We report 5-year safety and efficacy outcomes of the Aquablation procedure for the treatment of men with symptomatic benign prostatic hyperplasia and large-volume prostate glands.
A total of 101 men ...with moderate to severe benign prostatic hyperplasia symptoms and prostate volumes between 80 and 150 mL underwent a robotic-assisted Aquablation procedure in a prospective multicenter international trial (NCT03123250). Herein we report the final 5-year results.
The study successfully met its safety and efficacy performance goal, which was based upon transurethral resection of the prostate outcomes typically done in smaller prostates, at 3 months. Mean prostate volume was 107 mL (range 80-150) at baseline. Patient symptoms showed a significant improvement where the mean (SD) International Prostate Symptom Score of 22.6 (6.4) at baseline to 6.8 (4.6) at 5 years, resulting in a change score of 15.9 (7.7,
< .001). Uroflowmetry measurements also demonstrated improvement where the mean maximum urinary flow rate increased from 8.6 (SD 3.4) to 17.1 (9.8) mL/s at 5 years, resulting in a change score of 9.2 (11.1) mL/s at 5 years (
< .001). A regression analysis evaluating change in PSA as a function of baseline PSA across all time points out to 5 years resulted in a 50% reduction. A prespecified subgroup analysis using a baseline prostate volume cutoff of 100 mL showed no difference in efficacy outcomes through 5 years. Freedom from a secondary benign prostatic hyperplasia procedure at 5 years was 96.3% based on Kaplan-Meier.
At 5-years of prospective follow-up, the Aquablation procedure was shown to be safe with durable efficacy and low rates of retreatment in men with large prostates (80-150 mL).
Immunotherapy remains to be an appealing treatment option for prostate cancer with some documented promise. Prostate cancer is traditionally considered as an immunologically “cold” tumor with low ...tumor mutation burden, low expression of PD-L1, sparse T-cell infiltration, and a immunosuppressive tumor microenvironment (TME). Sipuleucel-T (Provenge) is the first FDA approved immunotherapeutic agent for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer (mCRPC); demonstrating a benefit in overall survival. However various clinical trials by immune checkpoint inhibitors (ICIs) and their combinations with other drugs have shown limited responses in mCRPC. Up to now, only a small subset of patients with mismatch repair deficiency/microsatellite instability high and CDK12 mutations can clinically benefit from ICIs and/or their combinations with other agents, such as DNA damage agents. The existence of a large heterogeneity in genomic alterations and a complex TME in prostate cancer suggests the need for identifying new immunotherapeutic targets. As well as designing personalized immunotherapy strategies based on patient-specific molecular signatures. There is also a need to adjust strategies to overcome histologic barriers such as tissue hypoxia and dense stroma. The racial differences of immunological responses between men of diverse ethnicities also merit further investigation to improve the efficacy of immunotherapy and better patient selection in prostate cancer.
Objective
To present 6‐month safety and effectiveness data from a multicentre prospective study of aquablation in men with lower urinary tract symptoms (LUTS) attributable to benign prostatic ...hyperplasia (BPH) with prostate volumes between 80 and 150 mL.
Methods
Between September and December 2017, 101 men with LUTSattributable to BPHwere prospectively enrolled at 16 centres in Canada and the USA.
Results
The mean prostate volume was 107 mL. The mean length of hospital stay after the aquablation procedure was 1.6 days (range: same day to 6 days). The primary safety endpoint (Clavien–Dindo grade 2 or higher or any grade 1 event resulting in persistent disability) at 3 months occurred in 45.5% of men, which met the study design goal of < 65% (P < 0.001). At 6 months, 22% of the patients had experienced a Clavien–Dindo grade 2, 14% a grade 3 and 5% a grade 4 adverse event. Bleeding complications requiring intervention and/or transfusion were recorded in eight patients prior to discharge and in six patients after discharge. The mean International Prostate Symptom Score improved from 23.2 ± 6.3 at baseline to 6.7 ± 5.1 at 3 months, meeting the study's primary efficacy endpoint goal (P < 0.001). The maximum urinary flow rate increased from 8.7 to 18.8 mL/s (P < 0.001) and post‐void residual urine volume decreased from 131 at baseline to 47 at 6 months (P < 0.0001). At 6 months, prostate‐specific antigen concentration reduced from 7.1 ± 5.9 ng/mL at baseline to 4.0 ± 3.9 ng/mL, a 44% reduction.
Conclusions
Aquablation is safe and effective in treating men with larger prostates (80–150 mL), without significant increase in procedure or resection time.
