Comparing Magnetic Resonance Imaging and Prostate-Specific Membrane Antigen-Positron Emission Tomography for Prediction of Extraprostatic Extension of Prostate Cancer and Surgical Guidance: A Prospective Nonrandomized Clinical Trial.

PURPOSE: Survivors of surgically managed prostate cancer may experience urinary incontinence and erectile dysfunction. Our aim was to determine if 68Ga-prostate-specific membrane antigen-11 positron emission tomography CT (PSMA-PET) in addition to multiparametric (mp) MRI scans improved surgical decision-making for nonnerve-sparing or nerve-sparing approach. MATERIALS AND METHODS: We prospectively enrolled 50 patients at risk for extraprostatic extension (EPE) who were scheduled for prostatectomy. After mpMRI and PSMA-PET images were read for EPE prediction, surgeons prospectively answered questionnaires based on mpMRI and PSMA-PET scans on the decision for nerve-sparing or nonnerve-sparing approach. Final whole-mount pathology was the reference standard. Sensitivity, specificity, positive predictive value, negative predictive value, and receiver operating characteristic curves were calculated and McNemar's test was used to compare imaging modalities. RESULTS: The median age and PSA were 61.5 years and 7.0 ng/dL. The sensitivity for EPE along the posterior neurovascular bundle was higher for PSMA-PET than mpMRI (86% vs 57%, P = .03). For MRI, the specificity, positive predictive value, negative predictive value, and area under the curve for the receiver operating characteristic curves were 77%, 40%, 87%, and 0.67, and for PSMA-PET were 73%, 46%, 95%, and 0.80. PSMA-PET and mpMRI reads differed on 27 nerve bundles, with PSMA-PET being correct in 20 cases and MRI being correct in 7 cases. Surgeons predicted correct nerve-sparing approach 74% of the time with PSMA-PET scan in addition to mpMRI compared to 65% with mpMRI alone (P = .01). CONCLUSIONS: PSMA-PET scan was more sensitive than mpMRI for EPE along the neurovascular bundles and improved surgical decisions for nerve-sparing approach. Further study of PSMA-PET for surgical guidance is warranted in the unfavorable intermediate-risk or worse populations. CLINICALTRIALS.GOV IDENTIFIER: NCT04936334.

High-intensity focused ultrasound with visually directed power adjustment for focal treatment of localized prostate cancer: systematic review and meta-analysis.

PURPOSE: To characterize patient outcomes following visually directed high-intensity focused ultrasound (HIFU) for focal treatment of localized prostate cancer. METHODS: We performed a systematic review of cancer-control outcomes and complication rates among men with localized prostate cancer treated with visually directed focal HIFU. Study outcomes were calculated using a random-effects meta-analysis model. RESULTS: A total of 8 observational studies with 1,819 patients (median age 67 years; prostate-specific antigen 7.1 mg/ml; prostate volume 36 ml) followed over a median of 24 months were included. The mean prostate-specific antigen nadir following visually directed focal HIFU was 2.2 ng/ml (95% CI 0.9-3.5 ng/ml), achieved after a median of 6 months post-treatment. A clinically significant positive biopsy was identified in 19.8% (95% CI 12.4-28.3%) of cases. Salvage treatment rates were 16.2% (95% CI 9.7-23.8%) for focal- or whole-gland treatment, and 8.6% (95% CI 6.1-11.5%) for whole-gland treatment. Complication rates were 16.7% (95% CI 9.9-24.6%) for de novo erectile dysfunction, 6.2% (95% CI 0.0-19.0%) for urinary retention, 3.0% (95% CI 2.1-3.9%) for urinary tract infection, 1.9% (95% CI 0.1-5.3%) for urinary incontinence, and 0.1% (95% CI 0.0-1.4%) for bowel injury. CONCLUSION: Limited evidence from eight observational studies demonstrated that visually directed HIFU for focal treatment of localized prostate cancer was associated with a relatively low risk of complications and acceptable cancer control over medium-term follow-up. Comparative, long-term safety and effectiveness results with visually directed focal HIFU are lacking.

Comparison of tracer kinetic models for 68Ga-PSMA-11 PET in intermediate-risk primary prostate cancer patients.

