Searched for: person:huangw06
in-biosketch:true
Treatment of Low-grade Intermediate-risk Nonmuscle-invasive Bladder Cancer With UGN-102 ± Transurethral Resection of Bladder Tumor Compared to Transurethral Resection of Bladder Tumor Monotherapy: A Randomized, Controlled, Phase 3 Trial (ATLAS)
Prasad, Sandip M; Huang, William C; Shore, Neal D; Hu, Brian; Bjurlin, Marc; Brown, Gordon; Genov, Pencho; Shishkov, Dimitar; Khuskivadze, Alexandre; Ganev, Tosho; Marchev, Dobri; Orlov, Igor; Kopyltsov, Evgeny; Zubarev, Vadim; Nosov, Alexander; Komlev, Dmitrii; Burger, Brent; Raju, Sunil; Meads, Andrew; Schoenberg, Mark
PURPOSE:Low-grade intermediate-risk nonmuscle-invasive bladder cancer is a chronic illness commonly treated by repetitive transurethral resection of bladder tumor. We compared the efficacy and safety of intravesical chemoablation with UGN-102 (a reverse thermal gel containing mitomycin), with or without subsequent transurethral resection of bladder tumor, to transurethral resection of bladder tumor alone in patients with low-grade intermediate-risk nonmuscle-invasive bladder cancer. MATERIALS AND METHODS:This prospective, randomized, phase 3 trial recruited patients with new or recurrent low-grade intermediate-risk nonmuscle-invasive bladder cancer to receive initial treatment with either UGN-102 once weekly for 6 weeks or transurethral resection of bladder tumor. Patients were followed quarterly by endoscopy, cytology, and for-cause biopsy. The primary end point was disease-free survival. All patients were followed for adverse events. RESULTS:Trial enrollment was halted by the sponsor to pursue an alternative development strategy after 282 of a planned 632 patients were randomized to UGN-102 ± subsequent transurethral resection of bladder tumor (n=142) or transurethral resection of bladder tumor monotherapy (n=140), rendering the trial underpowered to perform hypothesis testing. Patients were predominantly male and ≥65 years of age. Tumor-free complete response 3 months after initial treatment was achieved by 92 patients (65%) who received UGN-102 and 89 patients (64%) treated by transurethral resection of bladder tumor. The estimated probability of disease-free survival 15 months after randomization was 72% for UGN-102 ± transurethral resection of bladder tumor and 50% for transurethral resection of bladder tumor (hazard ratio 0.45). The most common adverse events (incidence ≥10%) in the UGN-102 group were dysuria, micturition urgency, nocturia, and pollakiuria. CONCLUSIONS:Primary, nonsurgical chemoablation with UGN-102 for the management of low-grade intermediate-risk nonmuscle-invasive bladder cancer offers a potential therapeutic alternative to immediate transurethral resection of bladder tumor monotherapy and warrants further investigation.
PMID: 37548555
ISSN: 1527-3792
CID: 5558712
Editorial Commentary
Persily, Jesse B.; Huang, William C.
SCOPUS:85164974344
ISSN: 2352-0779
CID: 5548552
Stimulated Raman histology as a method to determine the adequacy of renal mass biopsy and identify malignant subtypes of renal cell carcinoma
Mannas, Miles P; Deng, Fang-Ming; Belanger, Eric C; Jones, Derek; Ren, Joyce; Huang, William; Orringer, Daniel A; Taneja, Samir S
INTRODUCTION/BACKGROUND:Renal tumor biopsy requires adequate tissue sampling to aid in the investigation of small renal masses. In some centers the contemporary nondiagnostic renal mass biopsy rate may be as high as 22% and may be as high as 42% in challenging cases. Stimulated Raman Histology (SRH) is a novel microscopic technique which has created the possibility for rapid, label-free, high-resolution images of unprocessed tissue which may be viewed on standard radiology viewing platforms. The application of SRH to renal biopsy may provide the benefits of routine pathologic evaluation during the procedure, thereby reducing nondiagnostic results. We conducted a pilot feasibility study, to assess if renal cell carcinoma (RCC) subtypes may be imaged and to see if high-quality hematoxylin and eosin (H&E) could subsequently be generated. METHODS/MATERIALS/METHODS:. The cores were then processed as per routine pathologic protocols. The SRH images and hematoxylin and eosin (H&E) slides were then viewed by a genitourinary pathologist. RESULTS:The SRH microscope took 8 to 11 minutes to produce high-quality images of the renal biopsies. Total of 25 renal tumors including 1 oncocytoma, 3 chromophobe RCC, 16 clear cells RCC, 4 papillary RCC, and 1 medullary RCC were included. All renal tumor subtypes were captured, and the SRH images were easily differentiated from adjacent normal renal parenchyma. High quality H&E slides were produced from each of the renal biopsies after SRH was completed. Immunostains were performed on selected cases and the staining was not affected by the SRH image process. CONCLUSION/CONCLUSIONS:SRH produces high quality images of all renal cell subtypes that can be rapidly produced and easily interpreted to determine renal mass biopsy adequacy, and on occasion, may allow renal tumor subtype identification. Renal biopsies remained available to produce high quality H&E slides and immunostains for confirmation of diagnosis. Procedural application has promise to decrease the known rate of renal mass nondiagnostic biopsies, and application of convolutional neural network methodology may further improve diagnostic capability and increase utilization of renal mass biopsy among urologists.
