Objectives
To investigate the clinical utility of the Vesical Imaging-Reporting and Data System (VI-RADS) by comparing its diagnostic performance for muscle-invasive bladder cancer (MIBC) between ...radiologists and urologists based on multiparametric MRI, including three-dimensional (3D) fast spin-echo (FSE) T2-weighted acquisitions.
Methods
This study included 66 treatment-naïve patients (60 men, 6 women; mean age 74.0 years) with pathologically proven bladder cancer who underwent multiparametric MRI, including 3D FSE T2-weighted imaging, before transurethral bladder tumour resection between January 2010 and November 2018. The MRI scans were categorised according to the five-point VI-RADS score by four independent readers (two board-certified radiologists and board-certified urologists each), blinded to the histopathological findings. The VI-RADS scores were compared with the postoperative histopathological diagnosis. Interobserver agreement was assessed using weighted kappa coefficients. ROC analysis and generalised estimating equations were used to evaluate the diagnostic performance.
Results
Forty-nine (74.2%) and 17 (25.8%) tumours were confirmed to be non-MIBC and MIBC, respectively, based on pathological examination. The interobserver agreement was good-to-excellent between all pairs of readers (range, 0.73–0.91). The urologists’ sensitivity/specificity values for DCE-MRI VI-RADS scores were significantly lower than those of radiologists. No significant differences were observed for the overall VI-RADS score. The AUC for the overall VI-RADS score was 0.94, 0.92, 0.89, and 0.87 for radiologists 1 and 2 and urologists 1 and 2, respectively.
Conclusions
The VI-RADS score, based on multiparametric MRI including 3D FSE T2-weighted acquisitions, can be useful for radiologists and urologists to determine the bladder cancer muscle invasion status preoperatively.
Key Points
•
VI-RADS (using multiparametric MRI including 3D FSE T2-weighted acquisitions) achieves good to excellent interobserver agreement and has similar diagnostic performance for detecting muscle invasion by both radiologists and urologists.
•
The diagnostic performance of the overall VI-RADS score is high for both radiologists and urologists, particularly due to the dominant effect of diffusion-weighted imaging on the overall VI-RADS score.
•
The sensitivity and specificity values of the T2WI VI-RADS scores for four readers in our study (using 3D FSE T2-weighted acquisitions) were similar (with slightly higher specificity values) to previously published results (using 2D FSE T2-weighted acquisitions).
Mucin 1 C‐terminal subunit (MUC1‐C) has been introduced as a key regulator for acquiring drug resistance in various cancers, but the functional role of MUC1‐C in urothelial carcinoma (UC) cells ...remains unknown. We aimed to elucidate the molecular mechanisms underlying the acquisition of cisplatin (CDDP) resistance through MUC1‐C oncoprotein in UC cells. MUC1‐C expression was examined immunohistochemically in tumor specimens of 159 UC patients who received CDDP‐based perioperative chemotherapy. As a result, moderate to high MUC1‐C expression was independently associated with poor survival in UC patients. Using human bladder cancer cell lines and CDDP‐resistant (CR) cell lines, we compared the expression levels of MUC1‐C, multiple drug resistance 1 (MDR1), the PI3K‐AKT‐mTOR pathway, and x‐cystine/glutamate transporter (xCT) to elucidate the biological mechanisms contributing to the acquisition of chemoresistance. MUC1‐C was strongly expressed in CR cell lines, followed with MDR1 expression via activation of the PI3K‐AKT‐mTOR pathway. MUC1‐C also stabilized the expression of xCT, which enhanced antioxidant defenses by increasing intracellular glutathione (GSH) levels. MUC1 down‐regulation showed MDR1 inhibition along with PI3K‐AKT‐mTOR pathway suppression. Moreover, it inhibited xCT stabilization and resulted in significant decreases in intracellular GSH levels and increased reactive oxygen species (ROS) generation. The MUC1‐C inhibitor restored sensitivity to CDDP in CR cells and UC murine xenograft models. In conclusion, we found that MUC1‐C plays a pivotal role in the acquisition of CDDP resistance in UC cells, and therefore the combined treatment of CDDP with a MUC1‐C inhibitor may become a novel therapeutic option in CR UC patients.
Our present study demonstrated that mucin 1 C‐terminal peptide (MUC1‐C) plays a pivotal role in the acquisition of cisplatin (CDDP) resistance via multiple drug resistance 1 regulation and x‐cystine/glutamate transporter stabilization in urothelial cancer cells. The combined treatment of CDDP with a MUC1‐C inhibitor, GO‐203, may become a novel therapeutic option in CDDP‐resistant UC patients.
Purpose
To evaluate the oncological feasibility of pure laparoscopic radical nephroureterectomy (p-LRNU) for upper tract urothelial carcinoma (UTUC) compared with conventional LRNU (c-LRNU) using a ...propensity-adjusted multi-institutional collaboration dataset.
