Patient Reported Outcomes of Transperineal Prostate Biopsy With Tumescent Local Anesthesia.

OBJECTIVE: To report the outcomes of performing transperineal prostate biopsy in the office setting using the novel anesthetic technique of tumescent local anesthesia. We report anxiety, pain, and embarrassment of patients who underwent this procedure compared to patients who underwent a transrectal prostate biopsy using standard local anesthesia. MATERIALS AND METHODS: Consecutive patients undergoing either a transperineal prostate biopsy under tumescent local anesthesia or a transrectal prostate biopsy with standard local anesthetic technique were prospectively enrolled. The tumescent technique employed dilute lidocaine solution administered using a self-filling syringe. Patients were asked to rate their pain before, during, and after their procedure using a visual analog scale. Patient anxiety and embarrassment was assessed using the Testing Modalities Index Questionnaire. RESULTS: Between April 2021 and June 2022, 430 patients underwent a transperineal prostate biopsy using tumescent local anesthesia and 65 patients underwent a standard transrectal prostate biopsy. Patients who underwent a transperineal biopsy had acceptable but significantly higher pain scores than those who underwent a transrectal prostate biopsy (3.9 vs 1.6, P-value <.01). These scores fell to almost zero immediately following their procedure. Additionally, transperineal biopsy patients were more likely to experience anxiety (71% vs 45%, P < .01) and embarrassment (32% vs 15%, P < .01). CONCLUSION: Transperineal biopsy using local tumescent anesthesia is safe and well-tolerated. Despite the benefits, patients undergoing a transperineal prostate biopsy under tumescent anesthesia still experienced worse procedural pain, anxiety, and embarrassment. Additional studies examining other adjunctive interventions to improve patient experience during transperineal prostate biopsy are needed.

Initial Experience Performing In-office Ultrasound-guided Transperineal Prostate Biopsy Under Local Anesthesia Using the PrecisionPoint Transperineal Access System.

OBJECTIVE: To describe our procedural technique and initial outcomes performing in-office transperineal prostate biopsies using the PrecisionPoint Transperineal Access System (Perineologic, Cumberland, MD). PATIENTS AND METHODS: Following institutional review board approval, we retrospectively reviewed the records of men who underwent an in-office transperineal prostate biopsy using the PrecisionPoint device. Records were reviewed for baseline characteristics, biopsy results, and postbiopsy complications. RESULTS: Between January 4, 2017 and August 23, 2017, 43 men underwent an in-office transperineal prostate biopsy using the PrecisionPoint Transperineal Access System. Patients had a median serum prostate specific antigen level of 6.1 ng/mL (range 0.8-32.9). Of the 43 biopsies, 12 (27.9%) were performed for active surveillance of low-risk prostate cancer and 31 (72.1%) were performed for cancer screening. Overall, 21 (48.8%) men were found to have prostate cancer. Among those on active surveillance, cancer was detected in 8 of 12 (66.7%) patients, with 2 of 12 (16.7%) found to have Gleason ≥3 + 4 = 7 prostate cancer. Additionally, cancer was detected in 13 of 31 (41.9%) patients undergoing a biopsy for prostate cancer screening, with 5 (16.1%) found to have Gleason ≥3 + 4 = 7 disease. In total, 3 (7.0%) patients experienced a postbiopsy complication: 2 (4.7%) with urinary retention and 1 (2.3%) with gross hematuria requiring catheterization. No patient experienced an infectious complication despite omission of periprocedural antibiotics in all cases. CONCLUSION: The PrecisionPoint device allowed for the successful performance of in-office transperineal prostate biopsies under local anesthesia without the need for periprocedural antibiotics. We observed an acceptable cancer detection rate with no infectious complications.

Development of a Nationally Representative Coordinated Registry Network for Prostate Ablation Technologies.

PURPOSE: The accumulation of data through a prospective, multicenter coordinated registry network is a practical way to gather real world evidence on the performance of novel prostate ablation technologies. Urological oncologists, targeted biopsy experts, industry representatives and representatives of the FDA (Food and Drug Administration) convened to discuss the role, feasibility and important data elements of a coordinated registry network to assess new and existing prostate ablation technologies. MATERIALS AND METHODS: A multiround Delphi consensus approach was performed which included the opinion of 15 expert urologists, representatives of the FDA and leadership from high intensity focused ultrasound device manufacturers. Stakeholders provided input in 3 consecutive rounds with conference calls following each round to obtain consensus on remaining items. Participants agreed that these elements initially developed for high intensity focused ultrasound are compatible with other prostate ablation technologies. Coordinated registry network elements were reviewed and supplemented with data elements from the FDA common study metrics. RESULTS: The working group reached consensus on capturing specific patient demographics, treatment details, oncologic outcomes, functional outcomes and complications. Validated health related quality of life questionnaires were selected to capture patient reported outcomes, including the IIEF-5 (International Index of Erectile Function-5), the I-PSS (International Prostate Symptom Score), the EPIC-26 (Expanded Prostate Cancer Index Composite-26) and the MSHQ-EjD (Male Sexual Health Questionnaire for Ejaculatory Dysfunction). Group consensus was to obtain followup multiparametric magnetic resonance imaging and prostate biopsy approximately 12 months after ablation with additional imaging or biopsy performed as clinically indicated. CONCLUSIONS: A national prostate ablation coordinated registry network brings forth vital practice pattern and outcomes data for this emerging treatment paradigm in the United States. Our multiple stakeholder consensus identifies critical elements to evaluate new and existing energy modalities and devices.

