Faculty Bibliography

BACKGROUND:In-field or in-margin recurrence after partial gland cryosurgical ablation (PGCA) of prostate cancer (PCa) remains a limitation of the paradigm. Stimulated Raman histology (SRH) is a novel microscopic technique allowing real time, label-free, high-resolution microscopic images of unprocessed, un-sectioned tissue which can be interpreted by humans or artificial intelligence (AI). We evaluated surgical team and AI interpretation of SRH for real-time pathologic feedback in the planning and treatment of PCa with PGCA. METHODS:About 12 participants underwent prostate mapping biopsies during PGCA of their PCa between January and June 2022. Prostate biopsies were immediately scanned in a SRH microscope at 20 microns depth using 2 Raman shifts to create SRH images which were interpreted by the surgical team intraoperatively to guide PGCA, and retrospectively assessed by AI. The cores were then processed, hematoxylin and eosin stained as per normal pathologic protocols and used for ground truth pathologic assessment. RESULTS:Surgical team interpretation of SRH intraoperatively revealed 98.1% accuracy, 100% sensitivity, 97.3% specificity for identification of PCa, while AI showed a 97.9% accuracy, 100% sensitivity and 97.5% specificity for identification of clinically significant PCa. 3 participants' PGCA treatments were modified after SRH visualized PCa adjacent to an expected MRI predicted tumor margin or at an untreated cryosurgical margin. CONCLUSION/CONCLUSIONS:SRH allows for accurate rapid identification of PCa in PB by a surgical team interpretation or AI. PCa tumor mapping and margin assessment during PGCA appears to be feasible and accurate. Further studies evaluating impact on clinical outcomes are warranted.

INTRODUCTION/UNASSIGNED:Balancing surgical margins and functional outcomes is crucial during radical prostatectomy for prostate cancer. Stimulated Raman Histology (SRH) is a novel, real-time imaging technique that provides histologic images of fresh, unprocessed, and unstained tissue within minutes, which can be interpreted by either humans or artificial intelligence. METHODS/UNASSIGNED:Twenty-two participants underwent robotic-assisted laparoscopic radical prostatectomy (RALP) with intraoperative SRH surgical bed assessment. Surgeons resected and imaged surgical bed tissue using SRH and adjusted treatment accordingly. An SRH convolutional neural network (CNN) was developed and tested on 10 consecutive participants. The accuracy, sensitivity, and specificity of the surgical team's interpretation were compared to final histopathological assessment. RESULTS/UNASSIGNED:A total of 121 SRH periprostatic surgical bed tissue (PSBT) assessments were conducted, an average of 5.5 per participant. The accuracy of the surgical team's SRH interpretation of resected PSBT samples was 98%, with 83% sensitivity, and 99% specificity. Intraoperative SRH assessment identified 43% of participants with a pathologic positive surgical margin intraoperatively. PSBT assessment using the CNN demonstrated no overlap in tumor probability prediction between benign and tumor infiltrated samples, mean 0.30% (IQR 0.10-0.43%) and 26% (IQR 18-34%, p<0.005), respectively. CONCLUSION/UNASSIGNED:SRH demonstrates potential as a valuable tool for real-time intraoperative assessment of surgical margins during RALP. This technique may improve nerve-sparing surgery and facilitate decision-making for further resection, reducing the risk of positive surgical margins and minimizing the risk of recurrence. Further studies with larger cohorts and longer follow-up periods are warranted to confirm the benefits of SRH in RALP.

INTRODUCTION/BACKGROUND:Local disease recurrence following focal therapy (FT) for prostate cancer may be due to failure to eradicate focal disease or development of disease in the untreated prostate (in- and out-of-field recurrences). Several studies suggest in-field contrast enhancement (CE) on post-treatment multi-parametric (mp) MRI between 6-12 months following FT indicates residual disease. The present study assesses the incidence and oncologic implications of early CE observed following primary partial gland cryoablation (PPGCA). MATERIAL AND METHODS/METHODS:The surveillance protocol for men enrolled in our prospective outcomes study following PPGCA included mpMRI at 6-12 months, 2 years, 3.5 years, and 5 years. All cases of in-field early CE were re-reviewed retrospectively and graded using the previously described Prostate Imaging after Focal Ablation scoring system. All patients exhibiting early CE were re-evaluated by a single radiologist at 2-year mpMRI Results: A total of 320 men enrolled in our PPGCA outcomes study had at least 6 months of follow up. Three hundred fifteen (98%) of these men had undergone post-PPGCA mpMRI at 6-12 months. Of these men, 9 were found to have early in-field CE and 8 underwent repeat MRI at 2 years. In all 8 cases, the CE resolved on the 2-year mpMRI. Of these 8 patients, seven underwent repeat protocol biopsy at 2 years and in-field significant disease was detected in only 1 case. CONCLUSIONS:The most compelling evidence that early CE is not indicative of prostate cancer recurrence is that all lesions resolved within 24 months. While incidence of early CE is low, its consistent resolution calls into question the clinical significance of this finding after PPGCA.