BACKGROUND: 68Ga-PSMA-11 positron emission tomography enables the detection of primary, recurrent, and metastatic prostate cancer. Regional radiopharmaceutical uptake is generally evaluated in static images and quantified as standard uptake values (SUVs) for clinical decision-making. However, analysis of dynamic images characterizing both tracer uptake and pharmacokinetics may offer added insights into the underlying tissue pathophysiology. This study was undertaken to evaluate the suitability of various kinetic models for 68Ga-PSMA-11 PET analysis. Twenty-three lesions in 18 patients were included in a retrospective kinetic evaluation of 55-min dynamic 68Ga-PSMA-11 pre-prostatectomy PET scans from patients with biopsy-demonstrated intermediate- to high-risk prostate cancer. Three kinetic models-a reversible one-tissue compartment model, an irreversible two-tissue compartment model, and a reversible two-tissue compartment model, were evaluated for their goodness of fit to lesion and normal reference prostate time-activity curves. Kinetic parameters obtained through graphical analysis and tracer kinetic modeling techniques were compared for reference prostate tissue and lesion regions of interest. RESULTS: Supported by goodness of fit and information loss criteria, the irreversible two-tissue compartment model optimally fit the time-activity curves. Lesions exhibited significant differences in kinetic rate constants (K1, k2, k3, Ki) and semiquantitative measures (SUV and %ID/kg) when compared with reference prostatic tissue. The two-tissue irreversible tracer kinetic model was consistently appropriate across prostatic zones. CONCLUSIONS: An irreversible tracer kinetic model is appropriate for dynamic analysis of 68Ga-PSMA-11 PET images. Kinetic parameters estimated by Patlak graphical analysis or full compartmental analysis can distinguish tumor from normal prostate tissue.

Comparison of Tracer Kinetic Models for 68Ga-PSMA-11 PET in Intermediate Risk Primary Prostate Cancer Patients.

BACKGROUND: 68Ga-PSMA-11 positron emission tomography enables the detection of primary, recurrent, and metastatic prostate cancer. Regional radiopharmaceutical uptake is generally evaluated in static images and quantified as standard uptake values (SUV) for clinical decision-making. However, analysis of dynamic images characterizing both tracer uptake and pharmacokinetics may offer added insights into the underlying tissue pathophysiology. This study was undertaken to evaluate the suitability of various kinetic models for 68Ga-PSMA-11 PET analysis. Twenty-three lesions in 18 patients were included in a retrospective kinetic evaluation of 55-minute dynamic 68Ga-PSMA-11 pre-prostatectomy PET scans from patients with biopsy-demonstrated intermediate to high-risk prostate cancer. A reversible one-tissue compartment model, irreversible two-tissue compartment model, and a reversible two-tissue compartment model were evaluated for their goodness-of-fit to lesion and normal reference prostate time-activity curves. Kinetic parameters obtained through graphical analysis and tracer kinetic modeling techniques were compared for reference prostate tissue and lesion regions of interest. RESULTS: Supported by goodness-of-fit and information loss criteria, the irreversible two-tissue compartment model was selected as optimally fitting the time-activity curves. Lesions exhibited significant differences in kinetic rate constants (K1, k2, k3, Ki) and semiquantitative measures (SUV) when compared with reference prostatic tissue. The two-tissue irreversible tracer kinetic model was consistently appropriate across prostatic zones. CONCLUSIONS: An irreversible tracer kinetic model is appropriate for dynamic analysis of 68Ga-PSMA-11 PET images. Kinetic parameters estimated by Patlak graphical analysis or full compartmental analysis can distinguish tumor from normal prostate tissue.

Assessing extra-prostatic extension for surgical guidance in prostate cancer: Comparing two PSMA-PET tracers with the standard-of-care.

BACKGROUND: Incontinence and impotence occur following radical prostatectomy due to injury to nerves and sphincter muscle. Preserving nerves and muscle adjacent to prostate cancer risks positive surgical margins. Advanced imaging with MRI has improved cancer localization but limitations exist. OBJECTIVE: To measure the accuracy for assessing extra-prostatic extension at nerve bundles for 2 PSMA-PET tracers and to compare the PET accuracy to standard-of-care predictors including MRI and biopsy results. MATERIALS AND METHODS: We studied men with PSMA-targeted PET imaging, performed prior to prostatectomy in men largely with intermediate to high-risk prostate cancer, and retrospectively evaluated for assessment of extra-prostatic extension with whole-mount analysis as reference standard. Two different PSMA-PET tracers were included: 68Ga-PSMA-11 and 68Ga-P16-093. Blinded reviews of the PET and MRI scans were performed to assess extra-prostatic extension (EPE). Sensitivity and specificity for extra-prostatic extension were compared using McNemar's Chi2. RESULTS: Pre-operative PSMA-PET imaging was available for 71 patients with either 68Ga-P16-093 (n = 25) or 68Ga-PSMA-11 (n = 46). There were 24 (34%) with pT3a (EPE) and 16 (23%) with pT3b (SVI). EPE Sensitivity (87% vs. 92%), Specificity (77% vs. 76%), and ROC area (0.82 vs. 0.84) were similar between P16-093 and PSMA-11, respectively (P = 0.87). MRI (available in only 45) found high specificity (83%) but low sensitivity (60%) for EPE when using a published grading system. MRI sensitivity was significantly lower than the PSMA-PET (60% vs. 90%, P = 0.02), but similar to PET when using a >5 mm capsular contact (76% vs. 90%, P = 0.38). A treatment change to "nerve sparing" was recommended in 21 of 71 (30%) patients based on PSMA-PET imaging. CONCLUSIONS: Presurgical PSMA-PET appeared useful as a tool for surgical planning, changing treatment plans in men with ≥4+3 or multi-core 3+4 prostate cancer resulting in preservation of nerve-bundles.

