No abstract

No abstract

Objective: To determine the predictive value of the radiological response rate assessed by serial pelvic computed tomography scans for pathological response to neoadjuvant chemotherapy and clinical outcomes after radical cystectomy in bladder urothelial cancer patients. Methods: We retrospectively reviewed 59 patients with muscle-invasive bladder cancer who underwent radical cystectomy following neoadjuvant chemotherapy. Pretreatment and post-neoadjuvant chemotherapy computed tomography scans were evaluated by a single radiologist to determine the radiological response rate based on the largest diameter of the primary tumor. Association of the radiological response rate with pathological findings of the radical cystectomy specimen and postradical cystectomy clinical outcomes were assessed. Results: The pathological complete response rate was 25% (n = 15) and the median (range) radiological response rate was 0.58 (0.00-1.00). The radiological response rate was significantly associated with ≤pT1. Patients with pathological downstaging to ≤pTa/is or pT1, compared with those with pT2≤ tumor, had significantly better post-radical cystectomy recurrence-free survival (2-year survival 92.0, 88.9, 36.8%, respectively, P < 0.0001), disease-specific survival (2-year survival 95.8, 88.9, 47.3%, respectively, P < 0.0001) and overall survival (2-year survival 91.7, 88.9, 40.1%, respectively, P < 0.0001). Patients with a higher radiological response rate (≥0.57) had significantly better post-radical cystectomy recurrence-free survival (2-year survival 89.7 vs. 48.1%, P = 0.0011), disease-specific survival (2-year survival 93.2 vs. 48.2%, P < 0.0001) and overall survival (2-year survival 90.0 vs. 39.0%, P < 0.0001). Multivariate analyses using the Cox proportional hazard model revealed that the radiological response rate was an independent predictor for favorable pT stage and recurrence-free survival. Conclusion: The radiological response rate determined by pretreatment and post-chemotherapy computed tomography scans predicts the pathological outcome and post-radical cystectomy prognosis, which is clinically relevant and useful for patient counselling and decision-making.

No abstract

The prevalence of neuroendocrine prostate cancer (NEPC) arising from adenocarcinoma (AC) upon potent androgen receptor (AR) pathway inhibition is increasing. Deeper understanding of NEPC biology and development of novel therapeutic agents are needed. However, research is hindered by the paucity of research models, especially cell lines developed from NEPC patients. We established a novel NEPC cell line, KUCaP13, from tissue of a patient initially diagnosed with AC which later recurred as NEPC. The cell line has been maintained permanently in vitro under regular cell culture conditions and is amenable to gene engineering with lentivirus. KUCaP13 cells lack the expression of AR and overexpress NEPC‐associated genes, including SOX2, EZH2, AURKA, PEG10, POU3F2, ENO2, and FOXA2. Importantly, the cell line maintains the homozygous deletion of CHD1, which was confirmed in the primary AC of the index patient. Loss of heterozygosity of TP53 and PTEN, and an allelic loss of RB1 with a transcriptomic signature compatible with Rb pathway aberration were revealed. Knockdown of PEG10 using shRNA significantly suppressed growth in vivo. Introduction of luciferase allowed serial monitoring of cells implanted orthotopically or in the renal subcapsule. Although H3K27me was reduced by EZH2 inhibition, reversion to AC was not observed. KUCaP13 is the first patient‐derived, treatment‐related NEPC cell line with triple loss of tumor suppressors critical for NEPC development through lineage plasticity. It could be valuable in research to deepen the understanding of NEPC.