Optimal Strategies for Managing Prostate-specific Antigen Recurrence After Primary Radiotherapy in Prostate Cancer: The Finnish Perspective.

Biochemical recurrence after radiotherapy for prostate cancer is a clinical dilemma. Patients at low risk of disease progression can be safely monitored. In Finland, options for those with reasonable life expectancy include salvage high-dose-rate brachytherapy and transurethral ultrasound ablation under magnetic resonance imaging guidance.

Evolution of non-perfused volume after transurethral ultrasound ablation of prostate: A retrospective 12-month analysis.

Background: A detailed understanding of the non-perfused volume (NPV) evolution after prostate ablation therapy is lacking. The impact of different diseased prostate tissues on NPV evolution post-ablation is unknown. Purpose: To characterize the NPV evolution for three treatment groups undergoing heat-based prostate ablation therapy, including benign prostatic hyperplasia (BPH), primary prostate cancer (PCa), and radiorecurrent PCa. Materials and methods: Study design and data analysis were performed retrospectively. All patients received MRI-guided transurethral ultrasound ablation (TULSA). 21 BPH, 28 radiorecurrent PCa and 40 primary PCa patients were included. Using the T1-weighted contrast-enhanced MR image, the NPV was manually contoured by an experienced radiologist. All patients received an MRI immediately following the ablation. Follow-up included MRI at 3- and 12 months for BPH and radiorecurrent PCa patients and at 6- and 12 months for primary PCa patients. Results: A significant difference between BPH and radiorecurrent PCa patients was observed at three months (p < 0.0001, Wilcoxon rank sum test), with the median NPV decreasing by 77 % for BPH patients but increasing by 4 % for radiorecurrent PCa patients. At six months, the median NPV decreased by 97 % for primary PCa. Across all groups, although 40 % of patients had residual NPV at 12 months, it tended to be < 1 mL. Conclusion: The resolution of necrotic tissue after ablation was markedly slower for irradiated than treatment-naïve prostate tissue. These results may account for the increased toxicity observed after radiorecurrent salvage therapy. By 12 months, most necrotic prostate tissue had disappeared in every treatment group.

Scarpa Fascia Preservation to Reduce Seroma Rate on Massive Weight Loss Patients Undergoing Abdominoplasty: A Comparative Study.

(1) Background: An increasing number of patients undergo bariatric surgery and seek body contouring surgery after massive weight loss (MWL). Abdominoplasty itself is associated with a high complication rate in these patients, particularly due to seroma formation. Scarpa fascia preservation (SFP) has been proven to be an efficient method of reducing seroma rates. We aimed to evaluate the possible benefits of SFP on massive weight loss patients comparatively. (2) Methods: This is a single-center retrospective comparative study encompassing 202 MWL patients operated between 2009 and 2019 at Turku University Hospital. Patients included in the study had a preoperative weight loss greater than 30 kg. Of them, 149 went through traditional abdominoplasty and 53 abdominoplasties with SFP. The primary outcome measure was seroma occurrence, while secondary outcomes included drainage amount, hospital stay, surgical site occurrence, and need for blood transfusion. (3) Results: The only statistically significant difference between groups on patients' demographics was the sex ratio, favoring females in the control group (43:10, 81% vs. 130:19, 87%, p = 0.018). SFP significantly reduced seroma occurrence (9.4% vs. 26.2%, p = 0.011) and decreased mean drainage duration (3.7 ± 2.4 vs. 5.3 ± 3.2 days, p = 0.025). There was a trend towards lower drainage output (214.1 ± 162.2 mL vs. 341.9 ± 480.5 mL, p = 0.060) and fewer postoperative days on ward in the SFP group. Other complication incidences did not differ between the groups. The multivariable analysis did not show any significant factor for seroma formation or surgical site occurrence. (4) Conclusions: Preserving Scarpa fascia on MWL patients may result in decreased seroma occurrence and a shorter time to drain removal.

Deep learning prediction of non-perfused volume without contrast agents during prostate ablation therapy.