Temporal Study of Renal Volume Losses in Patients with Robotic Partial Nephrectomies.

Purpose: Robotic partial nephrectomies (RPNs) by their nature are associated with renal volume loss. Our goal of this study is to examine renal volume loss over time post partial nephrectomy. Materials and Methods: Fifty patients were followed for 1-year post-RPN with two-layer renorrhaphy and the sliding clip technique. This was done with a preoperative CT scan to assess renal mass and location. Patients post-RPN were imaged at time points 3 days, 6 months, and 12 months. Results: Patient demographics were 82% men with a median (interquartile range [IQR]) age of 57 (45-67) years and all were of Japanese descent. The medians (IQR) for warm ischemia time were 18 minutes (14-22), total operative time was 181.5 minutes (169.3-218.5), and estimated blood loss was 20 mL (10-50). The tumor characteristics had a median (IQR) diameter of 2.8 cm (2.5-3.4) with a RENAL score of 7 (6-8). The renal CT showed median (IQR) volume losses at 3 days of -1% (-7.1, 1.8), at 6 months of -15.3% (-20.6, -11.2), and at 12 months of -16.3% (-19.0, -12.8). Significance was seen at the 3 days to 6 months comparison for volume loss (p < 0.0001). Mean (standard deviation) estimated glomerular filtration rate (GFR) losses were as follows: at discharge 0.5% (12.9), 1 month -6.4% (11.8), 6 months -4.6% (9.8), and 12 months -3.6% (11.9). Statistical analysis showed significance for GFR loss at the comparison between discharge to 1 and 6 months (p = 0.01, p = 0.04). Conclusion: The initial volume loss seen postsurgery from resected healthy tissue was not significant and only became relevant at longer time points, suggesting that loss could be from atrophy. Volume loss over time supports the hypothesis that suture renorrhaphy is a primary cause of volume loss when warm ischemia time is <25 minutes.

High-intensity focused ultrasound for the treatment of prostate cancer: assessing location of failure after focal therapy in prostate cancer and review of histological characteristics and clinicopathologic correlates after treatment-a 5-year experience.

High-intensity focused ultrasound (HIFU) is a noninvasive treatment option used for localized prostate cancer or salvage surgery after failed radiation therapy. Histological changes in post-treatment needle biopsies are reviewed to better understand HIFU failures. Between 2016 and 2021, 50 patients with localized prostate cancer were enrolled and treated in this study. Of these, 10 patients underwent salvage therapy after radiation failure and 7 did not have post-treatment needle biopsies available for review and were excluded. Inclusion criteria included pathologically confirmed prostate cancer and clinical stage T1/T2 disease. We describe the histological changes in post-treatment needle biopsies as part of routine follow-up. Biopsies were examined for presence, distribution and extent of residual adenocarcinoma, Gleason score, and ablative tissue changes. A total of 33 patients underwent HIFU hemi-ablation treatment of localized prostate cancer as primary treatment with post-treatment biopsies available for review. The average mean age of the patients was 64 years (range, 52-81 years). The average PSA (prostate-specific antigen) level of the patients was 6.3 ng/mL (range, 2.4-14.7 ng/mL). The Gleason scores assigned in pretreatment prostate needle biopsies are as follows: 3 + 3 (1 case, 3%), 3 + 4 (21 cases, 64%), 4 + 3 (9 cases, 27%), and 4 + 4 (2 cases, 6%). In post-treatment needle biopsies, 33 cases (100%) showed variable degrees of fibrosis ranging from mild to moderate. Twenty-four of 33 cases (73%) showed necrosis usually associated with acute and/or chronic inflammation. Histological examination of benign glands revealed glandular heterogeneity including atrophy and basal cell hyperplasia. Eight cases (24%) had residual prostatic adenocarcinoma after treatment, of which 4 cases were assigned Gleason score: ≥3 + 4. In cases with residual adenocarcinoma, 8 cases (100%) showed nuclear enlargement, 5 cases (63%), cytoplasmic vacuolization, and 1 case (13%) showed nuclear pyknosis; otherwise, no discernible effects of treatment were seen. Morphological alterations included a spectrum of changes ranging from extensive coagulative stromal necrosis secondary to thermal injury to atrophic changes in benign prostatic tissue after HIFU treatment. Our findings also support the hypothesis that HIFU failure results from inadequate targeting rather than failure within a treated zone.

