Partial gland ablation with high intensity focal ultrasound impact on genito-urinary function and quality of life: our initial experience.

INTRODUCTION:   Partial gland ablation (PGA) using high intensity focal ultrasound (HIFU) is an alternative to active surveillance for low to intermediate risk localized prostate cancer.  This pilot study assessed quality of life (QoL) outcomes during the implementation of PGA-HIFU at our institution. MATERIALS AND METHODS:   We prospectively enrolled 25 men with a diagnosis of localized low/intermediate risk prostate cancer who elected to undergo PGA-HIFU in a pilot study at our institution between 2013 and 2016.  Patients underwent pre-treatment mpMRI and transrectal ultrasound-guided biopsies.  The primary endpoints were impact on patient-reported functional outcomes (erectile, urinary function, QoL) assessed at 1, 3, 6- and 12-months. RESULTS:   The median age was 64 years old (IQR 59.5-67).  Baseline median International Index of Erectile Function-15 score was 50, which decreased to 18 at 1 month (p < 0.0005), returned to baseline by 3 months and thereafter. International Prostate Symptom Score median at baseline was 8, which worsened to 12 at 1 month (p = 0.0088), and subsequently improved to baseline thereafter.  On the UCLA-Expanded Prostate Cancer Index Composite urinary function, there was a decrease in median score from 92.7 at baseline to 76.0 at 1 month (p < 0.0001), which improved to or above baseline afterwards.  QoL remained similar to baseline at each follow up period as assessed by EQ-5D and the Functional Cancer Therapy-Prostate score. CONCLUSIONS:   In this initial cohort of PGA-HIFU men at our institution, patients demonstrated a slight, but transient, deterioration in urinary and erectile function at 1 month prior to normalization.  All QoL metrics showed no impact upon 1 year of follow up post-treatment.

Prostate cancer detection rate with MRI-targeted biopsy alone using outpatient transperineal prostate biopsy.

INTRODUCTION: We aimed to compare the detection rate of prostate cancer (PCa) and clinically significant (cs)PCa by magnetic resonance imaging-guided targeted biopsy (MTBx) alone and MTBx plus systematic biopsy (SBx) using an outpatient transperineal (TP) approach under local anesthesia. METHODS: A retrospective study of patients who underwent outpatient TP prostate biopsy under local anesthesia at our tertiary institution between 2019 and 2022 was performed. To compare the proportions of PCa and csPCa in both pathways, McNemar's tests were used. Multivariable logistic regression model was fitted to determine the predictors of csPCa. RESULTS: Of 255 men included, 177 (69%) underwent MTBx alone. MTBx had similar detection rate for PCa (56%) and csPCa (47%) compared to the combination of MTBx and SBx (PCa, 61%; csPCa, 49%; p=0.1 and p=0.3, respectively). MTBx had lower median number of biopsy cores compared to the combination of MTBx and SBx (6 vs. 11, p<0.001). At multivariable logistic regression analysis, age (odds ratio [OR] 1.08 [1.04-1.13], p<0.001), prior negative biopsy (OR 0.19 [0.09-0.44], p<0.001), prostate-specific antigen density cutoff ≥ 0.15 (OR 3.17 [1.67-6.01], p<0.001), and prostate imaging reporting and data system ≥4 (OR 12.2 [4.21-35.6], p<0.001) were independent predictors of csPCa. CONCLUSIONS: MTBx showed similar diagnostic performance to the combination of MTBx and SBx in patients undergoing outpatient TP prostate biopsy. Future studies are needed to evaluate the role of MTBx in avoiding unnecessary biopsies.

Microbial cancer immunotherapy reprograms hematopoietic stem cells to enhance anti-tumor immunity.

Mycobacterium bovis BCG is the vaccine against tuberculosis and an immunotherapy for bladder cancer. When administered intravenously, BCG reprograms bone marrow hematopoietic stem and progenitor cells (HSPCs), leading to heterologous protection against infections. Whether HSPC-reprogramming contributes to the anti-tumor effects of BCG administered into the bladder is unknown. We demonstrate that BCG administered in the bladder in both mice and humans reprograms HSPCs to amplify myelopoiesis and functionally enhance myeloid cell antigen presentation pathways. Reconstitution of naive mice with HSPCs from bladder BCG-treated mice enhances anti-tumor immunity and tumor control, increases intratumor dendritic cell infiltration, reprograms pro-tumorigenic neutrophils, and synergizes with checkpoint blockade. We conclude that bladder BCG acts systemically, reprogramming HSPC-encoded innate immunity, highlighting the broad potential of modulating HSPC phenotypes to improve tumor immunity.