Uri Lindner

Image Guided Photothermal Focal Therapy for Localized Prostate Cancer: Phase I Trial

PURPOSE We ascertained the feasibility and safety of image guided targeted photothermal focal therapy for localized prostate cancer. MATERIALS AND METHODS Twelve patients with biopsy proven low risk prostate cancer underwent interstitial photothermal ablation of the cancer. The area of interest was confirmed and targeted using magnetic resonance imaging. Three-dimensional ultrasound was used to guide a laser to the magnetic resonance to ultrasound fused area of interest. Target ablation was monitored using thermal sensors and real-time Definity contrast enhanced ultrasound. Followup was performed with a combination of magnetic resonance imaging and prostate biopsy. Validated quality of life questionnaires were used to assess the effect on voiding symptoms and erectile function, and adverse events were solicited and recorded. RESULTS Interstitial photothermal focal therapy was technically feasible to perform. Of the patients 75% were discharged home free from catheter the same day with the remainder discharged home the following day. The treatment created an identifiable hypovascular defect which coincided with the targeted prostatic lesion. There were no perioperative complications and minimal morbidity. All patients who were potent before the procedure maintained potency after the procedure. Continence levels were not compromised. Based on multicore total prostate biopsy at 6 months 67% of patients were free of tumor in the targeted area and 50% were free of disease. CONCLUSIONS Image guided focal photothermal ablation of low risk and low volume prostate cancer is feasible. Early clinical, histological and magnetic resonance imaging responses suggest that the targeted region can be ablated with minimal adverse effects. It may represent an alternate treatment approach to observation or delayed standard therapy in carefully selected patients. Further trials are required to demonstrate the effectiveness of this treatment concept.

Real-time magnetic resonance imaging-guided focal laser therapy in patients with low-risk prostate cancer.

Two patients with low-risk prostate cancer (PCa) were treated with outpatient in-bore magnetic resonance imaging (MRI)-guided focal laser ablation. The tumor was identified on MRI. A laser fiber was delivered via a catheter inserted through a perineal template and guided to the target with MRI. The tissue temperature was monitored during laser ablation by MRI thermometry. Accumulated thermal damage was calculated in real time. Immediate post-treatment contrast-enhanced MRI confirmed devascularization of the target. No adverse events were noted. MRI-guided focal laser therapy of low-risk PCa is feasible and may offer a good balance between cancer control and side effects.

Focal Laser Ablation for Prostate Cancer Followed by Radical Prostatectomy: Validation of Focal Therapy and Imaging Accuracy

An increased incidence of low-risk prostate cancer (PCa) has led investigators to develop focal therapy as a management option for PCa. We evaluated the effects of focal laser ablation (FLA) on PCa tissue and the accuracy of magnetic resonance imaging (MRI) in determining ablated lesion volume by comparing the whole-mount histology and MRI in four patients that underwent FLA followed by radical prostatectomy. Ablated areas were characterized by homogeneous coagulation necrosis. The MRI-calculated ablated volume correlated well with histopathology. We found that FLA creates confluent ablation with no evidence of viable cells in treated regions. Postablation MRI is able to determine the ablation accurately.

Image guidance for focal therapy of prostate cancer

Focal therapy is an appealing strategy for any tumor and in time may prove to be a valuable treatment option for low-risk, carefully selected prostate cancer (PCa) patients. In an era where active surveillance is now considered a viable option for low-risk PCa patients, it is conceivable that organ-sparing treatments could also become an established option. The aim of focal therapy is to achieve long-term cancer control with minimal morbidity yet without the side effects of radical therapy. Although lacking in evidence, it remains intuitive that if we treat the smallest possible region of the prostate where to ensure cancer control by ablation (laser, cryotherapy or another ablative source), then there is less potential for untoward side effects. Thus, we believe the ultimate goal in focal therapy is to target specifically the cancerous site while ablating it and the smallest zone of normal prostate tissue around it to obtain cancer control. To achieve this goal, one is dependent on high-quality imaging to: locate the cancerous lesion and have it assist in guiding the ablative modality toward the lesion; monitor the ablation in real time; accurately assess the extent and totality of the ablation post-treatment and finally be used to follow-up and monitor the prostate in search of a recurrence of cancer in the treated area or the development ion new zones. This review seeks to discuss such issues focusing on imaging modalities as they relate to focal therapy of PCa.

Focal laser ablation for localized prostate cancer.