Urine leak (UL) and vascular complications (VC), i.e., pseudoaneurysms and arteriovenous fistulas are well-described complications of robotic-assisted partial nephrectomy (RAPN). Historically, UL incidence ranges from 0.3 to 17% and VC from 0.8 to 5.6%. We report the contemporary experience of UL and VC from a single, high-volume center in cases of RAPN. 447 patients were identified from an IRB-approved Renal Tumor Database of 2174 cases who underwent RAPN from 1/2017 to 5/2023. VC occurred in 9 cases (4 pseudoaneurysms, 1 AV fistula, 4 concurrent AV fistula/pseudoaneurysm), UL occurred in 9 (2.0%), and there was one concurrent case of VC and UL. Collecting-system entry occurred in five VC cases and five UL cases. For VCs, the median nephrometry score and maximal tumor diameter was 8 (IQR 3.0) and 3.8 (0.9) cm, respectively, and 8 (3.0) and 3.7 (1.1) cm for UL cases, respectively. Most complications occurred with tumors ≤ 4 mm from the collecting system (n = 7 VC, n = 6 UL). VCs presented after 18 (6.0) days, 6 with gross hematuria; 3 required clot irrigation, 1 required continuous bladder irrigation, and 8 required embolization. No patients required postoperative transfusion. Patients with UL presented after a median of 1 (12) day, with 5 cases detected by elevated creatinine in drain fluid and the remainder detected on routine ultrasound. The duration of UL was 13 (41) days with only 2 cases requiring stenting and one case requiring a drainage catheter. No patients required kidney re-operation or removal. Our rate of VC and UL following RAPN are low and consistent with other contemporary series. Complications occurred in patients with high nephrometry scores or tumors located close to the collecting system. Both complications generally present early and can be managed without kidney re-operation or removal.

The PRESERVE study (NCT04972097) aims to evaluate the safety and effectiveness of the NanoKnife System to ablate prostate tissue in patients with intermediate-risk prostate cancer (PCa). The NanoKnife uses irreversible electroporation (IRE) to deliver high-voltage electrical pulses to change the permeability of cell membranes, leading to cell death. A total of 121 subjects with organ-confined PCa ≤ T2c, prostate-specific antigens (PSAs) ≤ 15 ng/mL, and a Gleason score of 3 + 4 or 4 + 3 underwent focal ablation of the index lesion. The primary endpoints included negative in-field biopsy and adverse event incidence, type, and severity through 12 months. At the time of analysis, the trial had completed accrual with preliminary follow-up available. Demographics, disease characteristics, procedural details, PSA responses, and adverse events (AEs) are presented. The median (IQR) age at screening was 67.0 (61.0-72.0) years and Gleason distribution 3 + 4 (80.2%) and 4 + 3 (19.8%). At 6 months, all patients with available data (n = 74) experienced a median (IQR) percent reduction in PSA of 67.6% (52.3-82.2%). Only ten subjects (8.3%) experienced a Grade 3 adverse event; five were procedure-related. No Grade ≥ 4 AEs were reported. This study supports prior findings that IRE prostate ablation with the NanoKnife System can be performed safely. Final results are required to fully assess oncological, functional, and safety outcomes.

The treatment options for prostate cancer typically entail active surveillance, surgery, radiation, or a combination of the above. Disease recurrence remains a concern, with a wide range of recurrence rates having been reported in the literature. In the setting of recurrence, the salvage treatment options include salvage prostatectomy, salvage high-intensity focused ultrasound (HIFU), stereotactic body radiotherapy (SBRT), salvage brachytherapy, and salvage cryoablation. In this review, we analyze the currently available data related to salvage cryoablation for recurrent prostate cancer following radiation.

