Adjuvant Radiotherapy After Radical Cystectomy for Patients with High-risk Muscle-invasive Bladder Cancer: Results of a Multicentric Phase II Trial

TPS4591 Background: Radical cystectomy is the standard of care for patients with BCG-unresponsive high risk non-muscle invasive bladder cancer (NMIBC). Based on the reported efficacy of atezolizumab in metastatic urothelial carcinoma and the known expression of PD-L1 expression in NMIBC after BCG therapy, this trial will evaluate the activity of atezolizumab in BCG-unresponsive high risk NMIBC. Methods: This is a single arm phase II trial testing systemic atezolizumab (1200 mg IV) every 3 weeks for one year in 135 patients with BCG-unresponsive high risk NMIBC. The study will enroll 70 patients with CIS (with or without concomitant Ta/T1) and 65 with Ta/T1 only. Patients with CIS at baseline will undergo mandatory repeat biopsy at 6 months, and all other patients only for suspected recurrence. Patients with persistent CIS, high grade Ta/T1 recurrence or progression to muscle invasive or metastatic disease will be taken off treatment. The co-primary endpoints are: (1) complete response (CR) at 6 months in the CIS subgroup, and (2) event-free survival (EFS) at 18 months in the overall population. A hierarchical approach will be used to test the two co-primary endpoints. Secondary endpoints include duration of CR as well as progression-free, cystectomy-free, bladder cancer-specific and overall survival in all patients. Response will be correlated to expression of PD-L1 and CD8 by IHC, and to molecular subtypes and immune signatures by RNA-sequencing. Results: If ≥28 (40%) CIS patients respond, the agent will be considered promising. This design has a significance level of 4.6%, and a power of 96%. If the lower bound of the 90% confidence interval of the 18-month EFS excludes 20%, the investigators will conclude the regimen significantly improves EFS relative to historical data (type I error rate 0.05 and statistical power 0.93). Conclusion:Successful completion of this trial could lead to a new treatment paradigm for patients with BCG-unresponsive high risk NMIBC. Funding: NIH/NCI grants: CA180888, CA180819, CA180820, CA180821, and CA180863. Clinical trial information: NCT02844816.

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Adjuvant radiotherapy use after radical cystectomy in muscle-invasive bladder cancer: A survey of U.S. radiation oncologists.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.6_suppl.369 ◽

2017 ◽

Vol 35 (6_suppl) ◽

pp. 369-369

Author(s):

Abhishek Ashok Solanki ◽

Brendan Martin ◽

Mark Korpics ◽

Christina Small ◽

Matthew M. Harkenrider ◽

...

Keyword(s):

Bladder Cancer ◽

Logistic Regression ◽

High Risk ◽

Radical Cystectomy ◽

Adjuvant Radiotherapy ◽

Transitional Cell ◽

Invasive Bladder Cancer ◽

Muscle Invasive Bladder Cancer ◽

Radiation Oncologists ◽

Muscle Invasive

369 Background: Historic trials suggested significant toxicity with adjuvant radiotherapy (ART) after radical cystectomy for muscle-invasive bladder cancer (MIBC). However, recent trials have found improved locoregional control and the 2016 NCCN guidelines recommend ART consideration for select patients at high risk of local recurrence. ART practice patterns among U.S. radiation oncologists (ROs) are unknown, and we performed a survey to explore current trends. Methods: We conducted a survey of U.S. ROs regarding the management of patients with cT2-3N0M0 transitional cell MIBC. Responses were reported using descriptive statistics. Chi-square and univariate logistic regression (UVA) of clinical and demographic covariates were conducted, followed by multivariable logistic regression analyses (MVA) to identify factors predicting for ART use. Results: 277 ROs completed our survey. Nearly half (46%) use ART for MIBC. In ART-users, indications for ART include gross residual disease (93%), positive margins (92%), pathologic nodal involvement (64%), pT3 or T4 disease (46%), lymphovascular invasion (16%), and high-grade disease (13%). On UVA, ART use was associated with the number of years in practice (p=.043), pre-cystectomy RO consultation (p=0.004), primarily treating MIBC patients fit for cystectomy (p=0.009), and intensity-modulated radiotherapy (IMRT) use (p=0.009). On MVA, routine pre-cystectomy RO consultation (odds ratio [OR] 1.91, 95% confidence interval [CI]: 1.04-3.51; p=.037) and IMRT use (OR 2.77, 95% CI: 1.48-5.22; p=.002) remained associated with ART use. Conclusions: ART use is controversial in bladder cancer, yet is unexpectedly commonly used among U.S. radiation oncologists treating patients with MIBC after radical cystectomy. NRG GU001 is a randomized trial currently accruing patients with high-risk pathologic findings for observation or ART after cystectomy, and will hopefully clarify the role of ART and help identify patients benefiting from this adjuvant therapy. Whenever possible, patients should be enrolled in this study.

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