Objective To investigate the prognostic differences among pure urothelial carcinoma,squamous-differentiated urothelial carcinoma,and pure squamous cell carcinoma,so as to provide reference for postoperative risk stratification.Methods The clinical data of bladder cancer patients who visited the Department of Urology,Peking University First Hospital and underwent radical cystectomy during Jan.2005 and Jun.2024 were retrospectively analyzed.Patients were categorized into the pure urothelial carcinoma group(n=725),squamous-differentiated urothelial carcinoma group(n=189),and pure squamous cell carcinoma group(n=36).General characteristics,surgical approaches,pathological staging,muscle invasion status,and lymph node positivity were compared among the three groups.Kaplan-Meier survival curves were plotted,and prognostic differences among the groups were compared after 1∶1 propensity score matching between each pair.Independent risk factors of prognosis were identified with Cox multivariable regression.Results The pure squamous cell carcinoma group had a higher proportion of female patients(50.00％vs.25.24％vs.22.75％,P=0.002 4).Compared with the pure urothelial carcinoma group,the other two groups demonstrated higher proportions of stage Ⅲ+Ⅳ,higher rates of muscle invasion,and higher lymph node positivity,with the pure squamous cell carcinoma group showing the highest overall staging(69.45％vs.58.20％vs.29.38％,P＜0.000 1).Kaplan-Meier analysis showed that squamous-differentiated urothelial carcinoma group and pure squamous cell carcinoma group had significantly worse survival than the pure urothelial carcinoma group(P＜0.05),while the former two groups exhibited similar outcomes(P=0.85).After propensity score matching,postoperative survival curves among the three groups were not significantly different(all P＞0.05).In multivariable Cox proportional hazards models adjusting for confounders,prognosis was primarily associated with age,muscle invasion,and lymph-node positivity(P＜0.05);pathological subtype was not an independent predictor of postoperative survival.Conclusion In a cohort of non-metastatic patients undergoing radical cystectomy,pure squamous cell carcinoma and squamous-differentiated urothelial carcinoma presented with higher clinical and pathological staging and poorer unadjusted prognosis compared with pure urothelial carcinoma.However,postoperative survival did not differ significantly among the three groups in the same clinicopathological conditions.

Objective To investigate the prognostic differences among pure urothelial carcinoma,squamous-differentiated urothelial carcinoma,and pure squamous cell carcinoma,so as to provide reference for postoperative risk stratification.Methods The clinical data of bladder cancer patients who visited the Department of Urology,Peking University First Hospital and underwent radical cystectomy during Jan.2005 and Jun.2024 were retrospectively analyzed.Patients were categorized into the pure urothelial carcinoma group(n=725),squamous-differentiated urothelial carcinoma group(n=189),and pure squamous cell carcinoma group(n=36).General characteristics,surgical approaches,pathological staging,muscle invasion status,and lymph node positivity were compared among the three groups.Kaplan-Meier survival curves were plotted,and prognostic differences among the groups were compared after 1∶1 propensity score matching between each pair.Independent risk factors of prognosis were identified with Cox multivariable regression.Results The pure squamous cell carcinoma group had a higher proportion of female patients(50.00％vs.25.24％vs.22.75％,P=0.002 4).Compared with the pure urothelial carcinoma group,the other two groups demonstrated higher proportions of stage Ⅲ+Ⅳ,higher rates of muscle invasion,and higher lymph node positivity,with the pure squamous cell carcinoma group showing the highest overall staging(69.45％vs.58.20％vs.29.38％,P＜0.000 1).Kaplan-Meier analysis showed that squamous-differentiated urothelial carcinoma group and pure squamous cell carcinoma group had significantly worse survival than the pure urothelial carcinoma group(P＜0.05),while the former two groups exhibited similar outcomes(P=0.85).After propensity score matching,postoperative survival curves among the three groups were not significantly different(all P＞0.05).In multivariable Cox proportional hazards models adjusting for confounders,prognosis was primarily associated with age,muscle invasion,and lymph-node positivity(P＜0.05);pathological subtype was not an independent predictor of postoperative survival.Conclusion In a cohort of non-metastatic patients undergoing radical cystectomy,pure squamous cell carcinoma and squamous-differentiated urothelial carcinoma presented with higher clinical and pathological staging and poorer unadjusted prognosis compared with pure urothelial carcinoma.However,postoperative survival did not differ significantly among the three groups in the same clinicopathological conditions.