Focal High-Intensity Focused Ultrasound Ablation of the Prostate.

With the advancement of early detection tools for prostate cancer and ability to better localize disease, there has been increased interest in focal or targeted therapies that carry less morbidity than traditional whole-gland treatments. The Sonablate® high-intensity focused ultrasound (HIFU) device has Food and Drug Administration (FDA) 510(K) clearance in the United States for ablation of prostate tissue. HIFU utilizes an ultrasound (US) transducer that focuses US beams on a preset point as much as 4 cm from the energy source without injuring intervening tissue. The Sonablate system guides the surgeon step-by-step to perform effective ablation of a target lesion. The surgeon can assess treatment effect with tissue change monitoring, and care is taken to prevent rectal wall injury. We believe hemiablation is the most favorable focal HIFU treatment to optimize cancer control and minimize the side effects associated with whole gland therapy. We recommend considering HIFU ablation as an extension of active surveillance rather than definitive treatment. Further research on long-term oncologic and functional outcomes is warranted.

Folate-targeted intraoperative fluorescence, OTL38, in robotic-assisted laparoscopic partial nephrectomy.

OBJECTIVE: To investigate the safety and efficacy of OTL38, a folate-targeted, intraoperative fluorescence agent, in patients undergoing robotic-assisted laparoscopic partial nephrectomy. METHODS: Patients with proven or suspected localized renal cell carcinoma at a single academic institution were selected from 2016 to 2018. Patients received one dose of OTL38 at 0.025 mg/kg prior to robotic-assisted laparoscopic partial nephrectomy. The da Vinci Fluorescence Imaging Vision System was used to identify the tumor and inspect for residual disease after resection. Immunohistochemistry was performed to quantify folate receptor alpha in both the tumor and surrounding normal parenchyma. Patient follow-up was 1 month. Outcome data included descriptive statistics of the patient cohort and surgeon and pathologist surveys. RESULTS: Ten cases were performed. Mean patient age was 62.9 years (range = 50-70). Mean tumor size was 2.45 cm. Pathologic tumor stages ranged from T1a-T3a. Histologic tumor types included clear cell, chromophobe, type 1 papillary renal cell carcinoma and oncocytoma. The tumors did not fluoresce, while the surrounding normal parenchyma did show fluorescence. No adverse reactions were seen. Staining for folate receptor alpha was localized to the proximal renal tubules. Average staining in normal surrounding renal parenchyma was significantly greater than staining observed in tumor tissue (0.2086 vs 0.0467; p = 0.002). The mean difference in staining between tumor tissue and surrounding normal renal parenchyma was 0.1619 (95% CI = 0.0796-0.2442). CONCLUSIONS: Based on our initial experience, OTL38 shows potential as a safe, effective and easy to use tool to improve visualization and resection of renal tumors.

Delaying Cancer Cases in Urology during COVID-19: Review of the Literature.

PURPOSE: Coronavirus disease 2019 (COVID-19) is a global pandemic affecting hospital systems and the availability of resources for surgical procedures. Our aim is to provide guidance for urologists to help prioritize urological cancer surgeries. MATERIALS AND METHODS: We reviewed published literature on bladder cancer, upper tract urothelial carcinoma, penile cancer, testis cancer, prostate cancer, renal cancer and adrenal cancer. RESULTS: For muscle invasive bladder cancer delays should be less than roughly 10 weeks and neoadjuvant chemotherapy should be considered. Patients with nonmuscle invasive bladder cancer should be counseled appropriately based on risk and intravesical therapies can continue. Upper tract urothelial carcinoma should also be treated with minimal delays for high risk patients, especially with ureteral tumors. Surgery for T1 renal cancers when indicated can be delayed until adequate resources are available. Patients with T2 renal cancer should be considered for early surgery if there are unfavorable preoperative characteristics. Higher stage renal tumors should be considered for early surgery. An early multidisciplinary approach is recommended for metastatic renal cancers. High risk prostate cancer may need preferential treatment and consideration of neoadjuvant hormonal therapy. Penile cancer can have worse sexual or oncologic outcomes with prolonged surgical delay. Likewise, adrenal cancer is aggressive and needs early surgical treatment. Testicular cancer should be treated in a timely manner with surgery or chemotherapy, as indicated. CONCLUSIONS: This review should further assist urologists in recognizing patients with potentially aggressive tumor biology that warrants early treatment.

