scholarly journals PD-L1 promotes malignant progression by inducing EMT and enhancing stemness in muscle-invasive bladder cancer

Author(s):  
Fujin Jiang ◽  
Ying Ding ◽  
Ting Chen ◽  
Xianyun Zhang ◽  
Song Ma ◽  
...  

Abstract Objective: Despite radical treatment for aggressive muscle-invasive bladder cancer(MIBC), the prognosis remained poor. Programmed cell death ligand 1(PD-L1) plays an important role in suppressing immune responses.We investigate if PD-L1 and EMT synergistically contribute to MIBC progression. Methods: In vitro experiments, we evaluated the effects of PD-L1 on proliferation, invasion, migration of MIBC cells and studied the relationship between PD-L1 and CSC/EMT markers by overexpressing and knocking down PD-L. The association of PD-L1 with EMT was detected in MIBC human specimens and the synergistic effect of PD-L1and EMT was assessed by analysis of overall survival (OS). Results: Our data demonstrated that PD-L1 promotes proliferation, invasion and migration of MIBC cells. The positive correlation between PD-L1 and CSC/EMT markers was verified both in vitro experiments and in 130 MIBC specimens. Moreover, patients with positive PD-L1/positive EMT exhibited poorer overall survival than patients with other combinations. Conclusion: The close relationship between PD-L1 and EMT may offer potential therapeutic strategy that co-targeting PD-L1 and EMT may improve the prognosis of MIBC patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16530-e16530
Author(s):  
Natasza Posielski ◽  
Hannah Koenig ◽  
Nathan Jung ◽  
On Ho ◽  
John Paul Flores ◽  
...  

e16530 Background: National Comprehensive Cancer Network (NCCN) guidelines state partial cystectomy (PC) may be offered in select patients with clinical T2 (cT2) muscle invasive bladder cancer (MIBC) utilizing neoadjuvant chemotherapy (NAC) and pelvic lymphadenectomy (PLND). Our objective was to investigate utilization and survival outcomes of PC in a large contemporary cohort. Methods: Propensity matching was used to compare pathological and surgical outcomes in non-metastatic MIBC patients in the National Cancer Database undergoing PC or radical cystectomy (RC). Multivariate logistic regression was used to determine predictors of NAC, LND, peri-operative morbidity and mortality outcomes. This analysis was repeated in the subset with cT2 MIBC. Results: Of 31,306 T2-T4N0M0 patients, 1543 (4.9%) underwent PC. PC use was higher in older patients and most often (85%) performed for cT2 disease. The PC group was less likely to receive standard of care including NAC (11.4 vs 27.9%, p<0.001) and PLND (58.7 vs 92.5%, p<0.001) than the RC group. Pathological ≥T3 disease (pT3) was found in 39.4% and pos. nodes in 6.9% of PCs. Positive margins were higher in PC, 15.7 vs 10.6%, p<0.001. PC patients had shorter inpatient stay (4.2 vs 8.7 days, p<0.001), lower 30-day readmission (6.7 vs 9.6%, p<0.001), and decreased 30- and 90-day mortality (1.3 vs 1.8%, p<0.001 & 4.8 vs 4.9%, p=0.04). PC was an independent predictor of lack of NAC (OR 0.49, p<0.001) and PLND (OR 0.11, p<0.001), shorter LOS (b -4.66, <0.001), readmission rate (OR 0.72, p<0.001), and improved 30- and 90- day mortality (OR 0.55 & 0.75, p<0.001). In cT2 patients only: PLND and NAC were less utilized in PC (p<0.001), 32% were ≥pT3 and 6.6% node pos. In both full cohort and cT2 subset, PC was associated with slight improvement in time to mortality (Table) and overall survival (OS) (OR 1.44, p<0.001). Conclusions: PC is rarely used in treatment of MIBC. Despite guidelines, NAC and PLND are underutilized in PC. Care is required in selecting patients for PC as up to one third of cT2 patients have ≥pT3. In these likely highly selected patients, PC had lower peri-operative mortality and comparable OS to RC. Selection bias may play a role in these results and further investigation is needed to determine optimal candidates for PC.[Table: see text]


BMC Urology ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Agus Rizal A. H. Hamid ◽  
Fanny Riana Ridwan ◽  
Dyandra Parikesit ◽  
Fina Widia ◽  
Chaidir Arif Mochtar ◽  
...  

