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Clinical impact of T cells, B cells and the PD-1/PD-L1 pathway in muscle invasive bladder cancer: a comparative study of transurethral resection and cystectomy specimens.

ABSTRACT: In patients with muscle invasive bladder cancer (MIBC), neoadjuvant chemotherapy (NAC) prior to radical cystectomy has improved survival but there is an urgent unmet need to identify prognostic and predictive biomarkers to stratify patients who will benefit from treatment. This study aimed to examine the composition of tumor-infiltrating immune cells in MIBC, with particular reference to the clinical outcome and the potential modifying effect of NAC. To this end, the expression of CD8⁺ and FoxP3⁺ T cells, CD20⁺ B cells, PD-1⁺ and PD-L1⁺ immune cells and PD-L1⁺ tumor cells was evaluated by immunohistochemistry on tissue microarrays with paired transurethral resection (TURB) specimens, cystectomy specimens and lymph node metastases from 145 patients, 65 of whom had received NAC. Kaplan-Meier and Cox regression analyses were applied to assess the impact of investigated cell subsets on time to recurrence (TTR). In cystectomy specimens, high infiltration of the investigated immune cell populations, but not PD-L1⁺ tumor cells, were independently associated with a prolonged TTR, whereas in TURB specimens, this association was only seen for CD8⁺ lymphocytes. An additive beneficial prognostic effect of NAC was seen for the majority of the cell subsets but there was no significant interaction between any immune marker and NAC in relation to TTR. Furthermore, no differences in cell densities prior to NAC treatment were observed between complete and non-complete responders, or pre- and posttreatment in non-complete responders. In conclusion, immune cell infiltration provides important prognostic information in both pre- and postsurgical samples of MIBC, independently of NAC.

SUBMITTER: Wahlin S

PROVIDER: S-EPMC6791444 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Clinical impact of T cells, B cells and the PD-1/PD-L1 pathway in muscle invasive bladder cancer: a comparative study of transurethral resection and cystectomy specimens.

Wahlin Sara S Nodin Björn B Leandersson Karin K Boman Karolina K Jirström Karin K

Oncoimmunology 20190803 11

In patients with muscle invasive bladder cancer (MIBC), neoadjuvant chemotherapy (NAC) prior to radical cystectomy has improved survival but there is an urgent unmet need to identify prognostic and predictive biomarkers to stratify patients who will benefit from treatment. This study aimed to examine the composition of tumor-infiltrating immune cells in MIBC, with particular reference to the clinical outcome and the potential modifying effect of NAC. To this end, the expression of CD8<sup>+</sup ...[more]

PMID: 31646091

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Project description:OBJECTIVE:To explore the diagnostic performance of image technique based transurethral resection for bladder cancer, with white light-guided cystoscopy (WLC) as the reference standard. DESIGN:Systematic review and meta-analysis. DATA SOURCES:PubMed/MEDLINE, Web of Science, the Cochrane Library, Central Register of Controlled Trials and Embase from inception to 31 March 2018. METHODS:Included studies reported the diagnostic performance of photodynamic diagnosis (PDD) with 5-aminolevulinic acid (5-ALA), PDD with hexaminolevulinic acid (HAL) or narrow band imaging (NBI), with WLC as the reference standard at the patient or lesion level. The studies' risk of bias (RoB) was assessed using Quality Assessment of Diagnostic Studies-2. Data were pooled using a random effect diagnostic meta-analysis, and subgroup analyses were performed. RESULTS:Twenty-six studies comprising a total of 3979 patients were included in this diagnostic meta-analysis. Pooled sensitivity (SSY), specificity (SPY), diagnostic OR (DOR) and area under the receiver operating characteristic curve (AUROC) values were calculated per group for NBI, HAL and 5-ALA at the lesion or patient level. NBI showed significant diagnostic superiority compared with WLC at the lesion level (SSY 0.94, 95% CI 0.82 to 0.98; SPY 0.79, 95% CI 0.73 to 0.85; DOR 40.09, 95% CI 20.08 to 80.01; AUROC 0.88, 95% CI 0.85 to 0.91). NBI presented the highest DOR (358.71, 95% CI 44.50 to 2891.71) in the patient level. Subgroup analyses were performed on studies with low to moderate RoB and at least 100 patients at the lesion level. These results were consistent with those of the overall analysis. CONCLUSIONS:Pooled data indicated that image technique based transurethral resection (NBI, HAL and 5-ALA) showed diagnostic superiority compared with WLC. Moreover, NBI is potentially the most promising diagnostic intervention, showing the best diagnostic performance outcomes. Further prognostic outcomes of novel imaging technologies compared with those WLC should be explored in addition to current diagnostic performance analysis.

Project description:BackgroundTransurethral resection of bladder tumor (TURBT) is an essential procedure both for the treatment and staging of bladder cancer, particularly non-muscle invasive bladder cancer (NMIBC). The dissemination of cancer cells during resection and the consequent seeding into the bladder mucosa is the main cause of post-TURBT intravesical recurrence. Although the tumor dissemination is inevitable during conventional TURBT (cTURBT), this drawback can be overcome by tumor resection in one piece with intact surrounding normal tissues, referred to as en bloc resection. We previously described the photodynamic diagnosis (PDD)-assisted en bloc TURBT (EBTUR) technique and its favorable outcomes. Based on our preliminary studies, this randomized controlled trial was designed to evaluate the superiority of PDD-EBTUR to PDD-cTURBT.MethodsThe FLEBER study is a single-center randomized controlled trial in NMIBC patients who require TURBT. The longest diameter of the tumor must be between 6 and 30 mm. A total of 160 eligible patients will be enrolled after screening and randomly allocated to the PDD-EBTUR (experimental) and PDD-cTURBT (control) groups in a 1:1 ratio (80 cases to 80 cases). All patients will be treated using a single, immediate postoperative intravesical chemotherapy with epirubicin. The primary endpoint of this trial is the 2-year recurrence-free survival after surgery in pathologically proven low- or intermediate-risk NMIBC. All patients will be monitored by cystoscopy and urine cytology every 3 months for 2 years. Patient data including adverse events and complications, and data from frequency volume charts, pain scales, and health-related QOL questionnaires will be collected before and after the TURBT at indicated visits.DiscussionThe goal of this trial is to determine the potential benefits of PDD-cTURBT and PDD-EBTUR followed by a single immediate postoperative intravesical chemotherapy in patients with low- or intermediate-risk NMIBC who undergo TURBT. Ultimately, our findings will lead to the development of better interventions and potentially change the standard of care.Trial registrationThis clinical trial was prospectively registered with the UMIN Clinical Trials Registry on 1 August 2020. The reference number is UMIN000041273 , and the Ethics Committee of Nara Medical University Approval ID is 2702.

Dataset Information

Clinical impact of T cells, B cells and the PD-1/PD-L1 pathway in muscle invasive bladder cancer: a comparative study of transurethral resection and cystectomy specimens.

Publications

Clinical impact of T cells, B cells and the PD-1/PD-L1 pathway in muscle invasive bladder cancer: a comparative study of transurethral resection and cystectomy specimens.

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