Abstract
OBJECTIVES:
Irreversible electroporation (IRE) is a novel focal ablation technique applicable for treatment of prostate cancer (PCa). We aim to evaluate imaging findings of T1-weighted contrast-enhanced MRI after percutaneous IRE of low-risk PCa.
METHODS:
A total of 13 male patients underwent IRE of focal low-risk PCa and were included in this analysis. Prostate IRE was conducted using 2–4 electrodes being placed under CT-fluoroscopy guidance. Dynamic contrast-enhanced 3D isotropic fat-saturated T1-weighted MRI (DCE-MRI) was performed 24–72 hours before and 24–72 hours after ablation.
RESULTS:
Ablated prostate was either homogeneously (8/13 [62%]) or heterogeneously (5/13 [38%]) hypo attenuating. Peripheral contrast enhancement manifesting as a hyper attenuating margin was observed during the arterial (60 sec) (3/13 [23%]) and venous (240 sec) (10/13 [77%]) phase. The ablation defect showed a sharp (8/13 [62%]) or blurry (5/13 [38%]) margin.
CONCLUSIONS:
The results show a venous peripheral rim enhancement in most of the cases, indicating reactive hyperaemia. The heterogeneous appearance of the defect zone in some cases may be secondary to sustained vascularization.
Introduction
In the western hemisphere prostate cancer (Pca) is the most frequent form of cancer in the male population [1]. Early stages of prostate cancer are easier diagnosed using a blood screening test in which a prostate-specific antigen (PSA) is measured as it is highly sensitive especially for early –stage Pca. Prostate MRI has been shown to be a valuable tool for surgical and interventional planning [2] and some imaging features may even serve as a potential prognostic marker [3].
Standard therapeutic options range from active surveillance and extend to the surgical options including radical perineal or retropubic prostatectomy [4]. Other methods used – depending on the tumour grading include radiation therapy, chemotherapy, hormonotherapy and interventional treatments such as high – intensity focused ultrasound (HIFU) and irreversible electroporation (IRE).
Due to complications mainly caused by operative methods minimal invasive treatment modalities have gained more attention as they promise lower incidences of side – effects whilst still providing local tumour control [5, 6]. Oncological effectiveness of focal therapy is yet to be compared against standard of care [7].
IRE is a non-thermal soft tissue ablation technique using short pulsed but strong electrical fields causing permanent nanometre pores in the phospho– dilipid layer of the cell membrane [8]. Through this damage cells are unviable and go into apoptosis. Compared to other ablation treatments IRE doesn’t lead to a necrotic cell death [9]. This fact brings up the idea that axonal regeneration can be maintained and may help to reduce side effects of focal prostate treatment [10].
Minimal invasive radiologic therapies require a high accuracy of peri-procedural imaging especially during follow-up to rule out residual tumour tissue.
IRE being a novel ablation technique for the treatment of prostate cancer (Pca) our study aims to evaluate imaging findings of T1-weighted contrast-enhanced MRI after IRE of low-risk PCa.
Materials and methods
Patients and baseline characteristics
13 men with focal low-risk Pca identified by histopathology underwent percutaneous IRE ablation at our institution and were included into this study. All patients had given their informed consent both for IRE procedure and the participation in this study. This study conforms to the ethical guidelines of this journal [11].
The inclusion criteria for this clinical trial were: tumour stage cT1 or cT2a, N0, M0 according to the UICC TNM classification [12]. gleason score ≤6. no previous or simultaneous treatment for Pca.
IRE procedure
All IRE procedures were performed under full anaesthesia with deep muscle relaxation using the NanoKnife system (Angiodynamics, Latham, NY) by an experienced interventional radiologist. The electrodes were placed perineal in the prostate gland using CT fluoroscopy image guidance (CARE Vision, Somatom Sensation 16, Siemens Healthcare, Forchheim, Germany; CT parameters during fluoroscopy: tube voltage 120 kVp; effective tube current-time product 30 mAs; slice collimation 16 mm×0.75 mm).
Setting of the IRE generator was performed using the manufacturer’s instructions: electric field, 1500 V/cm needle distance; maximum voltage 3000 V; pulse length and pulses per cycle as recommended. The configuration as well as the number of electrodes necessary to adjust the ablation zone were chosen depending on the size and location of the Pca.
Imaging
Pre- and post-interventional imaging within a defined time frame (24–72 hours before and 24–72 hours after ablation) using contrast-enhanced 3-T MRI (Magnetom Skyra, Siemens Healthcare, Erlangen, Germany) was performed on all patients. According to PI-RADS classification system T2-weighted imaging (axial, coronary and sagittal), diffusion-weighted imaging (DWI) and dynamic contrast enhanced imaging (T1-weighted VIBE [volumetric interpolated breath-hold examination] sequences with fat suppression) was performed.
DCE-MRI imaging appearance of the ablation zones was assessed by two experienced readers in consensus for (1) enhancement of the ablated area in the late phase (240 sec) (Fig. 2) (2) peripheral enhancement in the early (60 sec) and late (240 sec) phase (Fig. 3) and (3) margin of the ablation defect in the late phase (Fig. 4).