Abstract Background Most patients with muscle-invasive bladder cancer (MIBC) developed metastasis within 2 years, even after radical cystectomy (RC). The recurrence rate of MIBC was more than 50% of the cases. A meta-analysis conducted by Yin et al. showed that neoadjuvant chemotherapy (NAC) + RC improves overall survival in MIBC compared with RC only. However, a new meta-analysis by Li et al. concluded that NAC + RC was not superior to RC only in improving overall survival. The inconsistencies of these studies required further comprehensive analysis to recommend NAC use in bladder cancer treatment. Therefore, this meta-analysis aims to analyze previous studies that compare the efficacy of NAC + RC versus RC only to improve overall survival of MIBC. Methods The articles were searched using Pubmed with keywords “muscle-invasive bladder cancer”, “neoadjuvant chemotherapy”, “cystectomy”, and “overall survival”. The articles that were published until June 2020 were screened. The overall survival outcome was analyzed as hazard ratio (HR) and presented in a forest plot. Result Seventeen studies were included in meta-analysis with a total sample of 13,391 patients, consist of 2890 received NAC followed by RC and 10,418 underwent RC only. Two studies used methotrexate/vinblastine/doxorubicin/cisplatin (MVAC), two studies used gemcitabine/cisplatin (GC), one study used Cisplatin-based regimen, one study used MVAC or GC, one study used gemcitabine/carboplatin (GCarbo) or GC or MVAC, one study used Cisplatin/Gemcitabine or MVAC, one study used Cisplatin only, one study used Cisplatin-based (GC, MVAC) or non-Cisplatin-based (combined paclitaxel/gemcitabine/carboplatin), one study used GC, MVAC, Carboplatin, or Gemcitabine/Nedaplatin (GN), and five studies did not mention the regimen The overall survival in the NAC + RC only group was significantly better than the RC only group (HR 0.82 [0.71–0.95], p = 0.009). Conclusion NAC + RC is recommended to improve overall survival in MIBC patients. A further study assessing side effects and quality of life regarding NAC + RC is needed to establish a strong recommendation regarding this therapy.


2019 ◽  
Vol 5 (3) ◽  
pp. 235-244 ◽  
Author(s):  
Benjamin W. Fischer-Valuck ◽  
Soumon Rudra ◽  
Prashant Gabani ◽  
Randall Brenneman ◽  
Ryan Mueller ◽  
...  

2017 ◽  
Vol 8 (5) ◽  
pp. 852-860 ◽  
Author(s):  
Junlong Wu ◽  
Fangning Wan ◽  
Haoyue Sheng ◽  
Guohai Shi ◽  
Yijun Shen ◽  
...  

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 428-428
Author(s):  
Shingo Hatakeyama ◽  
Ayumu Kusaka ◽  
Hirotake Kodama ◽  
Noriko Tokui ◽  
Hayato Yamamoto ◽  
...  

428 Background: The prognostic benefit of oncological follow-up to detect asymptomatic recurrence after radical cystectomy (RC) remains unclear. We aimed to assess whether routine follow-up to detect asymptomatic recurrence after RC improves patient survival. Methods: We retrospectively analyzed 581 RC cases for muscle invasive bladder cancer at four hospitals between May 1996 and February 2017. All patients had regular follow-up examinations with urine cytology, blood biochemical tests, and computed tomography after RC. We investigated the first site and date of tumor recurrence. Overall survival in patients with recurrence stratified by the mode of recurrence (asymptomatic group vs. symptomatic group) was estimated using the Kaplan–Meier method with the log–rank test. Cox proportional hazards regression analysis via inverse probability of treatment weighting (IPTW) was used to evaluate the impact of the mode of diagnosing recurrence on survival. Results: Of the 581 patients, 175 experienced relapse. Among those, 12 without adequate data were excluded. Of the remaining 163 patients, 76 (47%) were asymptomatic and 87 (53%) were symptomatic at the time of diagnosis. The most common recurrence site and symptom were lymph nodes (47%) and pain (53%), respectively. Time of overall survival after RC and from recurrence to death were significantly longer in the asymptomatic group than symptomatic group. A multivariate Cox regression analysis using IPTW showed that in the patients with symptomatic recurrence was an independent risk factor for overall survival after RC and survival from recurrence to death. Conclusions: Routine oncological follow-up for detection of asymptomatic recurrence contributes to a better prognosis after RC.


2018 ◽  
Vol 104 (6) ◽  
pp. 434-437
Author(s):  
Hakan Türk ◽  
Sıtkı Ün ◽  
Ahmet Cinkaya ◽  
Hilmi Kodaz ◽  
Murtaza Parvizi ◽  
...  

Introduction: Radical cystectomy (RC) is the main treatment option for patients with muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC), which carry the highest risk of progression. In this study, we investigated the effect of time from transurethral resection of the bladder (TUR-B) to cystectomy on lymph node positivity, cancer-specific survival and overall survival in patients with MIBC. Methods: The records were reviewed of 530 consecutive patients who had RC and pelvic lymphadenectomy procedures with curative intent performed by selected surgeons between May 2005 and April 2016. Our analysis included only patients with transitional cell carcinoma of the bladder; we excluded 23 patients with other types of tumor histology. Results: Patients who underwent delayed RC were compared with patients who were treated with early RC; both groups were similar in terms of age, gender, T stage, tumor grade, tumor differentiation, lymph node status and metastasis status. However, when both groups were compared for disease-free survival and overall survival, patients of the early-RC group had a greater advantage. Conclusions: The optimal time between the last TUR-B and RC is still controversial. A reasonable time for preoperative preparation can be allowed, but long delays, especially those exceeding 3 months, can lead to unfavorable outcomes in cancer control.


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