Predictors of Prostate-specific Membrane Antigen (PSMA/FOLH1) Expression in a Genomic Database.

OBJECTIVE: To assess predictors of prostate-specific membrane antigen (PSMA) expression in a genomic database; positron emission tomography with PSMA-targeted radiopharmaceuticals is increasingly being utilized. METHODS: The de-identified Decipher Biosciences database, which includes expression for more than 46,000 coding and noncoding genes per patient, was queried for expression of FOLH1 (PSMA). Prostate cancer patients who underwent radical prostatectomy and received the Decipher Test were included in the analysis. PSMA expression was compared to the Gleason Grade Group, Decipher risk category (a validated 22 biomarker genomic score), basal versus luminal molecular subtype, and androgen receptor activity. Multivariable regression analyses were performed. RESULTS: The Decipher de-identified Decipher Biosciences database contained 16,807 men who underwent prostatectomy with the average age being 65-year old and most being Gleason Grade Group 2 (35%) or 3 (27%). Higher Grade Group was associated with higher PSMA expression except in Grade Group 5 [Grade group: 1 (0.66), 2 (0.84), 3 (0.99), 4 (1.07), 5 (0.99), P <.001]. Luminal subtype was found to have much higher PSMA expression when compared to basal (1.01 vs 0.68, P <.001). The androgen receptor activity signature demonstrated a dramatic difference between basal (0.19) and luminal (0.62) subtypes (P <.001). In the multivariable model, luminal patients, high androgen receptor activity scores, and high Grade Groups were significantly associated with higher FOLH1 percentile rank (P <.001). CONCLUSION: High PSMA expression (FOLH1) was associated with high androgen receptor activity and luminal subtype. Genomic tests could aid in predicting, interpreting, and/or directing PSMA theranostics.

Robotic and open partial nephrectomy for intermediate and high complexity tumors: a matched-pairs comparison of surgical outcomes at a single institution.

Objective: To compare peri-operative factors and renal function following open partial nephrectomy (OPN) and robotic partial nephrectomy (RPN) for intermediate and high complexity tumors when controlling for tumor and patient complexity.Methods: A retrospective review of 222 patients undergoing partial nephrectomy was performed. Patients with intermediate (nephrometry score NS 7-9) or high (NS 10-12) complexity tumors were matched 2:1 for RPN:OPN using NS, Charlson Comorbidity Index (CCI), and BMI. Patient demographics, peri-operative values, renal function, and complication rates were analyzed and compared.Results: Seventy-four OPN patients were matched to 148 RPN patients with no difference in patient demographics. Estimated blood loss in OPN patients was significantly higher (368.5 vs 210.5 mL, p < 0.001) as was transfusion rate (17% vs 1.6%, p < 0.001). Warm ischemia time was longer in OPN (25.5 vs 19.7 min, p = 0.001) while operative time was reduced (200.5 vs 226.5 min, p = 0.010). RPN patients had significantly shorter hospitalizations (5.3 vs 3.0 days, p < 0.001). GFR decrease after one month was not statistically significant (12.9 vs 6.6 ml/min, p = 0.130). Clavien III-V complications incidence was higher for OPN compared to RPN although not significantly (20.3% vs 10.8%, p = 0.055).Conclusion: When matching for tumor and patient complexity, RPN patients had fewer high grade post-operative complications, decreased blood loss, and shorter hospitalizations. RPN is a safe option for patients with intermediate and high complexity tumors.

Renal Volume Loss During Partial Nephrectomy Due to Resected Healthy Parenchyma: A Tool for Quick Estimation.

Purpose: Our objective is to evaluate a technique for estimating the amount of healthy margin resected during partial nephrectomy (PN). Materials and Methods: The resected healthy margin volume was determined by planimetry (gold standard), which was performed in a prospective manner on 30 freshly resected renal masses by cross-sectional slicing every ∼5 mm. A single cross-sectional slice containing the largest tumor diameter (bivalved tumor) was chosen to build a model for estimating the amount of healthy kidney removed. This single-slice technique was then applied to a second series of patients (n = 39) status post PN. Three-dimensional models were created using pre- and postoperative CT scans to determine the overall volume loss following PN. Results: The median (range) for tumor diameter and tumor volume was 3.2 cm (1-6.1) and 10.7 cm3 (0.5-101.9), respectively, for the 30 PN specimens used to build the single-slice estimation equation. The median (range) healthy margin volume calculated by planimetry and single slice technique was 9.0 cm3 (1.0-22.1) and 7.8 cm3 (1.0-31.0), respectively (p = 0.37). The Pearson correlation was 0.84, and the median (range) percent difference between the planimetry and single slice techniques was -0.5% (-39% to 57%). For the 39 PN patients, the median (range) total renal volume loss, 25.8 cm3 (3-79), was significantly greater than the volume of healthy margin removed during resection, 5.7 cm3 (1-22), p < 0.001. Conclusions: The healthy margin resected during PN differs widely and can be estimated from a single cross-section. The healthy margin resected accounted for <50% of the total volume loss seen during PN.

