key: cord-0921673-4hynqy38
authors: Fischer-Valuck, Benjamin W.; Michalski, Jeff M.; Harton, Joanna G.; Birtle, Alison; Christodouleas, John P.; Efstathiou, Jason A.; Arora, Vivek K.; Kim, Eric H.; Knoche, Eric M.; Pachynski, Russell K.; Picus, Joel; Rao, Yuan James; Reimers, Melissa; Roth, Bruce J.; Sargos, Paul; Smith, Zachary L.; Zaghloul, Mohamed S.; Gay, Hiram A.; Patel, Sagar A.; Baumann, Brian C.
title: Management of muscle-invasive bladder cancer during a pandemic: Impact of treatment delay on survival outcomes for patients treated with definitive concurrent chemoradiation
date: 2020-06-22
journal: Clin Genitourin Cancer
DOI: 10.1016/j.clgc.2020.06.005
sha: 071350011332c4d350e7bcaa62370d3b4ab26e7f
doc_id: 921673
cord_uid: 4hynqy38

INTRODUCTION: During the COVID-19 pandemic, providers and patients must engage in shared decision-making to ensure that the benefit of early intervention for muscle-invasive bladder cancer (MIBC) exceeds the risk of contracting COVID-19 in the clinic setting. It is unknown whether treatment delays for MIBC patients eligible for curative chemoradiation (CRT) compromise long-term outcomes. PATIENTS AND METHODS: In this study, we used the National Cancer Database to investigate if there is an association between a ≥90-day delay from TURBT in initiating CRT and overall survival (OS). We included patients with cT2-4N0M0 MIBC from 2004-2015 who underwent TURBT and curative-intent concurrent CRT. Patients were grouped based on timing of CRT: ≤89 days after TURBT (‘earlier’) vs. ≥ 90 & <180 days after TURBT (‘delayed’). RESULTS: 1,387 (87.5%) received ‘earlier’ CRT (median 45 days post-TURBT, IQR: 34-59 days) and 197 (12.5%) received ‘delayed’ CRT (median 111 days post-TURBT, IQR: 98-130 days). Median OS was 29.0 months (95% CI, 26.0-32.0) versus 27.0 months (95% CI, 19.75-34.24) for ‘earlier’ and ‘delayed’ CRT, respectively (p=0.94). On multivariable analysis, delayed CRT was not associated with an OS difference: hazard ratio, 1.05 (95% CI, 0.87-1.27); p=0.60. CONCLUSION: While these results are limited and require validation, short strategic treatment delays during a pandemic can be considered based on clinician judgement.

• In our analysis, 12.5% of patients with muscle-invasive bladder cancer (MIBC) had a delay over 90 days (median 111 days) from transurethral resection of bladder tumor (TURBT) to starting definitive intent chemoradiation therapy (CRT) • Treatment delays over 90 days were more common for patients living in rural communities and for those living a further distance to treatment facility • We observed no difference in overall survival between patients treated with earlier CRT compared to those with delayed CRT • During pandemics such as COVID-19, short strategic delays in starting CRT can be considered on a case-by-case basis to reduce the patient's risk of contracting the infection. Clinician judgment is critical in making these decisions Abstract:

Introduction: During the COVID-19 pandemic, providers and patients must engage in shared decision-making to ensure that the benefit of early intervention for muscle-invasive bladder cancer (MIBC) exceeds the risk of contracting COVID-19 in the clinic setting. It is unknown whether treatment delays for MIBC patients eligible for curative chemoradiation (CRT) compromise long-term outcomes. (9) . The optimal timing of CRT after TURBT has not been determined. In this study, we sought to determine if there is an association between the timing of CRT initiation and overall survival (OS). We hypothesized that delays in initiating definitive CRT following TURBT may not be associated with decreased overall survival.

We identified cT2-4N0M0 MIBC patients between 18-90 years-old in the National (6), or no impact when the delay was <5 months (7). A SEER analysis, by contrast, reported that cT2N0 patients who underwent RC more than 11 weeks after NAC had worse OS than patients who underwent earlier RC (10) . For patients treated with RC alone, treatment delays may be associated with worse outcomes, but results in the literature are mixed (10) (11) (12) (13) (14) . It may be hypothesized that delays in cystectomy patients who do not receive NAC may lead to tumor progression and higher rates of positive margins or lymph node metastases which in turn decrease survival, whereas radiotherapy with radiosensitizing chemotherapy can effectively treat a larger target volume with less risk for a marginal miss than cystectomy.

This observational study has several limitations, many of which are inherent to the retrospective, non-randomized nature of the analysis. Firstly, it should be noted that the only method to definitively determine the effect of delays in CRT on OS is a randomized trial powered to detect such a difference. While we found no difference in OS for patients who had delayed CRT, this data was not prospectively collected nor randomized and powered to detect such a difference. Another notable limitation of the NCDB is that there is no reporting on oncologic outcomes such as recurrence-free survival, progression-free survival, or salvage cystectomy rates (15). It is therefore unclear if patients who were delayed had worse cancerspecific mortality even if their OS did not appear to be affected. Given the retrospective design using a population-based database, analyses are subject to selection biases and imbalances in measured and unmeasured variables. However, multivariable modeling was utilized to address potential confounding. Relatively few patients (12.2%) were delayed >150 days, so the impact of such a long delay is not well understood. Another limitation is the lack of key variables which are not included in the NCDB, including detailed information regarding extent and outcomes of the TUBRT as well as radiation treatment volumes (e.g. elective nodal irradiation vs bladder alone). Comprehensive information on chemotherapeutic agents (e.g. cisplatin vs non-cisplatin based) and their dosing are also not available in the NCDB. Surveillance schedules are also lacking in the NCDB. Lastly, the median OS for patient's in our cohort is lower than would be expected for trimodality bladder preservation in cystectomy candidates who have lower competing mortality risk due to other causes. It is unclear whether the results of this study would apply to trimodality bladder preservation patients. Caution should also be taken when applying these findings to more locally advanced disease (cT3/4) given the limited number of such patients included in the delayed CRT group (N=22).

While • In our analysis, 12.5% of patients with muscle-invasive bladder cancer (MIBC) had a delay over 90 days (median 111 days) from transurethral resection of bladder tumor (TURBT) to starting definitive intent chemoradiation therapy (CRT) • Treatment delays over 90 days were more common for patients living in rural communities and for those living a further distance to treatment facility • We observed no difference in overall survival between patients treated with earlier CRT compared to those with delayed CRT • During pandemics such as COVID-19, short strategic delays in starting CRT can be considered on a case-by-case basis to reduce the patient's risk of contracting the infection. Clinician judgment is critical in making these decisions

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Author contributions: Writing, data analysis: BFV, JMM, JGH, HAG, AB, JPC, SAP, BCB Critical review, editing, and approval of final manuscript: All authors