Patients with MRI-visible, biopsy proven prostate cancer (PI-RADS v2 score ³ 3) scheduled to undergo cPGA (n=20) were enrolled in our Institutional Review Board approved prospective study investigating advanced methods of data visualization for patients with prostate cancer. Patient-specific 3D prostate cancer models were developed as described below. A comparison group (n=20) composed of men undergoing cPGA using 2D planning techniques was retrospectively evaluated. The patient demographics for the 2D and 3D planning groups are shown in Table 1. Statistical analyses were performed in Matlab R2017a (The Mathworks Inc, Natick, MA). Continuous variables were compared using a t-test and categorical variables using the Mann-Whitney U-test.
Patient-Specific 3D Prostate Cancer Models
Patient-specific 3D anatomical prostate cancer models that highlight the prostate, prostate tumor, urethra, neurovascular bundles, and rectal wall were created from the mpMRI data . T2-weighted spin-echo sequence with high sampling efficiency (SPACE) images were used for the primary segmentation, and if necessary, in order to well-visualize the lesion, diffusion-weighted imaging (DWI) or dynamic contrast-enhanced (DCE) sequences were co-registered to the SPACE series. Regions of interest were segmented by a single user with 16 years of medical imaging experience (NW) using Mimics 21.0 (Materialise, Leuven, BE) and visualized in 3D format with computer-aided design (CAD) software (3-matic, Materialise, Leuven, BE).
Virtual cryotherapy probes were designed by the first author (NW) using the 3-matic CAD software to emulate the -40ºC isotherm volumes from published dimensions. Virtual -40ºC isotherms were created for 1.5cm, 2.5cm, 3.0cm, 4.0cm, and 5.0cm cryoprobe volumes (Figure 1).
3D Procedure Planning/Simulations
Virtual treatment simulation was performed by two of the co-authors (NW and JSW) in the 3-matic software for all patients in the 3D planning group pre-treatment and retrospectively post-treatment for the 2D planning group. The 3D prostate model was oriented in a supine position allowing the simulation to be performed in the same alignment as the cPGA operating procedure and a 1cm margin was created around each tumor. Virtual cryotherapy probes were then selected and manually placed into the software in a spatial orientation to ensure confluent -40ºC isotherm encompassing both the tumor and the margin. This model was assessed in multiple views to ensure treatment confluence. The distances between the center of each probe were measured in order to reproduce the plan during the operation. In addition, contours of the anatomy and selected cryotherapy probes were generated on the 2D MR images.
All cryoablation procedures were performed by the planning surgeon (JSW) under general anesthesia in a dorsal lithotomy position. A BK Flexfocus 800 biplanar ultrasound probe (model # 8808) attached to a Civco brachytherapy stand and stepper was utilized to visualize the prostate. Healthtronicsä cryoablation equipment was utilized to perform all ablations procedures.
2D Planning Method:
For patients undergoing treatment with 2D planning, the HealthtronicsTM software package was utilized to plan probe location. This software utilizes a 2D rigid registration of the prostate in an axial view on ultrasound. Probe placement is then guided by the 2D software in order to optimize probe-to-probe distance, probe-to-capsule distance, and probe -to urethra distance. This software does not utilize any MR-US fusion technology. MR tumor location is targeted using visual estimation. Visual estimation is performed preoperatively using image measurements on axial and sagittal MR images. These measurements are translated to real-time US imaging to achieve visual estimation in lesion targeting. Cryotherapy probes are then placed under axial and sagittal ultrasound guidance. Each needle is placed via a 16 gauge brachytherapy grid with 2.5 mm distance between each grid location.
3D Planning Method:
The same software and equipment as described above is utilized for 3D planning with the exception of the pre-treatment planning as described above. The location of the pre-planned cryoprobes are then placed according to the 3D treatment planning, also using visual estimation. Again, no fusion software was available on the ultrasound for these ablation procedures. Cryoablation Procedure:
After completing cryoablation needles according to the treatment plan, thermocouples are placed into specific treatment locations in order to provide real-time temperature monitoring of critical locations including treatment margins and safety monitors. Cystoscopy is then performed to ensure that no needles traverse the urethra. A urethral warming catheter is then placed. The cryoablation cycle is then initiated. Freezing proceeds from anterior needles to posterior glands. Propagation of the ice is monitored using ultrasound imaging in axial and sagittal views. Treatment efficacy is further assessed with real-time evaluation of thermocouple temperature to ensure achievement of target temperature in the treatment zone and to maintain sufficiently warm temperatures in critical regions such as the rectum and external sphincter. Two freeze-thaw cycles were performed. The total freeze time and nadir temperatures were recorded. Operating times were also recorded for patients. A Students t-test was performed to determine if there was a difference between 2D and 3D planning groups (Matlab 2017a, The Mathworks Inc, Natick, MA). The number of cryotherapy probes planned was compared to the number utilized.
Evaluation of Treatment
In order to measure treatment efficacy, treatment zone biopsy results at 6 months were evaluated. Post-operative MRI and PSA at 3 and 6 months were also performed. The Kruskal-Wallis H Test was performed to determine if there was a difference in positive biopsy rates for the 2D and 3D planning groups. Statistical evaluation was carried out in SPSS Software (IBM, Armonk, NY).