Variability of the Positive Predictive Value of PI-RADS for Prostate MRI across 26 Centers: Experience of the Society of Abdominal Radiology Prostate Cancer Disease-focused Panel.

Background Prostate MRI is used widely in clinical care for guiding tissue sampling, active surveillance, and staging. The Prostate Imaging Reporting and Data System (PI-RADS) helps provide a standardized probabilistic approach for identifying clinically significant prostate cancer. Despite widespread use, the variability in performance of prostate MRI across practices remains unknown. Purpose To estimate the positive predictive value (PPV) of PI-RADS for the detection of high-grade prostate cancer across imaging centers. Materials and Methods This retrospective cross-sectional study was compliant with the HIPAA. Twenty-six centers with members in the Society of Abdominal Radiology Prostate Cancer Disease-focused Panel submitted data from men with suspected or biopsy-proven untreated prostate cancer. MRI scans were obtained between January 2015 and April 2018. This was followed with targeted biopsy. Only men with at least one MRI lesion assigned a PI-RADS score of 2-5 were included. Outcome was prostate cancer with Gleason score (GS) greater than or equal to 3+4 (International Society of Urological Pathology grade group ≥2). A mixed-model logistic regression with institution and individuals as random effects was used to estimate overall PPVs. The variability of observed PPV of PI-RADS across imaging centers was described by using the median and interquartile range. Results The authors evaluated 3449 men (mean age, 65 years ± 8 [standard deviation]) with 5082 lesions. Biopsy results showed 1698 cancers with GS greater than or equal to 3+4 (International Society of Urological Pathology grade group ≥2) in 2082 men. Across all centers, the estimated PPV was 35% (95% confidence interval [CI]: 27%, 43%) for a PI-RADS score greater than or equal to 3 and 49% (95% CI: 40%, 58%) for a PI-RADS score greater than or equal to 4. The interquartile ranges of PPV at these same PI-RADS score thresholds were 27%-44% and 27%-48%, respectively. Conclusion The positive predictive value of the Prostate Imaging and Reporting Data System was low and varied widely across centers. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Milot in this issue.

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.

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.

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.

Contrast-enhanced ultrasonography for real-time monitoring of interstitial laser thermal therapy in the focal treatment of prostate cancer.

INTRODUCTION: We report a case study of the application of contrast-enhanced ultrasonography (CEUS) for intraoperative monitoring of thermal ablation of a single focus of prostate cancer. METHODS: A patient presented with biopsy-proven, solitary-focus, low-risk prostate cancer and was recruited into a clinical trial of interstitial laser thermal focal therapy. Multiparametric magnetic resonance imaging (MRI) was used to locate the single dominant focus, and photothermal ablation was performed at the tumour site under the guidance of transrectal ultrasonography. Transrectal CEUS using systemic bolus injections of the intravascular contrast agent Definity was performed immediately before, several times during and on completion of therapy. Lesions observed on CEUS were compared with treatment effect as measured by tissue devascularization on 1-week gadolinium (Gd)-enhanced MRI. RESULTS: Baseline images showed CEUS contrast-agent signal throughout the prostate. During and after treatment, large hypocontrast regions were observed surrounding the treatment fibres, indicating the presence of an avascular lesion resulting from photothermal therapy. Lesion size was found to increase during the delivery of thermal energy. Lesion size measured using CEUS (16 x 11 mm) was similar to the 7-day lesion measured using Gd-enhanced T(1)-weighted MRI. CONCLUSION: Focal therapy for prostate cancer requires both complete treatment of the dominant tumour focus and minimal morbidity. The application of CEUS during therapy appears to provide an excellent measure of the actual treatment effect. Hence, it can be used to ensure that the therapy encompasses the whole target but does not extend to surrounding critical structures. Future clinical studies are planned with comparisons of intraoperative CEUS to Gd-enhanced MRI at 7 days and whole-mount pathology samples.

Treatment planning and dose analysis for interstitial photodynamic therapy of prostate cancer.