Methods
Among the 503 UTUC patients who underwent RNU, we identified 219 who underwent c-LRNU (laparoscopic nephrectomy with open bladder cuff resection) and 72 who underwent p-LRNU (dissecting the kidney, ureter, and bladder cuff under complete laparoscopy). We adopted a propensity score (PS) matching method to achieve homogeneity with respect to patient backgrounds. PS matching-adjusted Cox-regression analysis was performed to evaluate the risk factors that influenced oncological outcomes.
Results
Sixty-eight p-LRNU and 68 c-LRNU patients were matched. Overall, 51 (37.0%) developed intravesical recurrence (IVR), 21 (15.4%) had disease recurrence, and 20 (14.7%) died. Patients who underwent p-LRNU had a significantly shorter operation time and less blood loss than those who underwent c-LRNU. Although no significant differences in 3-year recurrence-free survival were found between the two methods, atypical recurrence sites were observed in the p-LRNU group, including the brain, sigmoid colon, vagina, and peritoneum. Regarding IVR, the 3-year IVR-free survival rate was 41.8% in the p-LRNU group, which was significantly lower than that in the c-LRNU group (66.6%,
p
= 0.004). Multivariate analysis demonstrated that a history of bladder cancer, ureteral cancer, and p-LRNU were independent risk factors for subsequent IVR.
Conclusion
Although p-LRNU is less invasive, the current technique may increase the incidence of atypical disease recurrence and subsequent IVR due to extravesical and intravesical tumor dissemination.
Bacillus Calmette–Guérin induction with or without maintenance is the gold standard therapy for intermediate‐/high‐risk non‐muscle‐invasive bladder cancer; however, one‐third of patients treated with ...adequate bacillus Calmette–Guérin therapy do not achieve sufficient responses, and this is referred to as “bacillus Calmette–Guérin failure.” The term, bacillus Calmette–Guérin failure, is ambiguous and includes a very heterogeneous population of patients. By strictly focusing on patients who are unlikely to benefit from additional bacillus Calmette–Guérin therapy and who need to be treated with radical cystectomy, the new concept of “bacillus Calmette–Guérin unresponsive” was recently proposed, and might accelerate the development of novel therapeutic options for bacillus Calmette–Guérin‐unresponsive disease. A promising therapeutic strategy for bacillus Calmette–Guérin‐unresponsive disease is the blockade of the programmed cell death‐1/programmed cell death‐ligand 1 pathway, which is considered to be activated by bacillus Calmette–Guérin therapy. Several large clinical trials have been carried out to assess the potential of programmed cell death‐1/programmed cell death‐ligand 1 blockade in bacillus Calmette–Guérin‐naïve high‐risk non‐muscle‐invasive bladder cancer and bacillus Calmette–Guérin‐unresponsive disease. Furthermore, clinical trials that are targeting bacillus Calmette–Guérin‐unresponsive disease with other strategies, such as vaccines, gene therapy, and targeted and cytotoxic therapies, are ongoing. The findings of these trials are awaited in order to establish appropriate bladder‐sparing approaches for patients with bacillus Calmette–Guérin‐unresponsive disease.
Limited information is currently available on predictors of upper tract urothelial carcinoma (UTUC) recurrence in non-muscle-invasive bladder cancer (NMIBC) patients according to smoking history, ...although smoking probably contributes to urothelial carcinogenesis. Therefore, the present study aimed to identify independent predictors of UTUC recurrence in all patients and those with a smoking history. Our study population comprised 1190 NMIBC patients who underwent transurethral resection of bladder tumor. UTUC developed in 43 patients during the follow-up. A history of bacillus Calmette-Guérin (BCG) therapy was independently associated with a lower incidence of UTUC (HR = 0.43; P = 0.011). In a subgroup of NMIBC patients with a smoking history, concomitant carcinoma in situ (CIS) and a lower urinary pH (< 6) were independently associated with a higher incidence of UTUC recurrence (HR = 3.34, P = 0.006 and HR = 3.73, P = 0.008, respectively). Among patients with a longer smoking duration (≥ 20 years) or larger smoking intensity (≥ 20 cigarettes per day), those with lower urinary pH (< 6) had a significantly higher UTUC recurrence rate than their counterparts. These results suggest that BCG instillation may prevent UTUC recurrence in NMIBC patients, while a lower urinary pH and concomitant CIS increase the risk of UTUC recurrence in those with a smoking history.