The non-perfused volume (NPV) is an important indicator of treatment success immediately after prostate ablation. However, visualization of the NPV first requires an injection of MRI contrast agents into the bloodstream, which has many downsides. Purpose of this study was to develop a deep learning model capable of predicting the NPV immediately after prostate ablation therapy without the need for MRI contrast agents. A modified 2D deep learning UNet model was developed to predict the post-treatment NPV. MRI imaging data from 95 patients who had previously undergone prostate ablation therapy for treatment of localized prostate cancer were used to train, validate, and test the model. Model inputs were T1/T2-weighted and thermometry MRI images, which were always acquired without any MRI contrast agents and prior to the final NPV image on treatment-day. Model output was the predicted NPV. Model accuracy was assessed using the Dice-Similarity Coefficient (DSC) by comparing the predicted to ground truth NPV. A radiologist also performed a qualitative assessment of NPV. Mean (std) DSC score for predicted NPV was 85% ± 8.1% compared to ground truth. Model performance was significantly better for slices with larger prostate radii (> 24 mm) and for whole-gland rather than partial ablation slices. The predicted NPV was indistinguishable from ground truth for 31% of images. Feasibility of predicting NPV using a UNet model without MRI contrast agents was clearly established. If developed further, this could improve patient treatment outcomes and could obviate the need for contrast agents altogether. Trial Registration Numbers Three studies were used to populate the data: NCT02766543, NCT03814252 and NCT03350529. Supplementary Information: The online version contains supplementary material available at 10.1007/s13534-022-00250-y.

Safety and efficacy of MRI-guided transurethral ultrasound ablation for radiorecurrent prostate cancer in the presence of gold fiducial markers.

BACKGROUND: Safety and efficacy of ultrasound prostate ablation for radiorecurrent prostate cancer (PCa) in the presence of gold fiducial markers has not been previously reported. PURPOSE: To evaluate safety, functional, and early-stage oncological outcomes for patients with gold fiducial markers undergoing salvage magnetic resonance imaging (MRI)-guided transurethral ultrasound ablation (sTULSA) for radiorecurrent PCa. MATERIAL AND METHODS: Data were acquired from an ethics-approved, single-center phase-1 study. Eight patients with 18 total gold fiducial markers inside the planned treatment volume were identified. MRI controls were performed at three and 12 months, followed by PSMA-PET-CT imaging and biopsies at 12 months. A control cohort of 13 patients who underwent sTULSA without markers were also identified for safety profile comparison. Adverse events were reported using the Clavien-Dindo classification, and questionnaires including EPIC-26, IPSS, and IIEF-5 were collected. RESULTS: Of 18 markers, 2 (11%) were directly responsible for poor ultrasound penetration. However, there were no local recurrences at 12 months. PSA, prostate volume, and non-perfused volume all decreased over time. At 12 months, 11/18 (61%) of fiducial markers had disappeared via sloughing. The adverse event profile was similar between both patient cohorts, and when controlled for ablation type, no statistical difference in functional outcomes between the two cohorts was observed. CONCLUSION: Patients with radiorecurrent PCa with intraprostatic gold fiducial markers can be successfully treated with TULSA. The early-stage efficacy of sTULSA for patients with intraprostatic gold markers is encouraging and the safety profile is unaffected by marker presence.

Evolving imaging methods of prostate cancer and the emergence of magnetic resonance imaging guided ablation techniques.

Established therapies for prostate cancer (PCa), surgery and radiotherapy, treat the entire gland regardless of the location of the cancerous lesion within the prostate. Although effective, these methods include a significant risk of worsening genitourinary outcomes. Targeted image-guided cancer therapy has gained acceptance through improved PCa detection, localization, and characterization by magnetic resonance imaging (MRI). Minimally-invasive ablative techniques aim to achieve comparable oncological outcomes to radical treatment while preserving genitourinary function. Transurethral ultrasound ablation (TULSA) and next-generation transrectal high-intensity focused ultrasound (HIFU) utilize MRI guidance to thermally ablate prostate tissue under real-time MRI monitoring and active temperature feedback control. Previous trials performed by our group and others, including a large multicenter study in men with localized favorable-risk disease, have demonstrated that TULSA provides effective prostate ablation with a favorable safety profile and low impact on quality of life. Recently, MRI-guided HIFU focal therapy was also shown as a safe and effective treatment of intermediate-risk PCa. Here we review the current literature on ablative techniques in the treatment of localized PCa with a focus on TULSA and HIFU methods.

Detection of prostate cancer bone metastases with fast whole-body 99mTc-HMDP SPECT/CT using a general-purpose CZT system.

