Despite current treatment strategies, the 5-year overall survival of muscle-invasive bladder cancer (MIBC) is approximately 50%. Historically, radical cystectomy (RC) with neoadjuvant chemotherapy has been the first-choice treatment for this patient group. Recently, several studies have reported encouraging results of using immune checkpoint inhibitors (ICI) prior to RC. However, in recent years, bladder-sparing alternatives such as CRT have gained popularity. The effect of radiotherapy on the tumor microenvironment is an important rationale for combining CRT with ICI therapy. Worldwide, twelve immunochemoradiotherapy (iCRT) trials are ongoing. Each study employs a different chemotherapy and radiotherapy regimen and varies the timing of ICI administration concurrent to radiotherapy, adjuvant, or both. Five studies have presented (preliminary) results showing promising safety and short-term survival data. The first peer-reviewed publications are expected in the near future. The preclinical evidence and preliminary patient data demonstrate the potential of iCRT bladder-sparing treatment for bladder cancer.

Concurrent chemoradiotherapy (CRT) as a definitive treatment option for patients with nonmetastatic muscle-invasive bladder carcinoma (MIBC) is increasingly being applied in clinical practice. To assess the oncological and toxicity outcomes in a contemporary cohort of nonmetastatic MIBC patients treated with concurrent CRT in daily practice. Patients with nonmetastatic MIBC (cT2-4aN0M0) who had received CRT with curative intent between January 2010 and April 2020 in three centers were retrospectively identified. The CRT consisted of 66 Gy (or biologically equivalent) plus either mitomycin C and fluorouracil/capecitabine or cisplatinum. The primary endpoint was the 2-yr locoregional disease-free survival (LDFS) estimate. Secondary endpoints were complete response, disease-specific survival (DSS), overall survival (OS), bladder intact event-free survival (BI-EFS), and severe adverse events (<90 d of starting CRT). Kaplan-Meier survival and Cox multivariable regression analyses were performed. We included data of 240 MIBC patients with a median age of 74 yr and a median follow-up of 27 mo (interquartile range 11–44). Complete response on first cystoscopy after CRT was seen in 209 cases (90%). The 2-yr LDFS was 76% (95% confidence interval [CI] 70–82%); the 5-yr OS and DSS were 50% (95% CI 42–59%) and 70% (95% CI 62–79%), respectively. On multivariable analysis, cT2 versus cT3–4 tumor stage was significantly associated with better DSS (hazard ratio 1.02, 95% CI 1–1.05, p = 0.024). The 2-yr BI-EFS was 75% (95% CI 69–82%). Forty-three (17%) patients experienced a severe adverse event (grade ≥3). Limitations include retrospective design and heterogeneous administration of CRT. Concurrent CRT is a safe and effective treatment modality for nonmetastatic MIBC. Chemoradiotherapy for the treatment of muscle-invasive bladder carcinoma is increasingly being applied. In this study, we reviewed the outcomes of this bladder-sparing treatment using a series of patients treated in three hospitals in daily practice. We found that administration of chemoradiotherapy can be safe and effective.

Urothelial bladder cancer (UCB) care requires frequent follow-up cystoscopy and surgery. Confocal laser endomicroscopy (CLE), a probe-based optical technique for real-time microscopic evaluation, has shown promising accuracy for grading of UCB. We investigated the diagnostic accuracy of CLE-based assessment of the surgical radicality of the bladder resection bed (RB). We prospectively included 40 participants scheduled for transurethral resection of bladder tumors (TURBT) in two academic hospitals. Exclusion criteria were flat lesions, fluorescein allergy, and pregnancy. We performed CLE of the RB during TURBT. Histopathology of an RB biopsy was the reference test. Results at first cystoscopy 3 mo after TURBT are reported. A panel of two blinded observers evaluated the CLE images. The diagnostic accuracy of CLE for detection of detrusor muscle (DM) and residual tumor (rT) was calculated using 2 × 2 tables. Histopathology for 22 CLE-matched RB biopsies revealed rT in four cases (18%) and DM in 13 (59%). The quality of CLE imaging was low in four (18%), moderate in 16 (73%), and good in two (9%) cases. CLE was able to correctly predict rT in two of the four cases (50%) identified on histopathology. The sensitivity, specificity, positive predictive value, and negative predictive value were 0.5 (95% confidence interval [CI] 0.07–0.93), 0.83 (95% CI 0.59–0.96), 0.4 (95% CI 0.05–0.85), and 0.88 (95% CI 0.64–0.99) for CLE prediction of rT, and 0.69 (95% CI 0.39–0.91), 0.33 (95% CI 0.07–0.7), 0.6 (95% CI 0.32–0.84), and 0.43 (95% CI 0.1–0.82) for prediction of DM, respectively. Five patients (23%) had rT at 3-mo follow-up; CLE had predicted rT in three, and histopathology had revealed rT in two cases at TURBT. CLE does not appear to be a reliable tool for detecting rT or DM in the RB after TURBT. We investigated a special imaging technique called confocal laser endomicroscopy (CLE) for checking the bladder after surgery for bladder cancer in a group of 40 patients. CLE results were compared to traditional biopsy results and the patients were checked after 3 months. CLE was not very reliable in detecting any remaining cancer (only 50% accurate) or important muscle tissue in the surgical area, and the quality of the images varied. While CLE shows some promise, it is not currently a dependable method for evaluating the bladder after bladder cancer surgery.