PMID: 37225634
ISSN: 1873-2496
CID: 5508442
Editorial Commentary
Persily, Jesse B; Huang, William C
PMID: 37155951
ISSN: 2352-0787
CID: 5544502
Incidence of Benign Renal Masses in a Contemporary Cohort of Patients Receiving Partial Nephrectomy for Presumed Renal Cell Carcinoma
Vijay, Varun; Vokshi, Fjolla Hyseni; Smigelski, Michael; Nagpal, Shavy; Huang, William C
INTRODUCTION/BACKGROUND:Over the past decade and a half, advances in diagnostic imaging as well as an increased utilization of active surveillance (AS) and renal mass biopsy (RMB) have led to an improved ability to identify benign lesions prior to partial nephrectomy (PN). We seek to examine the incidence of benign pathology at the time of PN in a contemporary cohort of patients undergoing PN for presumed renal cell carcinoma (RCC). PATIENTS AND METHODS/METHODS:We performed a chart review on a prospectively maintained database on a series of patients who underwent PN between January 1, 2006 and December 31, 2021 for solid renal masses concerning for RCC. RESULTS:One thousand two hundred twenty-nine patients were included in the analysis, with 240 patients (19.2%) identified to have benign disease on final pathology. Of patients with benign disease, (23%) of patients had angiomyolipoma (AML) and 64% had oncocytoma. Between 2006 and 2021, there was a significant increase in the incidence of benign pathology after PN. When examining 3-year rolling averages over this same time period, the incidence of oncocytoma appeared to increase while the incidence of AML decreased. CONCLUSION/CONCLUSIONS:Despite improvements in diagnostic tools and increased utilization of active surveillance, the overall incidence of benign pathology, particularly oncocytoma, did not decrease over time in this contemporary cohort of patients undergoing PN.
PMID: 36535809
ISSN: 1938-0682
CID: 5394592
Single-cell analysis of localized prostate cancer patients links high Gleason score with an immunosuppressive profile
Adorno Febles, Victor R; Hao, Yuan; Ahsan, Aarif; Wu, Jiansheng; Qian, Yingzhi; Zhong, Hua; Loeb, Stacy; Makarov, Danil V; Lepor, Herbert; Wysock, James; Taneja, Samir S; Huang, William C; Becker, Daniel J; Balar, Arjun V; Melamed, Jonathan; Deng, Fang-Ming; Ren, Qinghu; Kufe, Donald; Wong, Kwok-Kin; Adeegbe, Dennis O; Deng, Jiehui; Wise, David R
BACKGROUND:Evading immune surveillance is a hallmark for the development of multiple cancer types. Whether immune evasion contributes to the pathogenesis of high-grade prostate cancer (HGPCa) remains an area of active inquiry. METHODS:Through single-cell RNA sequencing and multicolor flow cytometry of freshly isolated prostatectomy specimens and matched peripheral blood, we aimed to characterize the tumor immune microenvironment (TME) of localized prostate cancer (PCa), including HGPCa and low-grade prostate cancer (LGPCa). RESULTS: TILs. The PCa TME was infiltrated by macrophages but these did not clearly cluster by M1 and M2 markers. CONCLUSIONS:T cell exhaustion in localized PCa, a finding enriched in HGPCa relative to LGPCa. These studies suggest a possible link between the clinical-pathologic risk of PCa and the associated TME. Our results have implications for our understanding of the immunologic mechanisms of PCa pathogenesis and the implementation of immunotherapy for localized PCa.