BACKGROUND: We evaluated the effects of acquisition time, energy window width, and matrix size on the image quality, quantitation, and diagnostic performance of whole-body 99mTc-HMDP SPECT/CT in the primary metastasis staging of prostate cancer. METHODS: Thirty prostate cancer patients underwent 99mTc-HMDP SPECT/CT from the top of the head to the mid-thigh using a Discovery NM/CT 670 CZT system with list-mode acquisition, 50-min acquisition time, 15% energy window width, and 128 × 128 matrix size. The acquired list-mode data were resampled to produce data sets with shorter acquisition times of 41, 38, 32, 26, 20, and 16 min, narrower energy windows of 10, 8, 6, and 4%, and a larger matrix size of 256 × 256. Images were qualitatively evaluated by three experienced nuclear medicine physicians and quantitatively evaluated by noise, lesion contrast and SUV measurements. Diagnostic performance was evaluated from the readings of two experienced nuclear medicine physicians in terms of patient-, region-, and lesion-level sensitivity and specificity. RESULTS: The originally acquired images had the best qualitative image quality and lowest noise. However, the acquisition time could be reduced to 38 min, the energy window narrowed to 8%, and the matrix size increased to 256 × 256 with still acceptable qualitative image quality. Lesion contrast and SUVs were not affected by changes in acquisition parameters. Acquisition time reduction had no effect on the diagnostic performance, as sensitivity, specificity, accuracy, and area under the receiver-operating characteristic curve were not significantly different between the 50-min and reduced acquisition time images. The average patient-level sensitivities of the two readers were 88, 92, 100, and 96% for the 50-, 32-, 26-, and 16-min images, respectively, and the corresponding specificities were 78, 84, 84, and 78%. The average region-level sensitivities of the two readers were 55, 58, 59, and 56% for the 50-, 32-, 26-, and 16-min images, respectively, and the corresponding specificities were 95, 98, 96, and 95%. The number of equivocal lesions tended to increase as the acquisition time decreased. CONCLUSION: Whole-body 99mTc-HMDP SPECT/CT can be acquired using a general-purpose CZT system in less than 20 min without any loss in diagnostic performance in metastasis staging of high-risk prostate cancer patients.

Comparison of reprojected bone SPECT/CT and planar bone scintigraphy for the detection of bone metastases in breast and prostate cancer.

OBJECTIVE: The aim of this study was to compare reprojected bone SPECT/CT (RBS) against planar bone scintigraphy (BS) in the detection of bone metastases in breast and prostate cancer patients. METHODS: Twenty-six breast and 105 prostate cancer patients with high risk for bone metastases underwent 99mTc-HMDP BS and whole-body SPECT/CT, 1.5-T whole-body diffusion-weighted MRI and 18F-NaF or 18F-PSMA-1007 PET/CT within two prospective clinical trials (NCT01339780 and NCT03537391). Consensus reading of all imaging modalities and follow-up data were used to define the reference standard diagnosis. The SPECT/CT data were reprojected into anterior and posterior views to produce RBS images. Both BS and RBS images were independently double read by two pairs of experienced nuclear medicine physicians. The findings were validated against the reference standard diagnosis and compared between BS and RBS on the patient, region and lesion levels. RESULTS: All metastatic patients detected by BS were also detected by RBS. In addition, three metastatic patients were missed by BS but detected by RBS. The average patient-level sensitivity of two readers for metastases was 75% for BS and 87% for RBS, and the corresponding specificity was 79% for BS and 39% for RBS. The average region-level sensitivity of two readers was 64% for BS and 69% for RBS, and the corresponding specificity was 96% for BS and 87% for RBS. CONCLUSION: Whole-body bone SPECT/CT can be reprojected into more familiar anterior and posterior planar images with excellent sensitivity for bone metastases, making additional acquisition of planar BS unnecessary.

Magnetic resonance imaging-guided transurethral ultrasound ablation for benign prostatic hyperplasia: 12-month clinical outcomes of a phase I study.

OBJECTIVES: To investigate the safety and feasibility of magnetic resonance imaging (MRI)-guided transurethral ultrasound ablation (TULSA) for the treatment of benign prostatic obstruction (BPO). PATIENTS AND METHODS: An investigator-initiated, prospective, registered (NCT03350529), phase I study enrolled men with lower urinary tract symptoms due to benign prostatic hyperplasia in need of surgical intervention. Patients were followed for 12 months after TULSA. Uroflowmetry, prostate-specific antigen (PSA) level, and a comprehensive set of functional questionnaires including the Expanded Prostate cancer Index Composite-26, International Prostate Symptom Score (IPSS) and five-item version of the International Index of Erectile Function were obtained at baseline and every 3 months afterwards. MRI was obtained at baseline, and at 3 and 12 months after TULSA. Medication use before and after TULSA were recorded. Adverse events (AEs) were reported using the Clavien-Dindo classification. RESULTS: A total of 10 men underwent TULSA with no severe AEs encountered. The baseline median (interquartile range [IQR]) age and prostate volume were 68 (63-72) years and 53 (45-66) mL, respectively. At baseline, six patients were moderately symptomatic and four patients severely symptomatic. Nine patients at baseline were on BPO medication. The median (IQR) improvement in the IPSS was 82%, from 17.5 (15.3-23.0) at baseline to 4.0 (2.3-6.3) at 12 months. Similarly, the median maximum urinary flow rate improved by 101%, from a median (IQR) of 12.4 (8.8-17.6) mL/s at baseline to 21.8 (17.6-26.5) mL/s at 12 months. Improvements were already seen at 3 months. The median prostate volume and PSA reduction at 12 months were 33% and 48%, respectively. There were no changes in continence, sexual, erectile or bowel functions. At 12 months, five out of six men with normal ejaculatory function before TULSA reported normal antegrade ejaculations. All patients taking BPO medication before TULSA discontinued medication after TULSA. CONCLUSION: TULSA appears to be a safe and effective treatment for BPO, with promising 12-month follow-up outcomes. Further studies with larger cohorts are needed to confirm the observed results.