OBJECTIVE:To evaluate predictors of contralateral clinically significant prostate cancer (csPCa) in men with biopsy-proven unilateral lesions on magnetic resonance imaging (MRI). METHODS:We retrospectively identified men with no prior diagnosis of PCa with unilateral biopsy-confirmed csPCa within PI-RADS 2-5 lesions within our institutional biopsy database. Multivariate logistic regression was used to identify clinical predictors of contralateral disease. RESULTS:Four hundred ninety men met study inclusion criteria, of which 385 men (78.6%) had no contralateral csPCa and 105 men (21.4%) had contralateral csPCa (Fig. 1). Prior negative biopsy (OR 0.34 [0.14, 0.75], P = .012), prostate-specific antigen density (OR 18.8 [2.77, 249], P = .017), and tumor location in the transverse plane ("Posterior": OR 1.93 [1.02, 3.87], P = .048; "Throughout Transverse Plane": OR 6.56 [2.26, 19.6], P < .001) were significantly associated with contralateral csPCa in multivariate logistic regression models. However, there appear to be no attributes within the MRI-targeted tumor that reliably predict contralateral csPCa (Table 2). CONCLUSION/CONCLUSIONS:Approximately 20% of men with unilateral MRI findings and csPCa on targeted biopsy were found to have contralateral csPCa on systematic biopsy (SB). Prior negative biopsy was associated with a decreased odds of contralateral csPCa. Prostate-specific antigen density and tumor in the posterior aspect of or throughout the transverse plane were associated with increased odds of contralateral csPCA. Consideration of these clinical factors may afford an opportunity to only use SB in cases in which the odds of contralateral csPCa are high.

INTRODUCTION/BACKGROUND:We evaluate the rate of developing ciprofloxacin resistance in patients undergoing repeat prostate biopsies (PBx), associated risk factors, and impact on complications. MATERIALS AND METHODS/METHODS:We retrospectively evaluated pre-procedural rectal culture (RCx) data in men undergoing PBx from 1/1/2016 to 1/15/2021. Univariate and multivariate logistic regression were utilized to identify risk factors associated with development of antibiotic resistance. Complication rates were compared between ciprofloxacin-sensitive and ciprofloxacin-resistant patients. RESULTS:A total of 743 men underwent initial RCx. Initial RCx detected ciprofloxacin resistance in 22% of patients. A history of diabetes (p = 0.01), > 2 prior prostate biopsies (p = 0.01), and ciprofloxacin use (p = 0.002) were significant risk factors for ciprofloxacin resistance on initial RCx. The rate of new ciprofloxacin resistance following biopsy with standard ciprofloxacin prophylaxis on 1st and 2nd exposure was 17.2% and 9.1% respectively. The number of biopsy cores, interval antibiotic exposure and interval procedures performed between first and second RCx were not significant predictors of developing ciprofloxacin resistance. Patients who received a non-ciprofloxacin antibiotic between first and second RCx did not develop ciprofloxacin resistance. Antibiotic resistance profile did not significantly affect the rate or type of complications after various prostate procedures. CONCLUSIONS:Serial exposure to standard antibiotic prophylaxis for PBx and associated procedures can lead to development of ciprofloxacin resistance after each subsequent exposure. This carries important implications for serial biopsy and highlights the role for RCx prior to repeat biopsy.

OBJECTIVES/OBJECTIVE:To evaluate the interaction of patient age and Prostate Imaging-Reporting and Data System (PI-RADS) score in determining the grade of prostate cancer (PCa) identified on magnetic resonance imaging (MRI)-targeted biopsy in older men. PATIENTS AND METHODS/METHODS:From a prospectively accrued Institutional Review Board-approved comparative study of MRI-targeted and systematic biopsy between June 2012 and December 2022, men with at least one PI-RADS ≥3 lesion on pre-biopsy MRI and no prior history of PCa were selected. Ordinal and binomial logistic regression analyses were performed. RESULTS:A total of 2677 men met study criteria. The highest PI-RADS score was 3 in 1220 men (46%), 4 in 950 men (36%), and 5 in 507 men (19%). The median (interquartile range [IQR]) patient age was 66.7 (60.8-71.8) years, median (IQR) prostate-specific antigen (PSA) level was 6.1 (4.6-9.0) ng/mL, median (IQR) prostate volume was 48 (34-68) mL, and median (IQR) PSA density was 0.13 (0.08-0.20) ng/mL/mL. Clinically significant (cs)PCa and high-risk PCa were identified on targeted biopsy in 1264 (47%) and 321 (12%) men, respectively. Prevalence of csPCa and high-risk PCa were significantly higher in the older age groups. On multivariable analyses, patient age was significantly associated with csPCa but not high-risk PCa; PI-RADS score and the interaction of age and PI-RADS score were significantly associated with high-risk PCa but not csPCa. CONCLUSION/CONCLUSIONS:In our cohort, the substantial rate of high-risk PCa on MRI-ultrasound fusion targeted biopsies in older men, and its significant association with MRI findings, supports the value of pre-biopsy MRI to localise disease that could cause cancer mortality even in older men.