An Autophagy-Targeting Chimera Induces Degradation of Androgen Receptor Mutants and AR-v7 in Castration-Resistant Prostate Cancer.

Genetic alterations play a pivotal role in various human diseases, particularly cancer. The androgen receptor (AR) is a crucial transcription factor driving prostate cancer (PCa) progression across all stages. Current AR-targeting therapies utilize competitive AR antagonists or pathway suppressors.

Impact of Gene Expression Classifier Testing on Adjuvant Treatment Following Radical Prostatectomy: The G-MINOR Prospective Randomized Cluster-crossover Trial.

Background And Objective: Decipher is a tissue-based genomic classifier (GC) developed and validated in the post-radical prostatectomy (RP) setting as a predictor of metastasis. We conducted a prospective randomized controlled cluster-crossover trial assessing the use of Decipher to determine its impact on adjuvant treatment after RP.

Methods: Eligible patients had undergone RP within 9 mo of enrollment, had pT3-4 disease and/or positive surgical margins, and prostate-specific antigen <0.

A Novel Interaction between Chemokine and Phosphoinositide Signaling in Metastatic Prostate Cancer.

Prostate cancer commonly metastasizes to bone due to its favorable microenvironment for cell growth and survival. Currently, the standard of care for metastatic prostate cancer is medical castration in conjunction with chemotherapeutic agents and newer anti-androgen/androgen receptor therapies. While these therapies aim to improve the quality of life in patients with advanced disease, resistance to these therapies is inevitable prompting the development of newer therapies to contain disease progression.

Adaptor proteins mediate CXCR4 and PI4KA crosstalk in prostate cancer cells and the significance of PI4KA in bone tumor growth.

The chemokine receptor, CXCR4 signaling regulates cell growth, invasion, and metastasis to the bone-marrow niche in prostate cancer (PCa). Previously, we established that CXCR4 interacts with phosphatidylinositol 4-kinase IIIα (PI4KIIIα encoded by PI4KA) through its adaptor proteins and PI4KA overexpressed in the PCa metastasis. To further characterize how the CXCR4-PI4KIIIα axis promotes PCa metastasis, here we identify CXCR4 binds to PI4KIIIα adaptor proteins TTC7 and this interaction induce plasma membrane PI4P production in prostate cancer cells.

Can MRI Help Inform Which Men With a History of Multifocal High-Grade Prostatic Intraepithelial Neoplasia or Atypical Small Acinar Proliferation Remain at an Elevated Risk for Clinically Significant Prostate Cancer?

Purpose: We investigated the association of MRI findings in men with a previous diagnosis of atypical small acinar proliferation (ASAP) or multifocal high-grade intraepithelial neoplasia (HGPIN) with pathologic findings on repeat biopsy.

Materials And Methods: We retrospectively reviewed patients with ASAP/multifocal HGPIN undergoing a repeat biopsy in the Michigan Urological Surgery Improvement Collaborative registry. We included men with and without an MRI after the index biopsy demonstrating ASAP/multifocal HGPIN but before the repeat biopsy.

Does Urologist-level Utilization of Active Surveillance for Low-risk Prostate Cancer Correspond with Utilization of Active Surveillance for Small Renal Masses?

Active surveillance (AS) for prostate cancer (CaP) or small renal masses (SRMs) helps in limiting the overtreatment of indolent malignancies. Implementation of AS for these conditions varies substantially across individual urologists. We examined the Michigan Urological Surgery Improvement Collaborative (MUSIC) registry to assess for correlation of AS between patients with low-risk CaP and patients with SRM managed by individual urologists.

Upgrading on Per Protocol versus For Cause surveillance prostate biopsies: An opportunity to decreasing the burden of active surveillance.

Background: Most prostate cancer (PC) active surveillance (AS) protocols recommend "Per Protocol" surveillance biopsy (PPSBx) every 1-3 years, even if clinical and imaging parameters remained stable. Herein, we compared the incidence of upgrading on biopsies that met criteria for "For Cause" surveillance biopsy (FCSBx) versus PPSBx.

Methods: We retrospectively reviewed men with GG1 PC on AS in the Michigan Urological Surgery Improvement Collaborative (MUSIC) registry.

