Objective: Treatment efficacy of androgen deprivation therapy with radical prostatectomy for intermediate- to high-risk prostate cancer is less well-studied. The NEAR trial is a single-arm, phase II investigation of neoadjuvant apalutamide monotherapy and radical prostatectomy (RP) in the treatment of D’Amico intermediate- and high-risk prostate cancer (NCT03124433). Materials and methods: Patients with histologically-proven, D’Amico intermediate- to high-risk prostate adenocarcinoma received apalutamide 240 mg once-daily for 12 weeks followed by RP + /−lymphadenectomy. Primary outcome was pathological complete response (pCR) rate. Secondary outcomes included rate of biochemical response (defined by PSA < 0.03 ng/mL at week 24 from starting apalutamide without subsequent PSA relapse), treatment-related adverse events, and RP complication rates. Correlative biomarker analyses were performed to examine for molecular predictors of treatment responses. Results: From 2017 to 2019, 30 patients were recruited, of which 20 and 10 were high and intermediate risk, respectively; 25 completed treatment as per-protocol. We did not observe any pCR on trial; median reduction of cancer burden was 41.7% (IQR: 33.3%–60.0%). 18 out of 25 patients were classified as having a biochemical response (4 did not achieve PSA of <0.03 ng/mL at week 24 and 3 developed PSA relapse subsequently). Dry skin (N = 16; 53.3%), fatigue (N = 10; 33.3%) and skin rash (N = 9; 30.0%) were the most common adverse events, and there was no major peri-operative complication. We observed an association between tumours of low androgen receptor activity and PAM50 basal status with biochemical non-responders, albeit these molecular phenotypes were not associated with pathological response. Conclusions: A 12-week course of neoadjuvant apalutamide prior to RP did not meet the primary endpoint of pCR in this trial. Tumours with low androgen receptor activity or of the PAM50 basal subtype may have a reduced response to apalutamide.

Radiologists play a crucial role in pretreatment selection and posttreatment surveillance of patients undergoing focal therapy for primary prostate cancer.

The functional plasticity of tumor-infiltrating lymphocyte B–cells (TIL-B) spans from antitumor responses to noncanonical immune suppression. Yet, how the tumor microenvironment (TME) influences TIL-B development is still underappreciated. Our current study integrated single-cell transcriptomics and B cell receptor (BCR) sequencing to profile TIL-B phenotypes and clonalities in hepatocellular carcinoma (HCC). Using trajectory and gene regulatory network analysis, we were able to characterize plasma cells and memory and naive B cells within the HCC TME and further revealed a downregulation of BCR signaling genes in plasma cells and a subset of inflammatory TNF ⁺ memory B cells. Within the TME, a nonswitched memory B cell subset acquired an age-associated B cell phenotype (TBET ⁺ CD11c ⁺ ) and expressed higher levels of PD-L1, CD25, and granzyme B. We further demonstrated that the presence of HCC tumor cells could confer suppressive functions on peripheral blood B cells that in turn, dampen T cell costimulation. To the best of our knowledge, these findings represent novel mechanisms of noncanonical immune suppression in HCC. While previous studies identified atypical memory B cells in chronic hepatitis and across several solid cancer types, we further highlighted their potential role as regulatory B cells (Bregs) within both the TME and peripheral blood of HCC patients.

Introduction: Rectal cancer response to neoadjuvant long-course chemoradiotherapy (LCCRT) is assessed by magnetic resonance tumour regression grade (mrTRG) and this has an impact on surgical management. However, there is limited data on the correlation between mrTRG and pathological tumour regression grade (pTRG). This study aims to evaluate the correlation between mrTRG and pTRG and the prognostic value of mrTRG on survival. Methods: Between 2011 and 2016, patients with rectal cancer who underwent LCCRT and had post-LCCRT MRI were included in the study. Both mrTRG and pTRG were dichotomised into good responders (mrTRG 1–3 and pTRG 0–1) and poor responders (mrTRG 4–5 and pTRG 2–3). Correlation between mrTRG and pTRG was assessed with Cohen κ analysis. Survival analysis was performed with Kaplan–Meier test and Cox proportional hazard models. Results: There were 59 patients included in this study. There were significant reductions in anal sphincter and circumferential resection margin involvement in post-LCCRT MRI. Fair agreement was found between mrTRG and pTRG (κ=0.345). Sensitivity, specificity and accuracy of mrTRG 1–3 to predict good pathological response were 100%, 46.3% and 62.7%, respectively. On survival analysis, mrTRG 1–3 was not associated with improved overall survival and recurrence-free survival. Conclusions: While there is fair agreement in correlation between mrTRG and pTRG, MRI remains an objective, noninvasive assessment of tumour response. Further studies are required to improve the ability of mrTRG to predict good responders to LCCRT and evaluate its role as a prognostic marker for survival.