Primary Whole-gland Ablation for the Treatment of Clinically Localized Prostate Cancer: A Focal Therapy Society Best Practice Statement.

CONTEXT: Whole-gland ablation is a feasible and effective minimally invasive treatment for localized prostate cancer (PCa). Previous systematic reviews supported evidence for favorable functional outcomes, but oncological outcomes were inconclusive owing to limited follow-up. OBJECTIVE: To evaluate the real-world data on the mid- to long-term oncological and functional outcomes of whole-gland cryoablation and high-intensity focused ultrasound (HIFU) in patients with clinically localized PCa, and to provide expert recommendations and commentary on these findings. EVIDENCE ACQUISITION: We performed a systematic review of PubMed, Embase, and Cochrane Library publications through February 2022 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. As endpoints, baseline clinical characteristics, and oncological and functional outcomes were assessed. To estimate the pooled prevalence of oncological, functional, and toxicity outcomes, and to quantify and explain the heterogeneity, random-effect meta-analyses and meta-regression analyses were performed. EVIDENCE SYNTHESIS: Twenty-nine studies were identified, including 14 on cryoablation and 15 on HIFU with a median follow-up of 72 mo. Most of the studies were retrospective (n = 23), with IDEAL (idea, development, exploration, assessment, and long-term study) stage 2b (n = 20) being most common. Biochemical recurrence-free survival, cancer-specific survival, overall survival, recurrence-free survival, and metastasis-free survival rates at 10 yr were 58%, 96%, 63%, 71-79%, and 84%, respectively. Erectile function was preserved in 37% of cases, and overall pad-free continence was achieved in 96% of cases, with a 1-yr rate of 97.4-98.8%. The rates of stricture, urinary retention, urinary tract infection, rectourethral fistula, and sepsis were observed to be 11%, 9.5%, 8%, 0.7%, and 0.8%, respectively. CONCLUSIONS: The mid- to long-term real-world data, and the safety profiles of cryoablation and HIFU are sound to support and be offered as primary treatment for appropriate patients with localized PCa. When compared with other existing treatment modalities for PCa, these ablative therapies provide nearly equivalent intermediate- to long-term oncological and toxicity outcomes, as well as excellent pad-free continence rates in the primary setting. This real-world clinical evidence provides long-term oncological and functional outcomes that enhance shared decision-making when balancing risks and expected outcomes that reflect patient preferences and values. PATIENT SUMMARY: Cryoablation and high-intensity focused ultrasound are minimally invasive treatments available to selectively treat localized prostate cancer, considering their nearly comparable intermediate- to long term cancer control and preservation of urinary continence to other radical treatments in the primary setting. However, a well-informed decision should be made based on one's values and preferences.

Urinary Analysis of FGFR3 and TERT Gene Mutations Enhances Performance of Cxbladder Tests and Improves Patient Risk Stratification.

PURPOSE: Cxbladder tests are urinary biomarker tests for detection of urothelial carcinoma. We developed enhanced Cxbladder tests that incorporate DNA analysis of 6 single nucleotide polymorphisms for the FGFR3 and TERT genes, in addition to the current 5 mRNA biomarkers and clinical risk factors. MATERIALS AND METHODS: Two multicenter, prospective studies were undertaken in: (1) U.S. patients with gross hematuria aged ≥18 years and (2) Singaporean patients with gross hematuria or microhematuria aged >21 years. All patients provided a midstream urine sample and underwent cystoscopy. Samples were retrospectively analyzed using enhanced Cxbladder-Triage (risk stratifies patients), enhanced Cxbladder-Detect (risk stratifies patients and detects positive patients), and the combination enhanced Cxbladder-Triage × Cxbladder-Detect. RESULTS: In the pooled cohort (N=804; gross hematuria: n=484, microhematuria: n=320), enhanced Cxbladder-Detect had a sensitivity of 97% (95% CI 89%-100%), specificity of 90% (95% CI 88%-92%), and negative predictive value of 99.7% (95% CI 99%-100%) for detection of urothelial carcinoma. Overall, 83% of patients were enhanced Cxbladder-Detect-negative (ie, needed no further work-up). Of 133 enhanced Cxbladder-Detect-positive patients, 59 had a confirmed tumor, of which 19 were low-grade noninvasive papillary carcinoma or papillary urothelial neoplasm of low malignant potential. In total, 40 tumors were high-grade Ta, T1-T4, Tis, including concomitant carcinoma in situ. Of the 74 patients with normal cystoscopy, 41 were positive by single nucleotide polymorphism analysis. Enhanced Cxbladder-Triage and enhanced Cxbladder-Detect had significantly better specificity than the first-generation Cxbladder tests (P < .001). CONCLUSIONS: This study in ethnically diverse patients with hematuria showed the analytical validity of the enhanced Cxbladder tests.