[68Ga]Ga-P16-093 as a PSMA-Targeted PET Radiopharmaceutical for Detection of Cancer: Initial Evaluation and Comparison with [68Ga]Ga-PSMA-11 in Prostate Cancer Patients Presenting with Biochemical Recurrence.

PURPOSE: This study was undertaken to evaluate radiation dosimetry for the prostate-specific membrane antigen targeted [68Ga]Ga-P16-093 radiopharmaceutical, and to initially assess agent performance in positron emission tomography (PET) detection of the site of disease in prostate cancer patients presenting with biochemical recurrence. PROCEDURES: Under IND 133,222 and an IRB-approved research protocol, we evaluated the biodistribution and pharmacokinetics of [68Ga]Ga-P16-093 with serial PET imaging following intravenous administration to ten prostate cancer patients with biochemical recurrence. The recruited subjects were all patients in whom a recent [68Ga]Ga-PSMA-11 PET/X-ray computed tomography (CT) exam had been independently performed under IND 131,806 to assist in decision-making with regard to their clinical care. Voided urine was collected from each subject at ~ 60 min and ~ 140 min post-[68Ga]Ga-P16-093 injection and assayed for Ga-68 content. Following image segmentation to extract tissue time-activity curves and corresponding cumulated activity values, radiation dosimetry estimates were calculated using IDAC Dose 2.1. The prior [68Ga]Ga-PSMA-11 PET/CT exam (whole-body PET imaging at 60 min post-injection, performed with contrast-enhanced diagnostic CT) served as a reference scan for comparison to the [68Ga]Ga-P16-093 findings. RESULTS: [68Ga]Ga-P16-093 PET images at 60 min post-injection provided diagnostic information that appeared equivalent to the subject's prior [68Ga]Ga-PSMA-11 scan. With both radiopharmaceuticals, sites of tumor recurrence were found in eight of the ten patients, identifying 16 lesions. The site of recurrence was not detected with either agent for the other two subjects. Bladder activity was consistently lower with [68Ga]Ga-P16-093 than [68Ga]Ga-PSMA-11. The kidneys, spleen, salivary glands, and liver receive the highest radiation exposure from [68Ga]Ga-P16-093, with estimated doses of 1.7 × 10-1, 6.7 × 10-2, 6.5 × 10-2, and 5.6 × 10-2 mGy/MBq, respectively. The corresponding effective dose from [68Ga]Ga-P16-093 is 2.3 × 10-2 mSv/MBq. CONCLUSIONS: [68Ga]Ga-P16-093 provided diagnostic information that appeared equivalent to [68Ga]Ga-PSMA-11 in this limited series of ten prostate cancer patients presenting with biochemical recurrence, with the kidneys found to be the critical organ. Diminished tracer appearance in the urine represents a potential advantage of [68Ga]Ga-P16-093 over [68Ga]Ga-PSMA-11 for detection of lesions in the pelvis.

Prostate Specific Membrane Antigen Targeted Positron Emission Tomography of Primary Prostate Cancer: Assessing Accuracy with Whole Mount Pathology.