Fiducial markers and their impact on ablation outcome for patients treated with MR-guided transurethral ablation (TULSA): a retrospective technical analysis.

OBJECTIVES: Fiducial markers improve accuracy in external beam radiation therapy (EBRT) for treatment of prostate cancer (PCa). However, many patients recur after EBRT necessitating additional treatment, such as MR-guided transurethral ultrasound ablation (TULSA). Residual markers may compromise TULSA through ultrasound field distortions and generation of local susceptibility artifacts. The objective was to investigate how markers affect the ablation outcome during clinical TULSA treatments. SUBJECTS AND METHODS: A retrospective analysis was performed on nine patients with radiorecurrent PCa and residual markers who received TULSA. The MR susceptibility artifact was quantified as a function of marker type, size and orientation, in particular for thermometry. The spatial distribution of markers inside the prostate was recorded, and the resulting impact on the thermal dose was measured. The thermal dose measurements were directly compared to the residual enhancing prostatic tissue observed on the immediate and control post-TULSA contrast enhanced (CE) image. RESULTS: Successful thermal dose accumulation to the target boundary occurred for 14/20 (70%) of markers, confirmed with CE imaging. Gold markers situated simultaneously close to the urethra (≤12 mm) and far from the target boundary (≥13 mm) reduced the ultrasound depth of heating. Nitinol markers produced large, hypointense artifacts that disrupted thermometry and compromised treatment. Artifacts from gold markers were less pronounced, but when located near the target boundary, also affected treatment. CONCLUSION: Marker composition, orientation and location inside the prostate can all potentially impact treatment outcome. Proper patient selection through detailed MRI screening is critical to ensure successful radiorecurrent PCa treatment outcomes with TULSA.

Prospective comparison of 18F-PSMA-1007 PET/CT, whole-body MRI and CT in primary nodal staging of unfavourable intermediate- and high-risk prostate cancer.

PURPOSE: To prospectively compare 18F-prostate-specific membrane antigen (PSMA)-1007 positron emission tomography (PET)/CT, whole-body magnetic resonance imaging (WBMRI) including diffusion-weighted imaging (DWI) and standard computed tomography (CT), in primary nodal staging of prostate cancer (PCa). METHODS: Men with newly diagnosed unfavourable intermediate- or high-risk PCa prospectively underwent 18F-PSMA-1007 PET/CT, WBMRI with DWI and contrast-enhanced CT within a median of 8 days. Six readers (two for each modality) independently reported pelvic lymph nodes as malignant, equivocal or benign while blinded to the other imaging modalities. Sensitivity, specificity and accuracy were reported according to optimistic (equivocal lesions interpreted as benign) and pessimistic (equivocal lesions interpreted as malignant) analyses. The reference standard diagnosis was based on multidisciplinary consensus meetings where available histopathology, clinical and follow-up data were used. RESULTS: Seventy-nine patients completed all the imaging modalities, except for one case of interrupted WBMRI. Thirty-one (39%) patients had pelvic lymph node metastases, which were detected in 27/31 (87%), 14/31 (45%) and 8/31 (26%) patients by 18F-PSMA-1007 PET/CT, WBMRI with DWI and CT, respectively (optimistic analysis). In 8/31 (26%) patients, only 18F-PSMA-1007 PET/CT detected malignant lymph nodes, while the other two imaging modalities were reported as negative. At the patient level, sensitivity and specificity values for 18F-PSMA-1007 PET/CT, WBMRI with DWI and CT in optimistic analysis were 0.87 (95%CI 0.71-0.95) and 0.98 (95%CI 0.89-1.00), 0.37 (95%CI 0.22-0.55) and 0.98 (95%CI 0.89-1.00) and 0.26 (95%CI 0.14-0.43) and 1.00 (95%CI 0.93-1.00), respectively. CONCLUSION: 18F-PSMA-1007 PET/CT showed significantly greater sensitivity in nodal staging of primary PCa than did WBMRI with DWI or CT, while maintaining high specificity. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov ID: NCT03537391.