Histopathological features of recurrent prostate adenocarcinoma after high intensity focused ultrasound (HIFU) focal treatment: A case report.

High-intensity focused ultrasound (HIFU) is a focal therapeutic approach for localised non-metastatic prostate cancer. We report a 53-year-old man who failed active surveillance of prostatic adenocarcinoma in the right lobe and underwent HIFU focal therapy. He experienced an outfield recurrence in the contralateral lobe thereafter and underwent salvage radical prostatectomy. We discuss the histopathological features in the salvage radical prostatectomy post HIFU treatment, its relationship to the outfield recurrence and the management.

Automated Needle Targeting with X-ray (ANT-X) - Robot-assisted device for percutaneous nephrolithotomy (PCNL) with its first successful use in human.

INTRODUCTION: To make percutaneous access easier in PCNL, we developed Automated Needle Targeting with X-ray (ANT-X). METHOD: ANT-X uses an image registration software with a closed loop feedback system to autoalign the puncture needle to the desired calyx using the bullseye technique. We tried percutaneous punctures on a live pig model and compared the results with free-hand technique. We then performed our first PCNL in a human subject with the aid of ANT-X. Our patient was a 48 year-old gentleman with a 1.4cm left lower pole stone. RESULTS: Initial results for live animal trial showed radiation exposure for robot-assisted arm during puncture was reduced by 26% compared to the free-hand technique (8.2mGy vs 11.2mGy). In the human trial, obtaining percutaneous access was successful at first attempt. CONCLUSION: ANT-X system can help surgeons feel confident and potentially reduce complications, hence enabling more surgeons to adopt this procedure.

Is partial nephrectomy worth performing compared to radical nephrectomy for small, localised renal cortical tumours in geriatric patients?

INTRODUCTION: This study aimed to evaluate the likelihood of progression to chronic kidney disease (CKD) in a cohort of geriatric Asian patients who underwent either partial nephrectomy (PN) or radical nephrectomy (RN) for localised pT1 kidney tumours. METHODS: Geriatric patients aged > 65 years who underwent PN or RN from 2005 to 2014 for localised kidney masses < 7 cm at a single institution were reviewed retrospectively. Preoperative and postoperative estimated glomerular filtration rates (eGFRs) were calculated using the Modification of Diet in Renal Disease Study equation. Clinicopathological data was analysed for new-onset CKD after at least five years of follow-up. Postoperative complications were measured using the modified Clavien classification system. RESULTS: Among 67 patients, 36.4% had diabetes mellitus and 80.3% had hypertension. Pre-existing CKD with eGFR ≤ 60 mL/min/1.73 m2 was present in 23.3% of PN and 43.2% of RN patients. RN and PN patients had similar postoperative morbidity. Those who underwent PN had immediate decline followed by gradual improvement of kidney function at six months after surgery. This improvement was sustained even for patients with four years of clinical follow-up. Among patients with normal preoperative kidney function, new-onset CKD after surgery was found in 20.0% and 52.9% of PN and RN patients, respectively (p = 0.007). CONCLUSION: In our study, geriatric patients who underwent PN for localised kidney mass < 7 cm had immediate decline but gradual and sustained improvement in kidney function. PN also resulted in less new-onset CKD through a five-year follow-up period.

Clinical outcomes of external beam radiotherapy in patients with localized prostate cancer: Does dose escalation matter?