Clinical Experience with 18F-Labeled Small Molecule Inhibitors of Prostate-Specific Membrane Antigen.

Prostate cancer (PCa) is the most common noncutaneous malignancy diagnosed in men. Despite the large number of men who will suffer from PCa at some point during their lives, conventional imaging modalities for this important disease (contrast-enhanced computed tomography, bone scan, and MR imaging) have provided only marginal to moderate success in appropriately guiding patient management in certain clinical contexts. In this review, the authors discuss radiofluorinated small molecule radiotracers that have been developed to bind to the transmembrane glycoprotein prostate-specific membrane antigen, a target that is nearly universally overexpressed on PCa epithelial cells.

Absence of CHEK2*1100delC mutation in families with hereditary breast cancer in North America.

The CHEK2*1100delC mutation has been reported to confer a twofold increased risk of breast cancer among carriers. The frequency of the mutation varies among populations. The highest frequency has been described in Northern and Eastern European countries; the frequency may be much lower in North America. In this study, our aim was to determine the frequency of CHEK2*1100delC in members of breast cancer families who tested negative for a deleterious mutation in BRCA1/2 at the University of Michigan Comprehensive Cancer Center. We genotyped 102 members from 90 families for CHEK2*1100delC. Most of these families had several cases of breast cancer or ovarian cancer (or both), as well as multiple members with other cancer types in a single lineage. No CHEK2*1100delC mutations were detected in any of the 102 individuals, including 51 women diagnosed with breast cancer at an early age (<45 years), 8 women with bilateral breast cancer, 3 men with breast cancer, and 8 women with ovarian cancer. Our data are consistent with the reported very low frequency of CHEK2*1100delC mutations in North American populations (compared with Northern Europe), rendering CHEK2*1100delC such an unlikely culprit in BRCA1/2 negative families that routine testing of these families appears unwarranted.

Pomegranate fruit extract impairs invasion and motility in human breast cancer.

PURPOSE: Pomegranate fruit extracts (PFEs) possess polyphenolic and other compounds with antiproliferative, pro-apoptotic and anti-inflammatory effects in prostate, lung, and other cancers. Because nuclear transcription factor-kB (NF-kB) is known to regulate cell survival, proliferation, tumorigenesis, and inflammation, it was postulated that PFEs may exert anticancer effects at least in part by modulating NF-kB activity. EXPERIMENTAL DESIGN: The authors investigated the effect of a novel, defined PFE consisting of both fermented juice and seed oil on the NF-kB pathway, which is constitutively active in aggressive breast cancer cell lines. The effects of the PFE on NF-kB-regulated cellular processes such as cell survival, proliferation, and invasion were also examined. RESULTS: Analytical characterization of the bioactive components of the PFE revealed active constituents, mainly ellagitannins and phenolic acids in the aqueous PFE and conjugated octadecatrienoic acids in the lipid PFE derived from seeds.The aqueous PFE dose-dependently inhibited NF-kB-dependent reporter gene expression associated with proliferation, invasion, and motility in aggressive breast cancer phenotypes while decreasing RhoC and RhoA protein expression. CONCLUSION: Inhibition of motility and invasion by PFEs, coincident with suppressed RhoC and RhoA protein expression, suggests a role for these defined extracts in lowering the metastatic potential of aggressive breast cancer species.

Preclinical development of a bifunctional cancer cell homing, PKCepsilon inhibitory peptide for the treatment of head and neck cancer.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most frequent cancer worldwide, comprising approximately 50% of all malignancies in some developing nations. Our recent work identified protein kinase Cepsilon (PKCepsilon) as a critical and causative player in establishing an aggressive phenotype in HNSCC. In this study, we investigated the specificity and efficacy of HN1-PKCepsilon, a novel bifunctional cancer cell homing, PKCepsilon inhibitory peptide, as a treatment for HNSCC. HN1-PKCepsilon peptide was designed by merging two separate technologies and synthesized as a capped peptide with two functional modules, HN1 (cancer cell homing) and PKCepsilon (specific PKCepsilon inhibitory), connected by a novel linker module. HN1-PKCepsilon preferentially internalized into UMSCC1 and UMSCC36 cells, two HNSCC cell lines, in comparison with oral epithelial cells: 82.1% positive for UMSCC1 and 86.5% positive for UMSCC36 compared with 1.2% positive for oral epithelial cells. In addition, HN1-PKCepsilon penetrated HNSCC cells in a dose- and time-dependent manner. Consistent with these in vitro observations, systemic injection of HN1-PKCepsilon resulted in selective delivery of HN1-PKCepsilon into UMSCC1 xenografts in nude mice. HN1-PKCepsilon blocked the translocation of active PKCepsilon in UMSCC1 cells, confirming HN1-PKCepsilon as a PKCepsilon inhibitor. HN1-PKCepsilon inhibited cell invasion by 72 +/- 2% (P < 0.001, n = 12) and cell motility by 56 +/- 2% (P < 0.001, n = 5) in UMSCC1 cells. Moreover, in vivo bioluminescence imaging showed that HN1-PKCepsilon significantly (83 +/- 1% inhibition; P < 0.02) retards the growth of UMSCC1 xenografts in nude mice. Our work indicates that the bifunctional HN1-PKCepsilon inhibitory peptide represents a promising novel therapeutic strategy for HNSCC.