Partial-gland Cryoablation Outcomes for Localized Prostate Cancer in Patients with Magnetic Resonance Imaging (MRI)-visible and MRI-invisible Lesions

Background: Expert consensus recommends treatment of magnetic resonance imaging (MRI)-visible prostate cancer (PCa). Outcomes of partial-gland ablation (PGA) for MRI-invisible PCa remain unknown. Objective: To compare recurrence-free survival, adverse events, and health-related quality of life (HRQoL) outcomes following cryoablation of MRI-visible vs invisible PCa. Design, setting, and participants: We analyzed data for 75 men who underwent cryoablation therapy between January 2017 and January 2022. PCa identified on MRI-targeted and/or adjacent systematic biopsy cores was defined as MRI-visible, whereas PCa identified on systematic biopsy beyond the targeted zone was defined as MRI-invisible. Outcome measurements and statistical analysis: The primary outcome was recurrence at 12 mo after PGA, defined as the presence of clinically significant PCa (grade group [GG] ≥2) on surveillance biopsy. Adverse events were captured using the Clavien-Dindo classification and HRQoL was captured using the Expanded Prostate Cancer Index-Clinical Practice (EPIC-CP) tool. Results and limitations: Of the 58 men treated for MRI-visible and 17 treated for MRI-invisible lesions, 51 (88%) and 16 (94%), respectively, had at least one surveillance biopsy performed. There were no statistically significant differences in age, race, body mass index, biopsy GG, prostate-specific antigen, prostate volume, or treatment extent between the MRI-visible and MRI-invisible groups. Median follow-up was 44 mo (interquartile range 17–54) and did not significantly differ between the groups. The recurrence rate at 12 mo did not significantly differ between the groups (MRI-visible 39%, MRI-invisible 19%; p = 0.2), and log-rank survival analysis demonstrated no significant difference in recurrence-free survival (p = 0.15). Adverse event rates did not significantly differ (MRI-visible 29%, MRI-invisible 53%; p = 0.092); no man in the MRI-visible group had a Clavien-Dindo grade ≥III complication, while one subject in the MRI-invisible group had a Clavien-Dindo grade III complication. Median EPIC-CP urinary and sexual function scores were similar for the two groups at baseline and at 12 mo after PGA. Study limitations include the retrospective design and small sample size. Conclusions: We observed similar cancer control, adverse event, and HRQoL outcomes for MRI-visible versus MRI-invisible PCa in the first comparison of partial-gland cryoablation. Longer follow-up and external validation of our findings are needed to inform patient selection for PGA for MRI-invisible PCa. Patient summary: Patients with prostate cancer lesions that are not visible on magnetic resonance imaging (MRI) scans who undergo partial gland ablation may have similar treatment outcomes compared to patients with cancer lesions that are visible on MRI

Analysis of the Tumor Immune Microenvironment (TIME) in Clear Cell Renal Cell Carcinoma (ccRCC) Reveals an M0 Macrophage-Enriched Subtype: An Exploration of Prognostic and Biological Characteristics of This Immune Phenotype

There is a need to optimize the treatment of clear cell renal cell carcinoma (ccRCC) patients at high recurrence risk after nephrectomy. We sought to elucidate the tumor immune microenvironment (TIME) of localized ccRCC and understand the prognostic and predictive characteristics of certain features. The discovery cohort was clinically localized patients in the TCGA-Kidney Renal Clear Cell Carcinoma (KIRC) project (n = 382). We identified an M0 macrophage-enriched cluster (n = 25) in the TCGA-KIRC cohort. This cluster’s median progression-free survival (PFS) and overall survival (OS) were 40.4 and 45.3 months, respectively, but this was not reached in the others (p = 0.0003 and n = 9) with shorter PFS (p = 0.0006) was also identified in the Clinical Proteomics Tumor Analysis Consortium (CPTAC) cohort (n = 94). Through this characterization of the TIME in ccRCC, a cluster of patients defined by enrichment in M0 macrophages was identified that demonstrated poor prognosis and lower predicted ICB response. Pending further validation, this signature can identify localized ccRCC patients at high risk of recurrence after nephrectomy and who may require therapeutic approaches beyond ICB monotherapy

Application of the ERAs guidelines in pediatric urological surgery:a systematic review

Introduction: Consensus for enhanced recovery after Surgery (eraS) in pediatrics has been achieved in neonatal intestinal surgery, yet it is not widely utilized in pediatric urology. We investigated the application of eraS guidelines in pediatric urology, and determined its effects given the available level of evidence supporting the eraS protocol in children. eVideNCe aCQUiSiTioN: a systematic literature review including series providing adoption of fast-track recovery protocols for pediatric urology procedures was carried out. Main outcome measures were study characteristics, adherence to the 19 eraS items, complication rates and length of hospital stay. Sub-group analysis by surgery type (hypospadias versus major surgery) was performed. eVideNCe SyNTheSiS: Nine series with data from 1272 surgical pediatric cases were included. an enhanced recovery pathway was applied in 67.3% of the reports. Two series included patients undergoing hypospadias repair and eraS items were insufficiently reported. Studies including children undergoing major procedures mentioned a median of 15 eraS items, yet applied a median of 11 items. Median compliance rate was 88.9% (range 50-100). More eraS guideline items were reported (applied or mentioned) in the most recently published studies. CoNClUSioNS: There is limited reporting and use of the eraS guidelines in urologic surgery particularly in hypospadias repair; whilst in major surgery in children, adherence and compliance rates vary widely. in more recent series there was an increase in eraS items that have been mentioned and applied. Future research is needed to identify barriers and to overcome them in order to fully adopt and benefit from the ERAS pathway.</p

Thyroid and androgen receptor signaling are antagonized by μ-Crystallin in prostate cancer.

Androgen deprivation therapy (ADT) remains a key approach in the treatment of prostate cancer (PCa). However, PCa inevitably relapses and becomes ADT resistant. Besides androgens, there is evidence that thyroid hormone thyroxine (T4) and its active form 3,5,3'-triiodo-L-thyronine (T3) are involved in the progression of PCa. Epidemiologic evidences show a higher incidence of PCa in men with elevated thyroid hormone levels. The thyroid hormone binding protein μ-Crystallin (CRYM) mediates intracellular thyroid hormone action by sequestering T3 and blocks its binding to cognate receptors (TRα/TRβ) in target tissues. We show in our study that low CRYM expression levels in PCa patients are associated with early biochemical recurrence and poor prognosis. Moreover, we found a disease stage-specific expression of CRYM in PCa. CRYM counteracted thyroid and androgen signaling and blocked intracellular choline uptake. CRYM inversely correlated with [18F]fluoromethylcholine (FMC) levels in positron emission tomography/magnetic resonance imaging of PCa patients. Our data suggest CRYM as a novel antagonist of T3- and androgen-mediated signaling in PCa. The role of CRYM could therefore be an essential control mechanism for the prevention of aggressive PCa growth