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Efficacy of High Intensity Local Treatment for Metastatic Bladder Cancer
Alexander P. Cole, MD1, Thomas Seisen, MD2, Francisco Gelpi-Hammerschmidt, MD1, Nawar Hanna, MD1, Mark A. Preston, MD, MPH1, Quoc-Dien Trinh, MD1.
1Harvard Medical School, Brigham and Womens Hospital, Boston, MA, USA, 2Harvard Medical School, Center for Surgery and Public Health, Boston, MA, USA.

Introduction: There is evidence from other malignancies about the benefit of aggressive local treatment (LT) even in the setting of metastatic disease. Against a backdrop of stagnant mortality rates for metastatic Bladder Cancer (mBCa), we hypothesized that high-intensity LT of primary tumor, defined as the receipt of radical cystectomy or >50 Gy of radiation therapy to the bladder, may impact overall survival (OS).
Materials and Methods: Within the National Cancer Data Base (NCDB), we identified 3,753 patients who received a multi-agent systemic chemotherapy combined with either high-intensity vs. conservative LT for primary mBCa. We defined as high intensity localized therapy those, patients who received radical cystectomy (RC) or >50Gy of radiation therapy (RT) to the pelvis. The conservative LT included patients who did not receive LT, or patients who received TURBT alone and/or palliative RT <50Gy in the pelvis. Inverse probability of treatment weighting (IPTW)-adjusted Kaplan Meier curves and Cox regression analyses were used to compare the overall survival (OS) of patients who received high-intensity vs. conservative LT.
Results: Overall, 297 (7.91%) and 3,456 (92.09%) patients with mBCa underwent high-intensity and conservative LT. Following IPTW adjustment of all variables, the distribution of baseline patient characteristics was similar. IPTW-adjusted Kaplan-Meier curves showed that median OS was longer in the high-intensity LT group (14.92 months [IQR, 9.82-30.19 months] vs 9.95 months [IQR, 5.29-17.08 months]; P < 0.001). Furthermore, in IPTW-adjusted Cox regression analysis, high-intensity LT was associated with a significant OS benefit (HR = 0.56; 95% CI = [0.48-0.65]; P < 0.001).
Conclusions: We report an OS benefit for individuals presenting with mBCa treated with high-intensity LT, compared with their counterparts treated with conservative LT. While the findings are subject to the usual biases related to the observational study design, our preliminary data warrant further consideration for randomized clinical trials to explore this question, particularly given the poor prognosis associated with mBCa.


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