BACKGROUND: To report outcomes of localized prostate cancer treated with radical external beam radiation therapy (EBRT) in our institution over a 14-year period, and to determine the impact of dose escalation of prostate cancer outcomes. METHODS: Patients with T1-T4 N0 M0 prostate cancer who received radical EBRT between January 2002 and December 2015 were reviewed retrospectively. Clinical data were obtained via the institutional electronic medical records. The primary endpoint was 5-year overall survival (OS). The secondary endpoints were 5-year freedom from biochemical failure (FFBF) and treatment toxicities. RESULTS: A total of 200 eligible patients were identified. Median follow-up duration was 48 months. 13%, 36% and 51% of patients had low-, intermediate- and high-risk disease. Median dose was 79.2 Gy. The 5-year OS were 90%, 87% and 78% and FFBF were 94%, 100% and 81% for low-, intermediate- and high-risk patients, respectively. Multivariable analysis showed that Eastern Cooperate Oncology Group performance status 2 and Gleason grade group 5 were independent predictors of worse OS. The incidence of grade ≥2 proctitis was 24.5%. Dose escalation was significantly associated with increased incidence of grade ≥2 proctitis (odd ratio, 4.42; 95% confidence interval, 1.95-10.08; P < 0.01). CONCLUSION: Men with localized prostate cancer treated with EBRT in our population had excellent 5-year OS and biochemical outcomes. Dose escalation did not significantly improve these outcomes but was associated with significantly increased risk of grade ≥2 proctitis in our population. Future studies should be performed to identify patients who will benefit the most from dose-escalated EBRT.

Management of penile cancer in a Singapore tertiary hospital.

OBJECTIVES: To present our experience of managing penile squamous cell carcinoma (SCC) in a tertiary hospital in Singapore and to evaluate the prognostic value of the inflammatory markers neutrophil-lymphocyte ratio (NLR) and lymphocyte-monocyte ratio (LMR). PATIENTS AND METHODS: We reviewed our prospectively maintained Institutional Review Board-approved urological cancer database to identify men treated for penile SCC at our centre between January 2007 and December 2015. For all the patients identified, we collected epidemiological and clinical data. RESULTS: In all, 39 patients were identified who were treated for penile SCC in our centre. The median [interquartile range (IQR)] follow-up was 34 (16.5-66) months. Although very few (23%) of our patients with high-risk clinical node-negative underwent prophylactic inguinal lymph node dissection (ILND), they still had excellent 5-year recurrence-free survival (RFS; 90%) and cancer-specific survival (CSS; 90%). At multivariate analysis, higher N stage was significantly associated with worse RFS and CSS. Patients with a high NLR (≥2.8) had significantly higher T-stage (P = 0.006) and worse CSS (P < 0.001) than those with a low NLR. Patients with a low LMR (<3.3) had significantly higher T-stage (P = 0.013) and worse RFS (P = 0.009) and CSS (P < 0.022) than those with a high LMR. CONCLUSIONS: Although very few of our patients with intermediate- and high-risk clinical node-negative SCC underwent prophylactic ILND, they still had excellent 5-year RFS and CSS. However, survival was poor in patients with node-positive disease. The pre-treatment NLR and LMR could serve as biomarkers to predict the prognosis of patients with penile cancer.

MRI Fusion-Targeted Transrectal Prostate Biopsy and the Role of Prostate-Specific Antigen Density and Prostate Health Index for the Detection of Clinically Significant Prostate Cancer in Southeast Asian Men.

OBJECTIVE: To test the hypothesis that targeted biopsy has a higher detection rate for clinically significant prostate cancer (csPCa) than systematic biopsy. We defined csPCa as any Gleason sum ≥7 cancer. In patients with Prostate Imaging Reporting and Data System (PI-RADS) 3 lesions, to determine if factors, such as prostate-specific antigen density (PSAD) and prostate health index (PHI), can predict csPCa and help select patients for biopsy. MATERIALS AND METHODS: We report the first series of targeted biopsies in Southeast Asian men, with comparison against systematic biopsy. Consecutive patients were registered into a prospective institutional review board-approved database in our institution. We reviewed patients who underwent biopsy from May 2016 to June 2017. Inclusion criteria for our study were patients with at least one PI-RADS ≥3, and who underwent both targeted and systematic biopsies in the same sitting. RESULTS: There were 115 patients in the study, of whom 74 (64.3%) had a previous negative systematic biopsy. Targeted biopsies detected significantly less Gleason 6 cancers than systematic biopsies (p < 0.01), and demonstrated significantly higher sensitivity, specificity, positive predictive value, and negative predictive value (NPV) for the detection of csPCa. For patients with PI-RADS 3 lesions, PHI and PSAD were found to be the best predictors for csPCa. PSAD <0.10 ng/mL/mL had an NPV of 93% and sensitivity of 92%, while allowing 20% of patients to avoid biopsy. PHI cutoff of <27 would allow 34% of patients to avoid biopsy, with both sensitivity and NPV of 100%. CONCLUSIONS: Targeted prostate biopsies were found to be significantly superior to systematic biopsies for the detection of csPCa, while detecting less Gleason 6 cancer. Usage of PSAD and PHI cutoff levels in patients with PI-RADS 3 lesions may enable a number of patients to avoid unnecessary biopsy.

