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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

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

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/BACKGROUND: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.
PMID: 36656702
ISSN: 1911-6470
CID: 6059152

Demographic and Practice Trends of Rural Urologists in the U.S.: Implications for Workforce Policy

Garg, Tullika; Meeks, William D; Coward, R Matthew; Merrill, Suzanne B; Huang, William C; Burnett, Arthur L
INTRODUCTION/BACKGROUND:There is a shortage in the number of urologists needed to satisfy the needs of an aging U.S. POPULATION/METHODS:The urologist shortage may have a pronounced impact on aging rural communities. Our objective was to describe the demographic trends and scope of practice of rural urologists using data from the American Urological Association Census. METHODS:We conducted a retrospective analysis of American Urological Association Census survey data over a 5-year period (2016-2020), including all U.S.-based practicing urologists. Metropolitan (urban) and nonmetropolitan (rural) practice classifications were based on rural-urban commuting area codes for the primary practice location zip code. We conducted descriptive statistics of demographics, practice characteristics and specific rural-focused survey items. RESULTS:In 2020, rural urologists were older (60.9 years, 95% CI 58.5-63.3 vs 54.6 years, 95% CI 54.0-55.1) and were in practice longer (25.4 years, 95% CI 23.2-27.5 vs 21.2 years, 95% CI 20.8-21.5) than urban counterparts. Since 2016, mean age and years in practice increased for rural urologists but remained stable for urban urologists, suggesting an influx of younger urologists to urban areas. Compared with urban urologists, rural urologists had significantly less fellowship training and more frequently worked in solo practice, multispecialty groups and private hospitals. CONCLUSIONS:The urological workforce shortage will particularly impact rural communities and their access to urological care. We hope our findings will inform and empower policymakers to develop targeted interventions to expand the rural urologist workforce.
PMID: 37145722
ISSN: 2352-0787
CID: 5542262

Reply by Authors

Garg, Tullika; Meeks, William D; Coward, R Matthew; Merrill, Suzanne B; Huang, William C; Burnett, Arthur L
PMID: 37145766
ISSN: 2352-0787
CID: 5545002

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

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

A Prospective Pilot Study Investigating Performance of 18F-Fluciclovine PET Imaging for Detection of Prostate Cancer 2 Years Following Primary Partial Gland Cryoablation

Nazemi, Azadeh; Huang, William C; Wysock, James; Taneja, Samir S; Friedman, Kent; Gogaj, Rozalba; Lepor, Herbert
Purpose/UNASSIGNED:The goal of partial gland ablation (PGA) is to eradicate focal lesions of clinically significant prostate cancer (csPCa) with minimal adverse impact on functional outcomes. The primary objective of this study is to characterize the performance of 18F-Fluciclovine PET imaging for detection of prostate cancer following PGA. Materials and Methods/UNASSIGNED:Subjects 2 years following primary partial gland cryoablation (PPGCA) were invited to participate in an IRB-approved study providing they met the following inclusion criteria: a single reported mpMRI region of interest (ROI) concordant with biopsy Gleason Grade Group (GGG) < 4, no gross extra-prostatic extension on mpMRI, and no GGG > 1 or GGG 1 with a core length > 6 mm on contralateral systematic biopsy. 18F-Fluciclovine PET MRI imaging of the prostate was performed followed by in and out-of-field biopsies. Results/UNASSIGNED:Twenty-seven men who met eligibility criteria participated in the prospective study. In-field and out-of-field csPCa recurrence rate was 7.4% and 22.2%, respectively. The sensitivity and positive predictive value of mpMRI and PET imaging did not reach performance to reliably inform who should undergo prostate biopsy. Conclusion/UNASSIGNED:At 2 years following PPGCA, the rate of in-field csPCa was exceedingly low indicating a limited role for imaging to inform in-field biopsy decisions. The csPCa detection rate of out-of-field recurrence was 22% which provides an opportunity for imaging to inform out-of-field biopsy decisions. Based on our findings, 18F-Fluciclovine PET MRI cannot be used to inform who should undergo out-of-field prostate biopsy at 2 years following PPGCA.
PMCID:9276896
PMID: 35846414
ISSN: 1869-3474
CID: 5278802