Faculty Bibliography

BACKGROUND:There is increasing interest in ablative focal therapy (AFT) for treating clinically localized prostate cancer. The objective of the present study is to report treatment related complications and regret, functional and oncological outcomes of primary partial gland cryo-ablation (PPGCA) for men with low-risk prostate cancer associated with a multiparametric Magnetic Resonance Imaging (mpMRI) target. METHODS:The present analysis includes 54 subjects enrolled in an Institutional Review Board (IRB) approved outcomes registry with low-risk prostate cancer undergoing PPGCA whose disease was associated with an MRI target. The surveillance protocol included mpMRI at 6 months, 2, 3.5, and 5 years, and surveillance prostate biopsies. Clinically significant prostate cancer (csPCa) recurrence was defined as any biopsy core with Gleason pattern (GP4). Freedom-from-failure (FFF) included men who: did not experience prostate cancer mortality, develop metastasis or undergo whole gland salvage treatment (WGST). All men underwent at least 1 post-treatment biopsy. The International Prostate Symptom Score (IPSS), Sexual Health Inventory for Men (SHIM) and Treatment Related Regret (TRR) surveys were self-administered at 1 year. RESULTS:There were no day-of-surgery or 30-day postoperative hospital admissions. There were no rectal injuries or other technical complications. The 5-year freedom from csPCa recurrence and FFF was 84% and 96%, respectively. At 1 year, only 1 man used a protective pad and no men expressed significant TRR. Overall, the mean decreases in IPSS and SHIM scores between baseline and 1-year was 3.4 (34.7%) and 3.7 (20.4%), respectively. Erectile function was preserved in 72% of men by 1 year. CONCLUSION/CONCLUSIONS:The favorable oncological outcomes, absence of treatment related complications, Treatment Related Regret (TRR), urinary incontinence, rectal injury, improvement in lower urinary tract symptoms (LUTS), and modest changes in sexual function suggests PPGCA should be considered an option for managing selected cases of low-risk prostate cancer associated with an MRI target.

OBJECTIVES/OBJECTIVE:To compare the clinically significant prostate cancer detection rate (csPCaDR) and pathological characteristics of magnetic resonance imaging (MRI) visible (MRIv) and MRI invisible (MRIi) cancers among men undergoing surveillance after ablative focal therapy (AFT) for intermediate-risk PCa. PATIENTS AND METHODS/METHODS:A total of 305 five men enrolled in an Institutional Review Board-approved primary partial gland cryoablation (PPGCA) outcomes registry meeting the following inclusion criteria: an MRI region of interest (ROI) Prostate Imaging-Reporting and Data System 2-5 concordant with unilateral intermediate-risk disease (Gleason Grade Group [GGG] 2 or 3 disease), no gross extraprostatic extension on MRI, no GGG ≥2 contralateral to the ROI, and at least 6 months of follow-up. Protocol MRI was performed at 6, 24, 42 and 60 months. Biopsy indications evolved over time. Any Gleason pattern 4 (GP4) represented a clinically significant PCa recurrence (csPCaR). Pathological disease characteristics, csPCaDR, and salvage treatments were compared for MRIv and MRIi disease. Baseline and post-treatment characteristics were compared between MRIv and MRIi csPCaR. Ordinal and binary measures were compared with Mann-Whitney rank-sum test. Categorical testing for differences was performed with chi-square testing. RESULTS:Of 665 post-treatment MRIs, 87 (13.1%) and 578 (86.9%) were positive (+ve) and negative (-ve) for csPCaR, respectively. Biopsies were taken in 62 of the 87 +ve MRIs and 179 of the 578 -ve MRIs, with a csPCaDR of 43.5% and 10.6% for +ve and -ve MRI, respectively. Of the 46 csPCaRs, 28 (61%) and 18 (39%) were associated with +ve and -ve MRI, respectively. The median linear length of GP4 for MRIv and MRIi csPCaR was 2.6 and 0.6 mm, respectively (P = 0.08). Four (14%) and eight (44%) MRIv and MRIi csPCaRs were managed with continued active surveillance (P = 0.03). CONCLUSION/CONCLUSIONS:The cost and morbidity of surveillance following PPGCA can be safely reduced by avoiding biopsy in most cases with -ve MRI.

OBJECTIVE:To assess 5-year oncologic outcomes following primary partial gland cryo-ablation (PPGCA) in intermediate risk prostate cancer. METHODS:Of 476 men undergoing PPGCA enrolled in our prospective oncologic and functional outcomes study, 313 had MRI concordant intermediate risk prostate cancer with no out-of-field Gleason Grade Group (GGG) ≥2, gross extracapsular extension or extreme apical disease on pre-treatment mpMRI. PSA was monitored every 6 months, and mpMRI at 6-12, 24, 42 and 60 months. Protocol biopsy at 6-12 months and 24 months were discontinued after interim analysis showing low rates of clinically-significant prostate cancer (csPCa) defined as any GGG≥2 disease. Freedom-from-failure (FFF) was defined as no prostate cancer specific mortality, metastatic disease, or whole-gland salvage treatment (WGST) RESULTS: csPCa was detected in 33 (10.5%) subjects. 91 had ≥4.5 years of follow-up data with a mean of 8.9, 3.4, and 2.0 surveillance PSA tests, MRIs, and prostate biopsies; none were lost to follow-up. At 5-years, rates of freedom-from-recurrence of in-field, out-of-field and overall csPCa were 86% (95% CI: 78-96), 85% (95% CI: 63-94), and 70% (95% CI: 57-84). The proportion with freedom-from-failure (FFF) at 5 years was 89% (95% CI: 83-95). None died from prostate cancer, 1 (1%) developed metastasis, 15 (16.5%) underwent WGST, and 15 (16.5%) underwent salvage focal therapy (FT). Only 3 of 91 (3.3%) eligible men were noncompliant with 5-year surveillance protocol. CONCLUSION/CONCLUSIONS:Very encouraging intermediate-term oncological outcomes following PPGCA were observed with very high compliance to a rigorous prospective protocol for identifying recurrent csPCa.

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.

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.

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.

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.

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.