Throughout history, medicine has witnessed paradigm shifts that significantly change patient treatment. In surgical oncology, the introduction of lumpectomy revolutionized breast cancer treatment while partial nephrectomy has altered the management of kidney cancer. In both cases, organ preservation is combined with efficacious management of the cancer via a less invasive approach. Within urology, prostate cancer (PCa) may be the next to benefit from such a treatment paradigm. Current management of PCa involves either whole organ treatment, with the inherent side effects, while selected patients are eligible for active surveillance. Focal therapy offers a middle ground for low-risk patients with PCa, again using the principles of a minimally invasive treatment of the cancer, in this case using an energy source with few side effects, combined with maximal organ preservation. Because focal therapy for PCa is still in evolution, there is no consensus on the ideal energy source that should be used to ablate the PCa, imaging to monitor the tissue destruction in real time, how many treatments may be offered, and the ideal follow-up regimen. Long-term follow-up of patients is needed before it is recommended as a first-line treatment. Nevertheless, evidence is accumulating that radically treating PCa holds survival benefit for patients; however, the number of men needed to treat is considerable, with significant side effects; thus, more centers are investigating focal therapy as an option. This review focuses on the use of the laser as the energy source for focal ablation, while bringing historically relevant information regarding laser energy and highlighting the perceived advantageous of focal laser ablation.

A system for MRI‐guided transperineal delivery of needles to the prostate for focal therapy

PURPOSE To demonstrate the capabilities of a new magnetic resonance imaging (MRI)-guided system for delivering needles to the prostate for focal therapy. Included is a presentation of the design of the system and its user interface, evaluation of MR-compatibility, and quantitative evaluation of guidance accuracy and repeatability within the bore of a clinical MRI scanner. METHODS The use of MRI for visualization of tumors, intraoperative visualization of interventional tools, and thermometry for controlled ablation of lesions is becoming increasingly prevalent. In this work, the authors present a prototype system for guiding needles to prostate tumors within the bore of an MRI scanner for use in focal laser thermal ablation of prostate tumors. The system consists of a manually actuated trajectory alignment device that allows a physician to precisely align a set of needle guides with an intended target in the prostate within the bore of a clinical closed-bore MRI scanner. Needle insertion is then performed transperineally, with the patient in the bore of the MRI, and custom software provides monitoring of thermal ablative procedures. RESULTS The system is shown to have a minimal effect on image distortion, and only a 6% decrease in image signal-to-noise ratio. Through needle insertion tests in tissue-mimicking phantoms, the systems potential for reliably guiding needles to intra-MR targets within 2.64 mm has been demonstrated. Use of the system to deliver focal laser ablation therapy to two patients showed that it can be used to deliver needles with minimal disruption of workflow, and in less time than when insertions are performed freehand or with a fixed grid template. CONCLUSIONS A system for delivering needles to a patients prostate for focal therapy within the bore of an MRI scanner has been developed. Results from needle insertion tests in phantoms suggest that the system has the potential to provide accurate delivery of focal therapy to prostate tumors of the smallest clinically significant size. Initial tests in two patients showed that needle deflection was larger than in phantoms, but methods of manually compensating for this effect were employed and needles were delivered to treatment sites with sufficient accuracy to deliver effective treatment. In addition, the treatment was delivered in less time than with a fixed grid template or freehand insertions. Despite this success, methods of reducing needle deflection are needed in order to fully utilize the potential of this system, and further reduce total procedure time.

Real-Time MRI-Guided Focused Ultrasound for Focal Therapy of Locally Confined Low-Risk Prostate Cancer: Feasibility and Preliminary Outcomes