Because survivin is selectively expressed in and associated with an unfavorable prognosis in transitional cell carcinoma of the bladder (TCC), we treated T-24 cells with survivin siRNA. Survivin ...siRNA treatment caused a profound decrease of survivin protein that was associated with decreased cell growth, a specific G2/M arrest and increased cytochrome c release. Microarray analysis of apoptosis genes showed that levels of 14/114 gene products were decreased after 72 hours treatment with survivin siRNA, including survivin, three TNF receptors, Akt, c-Abl, caspases and their related genes and Bcl-2 and NF-κB signaling related genes. TNFR1, pro-caspase-2 and Akt protein levels were decreased after survivin siRNA treatment for 48 and 72 hours. Downregulation of survivin causes changes in mitosis and apoptosis, which may be related to changes in TNF receptors and NF-κB signaling.
Multiple clinical trials have demonstrated that intravesical Bacillus Calmette-Guérin (BCG) treatment reduces recurrences and progression in patients with non-muscle-invasive bladder cancer (NMIBC). ...However, although BCG has been in use for almost 40 years, this agent is often underutilized and practice patterns of administration vary. This neglect is most likely caused by uncertainties about the optimal use of BCG, including unawareness of optimal treatment schedules and about patient populations that most benefit from BCG treatment. To address this deficit, a focus group of specialized urologic oncologists (urologists, medical oncologists and radiation oncologists) reviewed the current guidelines and clinical evidence, discussed their experiences and formed a consensus regarding the optimal use of BCG in the management of patients with NIMBC. The experts concluded that continuing therapy with 3-week BCG maintenance is superior to induction treatment only and is the single most important factor in improving outcomes in patients with NMIBC. They also concluded that a reliable alternative to radical cystectomy in truly BCG-refractory disease remains the subject of clinical trials. In addition, definitions for common terms of BCG failure, such as BCG-refractory and BCG-intolerant, have been formulated.
In this large, diverse population of men with newly diagnosed unfavourable intermediate- to very-high-risk prostate cancer, 18F-rhPSMA-7.3 positron emission tomography/computed tomography was shown ...to be well tolerated and to provide clinically useful information regarding the identification of both N1 and M1 disease prior to surgery.
Radiohybrid (rh) 18F-rhPSMA-7.3 is a novel high-affinity prostate-specific membrane antigen (PSMA)-targeting radiopharmaceutical for prostate cancer (PCa) imaging.
To evaluate the diagnostic performance and safety of 18F-rhPSMA-7.3 in newly diagnosed PCa patients planned for prostatectomy.
Data on 18F-rhPSMA-7.3 were reported from the phase 3 prospective, multicentre LIGHTHOUSE study (NCT04186819).
Patients underwent positron emission tomography/computed tomography (PET/CT) 50–70 min after an injection of 296 MBq 18F-rhPSMA-7.3. Images were interpreted locally and by three blinded independent readers. The coprimary endpoints were patient-level sensitivity and specificity for the detection of pelvic lymph node (PLN) metastases, validated using histopathology at PLN dissection. Prespecified statistical thresholds (lower bounds of 95% confidence interval CI) were set at 22.5% for sensitivity and 82.5% for specificity.
Of 372 patients screened, 352 had evaluable 18F-rhPSMA-7.3-PET/CT and 296 (99 33% with unfavourable intermediate-risk UIR and 197 67% with high-/very-high-risk VHR PCa) subsequently underwent surgery. As per the independent reads, 23–37 (7.8–13%) patients had 18F-rhPSMA-7.3–positive PLN. Seventy (24%) patients had one or more positive PLNs on histopathology. The sensitivity for PLN detection was 30% (95% CI, 19.6–42.1%) for reader 1, 27% (95% CI, 17.2–39.1%) for reader 2, and 23% (95% CI, 13.7–34.4%) for reader 3, not meeting the prespecified threshold. Specificity was 93% (95% CI, 88.8–95.9%), 94% (95% CI, 89.8–96.6%), and 97% (95% CI, 93.7–98.7%), respectively, exceeding the threshold for all readers. Specificity was high (≥92%) across both risk stratifications. Sensitivity was higher among high-risk/VHR (24–33%) than among UIR (16–21%) patients. Extrapelvic (M1) lesions were reported for 56–98/352 (16–28%) patients who underwent 18F-rhPSMA-7.3-PET/CT irrespective of surgery. Verification of these (predominantly by conventional imaging) gave a verified detection rate of 9.9–14% (positive predictive value, 51–63%). No serious adverse events were observed.