This study aimed to clarify the clinical characteristics and oncological outcomes of patients with upper tract urothelial carcinoma (UTUC) who developed muscle‐invasive bladder cancer (MIBC) after ...radical nephroureterectomy (RNU). We identified 966 pTa‐4N0‐2M0 patients with UTUC who underwent RNU and clarified the risk factors for MIBC progression after initial intravesical recurrence (IVR). We also identified 318 patients with primary pT2‐4N0‐2M0 MIBC to compare the oncological outcomes with those of patients with UTUC who developed or progressed to MIBC. Furthermore, immunohistochemical examination of p53 and FGFR3 expression in tumor specimens was performed to compare UTUC of MIBC origin with primary MIBC. In total, 392 (40.6%) patients developed IVR after RNU and 46 (4.8%) developed MIBC at initial IVR or thereafter. As a result, pT1 stage on the initial IVR specimen, concomitant carcinoma in situ on the initial IVR specimen, and no intravesical adjuvant therapy after IVR were independent factors for MIBC progression. After propensity score matching adjustment, primary UTUC was a favorable indicator for cancer‐specific death compared with primary MIBC. Subgroup molecular analysis revealed high FGFR3 expression in non‐MIBC and MIBC specimens from primary UTUC, whereas low FGFR3 but high p53 expression was observed in specimens from primary MIBC tissue. In conclusion, our study demonstrated that patients with UTUC who develop MIBC recurrence after RNU exhibited the clinical characteristics of subsequent IVR more than those of primary UTUC. Of note, MIBC subsequent to UTUC may have favorable outcomes, probably due to the different molecular biological background compared with primary MIBC.
We conducted a multicenter cohort study describing the clinicopathological characteristics of muscle‐invasive bladder recurrence developed after surgical management of upper tract urothelial carcinoma.
Purpose
Using conditional survival (CS) analysis, we investigated whether the duration of survival without biochemical recurrence (BCR) of prostate cancer after laparoscopic radical prostatectomies ...(LRP) affected the BCR rate. We also investigated the impact of well-known risk factors for BCR.
Methods
Between 2002 and 2014, 627 consecutive patients underwent LRPs at our institution. Prostate-specific antigen (PSA) concentrations above 0.2 ng/mL were defined as BCR. Conditional BCR-free survival rates were determined through Kaplan–Meier analysis. Assessment of potential BCR risk factors was performed using a Cox proportional hazard analysis.
Results
The 10-year BCR-free rates after LRP increased to 82.4%, 84.5%, 86.6%, 90.1%, and 94.7% in patients surviving 1, 2, 3, 5, and 7.5 years without BCR, respectively. Multivariate analyses of age, PSA concentrations, neoadjuvant therapy, and pathological findings were performed for all patients. In all patients, positive surgical margins (PSM) and Gleason Grade Groups (GG) ≥ 4 were independent risk factors for BCR (
p
< 0.001, hazard ratio HR = 2.45; and
p
< 0.001, HR = 2.83, respectively,). Similarly, PSM and GG ≥ 4 were significant risk factors in patients surviving 1–5 years without BCR. No clear risk factors were observed in patients surviving > 5 years without BCR after LRPs.
Conclusions
The BCR-free rate increased with time after LRP. It is recommended that patients with PSM, GG ≥ 4, or with both factors are strictly monitored for 5 years postoperatively. CS analysis is particularly useful for predicting the postoperative course of patients.
•We focused on platinum-resistant urothelial carcinoma patients who received pembrolizumab treatment.•Pretreatment neutrophil-to-lymphocyte ratio levels were higher in patients with PD or SD after ...pembrolizumab treatment.•Pretreatment neutrophil-to-lymphocyte ratio ≥3.35 was the independent indicator of worse clinical outcomes.•Patients with postpembrolizumab neutrophil-to-lymphocyte ratio that had decreased ≥25% had good prognosis.
We investigated the relationship between pretreatment neutrophil-to-lymphocyte ratio (pre-NLR) levels just before the initiation of treatment with pembrolizumab and clinical outcomes in platinum-resistant metastatic urothelial carcinoma (UC) patients treated with pembrolizumab.
Our study population comprised 78 patients diagnosed with metastatic UC and treated with pembrolizumab after platinum-based chemotherapy at our institutions between December 2017 and April 2019. We examined the relationships between pre-NLR levels just before pembrolizumab treatment and clinical outcomes. A pre-NLR level of ≥3.35 was defined as elevated according to a calculation by a receiver-operating curve analysis.
The high pre-NLR group consisted of 33 patients (42.3%). Overall, 29.5% of patients had a clinical response and the sum of the target lesion longest diameter was decreased in 18.8% of the high pre-NLR group, which was significantly lower than that in the low pre-NLR group (58.1%, P = 0.005). Six-month progression-free survival and cancer-specific survival rates for the high pre-NLR group were 9.1 and 58.0%, which were significantly lower than those for their counterpart (45.9 and 89.1%, P < 0.001 and P = 0.002, respectively). The pre-NLR level was an independent indicator of disease progression and cancer-specific death (P < 0.001 and P = 0.003). Furthermore, patients with a postpembrolizumab NLR level that had decreased ≥25% from the pre-NLR level had significantly lower disease progression and cancer-specific death rates than their counterparts (P = 0.01 and P = 0.022, respectively).
Elevated pre-NLR may be a novel biomarker for identifying poor responders to pembrolizumab among platinum-resistant metastatic UC patients.
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