OBJECTIVE Focal therapy is an emerging approach to the treatment of localized prostate cancer. The purpose of this study was to report the 6-month follow-up oncologic and functional data of the initial phase 1 trial of patients treated with focal transrectal MRI-guided focused ultrasound in North America. SUBJECTS AND METHODS Four patients with a prostate-specific antigen (PSA) level of 10 ng/mL or less, tumor classification cT2a or less, and a Gleason score of 6 (3 + 3) were prospectively enrolled in the study and underwent multiparametric MRI and transrectal ultrasound-guided prostate systematic biopsy. Under MRI guidance and real-time monitoring with MR thermography, focused high-frequency ultrasound energy was delivered to ablate the target tissue. The incidence and severity of treatment-related adverse events were recorded along with responses to serial quality-of-life questionnaires for 6 months after treatment. Oncologic outcomes were evaluated with multiparametric MRI and repeat transrectal ultrasound-guided biopsy 6 months after treatment. RESULTS Four patients with a total of six target lesions were treated and had complications graded Clavien-Dindo I or less. Quality-of-life parameters were similar between baseline and 6-months. All four patients had normal MRI findings in the treated regions (100%), biopsy showed that three patients (75%) were clear of disease in the treated regions, representing complete ablation of five target lesions (83%). All patients had at least one Gleason 6-positive core outside of the treated zone. CONCLUSION MRI-guided focused ultrasound is a feasible method of noninvasively ablating low-risk prostate cancers with low morbidity. Further investigation and follow-up are warranted in a larger patient series with appropriate statistical analysis of oncologic and functional outcome measures.

An update on focal therapy for prostate cancer

Globally, the increased uptake of serum PSA level screening led to an increase in the number of diagnoses of low-risk and intermediate-risk prostate cancer. Traditionally, these patients have been considered for either active surveillance programmes or radical whole-gland therapies, such as prostatectomy or radiotherapy. Focal therapy is an emerging treatment option that involves the focal ablation of prostate cancer with preservation of surrounding healthy tissue. This approach might result in reduced morbidity when compared with whole-gland therapies. In current practice, much controversy surrounds optimal patient selection and preoperative tumour localization strategies. Focal therapy modalities include cryotherapy, high-intensity focused ultrasound, laser ablation, photodynamic therapy, irreversible electroporation, radiofrequency ablation and focal brachytherapy. However, as long-term oncological data for focal therapies are lacking, formal recommendations for its use cannot be made.

Focal magnetic resonance guided focused ultrasound for prostate cancer: Initial North American experience

The treatment of low-risk prostate cancer is a common clinical dilemma between standard curative whole gland therapy (and its associated quality of life diminishing side effects) and active surveillance (and its low, but real, risk of progression). The goal of focal therapy in low-risk prostate cancer is to achieve the best balance between cancer control and maintenance of quality of life. Magnetic resonance-guided focused ultrasound (MRgFUS) surgery is a non-invasive thermal ablation method that integrates magnetic resonance imaging for target identification, treatment planning and closed-loop control of thermal deposition and focused ultrasound for thermal ablation of the tumour target. This novel transrectal system allows for tumour localization, targeting and monitoring of tumour target ablation in real time, while simultaneously preserving adjacent normal tissue thereby minimizing the side effects of standard curative surgical or radiation therapy. We report the first North American clinical experience of treatment of localized prostate cancer with focal MR-guided transrectal focused ultrasound (clinicaltrial.gov identifier NCT01226576).

Construction and Evaluation of an Anatomically Correct Multi-Image Modality Compatible Phantom for Prostate Cancer Focal Ablation

PURPOSE Focal therapy using lasers is emerging as an alternative strategy for prostate cancer treatment. However, to our knowledge no anatomically correct models are available to test imaging and ablation techniques. Animal models present ethical, anatomical and cost challenges. We designed and validated an inexpensive but anatomically correct prostate phantom incorporating tumor, rectum and urethra that can be used for simulated and experimental magnetic resonance guided focal intervention. Our secondary aim was to asses the phantom using other imaging modalities. MATERIALS AND METHODS The phantom, which was constructed of ballistic gel, includes an 80 gm prostate with urethra, tumor, perineum and rectum. Gadolinium was added to make the gel visible to magnetic resonance imaging. To recreate a tumor an irregularly shaped 5 cc volume of coagulable gel was inserted into the prostate phantom. The phantom was evaluated using magnetic resonance, computerized tomography and transrectal ultrasound. Thermal ablation was delivered via interstitial placement of laser fibers. Magnetic resonance thermometry was done to record real-time tissue temperatures during thermal ablation. RESULTS With all modalities tested the phantom emulated human prostate anatomy. The coagulable gel tumor allowed us to generate focal thermal lesions. The phantom had magnetic resonance imaging properties comparable to in vivo properties, allowing ablative zones to be accurately assessed and magnetic resonance thermometry to be done. CONCLUSIONS The phantom is a useful tool to test different aspects of thermal focal ablation for prostate cancer using multiple imaging modalities, particularly magnetic resonance. It is inexpensive and easily constructed, and may be considered a valuable model to train on and teach focal therapy.