A Prospective Comparison of 18F-prostate-specific Membrane Antigen-1007 Positron Emission Tomography Computed Tomography, Whole-body 1.5 T Magnetic Resonance Imaging with Diffusion-weighted Imaging, and Single-photon Emission Computed Tomography/Computed Tomography with Traditional Imaging in Primary Distant Metastasis Staging of Prostate Cancer (PROSTAGE).

BACKGROUND: Computed tomography (CT) and bone scintigraphy (BS) are the imaging modalities currently used for distant metastasis staging of prostate cancer (PCa). OBJECTIVE: To compare standard staging modalities with newer and potentially more accurate imaging modalities. DESIGN, SETTING, AND PARTICIPANTS: This prospective, single-centre trial (NCT03537391) enrolled 80 patients with newly diagnosed high-risk PCa (International Society of Urological Pathology grade group ≥3 and/or prostate-specific antigen [PSA] ≥20 and/or cT ≥ T3; March 2018-June 2019) to undergo primary metastasis staging with two standard and three advanced imaging modalities. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The participants underwent the following five imaging examinations within 2 wk of enrolment and without a prespecified sequence: BS, CT, 99mTc-hydroxymethylene diphosphonate (99mTc-HMDP) single-photon emission computed tomography (SPECT)-CT, 1.5 T whole-body magnetic resonance imaging (WBMRI) using diffusion-weighted imaging, and 18F-prostate-specific membrane antigen-1007 (18F-PSMA-1007) positron emission tomography(PET)-CT. Each modality was reviewed by two independent experts blinded to the results of the prior studies, who classified lesions as benign, equivocal, or malignant. Pessimistic and optimistic analyses were performed to resolve each equivocal diagnosis. The reference standard diagnosis was defined using all available information accrued during at least 12 mo of clinical follow-up. Patients with equivocal reference standard diagnoses underwent MRI and/or CT to search for the development of anatomical correspondence. PSMA PET-avid lesions without histopathological verification were rated to be malignant only if there was a corresponding anatomical finding suspicious for malignancy at the primary or follow-up imaging. RESULTS AND LIMITATIONS: Seventy-nine men underwent all imaging modalities except for one case of interrupted MRI. The median interval per patient between the first and the last imaging study was 8 d (interquartile range [IQR]: 6-9). The mean age was 70 yr (standard deviation: 7) and median PSA 12 ng/mL (IQR:7-23). The median follow-up was 435 d (IQR: 378-557). Metastatic disease was detected in 20 (25%) patients. The imaging modality 18F-PSMA-1007 PET-CT had superior sensitivity and highest inter-reader agreement. The area under the receiver-operating characteristic curve (AUC) values for bone metastasis detection with PSMA PET-CT were 0.90 (95% confidence interval [CI]: 0.85-0.95) and 0.91 (95% CI: 0.87-0.96) for readers 1 and 2, respectively, while the AUC values for BS, CT, SPECT-CT, and WBMRI were 0.71 (95% CI: 0.58-0.84) and 0.8 (95% CI: 0.67-0.92), 0.53 (95% CI: 0.39-0.67) and 0.66 (95% CI: 0.54-0.77), 0.77 (95% CI: 0.65-0.89) and 0.75 (95% CI: 0.62-0.88), and 0.85 (95% CI: 0.74-0.96) and 0.67 (95% CI: 0.54-0.80), respectively, for the other four pairs of readers. The imaging method 18F-PSMA-1007 PET-CT detected metastatic disease in 11/20 patients in whom standard imaging was negative and influenced clinical decision making in 14/79 (18%) patients. In 12/79 cases, false positive bone disease was reported only by PSMA PET-CT. Limitations included a nonrandomised study setting and few histopathologically validated suspicious lesions. CONCLUSIONS: Despite the risk of false positive bone lesions, 18F-PSMA-1007 PET-CT outperformed all other imaging methods studied for the detection of primary distant metastasis in high-risk PCa. PATIENT SUMMARY: In this report, we compared the diagnostic performance of conventional and advanced imaging. It was found that 18F-prostate-specific membrane antigen-1007 positron emission tomography/computed tomography (18F-PSMA-1007 PET-CT) was superior to the other imaging modalities studied for the detection of distant metastasis at the time of initial diagnosis of high-risk prostate cancer. PSMA PET-CT also appears to detect some nonmetastatic bone lesions.