Purpose: Urothelial bladder cancer (UCB) care requires frequent follow-up cystoscopy and surgery. Confocal laser endomicroscopy (CLE) is a probe-based optical technique that can provide real-time microscopic evaluation with the potential for outpatient grading of UCB. This study aims to investigate the diagnostic accuracy and interobserver variability for the grading of UCB with CLE during flexible cystoscopy (fCLE). Methods: Participants scheduled for transurethral resection of papillary bladder tumors were prospectively included for intra-operative fCLE. Exclusion criteria were flat lesions, fluorescein allergy or pregnancy. Two independent observers evaluated fCLE, classifying tumors as low- or high-grade urothelial carcinoma (LGUC/HGUC) or benign. Interobserver agreement was calculated with Cohens kappa (κ) and diagnostic accuracy with 2 × 2 tables. Histopathology was the reference test. Results: Histopathology of 34 lesions revealed 14 HGUC, 14 LGUC and 6 benign tumors. Diagnostic yield for fCLE was 80–85% with a κ of 0.75. Respectively, sensitivity, specificity, NPV and PPV were: for benign tumors 0–20%, 96–100%, unmeasureable-50% and 87%, for LGUC 57–64%, 41–58%, 44–53% and 54–69% and for HGUC 38–57%, 56–68%, 38–57% and 56–68%, with an interobserver agreement of κ 0.61. Conclusion: fCLE is currently insufficient to grade UCB.

4531 Background: Neoadjuvant nivolumab (nivo) + ipilimumab (ipi) prior to radical cystectomy showed efficacy in localized MIBC. The safety of PD-1 and PDL-1+CTLA4 inhibition concurrent with CRT in localized MIBC has not been assessed. We present the first clinical trial data on concurrent 3 doses of q4w nivo 480mg (cohort1) and concurrent 4 doses of q3w nivo 3mg/kg + ipi 1kg/mg (nivo3+ipi1, cohort2) in combination with Mitomycin C/Capecitabin (MMC/Cape) CRT. Methods: We report the first 2 cohorts of a phase 1b, EC approved, study with nivo only or nivo3+ipi1 added to MMC/Cape CRT. CRT consists of MMC i.v. on day 1 with Cape 750mg/m2 on days of radiotherapy. Radiotherapy schedule comprises a 20x2Gy whole bladder irradiation with a simultaneous tumorboost of 20x0.75Gy. Patients with MIBC, T2-4N0-1, ECOG performance status <2 were included. A dose escalation scheme, with a staggered enrollment is used. The first 10 patients received nivo 480mg on week 1, 5, 9. Cohort2 of 10 patients received nivo3+ ipi1 at week 1, 4, 7 and 10. Relevant severe Adverse Events (AEs) were registered as Dose Limiting Toxicity (DLT) when they occurred within 6 weeks after start of treatment. Clinical efficacy is evaluated by cystoscopy and CT at week 12 and 24. Results: Both cohorts enrolled 10 patients. Median age was 68 [IQR 61-75] and 70 [IQR 66-75] years in cohort1 and 2, respectively. In cohort1 no patients experienced DLT. No dose reductions were applied. In cohort2, 2 patients experienced DLT, 1 trombocytopenia (grade 4) and 1 asystole (grade 5). 50% of patients did not receive all 4 q3w nivo3+ipi1 infusions, due to AEs. Table 1 reports an overview of AEs. In cohort2 6 SAE’s occurred in 3 patients. Median follow up is 71 [IQR 59-86] and 30 weeks [IQR 12-45] in cohort1 and 2, respectively. 1year OS and DFS is 100% in cohort1. Conclusions: Concurrent 3 doses nivo 480mg q4w added to MMC/Cape based CRT is feasible with a favorable toxicity profile and shows promising efficacy in MIBC patients. An escalated regimen with 4 doses nivo 3mg/kg + ipi 1mg/kg q3w concurrent to CRT shows acceptable toxicity. Cohort3 with ipi 3mg/kg and nivo 1mg/kg is enrolling. Clinical trial information: NCT03844256. [Table: see text]

BACKGROUND: Health Related Quality of Life (HRQoL) is an important factor regarding treatment for localized Muscle Invasive Bladder Carcinoma (MIBC), as it may affect choice of treatment. The impact of chemoradiotherapy (CRT) for MIBC on HRQoL has not yet been well-established. OBJECTIVE: To systematically evaluate evidence regarding HRQoL as assessed by validated questionnaires after definitive treatment with CRT for localized MIBC. METHODS: We performed a critical review of PubMed/MEDLINE, EMBASE, and the Cochrane Library in October 2020. Two reviewers independently screened articles for eligibility and assessed the methodological quality of the included articles using Joanna Briggs Institute critical appraisal tools. A narrative synthesis was undertaken. RESULTS: Of 579 articles identified, 11 studies were eligible for inclusion, including three RCTs and 8 non-randomized studies, reporting on HRQoL data for 606 CRT patients. Global health declined at End of Treatment (EoT), and recovered 3 months following treatment. Physical function declined from baseline at EoT and recovered between 3 and 24 months and was maintained at 5 years follow up. CRT had little effect on social and emotional function in the short-term, but HRQoL results in the long-term were lower compared to the general population. Urinary function declined from baseline at EoT, but returned to baseline at 6 months following CRT. After initial decline in bowel function, a complete return to baseline occurred 4 years following treatment. The majority of studies assessing sexual function showed no to little effect on sexual function. CONCLUSIONS: HRQoL recovers to baseline within 3 months to 2 years in almost all domains. The amount of available evidence regarding HRQoL following CRT for MIBC is limited and the quality of evidence is low.