PMID: 36988342
ISSN: 1097-0045
CID: 5463282
Impact of 3D printed models on quantitative surgical outcomes for patients undergoing robotic-assisted radical prostatectomy: a cohort study
Wake, Nicole; Rosenkrantz, Andrew B; Huang, Richard; Ginocchio, Luke A; Wysock, James S; Taneja, Samir S; Huang, William C; Chandarana, Hersh
BACKGROUND:Three-dimensional (3D) printed anatomic models can facilitate presurgical planning by providing surgeons with detailed knowledge of the exact location of pertinent anatomical structures. Although 3D printed anatomic models have been shown to be useful for pre-operative planning, few studies have demonstrated how these models can influence quantitative surgical metrics. OBJECTIVE:To prospectively assess whether patient-specific 3D printed prostate cancer models can improve quantitative surgical metrics in patients undergoing robotic-assisted radical prostatectomy (RARP). METHODS:Patients with MRI-visible prostate cancer (PI-RADS V2 ≥ 3) scheduled to undergo RARP were prospectively enrolled in our IRB approved study (n = 82). Quantitative surgical metrics included the rate of positive surgical margins (PSMs), operative times, and blood loss. A qualitative Likert scale survey to assess understanding of anatomy and confidence regarding surgical approach was also implemented. RESULTS:The rate of PSMs was lower for the 3D printed model group (8.11%) compared to that with imaging only (28.6%), p = 0.128. The 3D printed model group had a 9-min reduction in operating time (213 ± 42 min vs. 222 ± 47 min) and a 5 mL reduction in average blood loss (227 ± 148 mL vs. 232 ± 114 mL). Surgeon anatomical understanding and confidence improved after reviewing the 3D printed models (3.60 ± 0.74 to 4.20 ± 0.56, p = 0.62 and 3.86 ± 0.53 to 4.20 ± 0.56, p = 0.22). CONCLUSIONS:3D printed prostate cancer models can positively impact quantitative patient outcomes such as PSMs, operative times, and blood loss in patients undergoing RARP.
PMID: 36749368
ISSN: 2366-0058
CID: 5420812
Prostate magnetic resonance imaging-targeted biopsy global grade correlates better than highest grade with prostatectomy grade
Ren, Joyce; Melamed, Jonathan; Taneja, Samir S; Wysock, James S; Huang, William C; Lepor, Herbert; Deng, Fang-Ming
BACKGROUND:Magnetic resonance imaging (MRI)-targeted prostate biopsy has become an increasingly common method of diagnosing prostate cancer. A previous study from our institution demonstrated that the biopsy global Grade Group (gGG, aggregate GG of all positive cores) and highest Grade Group (hGG in any core) both show substantial concordance with the Grade Group at radical prostatectomy (RPGG) while the discordance predominantly consists of upgrading in gGG and downgrading in hGG. We performed a larger cohort study focused on biopsy cases in which gGG and hGG differ, to determine their relative concordance with RPGG. METHODS:We conducted a retrospective review of radical prostatectomy specimens with prior MRI-targeted biopsies from our institution between 2016 and 2020. Separate gGG and hGG were assigned to each MRI-targeted lesion. Targeted lesions with different gGG versus hGG were segregated from those with identical gGG and hGG. The concordance of biopsy GG with RPGG was evaluated using κ coefficient analysis. RESULTS:Of the 489 lesions with MRI-targeted biopsies, 82 (17%) differed in gGG versus hGG. The gGG of 46 (56%), 33 (40%), and 3 (4%) lesions were unchanged, upgraded, and downgraded at radical prostatectomy, respectively (κ= 0.302, weighted κ = 0.334). The hGG of 24 (29%), 9 (11%), and 49 (60%) lesions were unchanged, upgraded, and downgraded at radical prostatectomy, respectively (κ = 0.040, weighted κ = 0.198). When stratified by the biopsy GG, gGG showed the highest concordance in GG2 (61%) and GG3 (54%) lesions. The hGG resulted in substantial downgrading (60%) with less optimal concordance regardless of the biopsy GG. Neither the prebiopsy prostate specific antigen level nor the PI-RADS score was predictive of upgrading of gGG. CONCLUSIONS:When gGG and hGG differ, gGG method more accurately predicts the RPGG than hGG, particularly in GG2 and GG3 lesions which comprised the majority of targeted lesions.