Gland segmentation in prostate histopathological images.

Glandular structural features are important for the tumor pathologist in the assessment of cancer malignancy of prostate tissue slides. The varying shapes and sizes of glands combined with the tedious manual observation task can result in inaccurate assessment. There are also discrepancies and low-level agreement among pathologists, especially in cases of Gleason pattern 3 and pattern 4 prostate adenocarcinoma. An automated gland segmentation system can highlight various glandular shapes and structures for further analysis by the pathologist. These objective highlighted patterns can help reduce the assessment variability. We propose an automated gland segmentation system. Forty-three hematoxylin and eosin-stained images were acquired from prostate cancer tissue slides and were manually annotated for gland, lumen, periacinar retraction clefting, and stroma regions. Our automated gland segmentation system was trained using these manual annotations. It identifies these regions using a combination of pixel and object-level classifiers by incorporating local and spatial information for consolidating pixel-level classification results into object-level segmentation. Experimental results show that our method outperforms various texture and gland structure-based gland segmentation algorithms in the literature. Our method has good performance and can be a promising tool to help decrease interobserver variability among pathologists.

Upper tract urothelial carcinoma: a different disease entity in terms of management.

Upper tract urothelial carcinomas (UTUCs) consist of 5%-10% of all urothelial carcinomas, the rest being urothelial carcinomas of the bladder (UCB). There is increasing evidence to show that UTUC is a distinct disease entity from UCB based on phenotypical and genotypical (genetic and epigenetic) differences. This may account for why the natural history of UTUC is different from that of UCB, with >60% of UTUCs and only 15%-25% of UCB presenting with invasion at diagnosis. Management of UTUC is thus different from UCB in a variety of ways, ranging from surgical management, postoperative instillation therapy, postoperative surveillance and medical management (neoadjuvant and adjuvant chemotherapy). This review paper aims to highlight these differences with an emphasis on the distinct management of UTUC, along with the latest updates.

A rare case of intratesticular leiomyoma.

A 47-year-old man presented with a scrotal swelling. Ultrasonography of the testes showed that it was an extratesticular swelling. However, the swelling was intraoperatively found to be intratesticular. Histology showed an intratesticular leiomyoma, which is extremely rare.

Extent of pelvic lymph node dissection and the impact of standard template dissection on nomogram prediction of lymph node involvement.

BACKGROUND: Our current lymph node involvement (LNI) nomogram was created using patients receiving both limited and standard lymph node dissection (LND). Over time, refinements in technique could affect the diagnostic yield from LND. OBJECTIVE: Our aim was to validate our existing LNI nomogram or develop a new nomogram with updated prediction coefficients that reflect the current standard LND template during radical prostatectomy (RP). We hypothesized that the existing nomogram would demonstrate good discrimination but poor calibration in a contemporary series of standard LND. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis of 4176 consecutive primary RP patients was performed, including open procedures (3097 patients from 2000 to 2008) and laparoscopic procedures (1079 patients from 2005 to 2008). After excluding 127 patients (3%) with limited LND, 10 (0.2%) with pretreatment prostate-specific antigen (PSA) >50 ng/ml, and 318 (8%) with incomplete data, the final cohort totaled 3721 patients. The nomograms were evaluated using receiver operating characteristic analysis, calibration plots, and decision-curve analysis. INTERVENTIONS: Patients received open or laparoscopic (conventional and robot-assisted) RP and standard LND in our center. MEASUREMENTS: Assessments were obtained using preoperative PSA, biopsy Gleason score, and clinical stage. RESULTS AND LIMITATIONS: The median number of nodes removed was 11, with ∼60% of patients having at least 10 nodes removed (n=2224). Overall, 5.2% of patients (n=194) had positive lymph nodes. The new nomogram had very high discriminative accuracy (area under the curve: 0.862). The decision-curve analysis showed that the new nomogram had the highest clinical net benefit for all reasonable threshold probabilities. CONCLUSIONS: The new nomogram shows improved calibration when predicting lymph node invasion in a contemporary cohort of patients with prostate cancer exclusively treated with RP and standard LND. This nomogram will be used as the preferred predictive model for counseling patients and developing studies at our institution.