PURPOSE: We evaluated which lesions are detected and missed on [68Ga]Ga-PSMA (prostate specific membrane antigen)-11 positron emission tomography in patients with primary prostate cancer. MATERIALS AND METHODS: Patients undergoing radical prostatectomy were enrolled in this prospective observational study. Patients underwent [68Ga]Ga-PSMA-11 positron emission tomography/computerized tomography or positron emission tomography/magnetic resonance imaging prior to surgery and received a dose of [68Ga]Ga-PSMA-11 intraoperatively for positron emission tomography of extirpated specimens. Whole mount pathology was performed with lesion and intralesion based analysis to determine the characteristics of lesions detected or not detected by PSMA positron emission tomography. Lesion volume was determined by planimetry and clinically significant lesion volume was calculated as lesion volume × fraction pattern 4/5. RESULTS: On whole mount analysis 30 cancerous lesions were found in a total of 15 patients, including 4, 15, 4, 1 and 6 which were Grade Group 1, 2, 3, 4 and 5, respectively. PSMA-positron emission tomography detected 100% of primary/index lesions and 8 of 11 (82%) secondary lesions. All Grade Group 3-5 lesions were detected vs 12 of 15 Grade Group 2 lesions. When comparing Grade Group 2 vs 3-5, lesion size was similar (p=0.48) but the standardized uptake value was lower for Grade Group 2 vs 3-5 (5.3 vs 7.9, p=0.03). The 3 missed lesions showed 10% or less of pattern 4 and a Gleason pattern 4/5 volume of less than 0.1 cm3. CONCLUSIONS: PSMA positron emission tomography detected 100% of primary/index lesions in this study. The 3 missed secondary lesions were small and had a low percent of pattern 4. This argues for further study to better understand what defines clinically significant prostate cancer, which would assist in determining whether small lesions that become challenging to detect by [68Ga]Ga-PSMA-11 positron emission tomography confer a risk to the patient.

Renorrhaphy techniques and effect on renal function with robotic partial nephrectomy.

PURPOSE: The role of robotic partial nephrectomy (RPN) is becoming increasingly prevalent in managing small renal masses. Renal functional outcomes have been reported with relation to the amount of healthy renal parenchyma resected and ischemia time; however, there is limited data on the effect of renorrhaphy on long-term renal function. Our aim is to evaluate the impact of renorrhaphy technique on renal functional outcomes. METHODS: A nonsystematic literature review was performed to retrieve articles assessing renorrhaphy techniques and renal function outcomes, specifically focusing on single-layer vs. traditional two-layer renorrhaphy. RESULTS: Performing single-layer renorrhaphy while omitting cortical renorrhaphy appears to improve renal function postoperatively, based on very limited studies in the literature that were evaluated. CONCLUSION: Single-layer renorrhaphy may be associated with improved postoperative renal function and could prove to be useful in patients with chronic renal insufficiency or solitary kidney. The ongoing clinical trial NCT02131376 may provide further information on the impact of renorrhaphy technique on long-term renal function.

A novel preoperative model to predict 90-day surgical mortality in patients considered for renal cell carcinoma surgery.

INTRODUCTION: Surgical benefits for renal cell carcinoma must be weighed against competing causes of mortality, especially in the elderly patient population. We used a large cancer registry to evaluate the impact of patient and cancer-specific factors on 90-day mortality (90DM). A nomogram to predict the odds of short-term mortality was created. MATERIALS AND METHODS: The National Cancer Database was queried to identify all patients with clinically localized, nonmetastatic disease treated with partial or radical nephrectomy. Using a random sample of 60%, multiple logistic regression with 90DM outcomes were performed to identify preoperative variables associated with mortality. Variables included age, sex, race, co-morbidity score, tumor size, and presence of a thrombus. A nomogram was created and tested on the remaining 40% of patients to predict 90DM. RESULTS: 183,407 patients met inclusion criteria. Overall 90DM for the cohort was 1.9%. All preoperative variables significantly influenced the risk of 90DM. Patient age was by far the strongest predictor. Nomogram scores ranged from 0 to 12. Compared to patients with 0 to 1 points, those with 2 to 3 (odds ratio [OR] 2.89, 2.42-3.46; P < 0.001), 4 to 5 (OR 6.25, 5.26-7.43; P < 0.001), and >6 (OR 12.86, 10.83-15.27; P < 0.001) were at incrementally significantly higher odds of 90DM. Being >80 years of age alone placed patients into the highest risk of surgical mortality. CONCLUSIONS: Management of localized kidney cancer must consider competing causes of mortality, especially in elderly patients with multiple co-morbidities. We present a preoperative tool to calculate risk of surgical short-term mortality to aid surgeon-patient counseling.

Assessing Cost of Robotic Utilization in Partial Nephrectomy with Increasing Utilization.