Acute and subacute prostate MRI findings after MRI-guided transurethral ultrasound ablation of prostate cancer.

BACKGROUND: Magnetic resonance imaging (MRI)-guided transurethral ultrasound ablation (TULSA) is an emerging method for treatment of localized prostate cancer (PCa). TULSA-related subacute MRI findings have not been previously characterized. PURPOSE: To evaluate acute and subacute MRI findings after TULSA treatment in a treat-and-resect setting. MATERIAL AND METHODS: Six men with newly diagnosed MRI-visible and biopsy-concordant clinically significant PCa were enrolled and completed the study. Eight lesions classified as PI-RADS 3-5 were focally ablated using TULSA. One- and three-week follow-up MRI scans were performed between TULSA and robot-assisted laparoscopic prostatectomy. RESULTS: TULSA-related hemorrhage was detected as a subtle T1 hyperintensity and more apparent T2 hypointensity in the MRI. Both prostate volume and non-perfused volume (NPV) markedly increased after TULSA at one week and three weeks after treatment, respectively. Lesion apparent diffusion coefficient values increased one week after treatment and decreased nearing the baseline values at the three-week MRI follow-up. CONCLUSION: The optimal timing of MRI follow-up seems to be at the earliest at three weeks after treatment, when the post-procedural edema has decreased and the NPV has matured. Diffusion-weighted imaging has little or no added diagnostic value in the subacute setting.

Palliative MRI-guided transurethral ultrasound ablation for symptomatic locally advanced prostate cancer.

PURPOSE: Locally advanced prostate cancer can cause bladder outlet obstruction, gross hematuria and frequent hospitalization. While these complications are commonly treated by palliative transurethral resection of the prostate, the improvement is often insufficient. The purpose of this study was to evaluate the safety and feasibility of MRI-guided transurethral ultrasound ablation as an alternative palliative treatment option (pTULSA) for men suffering from symptomatic locally advanced prostate cancer. METHODS: This prospective, phase one study included 10 men in need of palliative surgical intervention due to urinary retention and gross hematuria caused by locally advanced prostate cancer. Patients were followed for 1 year at 3-month intervals. Time without catheter, time without hematuria, reduction in hospitalization time, and adverse events were measured. RESULTS: Ten patients with locally advanced prostate cancer were enrolled, all having continuous catheterization due to urinary retention and nine had gross hematuria before treatment. At 1 week post-pTULSA five patients were catheter-free. At last follow-up catheter-free and gross hematuria-free rates were 70% and 100%, respectively. Average hospitalization time from local complications reduced from 7.3 to 1.4 days in the 6 months before and after pTULSA. No > Grade 2 treatment related adverse events were reported, with all five being urinary tract infections. CONCLUSIONS: pTULSA appears safe and feasible for palliative ablation of locally advanced prostate cancer. The therapy seems to accomplish long-term hematuria control, can relieve bladder outlet obstruction in selected patients, and seems to reduce the burden of hospitalization due to local complications. Trial Registration Number: NCT03350529.

Salvage Magnetic Resonance Imaging-guided Transurethral Ultrasound Ablation for Localized Radiorecurrent Prostate Cancer: 12-Month Functional and Oncological Results.