Renal oncocytosis: management and clinical outcomes.

PURPOSE: Renal oncocytosis is a rare pathological condition in which renal parenchyma is diffusely involved by numerous oncocytic nodules in addition to showing a spectrum of other oncocytic changes. We describe our experience with renal oncocytosis, focusing on management and outcomes. MATERIALS AND METHODS: A total of 20 patients with a final pathological diagnosis of renal oncocytosis from July 1995 through June 2009 were included in the analysis. Patient demographics, intraoperative variables and postoperative outcomes are reported. RESULTS: Median age at nephrectomy was 71 years (IQR 59-75). Of the patients 15 (75%) had bilateral disease. There were 23 operations (9 right side, 14 left side) performed on 20 patients, and of these procedures 13 (57%) were partial nephrectomies and 10 (43%) were radical nephrectomies. Median dominant tumor mass diameter was 4.1 cm (IQR 3-6.4, range 1 to 14.6). The most common dominant tumor histology was hybrid tumor between oncocytoma and chromophobe renal cell carcinoma in 13 of 23 specimens (57%), followed by chromophobe renal cell carcinoma in 6 (26%), oncocytoma in 3 (13%) and conventional renal cell carcinoma in 1 (4%). Ten patients (50%) had preexisting chronic kidney disease before nephrectomy and chronic kidney disease developed in 5 more after surgery. After a median followup of 35 months no patients had metastatic disease. CONCLUSIONS: Patients with renal oncocytosis usually present with multiple and bilateral renal nodules. Half of the patients had chronic kidney disease at diagnosis and 25% had new onset of chronic kidney disease. No patient had distant metastatic disease during followup. Our management approach is to perform partial nephrectomy when possible and then use careful surveillance of the remaining renal masses.

Clinical characteristics and outcomes of patients with recurrence 5 years after nephrectomy for localized renal cell carcinoma.

PURPOSE: We analyzed characteristics in patients with recurrent renal cell carcinoma 5 years or later after nephrectomy and determined predictors of survival after recurrence. MATERIALS AND METHODS: From July 1989 to October 2008 at total of 2,368 nephrectomies were done for clinically localized, unilateral renal cell carcinoma at our institution. Of 256 patients with disease recurrence 44 had recurrence 5 years or more after nephrectomy. We compared clinicopathological characteristics in patients with disease recurrence before vs after 5 years. Survival from time of recurrence was assessed based on Memorial Sloan-Kettering Cancer Center risk score, symptoms at recurrence, metastasectomy, tumor diameter, and recurrence stage and site. RESULTS: Patients with late recurrence tended to have fewer symptoms at presentation, smaller tumors (median 8.5 vs 7 cm) and less aggressive disease (pT1 in 18% vs 39%). Median overall survival was 6.1 years from time of recurrence. Five-year actuarial survival was 85% in 28 patients at favorable risk and 14% in 10 at intermediate risk (log rank p <0.001). The 5-year estimated overall survival rate was 72% in 31 patients with incidentally detected recurrence and 39% in 11 with symptoms at recurrence (log rank p = 0.01). CONCLUSIONS: Data suggest that patients with cancer recurrence 5 years after nephrectomy are at favorable risk and have long-term median survival. A favorable Memorial Sloan-Kettering Cancer Center risk score and absent symptoms related to metastasis are associated with longer survival in these patients.

Extended pelvic lymph node dissection in robotic-assisted radical prostatectomy: surgical technique and initial experience.