PURPOSE: To evaluate trends in utilization of robotic assistance in partial nephrectomy (PN) and assess the association between cost and utilization. PATIENTS AND METHODS: Using the 2009-2012 Nationwide Inpatient Sample database, we identified all adult (>17 years) patients undergoing PN for localized primary renal malignancy. Coding for robotic assistance (17.4 × ) began in the final quarter of 2008. The primary outcome was total hospital cost exclusive of physician fees. A multiple linear regression model was used to adjust for patient and hospital characteristics. RESULTS: Between 2009 and 2012, there were 32,664 (58%) open, 3498 (6%) laparoscopic, and 20,350 (36%) robot-assisted partial nephrectomies performed in the United States. Between 2009 and 2012, the total number of partial nephrectomies semiannually increased by 93% (5114-9845) with robotic partial nephrectomies (RPNs) representing >80% of the increase. RPN increased from 1029 cases in the first half of 2009 to 4840 in the last half of 2012 and surpassed utilization of open nephrectomy. The proportion of all partial nephrectomies performed with robotic assistance increased from 20% to 49% during the same period. After adjusting for demographics, Charlson comorbidity index, and hospital region, RPN went from $1,464 (p = 0.009) more than open in 2009 to $456 (p = 0.28) less than open in 2012. CONCLUSIONS: Utilization of RPN surpassed open in 2012 in the United States. The difference in cost between the robotic and open approaches decreased during the study period and by 2011 was not statistically different.

Impact of positive surgical margins on overall survival after partial nephrectomy-A matched comparison based on the National Cancer Database.

INTRODUCTION: The impact of positive surgical margins (PSM) in partial nephrectomy (PN) has been a controversy. Previous studies on the relationship between PSM and overall survival (OS) were either underpowered or had highly dissimilar groups. We used the National Cancer Database with propensity score matching to determine the association between PSM and OS after PN. MATERIALS AND METHODS: We identified patients with T1/T2 N0M0 renal cancer treated with PN between 2004 and 2009, and divided them into 2 groups based on their margin status. We used propensity score matching to ensure similarities in age, comorbidity score (CCI), tumor size, histology, and grade between groups. Covariates were compared by χ2 test. Cox multiple regression was used to estimate the hazard ratios (HR) for all-cause mortality. OS between matched groups were compared by log-rank, Breslow and Tarone-Ware tests. RESULTS: After excluding those with missing data on margin or survival status, 20,762 patients were eligible for matching. Each matched group had 1,265 patients, similar in age, sex, race, CCI, tumor size, histology, and grade. There were 386 recorded all-cause mortalities over a median follow-up duration of 72.6 months. Cox multiple regression showed a higher risk of all-cause mortality among cases with PSM (HR: 1.393, P = 0.001). Old age, high CCI, and large tumors had higher risks, while papillary and chromophore histologic subtypes had lower risks. PSM was associated with significantly worse OS by log-rank, Breslow, and Tarone-Ware tests. CONCLUSION: PSM is associated with significantly worse OS after PN.

Intraoperative Mannitol Not Essential During Partial Nephrectomy.

OBJECTIVE: Intraoperative mannitol is routinely administered for renoprotection in partial nephrectomy (PN). However, there is a paucity of evidence supporting mannitol's renoprotective effect. We performed a retrospective study of mannitol's efficacy in PN. MATERIALS AND METHODS: Using an institutional database, patients undergoing PN from 2006 to 2016 were retrospectively identified and divided into two groups based on mannitol use. Cases with missing serum creatinine measurements were excluded. Mannitol use was dependent on surgeon preference. An independent-samples t-test was used to compare 6-month postoperative estimated glomerular filtration rate (eGFR) between mannitol groups and to compare 6-month eGFR between mannitol dose for patients who received mannitol. Multivariate linear regression was used to estimate 6-month eGFR when adjusting for multiple covariates that were considered clinically relevant to postoperative renal function. RESULTS: Of the patients, 476 patients were eligible for analysis and 286 received mannitol. Preoperative eGFR (7.8 ± 21.4 mL/minute/1.73 m2 vs 75.3 ± 23.1 mL/minute/1.73 m2, p = 0.223) and tumor size (3.5 ± 1.7 cm vs 3.4 ± 1.5 cm, p = 0.532) were matched between the mannitol (M+) and no mannitol (M-) groups, whereas warm ischemic time (22.5 ± 11.2 minutes vs 15.0 ± 10.2 minutes, p < 0.001) was longer in the M+ group. There was no significant difference in 6-month eGFR between mannitol groups (70.6 ± 22.2 mL/minute/1.73 m2 vs 68.0 ± 23.9 mL/minute/1.73 m2, p = 0.225). No significant association between mannitol dose and 6-month eGFR was found. Covariates that significantly predicted 6-month eGFR in our multivariate model were age (ß = 0.052, p = 0.042) and preoperative eGFR (ß = 0.843, p < 0.001). In addition, neither the use of renal cooling nor the surgical approach (open vs minimally invasive) was significantly associated with 6-month eGFR. CONCLUSION: Mannitol did not demonstrate renoprotective effects based on analysis of 6-month postoperative eGFR. In addition, neither the surgical approach nor the use of renal cooling significantly predicted postoperative renal function.