PMID: 36461793
ISSN: 1097-0045
CID: 5374232
A prospective study of cancer detection rates following early repeat imaging and biopsy of PI-RADS 4 and 5 regions of interest exhibiting no clinically significant prostate cancer on prior biopsy
Becher, Ezequiel; Wysock, James S.; Taneja, Samir S.; Huang, William C.; Lepor, Herbert
Introduction: We aimed to determine cancer detection rates following early repeat multiparametric magnetic resonance imaging (mpMRI) and biopsy of Prostate Imaging-Reporting and Data System (PI-RADS), v2.1 4 and 5 regions of interest (ROI) exhibiting no clinically significant prostate cancer (csPCa) on prior biopsy and to identify predictors for these missed csPCa. Methods: Between January 2019 and August 2020, 36 men with 38 PI-RADS 4 or 5 ROI with no evidence of csPCa (defined as Gleason grade group [GGG] >1) on prior MRI fusion target biopsy (MRFTB) + systematic biopsy (SB) were invited to participate in the present prospective study. All men underwent repeat mpMRI and persistent PI-RADS >2 ROI were advised to undergo repeat MRFTB+SB. Cancer detection rates of any and csPCa were determined. Relative risk was calculated to analyze association of baseline variables with the finding of csPCa on repeat biopsy. Results: Of the 38 initial PI-RADS 4 and 5 ROI, on followup mpMRI, 14 were downgraded to PI-RADS 1/2 and, per protocol, did not undergo repeat biopsy and; eight (33%), 12 (50%), and four (17%) were PI-RADS 3, 4, and 5 respectively. Of these 24 persistently suspicious mpMRI ROI, 20 (83%) underwent repeat biopsy and six (30%), six (30%), and eight (40%) were benign, GGG 1, and GGG >1, respectively. Only prostate-specific antigen ≥10 ng/mL was a predictor for missed csPCa. Conclusions: Our prospective study supports a recommendation for early repeat mpMRI of all PI-RADS 4 or 5 ROI exhibiting no csPCa, with repeat MRFTB + SB of persistent PI-RADS >2 ROI .
SCOPUS:85137682855
ISSN: 1911-6470
CID: 5330462
Axumin (18F-Fluciclovine) PET imaging in men exhibiting no clinically significant cancer on initial negative biopsy of PI-RADS 4 and 5 regions of interest
Becher, Ezequiel; Karls, Shawn; Tong, Angela; Wysock, James S; Taneja, Samir S; Huang, William C; Lepor, Herbert
PURPOSE/OBJECTIVE:F-Fluciclovine) PET/MRI informs the decision to perform an early repeat biopsy of PI-RADS 4/5 region of interest (ROI) exhibiting no clinically significant prostate cancer (csPCa) on initial biopsy. METHODS:This prospective study enrolled men with at least one PI-RADS 4/5 ROI on multi-parametric MRI and no csPCa on prior biopsy defined as Gleason grade group (GGG) > 1. All men underwent an Axumin PET/MRI and only-persistent PI-RADS > 2 ROI were advised to undergo a repeat biopsy. A PET cancer suspicion score (PETCSS) was internally developed to stratify PET avid lesions according to their suspicion of harboring csPCa. The sensitivity, specificity, positive (PPV) and negative predictive value (NPV) of the PETCSS for predicting csPCa were assessed. Relative risk was calculated to analyze the association of baseline variables with csPCa on repeat biopsy. RESULTS:Thirty-eight ROI on 36 enrolled men were analyzed. Fourteen (36.8%) were downgraded to PI-RADS 1/2 and were not subjected to repeat biopsy. Thirteen (92.9%) of these downgraded scans also exhibited low-risk PETCSS. Overall, 18/22 (81.2%) subjects underwent a repeat per protocol biopsy. Of the 20 ROI subjected to repeat biopsy, eight (40%) were found to harbour csPCa. The sensitivity, specificity, PPV and NPV of the PETCSS were 50, 50, 40, and 60%, respectively. No predictor of csPCa was found in the risk analysis. CONCLUSION/CONCLUSIONS:Our pilot study showed that both MRI and PET sequences have limited performance for identifying those persistently suspicious PI-RADS 4/5 ROI that are found to harbor csPCa on repeat biopsy.
PMCID:9532230
PMID: 36197506
ISSN: 1433-8726
CID: 5357902