluated concordance of model-determined laterality with final surgical pathology. A total of 173 patients were identified with biopsy coordinates and surgical pathology available. Based on CART analysis, in addition to biopsy- and MRI-confirmed disease unilaterality, patients should be further screened for cancer detected within 7mm of midline in a 40mL prostate, which equates to the central third of any-sized prostate by radius. The area under the curve for this DT was 0.82. Standard diagnostics and the DT correctly identified disease laterality in 73% and 80% of patients, respectively (P=0.13). Of the patients identified as unilateral by standard diagnostics, 47% had undetected contralateral disease or were otherwise incorrectly identified. This error rate was reduced to 17% (P=0.01) with the DT. Using spatial tracking from fusion devices, a DT was more reliable for identifying laterality of prostate cancer compared to standard diagnostics. Patients with cancer detected within the central third of the prostate by radius are poor hemi-gland ablation candidates due to the risk of midline extension of tumour.

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

ObjectivesTo assess clinicopathologic factors on MR/US fusion biopsy that might predict failure of theoretical selection criteria for prostatic hemigland ablation (HA). Subjects and methodsA 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. ResultsOf 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. ConclusionsIn 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.

Rectal wall saline displacement for improved margin during MRI-guided cryoablation of primary and recurrent prostate cancer.

To describe safety, efficacy, and added oncologic margin of saline displacement of the rectal wall during MRI-guided cryoablation of primary and recurrent prostate cancer. A retrospective review was conducted for patients who underwent MRI-guided cryoablation with saline displacement of the rectal wall for treatment of primary and recurrent prostate cancer over a 2-year period. Saline displacement was used when the distance from the edge of the ablation area to the rectal wall was insufficient to provide at least a 5-mm treatment margin. Pre- and post-ablation rectal wall displacement distances as well as ablative zone margins were assessed with MRI. Saline displacement distance was measured from the rectal wall to the edge of the lesion for focal lesion ablation and from the edge of the prostate for hemi-gland ablation. Immediate and intermediate-term complications were assessed. Saline displacement was used in 25 patients undergoing MRI-guided cryoablation. Twenty-one patients underwent salvage cryoablation, while four patients had it as primary treatment for prostate cancer. Median pre- and post- saline displacement rectal wall displacement distances were 6.0 and 11.2mm, respectively (P < 0.0001). Median-added oncologic margin achieved by saline displacement was 4.6mm (range 0.6-26.5). Median follow-up was 14months (range 5-29). There were no intra-procedural complications and 3 patients experienced minor (Clavien-Dindo grade I) complications. One rectal complication occurred in a patient undergoing salvage cryotherapy with a history of extensive pelvic surgery and radiation. Saline infusion at the time of MRI- guided cryoablation for prostate cancer resulted in increased distances between the target lesion and rectum. This is a useful technique in providing an added oncologic margin when treating lesions close to the rectal wall.

MP78-04 PREDICTING PROSTATE CANCER FOCAL THERAPY ELIGIBILITY WITH MACHINE LEARNING

INTRODUCTION AND OBJECTIVES:Focal therapies such as hemi-gland ablation (HGA) are evolving treatment options for prostate cancer. However, limitations in current diagnostics--biopsy Gleason score, ...

Defining the index lesion for salvage partial gland ablation after radiation therapy for localized prostate cancer.

105 Background: Our objective was to evaluate the impact of MRI and systematic biopsy characteristics to identify the index lesion for salvage partial gland ablation using tumor maps from whole mount slides of salvage radical prostatectomy (sRP) specimen. Methods: We identified 225 patients who underwent sRP between 2000 and 2014 and a tumor map was created from whole-mount slides in 77 patients. Among these patients, we selected men with a priori pre-treatment criteria considered eligible for PGA, including, biopsy proven unilateral disease concordant with a region of interest (ROI) on MRI, and excluding men with imaging suspicious for extra-capsular extension (ECE), seminal vesicle Invasion (SVI) or lymph node involvement (LNI). We describe the correlation between pre-treatment clinical characteristics and final radical prostatectomy whole mount specimen to select men eligible for PGA defined as hemi-gland ablation. Results: Among 77 patients with a tumor map of entirely-submitted and whole-mounted specimens, 15 patients were determined to be eligible for partial gland ablation based on pre-treatment clinical characteristics. The mean age was 60 years and median time from primary RT was 48 months. The median (IQR) tumor volume of the index lesion was 0.3 (0.4) cc. The location of the index lesion was determined to be the apex, mid-gland and base in 77%, 100% and 15% of patients, respectively. The median distance of the index tumor to the urethra was 0.5 (0.2) cm. The index tumor was confined to one lobe and concordant to the biopsy pathology and MRI data in all 15 patients (100%). There was no ECE, LNI or SVI identified in the sRP specimens. To account for those patients who did not have a tumor map of the whole-mount specimen, a sensitivity analysis was performed and determined that the clinical characteristics of the 77 patients with tumor maps were comparable to the entire 225 sRP cohort. Conclusions: Clinical characteristics guided by biopsy findings and MRI data can be used to select men for PGA with recurrent localized prostate cancer after radiation therapy and based on tumor maps from sRP specimen, we propose that salvage hemi-gland ablation including periurethral tissue is feasible.

Focal Therapy is an Option for the Majority of Localised Prostate Cancers: A Histopathological Study of Contemporary UK Radical Prostatectomies

Objectives: Focal therapy for prostate cancer offers a management option intermediate between active surveillance and radical therapy for small volume, low grade localised prostate cancer. We studied a series of UK radical prostatectomies (RP) performed for organ-confined prostate cancer to identify the proportion of cases potentially suitable for pure lesion only focal therapy (PLFT) or focal hemi-gland ablation (FHA). Methods: The pathological features of 309 RP specimens were studied. Patients were grouped into the following categories: group A: unifocal cancer; group B: multifocal disease where only the index cancer was significant (Epstein's criteria); group C: unilateral multifocal significant disease; group D: bilateral multifocal significant disease. Results: 56% (172) patients were candidates for PLFT, including 70 group A cases plus 102 group B cases. Group C comprised 4% (11) cases who are candidates for FHA. Thus 60% (183) cases were candidates for either PLFT or FHA. Conclusions: A significant number of patients are potential candidates for focal therapy in this RP series. We encourage prospective clinical trials investigating the oncological safety and outcomes of focal therapy in treating low and intermediate risk localised prostate cancer.