Adaptor proteins mediate CXCR4 and PI4KA crosstalk in prostate cancer cells and the significance of PI4KA in bone tumor growth.

The chemokine receptor, CXCR4 signaling regulates cell growth, invasion, and metastasis to the bone-marrow niche in prostate cancer (PCa). Previously, we established that CXCR4 interacts with phosphatidylinositol 4-kinase IIIα (PI4KIIIα encoded by PI4KA) through its adaptor proteins and PI4KA overexpressed in the PCa metastasis. To further characterize how the CXCR4-PI4KIIIα axis promotes PCa metastasis, here we identify CXCR4 binds to PI4KIIIα adaptor proteins TTC7 and this interaction induce plasma membrane PI4P production in prostate cancer cells.

The Use and Short-term Outcomes of Active Surveillance in Men With National Comprehensive Cancer Network Favorable Intermediate-risk Prostate Cancer: The Initial Michigan Urological Surgery Improvement Collaborative Experience.

Purpose: National Comprehensive Cancer Network favorable intermediate-risk prostate cancer is a heterogeneous disease with varied oncologic and survival outcomes. We describe the Michigan Urological Surgery Improvement Collaborative's experience with the use of active surveillance and the short-term oncologic outcomes for men with favorable intermediate-risk prostate cancerMaterials and Methods:We reviewed the Michigan Urological Surgery Improvement Collaborative registry for men diagnosed with favorable intermediate-risk prostate cancer from 2012-2020. The proportion of men with favorable intermediate-risk prostate cancer managed with active surveillance was calculated by year of diagnosis.

Trials in the Key of G: Building Level 1 Evidence on the Real-world Effectiveness of Prostate Biomarkers.

A number of genomic classifiers are available to aid in shared decision-making for men with localized prostate cancer; however, there is no high-level evidence assessing their clinical utility. The two randomized controlled trials in this report prospectively evaluate the use of gene expression classifier testing at the time of cancer diagnosis and after surgical treatment.

The added influence of genomics and post-MRI confirmatory biopsy results to MRI results alone on medical decision making for men with favorable risk prostate cancer being considered for active surveillance.

Background: We examined how the results of genomic classifier (GC) or post-magnetic resonance imaging confirmatory biopsy (pMRI-CBx) influenced management strategy for men with an MRI considering active surveillance (AS).

Methods: We reviewed the Michigan Urological Surgery Improvement Collaborative registry for men with favorable-risk prostate cancer. Among men with an MRI after the diagnostic biopsy (n = 1162) a subset also had GC (n = 126) or pMRI-CBx (n = 309).

Five-year follow-up study of a population-based prospective cohort of men with low-risk prostate cancer: the treatment options in prostate cancer study (TOPCS): study protocol.

Introduction: Active surveillance (AS) is recommended for men with low-risk prostate cancer (LRPC) to reduce overtreatment and to maintain patients' quality of life (QOL). However, whether African American (AA) men can safely undergo AS is controversial due to concerns of more aggressive disease and lack of empirical data on the safety and effectiveness of AS in this population. Withholding of AS may lead to a lost opportunity for improving survivorship in AA men.

Practice-Level Variation in the Decision to Biopsy Prostate Imaging-Reporting and Data System 3 Lesions in Favorable-Risk Prostate Cancer Patients.

Objective: To examine practice-level variation in the management of magnetic resonance imaging (MRI) Prostate Imaging-Reporting and Data System (PI-RADS) 3 lesions in men with favorable-risk prostate cancer (FRPC) considering or on active surveillance (AS).

Patients And Methods: We reviewed the Michigan Urological Surgery Improvement Collaborative registry for FRPC men (GG1 and low-volume GG2) undergoing MRI from January 2013 to March 2020. The primary outcome was to assess practice-level variation in time from MRI to biopsy and MRI to treatment for PI-RADS 3 lesions.

Delayed radical prostatectomy after a period of active surveillance is not associated with the use of secondary treatments compared with immediate prostatectomy.

Background: We evaluated the use of secondary treatments in men with grade group (GG) 1 PC following a period of active surveillance (AS) compared with men undergoing immediate radical prostatectomy (RP) to evaluate what is potentially lost in terms of cancer control, if a patient trials AS and transitions to treatment.