Across all risk stratifications, 18F-rhPSMA-7.3-PET/CT had high specificity, meeting the specificity endpoint. The sensitivity endpoint was not met, although higher sensitivity was noted among high-risk/VHR than among UIR patients. Overall, 18F-rhPSMA-7.3-PET/CT was well tolerated, and identified N1 and M1 disease prior to surgery in newly diagnosed PCa patients.
In order to select the most appropriate treatment for patients with prostate cancer, it is critical to diagnose the disease burden accurately at initial diagnosis. In this study, we investigated a new diagnostic imaging agent in a large population of men with primary prostate cancer. We found it to have an excellent safety profile and to provide clinically useful information regarding the presence of disease beyond the prostate.
(1) Background: The effectiveness of deep learning artificial intelligence depends on data availability, often requiring large volumes of data to effectively train an algorithm. However, few studies ...have explored the minimum number of images needed for optimal algorithmic performance. (2) Methods: This institutional review board (IRB)-approved retrospective review included patients who received prostate magnetic resonance imaging (MRI) between September 2014 and August 2018 and a magnetic resonance imaging (MRI) fusion transrectal biopsy. T2-weighted images were manually segmented by a board-certified abdominal radiologist. Segmented images were trained on a deep learning network with the following case numbers: 8, 16, 24, 32, 40, 80, 120, 160, 200, 240, 280, and 320. (3) Results: Our deep learning network’s performance was assessed with a Dice score, which measures overlap between the radiologist’s segmentations and deep learning-generated segmentations and ranges from 0 (no overlap) to 1 (perfect overlap). Our algorithm’s Dice score started at 0.424 with 8 cases and improved to 0.858 with 160 cases. After 160 cases, the Dice increased to 0.867 with 320 cases. (4) Conclusions: Our deep learning network for prostate segmentation produced the highest overall Dice score with 320 training cases. Performance improved notably from training sizes of 8 to 120, then plateaued with minimal improvement at training case size above 160. Other studies utilizing comparable network architectures may have similar plateaus, suggesting suitable results may be obtainable with small datasets.
Abstract Objectives Multi-parametric prostate magnetic resonance imaging (MRI) is considered the current imaging standard for detection and staging of prostate cancer. The combination of anatomical ...and functional imaging provided in this exam significantly increases the accuracy of prostate cancer detection. Computed tomography (CT) imaging has so far been found to be lacking in this regard, however observations at our academic institution as well as evidence present in the literature support the proposition that CT could indeed be helpful in detecting prostate abnormalities that correspond to neoplasm. The purpose of this study was to prove that areas of focal mass-like enhancement on CT imaging directly correlate with prostate neoplasms as revealed on multi-parametric MRI and follow-up targeted biopsy. Materials and methods This was a single institution retrospective study with 27 male subjects. Inclusion criteria required subjects to have a multi-parametric MRI of the prostate between January 1, 2014 and June 1, 2015 and a pelvic venous phase contrast-enhanced CT study between January 1, 2000 and June 1, 2015. Two blinded Radiologists read subjects' CT scans for any abnormalities of the prostate. CT and multi-parametric MRI results were compared and were considered concordant if focal or mass like enhancement to a greater degree than the background parenchyma was detected in the same areas of the prostate on CT scan as areas of decreased T2 signal, perfusion abnormalities, and restricted diffusion on multi-parametric MRI. Results CT results were directly compared to multi-parametric MRI findings and biopsy results. The overall agreement of MRI and CT is 85.19% (95% CI: 67.52–94.08%). The positive percent agreement is 78.95% (95% CI: 54.43–93.95%) and the negative percent agreement is 100.0% (95% CL: 63.06–100.0%). When CT results are directly compared to biopsy results, sensitivity and specificity of CT are 63.64% (95% CI: 30.79–89.07%) and 100.0% (95% CI: 47.82–100.0%). The positive predictive value (PPV) is 100.0% (95% CI: 59.04–100.0%) and the negative predictive value (NPV) is 55.56% (95% CI: 21.2–86.3%). When compared to MRI, CT has a lower sensitivity and a higher specificity, as well as a higher PPV and NPV. Logistic regression analysis did not show a significant relationship between concordance of MRI and CT and Gleason score, time between studies, age, and Prostate-specific antigen (PSA) level. Conclusion Incidental focal areas of mass-like enhancement in the peripheral prostate detected on venous phase contrast-enhanced CT imaging may indeed correlate with prostate neoplasm and it would be prudent to suggest further work-up with PSA and perhaps multi-parametric MRI, especially in high-risk patients.
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