Calculation of the prostate gland volume using contrast-enhanced T1-weighted sequences and manual 3d segmentation in OsiriX medical image viewer.
T1-weighted contrast-enhanced MRI images in the venous phase showing (a) a heterogeneous pattern of enhancement and non-enhancement in the ablation zone and (b) a homogenous non-enhancement of the ablation area.
T1-weighted contrast-enhanced MRI image in the late phase with a strong peripheral rim enhancement in the periphery of the ablation zone one day after percutaneous IRE.
T1-weighted contrast-enhanced MRI images showing a (a) blurry and (b) sharp margin of the ablation zone.
Further MRI scans after IRE were acquired according to our routine follow-up protocol: 6 weeks, 3 and 6 months after ablation. Prostate volume was determined in the dynamic contrast enhanced sequences for all examinations using manual 3d segmentation of the contrast enhanced sequences using OsiriX® medical image viewer (Fig. 1).
The analysis was performed using R (version 3.4.0, R Foundation for Statistical Computing, Vienna, Austria). To test for differences of prostate volume and diameter of the ablation zones during follow-up we employed a Friedman test for repeated measures. A p value of p < 0.05 was considered the cut-off point of statistical significance.
Results
13 patients underwent IRE of Pca during the study period. Baseline patient, prostate gland and tumour characteristics are shown in Table 1.
Baseline patient demographics, prostate and tumour characteristics
Baseline patient demographics, prostate and tumour characteristics
Post-procedure (24–72 hours) DCE-MR imaging showed either homogeneously (8/13 [62%]) or heterogeneously (5/13 [38%]) hypo attenuation of the ablation zone in the late phase. Enhancement of the ablation margin could be observed during the early (3/13 [23%]) and late (10/13 [77%]) phase. The ablation defect showed a sharp (8/13 [62%]) or blurry (5/13 [38%]) margin.
Prostate gland volume from one day before ablation until 6 months after IRE is shown in Table 2. There was a significant volume reduction over time (p < 0.01) compared to the baseline for all time periods during follow-up.
Prostate gland volume as determined by 3D MRI segmentation before IRE (baseline) and during follow-up. The prostate gland volume decreased over time in relation to the baseline
IRE, a non-thermal tissue ablation technique, has been shown to be feasible for treatment of early-stage localized Pca. Other than the radical therapeutic options IRE protects vascular and neuronal structures leading to a lower number of side effects [5, 6].
Both CEUS and contrast-enhanced MRI seem to be reasonable imaging modalities to visualize and evaluate the ablation area after IRE of Pca [13]. However, there is currently no information about typical changes of microcirculation, i.e. the enhancement pattern of the ablation zone after IRE. This limits the applicability of post-IRE DCE-MRI, as understanding the expected imaging appearance is necessary to properly interpret the post-ablative appearance of the ablation area and its surroundings.
Therefore, the aim of our study was to assess the image findings in DCE-MRI after IRE of Pca.
We have evaluated the involution of the prostate gland after IRE in a previous study using CEUS and the ellipsoid formula for an estimation of prostate gland volume before and after IRE [14]. In our previous study, the mean percentage changes of the prostate gland to the baseline volume were –34% after 6 weeks, –46% after 3 months and –54% after 6 months. In our current study, we used manual 3D segmentation of the prostate to obtain more accurate results. The changes of the prostate gland volume were similar with a decrease of –31% after 6 weeks, –44% after 3 months and –55% after 6 months.
The involution of the prostate is probably due to necrosis of the ablation area with disintegration and conversion to fibrotic tissue as previously described in studies with pathology correlation [15, 16]. Comparable results have been reported in publications regarding IRE of liver tumours where a similar reduction of the ablation area volume within the first 4 months after treatment was described [17].
Post-procedure contrast enhanced MR imaging showed persistent heterogeneous attenuation of the ablation area in 5/13 patients (38%). The heterogeneous appearance of the defect zone in some cases may be secondary to sustained vascularisation. A previous study about the microcirculation after IRE of liver tumours using CEUS has shown a decreased but sustained micro vascularization of the ablation zone [18] which is in line with our findings.
Another important finding in our study was persistent marked enhancement of the ablation margin in 10/13 patients (77%) in the venous phase. This image feature probably represents a zone of reversible electroporation as has been discussed in earlier studies about imaging findings after IRE of liver tumours [17].
This study is limited by the relatively low number of patients, its retrospective design, the single-centre setup and the lack of histological correlation. Further long-term multi-modality imaging studies should be conducted to document the changes after IRE of Pca.
Conclusion
For diagnostic evaluation, it is important to know the changes of the prostate gland volume and imaging features after focal IRE of Pca. Therefore, in our study we documented the involution of the prostate gland volume as well as the imaging characteristics in contrast-enhanced MRI immediate after ablation. There was a significant involution of the prostate gland during the first 6 months combined with a typical rim enhancement of the ablation margin which may correspond with the area of reversible electroporation.