Muscle-invasive bladder cancer (MIBC) is the predominant type of muscle-invasive urothelial carcinoma (MIUC). MIBC features an unfavorable prognosis with limited treatment approaches. The backbone of treatment strategy was neoadjuvant chemotherapy followed by radical cystectomy before 2021. Immunotherapy represented by nivolumab has gained breakthrough results in adjuvant setting, demonstrating significant improvement in disease free survival in high-risk MIUC population, and become a standard of care for MIUC adjuvant therapy since 2021. Immunotherapy has both efficacy and safety advantages compared to adjuvant chemotherapy. Predictors for adjuvant therapy response in MIUC have yet not been identified. The most evaluated predictive biomarkers to date for immune checkpoint inhibitor treatment response are programmed death ligand 1 (PD-L1) expression and circulating tumour DNA (ctDNA), etc. Further research is crucial to assess the value of the biomarkers. Studies of perioperative immunotherapy combined with chemotherapy or antibody-drug conjugate are ongoing. Combined immunotherapy as part of bladder-sparing treatment regimen for MIUC is limited to small scale studies and has shown promising early outcomes. Further phase 3 clinical trials are underway to add mature data to bladder-sparing strategies incorporating immune checkpoint inhibitors in adjuvant setting.

Muscle-invasive bladder cancer (MIBC) is the predominant type of muscle-invasive urothelial carcinoma (MIUC). MIBC features an unfavorable prognosis with limited treatment approaches. The backbone of treatment strategy was neoadjuvant chemotherapy followed by radical cystectomy before 2021. Immunotherapy represented by nivolumab has gained breakthrough results in adjuvant setting, demonstrating significant improvement in disease free survival in high-risk MIUC population, and become a standard of care for MIUC adjuvant therapy since 2021. Immunotherapy has both efficacy and safety advantages compared to adjuvant chemotherapy. Predictors for adjuvant therapy response in MIUC have yet not been identified. The most evaluated predictive biomarkers to date for immune checkpoint inhibitor treatment response are programmed death ligand 1 (PD-L1) expression and circulating tumour DNA (ctDNA), etc. Further research is crucial to assess the value of the biomarkers. Studies of perioperative immunotherapy combined with chemotherapy or antibody-drug conjugate are ongoing. Combined immunotherapy as part of bladder-sparing treatment regimen for MIUC is limited to small scale studies and has shown promising early outcomes. Further phase 3 clinical trials are underway to add mature data to bladder-sparing strategies incorporating immune checkpoint inhibitors in adjuvant setting.

Objective:To study the value of urine-based multi-dimensional bioinformatics evaluation model (utLIFE model) in early diagnosis and postoperative monitoring of upper urinary tract urothelial carcinoma (UTUC).Methods:Morning urine samples of patients clinically diagnosed with UTUC without bladder cancer from Peking University First Hospital from August 2022 to October 2022 were collected. Urine samples were collected before and after surgery, and DNA was extracted for gene sequencing. The utLIFE model previously constructed by our center was used to calculate the score, based on 155 gene mutation sites and copy number variation, and the score ≥60 was defined as utLIFE positive. The sensitivity of utLIFE model in diagnosis of UTUC was analyzed with postoperative pathology as the gold standard. The utLIFE scores before and after operation were also compared.Results:A total of 53 patients were included in this study, all of whom were confirmed as UTUC by postoperative pathology. The median age of patients was 66 (59, 72) years. Twenty-four cases (45.3%) of UTUC tumors were located in the renal pelvis, 26 cases (49.1%) were located in the ureter, and 2 cases (5.7%)involved both ureter and renal pelvis. There were 27 patients (50.9%) at T 1stage and 26 patients (49.1%) at ≥T 2 stage. Preoperative utLIFE score of 53 patients was 79 (70, 84). The sensitivity of preoperative utLIFE diagnosis of UTUC was 96.2% (51/53). utLIFE showed similar high sensitivity in T 1 stage and ≥T 2 stage [100.0% (27/27) vs. 92.3% (24/26), P=0.236], in N 0 and ≥N 1 stage [ 95.0% (38/40) vs. 100.0% (5/5), P=1.000]. In addition, the sensitivity of preoperative utLIFE was higher than that of urine cytology [ 95.2% (20/21) vs. 23.8% (5/21). P<0.001], fluorescence in situ hybridization (FISH) [ 92.6% (25/27) vs. 55.5% (15/27), P=0.004] and ureteroscopy [ 86.7% (13/15) vs. 60.0% (9/15), P=1.000]. A total of 45 patients postoperative utLIFE samples were collected, and the postoperative utLIFE score was significantly lower than that of preoperative [ 36 (18, 61) vs. 79 (70, 84), P<0.001]. Conclusions:utLIFE, as a non-invasive urine DNA bioinformatics assessment model, is significantly superior to cytology and FISH in early detection and has high sensitivity in diagnosis of UTUC, and can reflect perioperative minimal residual disease levels.

Humans ; Mental Retardation, X-Linked/genetics* ; Methyl-CpG-Binding Protein 2/genetics* ; Gene Duplication