Methods: We reviewed the Michigan Urological Surgery Improvement Collaborative (MUSIC) registry for men with GG1 PC undergoing RP from April 2012 to July 2018. Men were classified into groups based on time from diagnosis to RP: immediate (surgery within 1 year of diagnosis) and delayed RP (surgery >1 year after initiation of AS).

Does the type of cryoprobe affect oncological and functional outcomes in men with clinically localized prostate cancer treated with primary whole gland prostate cryoablation?

Background: This study aimed to compare the oncological and functional outcomes of primary whole gland cryoablation of the prostate using the variable ice cryoprobe (V-Probe) and the conventional fixed-size ice probe.

Materials And Methods: We reviewed the Cryo On-Line Data Registry for men who were treated with primary whole gland prostate cryoablation from 2000 through 2017. A multivariate Cox proportional hazards model was used to compare timing to biochemical recurrence between the V-Probe and fixed-size ice probe after adjusting for preoperative prostate-specific antigen (PSA), neoadjuvant androgen deprivation therapy, preoperative Gleason score, and preoperative T stage.

Association of lymph node yield with overall survival in patients with pathologically node negative prostate cancer.

We investigated the association between lymph node yield (LNY) with overall survival (OS) and post-radical prostatectomy (RP) secondary treatments among men with pathologically node negative (pN0) prostate cancer. We reviewed the National Cancer Database for men with Gleason Grade Group 2 or higher prostate cancer treated with RP and had pathologically node-negative disease. LNY was modeled as a continuous and categorical variable grouped by quartiles of LNY.

Large Retroperitoneal Paraganglioma Associated with Germline Mutation of the Succinate Dehydrogenase Gene.

Paragangliomas (PGLs) are rare neural tumors that can be benign or malignant and often associated with familial syndromes. We present a case of a 23-year-old male with a large retroperitoneal PGL found incidentally during the workup of elevated liver enzymes. After surgical excision, the patient was found to have an autosomal dominant mutation in the succinate dehydrogenase B (SDHB) gene, which when compared to sporadic PGLs or other familial syndromes is associated with a higher risk of tumor recurrence, occult metastasis, and development of other cancers.

Clinical Efficacy of Enzalutamide vs Bicalutamide Combined With Androgen Deprivation Therapy in Men With Metastatic Hormone-Sensitive Prostate Cancer: A Randomized Clinical Trial.

Importance: Black patients have been underrepresented in prospective clinical trials of advanced prostate cancer. This study evaluated the efficacy of enzalutamide compared with bicalutamide, with planned subset analysis of Black patients with metastatic hormone-sensitive prostate cancer (mHSPC), which is a disease state responsive to androgen deprivation therapy (ADT).

Objective: To compare the efficacy of enzalutamide vs bicalutamide in combination with ADT in men with mHSPC, with a subset analysis of Black patients.

Urologists' Perceptions of Active Surveillance and Their Recommendations for Low-risk Prostate Cancer Patients.

Objective: To assess practicing urologists' attitudes and perceptions of active surveillance (AS) and other treatment options for low-risk prostate cancer.

Methods: This was a cross-sectional survey of urologists practicing in Michigan and Georgia. Urologists were asked about perceptions and practices pertaining to AS.

Adrenal Metastases as Sanctuary Sites in Advanced Renal Cancer.

Involvement of the adrenal gland in kidney cancer represents a unique site of metastasis with a distinct clinical course. The cases are typically resistant to immune therapy and need local therapy management. A case series of patients with adrenal metastases was reviewed to highlight the nuances of clinical course and therapy.

Association of Surgical Delay and Overall Survival in Patients With T2 Renal Masses: Implications for Critical Clinical Decision-making During the COVID-19 Pandemic.

Objective: To test for an association between surgical delay and overall survival (OS) for patients with T2 renal masses. Many health care systems are balancing resources to manage the current COVID-19 pandemic, which may result in surgical delay for patients with large renal masses.

Methods: Using Cox proportional hazard models, we analyzed data from the National Cancer Database for patients undergoing extirpative surgery for clinical T2N0M0 renal masses between 2004 and 2015.