BACKGROUND: Up to half of all men who undergo primary radiotherapy for localized prostate cancer (PCa) experience local recurrence. OBJECTIVE: To evaluate the safety and early functional and oncological outcomes of salvage magnetic resonance imaging-guided transurethral ultrasound ablation (sTULSA) for men with localized radiorecurrent PCa. DESIGN SETTING AND PARTICIPANTS: This prospective, single-center phase 1 study (NCT03350529) enrolled men with biopsy-proven localized PCa recurrence after radiotherapy. Multiparametric magnetic resonance imaging (mpMRI) and 18F prostate-specific membrane antigen-1007 (18F PSMA-1007) positron emission tomography (PET)-computed tomography (CT) were used to confirm organ-confined disease localization. Patients underwent either whole-gland or partial sTULSA, depending on their individual tumor characteristics. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patients were followed at 3-mo intervals. Adverse events (AEs, Clavien-Dindo scale), functional status questionnaires (Expanded Prostate Cancer Index [EPIC]-26, International Prostate Symptom Score, International Index of Erectile Function-5), uroflowmetry, and prostate-specific antigen (PSA) were assessed at every visit. Disease control was assessed at 1 yr using mpMRI and 18F-PSMA-1007 PET-CT, followed by prostate biopsies. RESULTS AND LIMITATIONS: Eleven patients (median age 69 yr, interquartile range [IQR] 68-74) underwent sTULSA (3 whole-gland, 8 partial sTULSA) and have completed 12-mo follow-up. Median PSA was 7.6 ng/ml (IQR 4.9-10) and the median time from initial PCa diagnosis to sTULSA was 11 yr (IQR 9.5-13). One grade 3 and three grade 2 AEs were reported, related to urinary retention and infection. Patients reported a modest degradation in functional status, most significantly a 20% decline in the EPIC-26 irritative/obstructive domain at 12 mo. A decline in maximum flow rate (24%) was also observed. At 1 yr, 10/11 patients were free of any PCa in the targeted ablation zone, with two out-of-field recurrences. Limitations include the nonrandomized design, limited sample size, and short-term oncological outcomes. CONCLUSIONS: sTULSA appears to be safe and feasible for ablation of radiorecurrent PCa, offering encouraging preliminary oncological control. PATIENT SUMMARY: We present safety and 1-yr functional and oncological outcomes of magnetic resonance imaging-guided transurethral ultrasound ablation (TULSA) as a salvage treatment for local prostate cancer recurrence after primary radiation. Salvage TULSA is safe and shows the ability to effectively ablate prostate cancer recurrence, with acceptable toxicity.

Feasibility of MRI-guided transurethral ultrasound for lesion-targeted ablation of prostate cancer.

Background: MRI-guided transurethral ultrasound ablation (TULSA) has been evaluated for organ-confined prostate cancer (PCa). The purpose of this study was to assess the safety and toxicity, accuracy and short-term evolution of cell-death after lesion-targeted TULSA.Methods: This prospective, registered, Phase-I treat-and-3-week-resect-study enrolled six patients with MRI-visible-biopsy-concordant PCa. Lesions were targeted using TULSA with radical intent, except near neurovascular bundles (NVB). Robot-assisted-laparoscopic-prostatectomy (RALP) was performed at 3 weeks. Post-TULSA assessments included MRI (1 and 3 weeks), adverse events and quality-of-life (QoL) to 3 weeks, followed by RALP and whole-mount-histology. Treatment accuracy and demarcation of thermal injury were assessed using MRI and histology.Results: Six patients (median age = 70 years, prostate volume = 60 ml, PSA = 8.9 ng/ml) with eight biopsy-confirmed MRI-lesions (PIRADS ≥3) were TULSA-treated without complications (median sonication and MRI-times of 17 and 117 min). Foley-catheter removal was uneventful at 2-3 days. Compared to baseline, no differences in QoL were noted at 3 weeks. During follow-up, MRI-derived non-perfused-volume covered ablated targets and increased 36% by 3 weeks, correlating with necrosis-area on histology. Mean histological demarcation between complete necrosis and outer-limit-of-thermal-injury was 1.7 ± 0.4 mm. Coagulation necrosis extended to capsule except near NVB, where 3 mm safety-margins were applied. RALPs were uncomplicated and histopathology showed no viable cancer within the ablated tumor-containing target.Conclusions: Lesion-targeted TULSA demonstrates accurate and safe ablation of PCa. A significant increase of post-TULSA non-perfused-volume was observed during 3 weeks follow-up concordant with necrosis on histology. TULSA achieved coagulation necrosis of all targeted tissues. A limitation of this treat-and-resect-study-design was conservative treatment near NVB in patients scheduled for RALP.

Histopathological evaluation of prostate specimens after thermal ablation may be confounded by the presence of thermally-fixed cells.