With the development of new photosensitizers that are activated by light at longer wavelengths, interstitial photodynamic therapy (PDT) is emerging as a feasible alternative for the treatment of larger volumes of tissue. Described here is the application of PDT treatment planning software developed by our group to ensure complete coverage of larger, geometrically complex target volumes such as the prostate. In a phase II clinical trial of TOOKAD vascular targeted photodynamic therapy (VTP) for prostate cancer in patients who failed prior radiotherapy, the software was used to generate patient-specific treatment prescriptions for the number of treatment fibres, their lengths, their positions and the energy each delivered. The core of the software is a finite element solution to the light diffusion equation. Validation against in vivo light measurements indicated that the software could predict the location of an iso-fluence contour to within approximately +/-2 mm. The same software was used to reconstruct the treatments that were actually delivered, thereby providing an analysis of the threshold light dose required for TOOKAD-VTP of the post-irradiated prostate. The threshold light dose for VTP-induced prostate damage, as measured one week post-treatment using contrast-enhanced MRI, was found to be highly heterogeneous, both within and between patients. The minimum light dose received by 90% of the prostate, D(90), was determined from each patient's dose-volume histogram and compared to six-month sextant biopsy results. No patient with a D(90) less than 23 J cm(-2) had complete biopsy response, while 8/13 (62%) of patients with a D(90) greater than 23 J cm(-2) had negative biopsies at six months. The doses received by the urethra and the rectal wall were also investigated.

MRI and contrast-enhanced ultrasound monitoring of prostate microwave focal thermal therapy: an in vivo canine study.

PURPOSE: To compare the value of diffusion-weighted MRI (DWI), dynamic contrast-enhanced (DCE) MRI, and microbubble contrast-enhanced ultrasound (CEUS) for assessment of the thermal lesion created by interstitial microwave heating of the normal canine prostate. MATERIALS AND METHODS: A microwave antenna was inserted into each lobe of the prostate in seven dogs to induce coagulation necrosis. Immediately after therapy the lesion was assessed using CEUS, DCE-MRI, and DWI. The prostates were excised, photographed, and prepared for hematoxylin and eosin staining. Results from posttreatment MRI and ultrasound were compared to histology. RESULTS: The apparent diffusion coefficient (ADC) was slightly lowered within the thermal lesion but was drastically reduced in a ring-like region that corresponds to a grossly appearing red thermal damage zone immediately peripheral to the central coagulum. Both DCE-MRI and CEUS delineated a smaller area of vascular damage, for which the borders lie within the red zone. CONCLUSION: The red zone encompasses a range of vascular responses, including hyperemia and hemostasis, and is known to progress to necrosis and tissue nonviability. DWI clearly depicts this zone as a region of sharply reduced ADC, and may be better than contrast-enhanced imaging for accurate assessment of the eventual full extent of thermal damage.

Vascular-targeted photodynamic therapy (padoporfin, WST09) for recurrent prostate cancer after failure of external beam radiotherapy: a study of escalating light doses.

OBJECTIVE: To report on the efficacy of TOOKAD (WST 09; NegmaLerads, Magny-Les-Hameaux, France) vascular-targeted photodynamic therapy (VTP) as a method of whole-prostate ablation in patients with recurrent localized prostate cancer after the failure of external beam radiotherapy (EBRT). PATIENTS AND METHODS: Patients received a fixed photosensitizer dose of 2 mg/kg and patient-specific light doses as determined by computer-aided treatment planning. Up to six cylindrical light-diffusing delivery fibres were placed transperineally in the prostate under ultrasonographic guidance. The treatment response was assessed by measuring serum prostate-specific antigen (PSA) levels, lesion formation (avascular areas of tissue) measured on 7-day gadolinium-enhanced T1-weighted magnetic resonance imaging (MRI) and a 6-month biopsy. RESULTS: Treatment of the whole prostate was possible with minimal effects on surrounding organs. An increased light dose improved the tissue response, with MRI-detectable avascular lesions, encompassing up to 80% of the prostate in some patients. A complete response, as determined by the 6-month biopsy, required that patients received light doses of at least 23 J/cm(2) in 90% of the prostate volume (D(90) > 23 J/cm(2)). Of the 13 patients who received at least this light dose, eight were biopsy-negative at 6 months. In this group of eight patients, PSA levels decreased and did so to negligible levels for those patients with a baseline PSA level of <5 ng/mL. Side-effects were modest and self-limited in most patients; there were recto-urethral fistulae in two patients, one of which closed spontaneously. CONCLUSIONS: TOOKAD-VTP can produce large avascular regions in the irradiated prostate, and result in a complete negative-biopsy response at high light doses. A response rate of more than half for those patients receiving the highest light doses shows the clinical potential of TOOKAD-VTP to manage recurrence of prostatic carcinoma after EBRT.