OBJECTIVES: To describe, and show in the accompanying video segments, a technique for extended pelvic lymph node dissection (ePLND) in robotic-assisted radical prostatectomy (RARP) and report our clinicopathologic and perioperative outcomes. The extent of pelvic lymphadenectomy during radical prostatectomy has not been standardized. However, evidence demonstrates that an ePLND yields a greater number of positive nodes. METHODS: A total of 32 patients with clinically localized prostate cancer underwent RARP with ePLND by a single surgeon (J.C.) between January and August 2008. The template for the ePLND included the obturator, hypogastric, external iliac, and common iliac lymph nodes up to the bifurcation of the aorta. Systematic review and grading of adverse events were performed. RESULTS: The median number of lymph nodes retrieved was 18 (interquartile range [IQR] 12-28). Four patients (12.5%) had lymph node metastases. Of the 4 patients with lymph node metastases, 1 patient (25%) had the involved lymph node exclusively in the common iliac region. Median operative time for the ePLND was 72 minutes (IQR 66-86). Median hospital length of stay was 2.0 days (IQR 2.0-2.8). Graded complications included 13 grade 1 events and 1 grade 2 event, with 1 grade 1 event being considered related to ePLND. No clinically presenting lymphoceles or thrombotic events were encountered. CONCLUSIONS: An ePLND during RARP is technically feasible and appears to have minimal morbidity. It produces a high lymph node yield and may result in improved pathologic staging.

Lymph node dissection during robotic-assisted laparoscopic prostatectomy: comparison of lymph node yield and clinical outcomes when including common iliac nodes with standard template dissection.

OBJECTIVE: To compare the perioperative outcomes of standard pelvic to full-template lymph node (LN) dissection (LND) during robotic-assisted laparoscopic prostatectomy (RALP). PATIENTS AND METHODS: The study included 94 patients undergoing RALP with LND between January 2007 and August 2008, by one surgeon. In February 2008 the LND template was modified to include common iliac and medial hypogastric LNs. Clinical and pathological patient characteristics were analysed, including total number of retrieved and positive LNs in each area of dissection, operative duration and complications. RESULTS: Of the 94 patients, 62 underwent standard LND (group 1) and 32 underwent full-template pelvic LND (group 2). The median (mean) number of LNs retrieved in groups 1 and 2 were 12 (13.3) and 17.5 (21.4), respectively. Of the five patients with positive LNs (5%), four were in group 2 (13%); two of these patients had positive LNs in the common iliac dissection, and for one of these patients it was the sole site of involvement. Deep venous thrombosis, pulmonary embolism or transient neuropraxia occurred in six patients (five in group 1 and one in group 2). The median additional operative time for resection of common and internal LNs was 25 min. CONCLUSIONS: LN yield increased and additional sites of LN metastases were identified during full-template pelvic LND during RALP. This modification was not associated with an increased rate of complications. Derived benefits of including additional nodal dissection and the effect on staging accuracy remain to be determined.

Omental roll-up: a technique for islet engraftment in a large animal model.

BACKGROUND: Attrition of transplanted islets is significant after hepatic embolization. This study was designed to investigate a novel surgical technique for islet transplantation into the omentum. This site allows placement of the islets in a three-dimensional (3D) matrix, with growth factors, to temporarily culture the islets in vivo while revascularization progresses. MATERIALS AND METHODS: Five female dogs (three partial and two total pancreatectomies) received an autologous islet transplant in the omentum. Islets were suspended in 1 mL of PBS containing 10 ug of vascular endothelial growth factor (VEGF). Fresh autologous plasma (10 mL) was mixed with the islet/VEGF suspension. The coagulum containing the islets and VEGF was then placed on the greater omentum. The leading edge of omentum was rolled up to secure the islet/VEGF/coagulum in position and to present the thin islet layer with two omental surfaces for implantation. Omentum was recovered at 2, 13, 21, 42, and 180 d. RESULTS: Immunohistochemical staining for synaptophysin, glucagon, and insulin confirmed the presence of transplanted islets in all omenta. Insulin and C peptide production from the omental islets was confirmed in portal venous samples, and normalization of morning glucose levels beginning on day 7 was seen in the total pancreatectomy experiment. CONCLUSIONS: Autologous islets implant in rolled-up omentum when placed as a VEGF/autologous plasma coagulum. This technique has potential benefits, including the opportunity to accelerate revascularization and to investigate local strategies for modulating the immune response.