Purpose: Prostate cancer can be eradicated with heat exposure. However, high and rapid temperature elevations may cause thermofixation giving the appearance of viable tissue. The purpose was to characterize the immunoprofile and evaluate the viability of prostate regions with suspected thermofixation. Methods and materials: A prospective, ethics-approved and registered study (NCT03350529) enrolled six patients with MRI-visible, biopsy-concordant prostate cancer to undergo lesion-targeted MRI-guided transurethral ultrasound ablation (TULSA) followed by radical prostatectomy at 3 weeks, to evaluate the accuracy and efficacy of TULSA with whole-mount histology as a reference standard. If ambiguity about complete necrosis within the ablated region remained after hematoxylin-eosin staining, viability was assessed by immunohistochemistry. Treatment day MRI-thermometry and 3-week contrast-enhanced MRI post-TULSA were examined to assess ablation success and correlation with histopathology. Results: One patient presented with an apparently viable subregion inside the ablated area, surrounded by necrosis on H&E staining, located where temperature was highest on MRI-thermometry and tissues completely devascularized on MRI. Immunoprofile of the apparently viable tissue revealed changes in staining patterns suggesting thermofixation; the most significant evidence was the negative cytokeratin 8 staining detected with Cam5.2 antibody. A comprehensive literature review supports these observations of thermofixation with similar findings in prostate and other tissues. Conclusion: Thermally-fixed cells can sustain morphology on H&E staining. Misinterpretation of treatment failure may occur, if this phenomenon is not recognized and immunohistochemistry performed. Based on the previous literature and the current study, Cam5.2 staining for cytokeratin 8 appears to be a practical and reliable tool for distinguishing thermally-fixed from viable cells.

Transurethral ultrasound therapy of the prostate in the presence of calcifications: A simulation study.

PURPOSE: Transurethral ultrasound therapy is an investigational treatment modality which could potentially be used for the localized treatment of prostate cancer. One of the limiting factors of this therapy is prostatic calcifications. These attenuate and reflect ultrasound and thus reduce the efficacy of the heating. The aim of this study is to investigate how prostatic calcifications affect therapeutic efficacy, and to identify the best sonication strategy when calcifications are present. METHODS: Realistic computational models were used on clinical patient data in order to simulate different therapeutic situations with naturally occurring calcifications as well as artificial calcifications of different sizes (1-10 mm) and distances (5-15 mm). Furthermore, different sonication strategies were tested in order to deliver therapy to the untreated tissue regions behind the calcifications. RESULTS: The presence of calcifications in front of the ultrasound field was found to increase the peak pressure by 100% on average while the maximum temperature only rose by 9% during a 20-s sonication. Losses in ultrasound energy were due to the relatively large acoustic impedance mismatch between the prostate tissue and the calcifications (1.63 vs 3.20 MRayl) and high attenuation coefficient (0.78 vs 2.64 dB/MHz1.1 /cm), which together left untreated tissue regions behind the calcifications. In addition, elevated temperatures were seen in the region between the transducer and the calcifications. Lower sonication frequencies (1-4 MHz) were not able to penetrate through the calcifications effectively, but longer sonication durations (20-60 s) with selective transducer elements were effective in treating the tissue regions behind the calcifications. CONCLUSIONS: Prostatic calcifications limit the reach of therapeutic ultrasound treatment due to reflections and attenuation. The tissue regions behind the calcifications can possibly be treated using longer sonication durations combined with proper transducer element selection. However, caution should be taken with calcifications located close to sensitive organs such as the urethra, bladder neck, or rectal wall.

Neoadjuvant Chemotherapy Does Not Increase the Morbidity of Radical Cystectomy: A 10-year Retrospective Nationwide Study.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is underutilized in the treatment of bladder cancer (BC). OBJECTIVE: To investigate the effect of NAC on the risk of surgical complications for radical cystectomy (RC) in a population-based setting. DESIGN, SETTING, AND PARTICIPANTS: All radical cystectomies performed in Finland during 2005-2014 were included in the study. Data were collected retrospectively using a web-based data collection platform. Complications were recorded for 90 d using the Clavien classification. Patients treated with NAC were compared to patients receiving RC alone using three cohorts and approaches: the entire cohort, a neoadjuvant period cohort, and a matched cohort. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: For all three cohorts, odds ratios (ORs) were estimated using simple binary logistic regression. In addition, a multivariable stratified logistic model with propensity score was used. For the matched cohort analysis, both univariate and adjusted analyses were carried out. RESULTS AND LIMITATIONS: During 2005-2014, 1427 RCs were performed in Finland, of which 1385 were included in the analyses. NAC was introduced in 2008, and 231 patients (16%) were assigned to NAC and 214 (15%) received two or more cycles of chemotherapy. Within 90 d, 61% of patients experienced complications and mortality was 4% (1.9% in the NAC group, and 4.4% in the RC-alone group). In simple binary logistic regression, NAC patients had significantly fewer complications, but this was not observed in multivariable or propensity score analyses. In the matched cohort analyses, no differences in complication rates could be observed. None of the analyses demonstrated higher complication rates in the NAC group. CONCLUSIONS: Our retrospective study reports on nationwide use of NAC for BC and demonstrates that NAC does not increase RC morbidity. PATIENT SUMMARY: Chemotherapy given before radical surgery does not increase severe postoperative complications in the treatment of bladder cancer.