Prostate gland: MR imaging appearance after vascular targeted photodynamic therapy with palladium-bacteriopheophorbide.

PURPOSE: To prospectively evaluate the magnetic resonance (MR) imaging appearance of the prostate and periprostatic tissues after vascular targeted photodynamic therapy (VTP) with palladium-bacteriopheophorbide for locally recurrent carcinoma after external beam radiation therapy. MATERIALS AND METHODS: Informed consent was obtained from all patients, and approval was obtained from the ethics review boards of all participating institutions. Nonenhanced T2-weighted and dynamic gadolinium-enhanced T1-weighted MR imaging examinations were performed at baseline and 1 week, 4 weeks, and 6 months after VTP in 25 men (age range, 58-83 years; mean age, 73 years) as part of a prospective phase I/II trial. Percentage of MR-depicted necrosis was defined as the volume of nonenhancing prostatic tissue 1 week after VTP divided by the volume of the prostate. Patterns of intra- and extraprostatic necrosis were recorded. Pearson correlation coefficients were used to test correlations between necrosis and prostate-specific antigen level. RESULTS: Contrast material-enhanced T1-weighted MR images obtained 1 week after therapy showed necrosis in all patients. Treatment margins were irregular in 21 of 25 patients. T2-weighted images showed no clear treatment boundaries in any patient. Extraprostatic necrosis involved the puborectalis or levator ani muscles in 22, obturator internus muscle in 12, periprostatic veins in three, pubic bone marrow in four, and anterior rectal wall in nine of the 25 patients. The neurovascular bundle appeared to be spared in all patients. Percentage of MR-depicted intraprostatic necrosis was correlated with percentage decrease in prostate-specific antigen level (from baseline) at 4 weeks (r=0.41, P=.04) and 12 weeks (r=0.45, P=.02). CONCLUSION: Contrast-enhanced MR imaging depicts irregular margins of intraprostatic treatment effect. This finding suggests varied tissue sensitivities to VTP with palladium-bacteriopheophorbide.

Characterization of changes in therapeutic ultrasound transducer performance over time using the angular spectrum method.

Strongly focused large aperture transducers used in high-intensity focused ultrasound treatments are prone to manufacturing defects and degradation. Current methods for evaluating transducer quality measure only bulk physical changes of transducers. We have determined the pressure distribution at the transducer surface, using the angular spectrum method, to detect defects of the transducer. Three therapeutic transducers were investigated. The pressure distribution at the focal plane of each transducer was measured and input into a back-projection algorithm to calculate the pressure distribution at the transducer surface. A number of scan window sizes were used for the pressure distribution measurement at the focal plane to determine the effect on the resolution of the calculated pressure distribution at the transducer surface. Results showed that one transducer might have suffered manufacturing defects. The second transducer degraded over 1 year of use with one half of the transducer suffering a partial loss of efficiency. The third transducer remained unchanged over 1 year. The scan window of 40 mm X 40 mm at the focal plane was required to identify defects 6 mm in diameter on the transducer surface. The results demonstrate that the angular spectrum method could be a useful tool for evaluating transducer quality.

Interstitial microwave thermal therapy for prostate cancer.

Thermal therapy is used to kill tumors by heating them to temperatures >50 degrees C for an extended period of time. Cell death results from thermal coagulation. The energy sources available for this approach include radiofrequency electrodes, microwave antennas, laser fiberoptics, and ultrasound transducers. Each of these modalities has the potential to be delivered in a minimally invasive manner, and many theoretical and experimental investigations of these devices have been performed. This review describes current knowledge of interstitial microwave thermal therapy for prostate cancer. Examples are given from an ongoing trial in patients who have recurrent or persistent disease following radiation therapy. Future directions for pretreatment planning and real-time monitoring and control are discussed. These techniques have the potential to optimize treatments on a patient-specific basis and will be instrumental in planned future trials of this therapy as first line for prostate cancer.

Feasibility of salvage interstitial microwave thermal therapy for prostate carcinoma following failed brachytherapy: studies in a tissue equivalent phantom.

Thermal therapy is an experimental treatment to destroy solid tumours by heating them to temperatures ranging from 55 degrees C to 90 degrees C, inducing thermal coagulation and necrosis of the tumour. We are investigating the feasibility of interstitial microwave thermal therapy as a salvage treatment for prostate cancer patients with local recurrence following failed brachytherapy. Due to the electrical and thermal conductivity of the brachytherapy seeds, we hypothesized that the seeds could scatter the microwave energy and cause unpredictable heating. To investigate this, a 915 MHz helical antenna was inserted into a muscle-equivalent phantom with and without brachytherapy seeds. Following a 10 W, 5 s input to the antenna, the temperature rise was used to calculate absorbed power, also referred to as specific absorption rate (SAR). Plane wave models based on Maxwell's equations were also used to characterize the electromagnetic scattering effect of the seeds. In addition, the phantom was heated with 8 W for 5 min to quantify the effect of the seeds on the temperature distribution during extended heating. SAR measurements indicated that the seeds had no significant effect on the shape and size of the SAR pattern of the antenna. However, the plane wave simulations indicated that the seeds could scatter the microwave energy resulting in hot spots at the seed edges. Lack of experimental evidence of these hot spots was probably due to the complex polarization of the microwaves emitted by the helical antenna. Extended heating experiments also demonstrated that the seeds had no significant effect on the temperature distributions and rates of temperature rise measured in the phantom. The results indicate that brachytherapy seeds are not a technical impediment to interstitial microwave thermal therapy as a salvage treatment following failed brachytherapy.

The uncertainty of radio frequency treatment of renal cell carcinoma: findings at immediate and delayed nephrectomy.

PURPOSE: Radio frequency thermal therapy for the ablation of renal cell carcinoma has been reported. Outcomes are usually measured by imaging alone. We have performed ex vivo and in vivo experiments using radio frequency in porcine models in our laboratory. We now report our early experience in the treatment of renal cell carcinoma in patients who underwent post-radio frequency radical or partial nephrectomy. MATERIALS AND METHODS: We treated 10 patients diagnosed with small renal masses with radio frequency. All masses were biopsied before treatment. In 4 patients 5 renal cell carcinomas were treated with radio frequency after surgical exposure of the tumor followed immediately by partial or radical nephrectomy (acute group). Six other patients were treated percutaneously with ultrasound or computerized tomography guided radio frequency under local anesthesia and intravenous sedation 7 days before partial or radical nephrectomy (delayed group). A median of 2 radio frequency cycles was applied. Mean total heating time was 17 minutes 15 seconds. Specimens were analyzed grossly and histologically. Triphasic contrast-enhanced computerized tomography and/or magnetic resonance imaging was performed before and 7 days after radio frequency treatment in the delayed group. RESULTS: Mean radiological largest diameter of all 11 masses was 2.4 cm. and mean gross diameter was 2.2 cm. Pathological examination demonstrated residual viable tumor in approximately 5% of the volume in 4 of the 5 tumors in the acute group and in 3 of the 6 masses of the delayed group. In 1 delayed case the viable tumor appeared to be in contact with the renal vein. No significant complications were observed in 9 of the 10 patients. In 1 delayed case, a subcapsular hepatic hematoma, biliary fistula and pneumonia developed and resolved. CONCLUSIONS: Based on our experience, we continue to consider percutaneous radio frequency for the treatment of small renal cell carcinomas as a potentially curative therapy. However, complete tumor cell death appears to be difficult to achieve with our current treatment protocol. More phase II testing is indicated to ensure that this technique is an effective and reproducible treatment alternative.