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Trends in Treatment Strategies and Comparison of Outcomes in Lymph Node Positive Bladder Cancer: An Analysis of the National Cancer Database

      OBJECTIVE

      To utilize a national dataset to compare outcomes and demonstrate trends in treatment for lymph node positive bladder cancer (N+ BC).

      METHODS

      The National Cancer Database (2006-2014) was queried for cT2-4N1-3M0 N+ BC patients treated with radical cystectomy alone (RC), neoadjuvant chemotherapy (NAC), adjuvant chemotherapy (AC), chemoradiation (CRT), chemotherapy alone (CT), or no definitive treatment (NT). Survival by treatment was analyzed using Kaplan-Meier and multivariable Cox-proportional hazards regression. Pathologic down-staging was analyzed using univariable and multivariable logistic regression models. A univariable logistic regression model of treatment by year identified treatment trends.

      RESULTS

      Among 3241 patients (cN1, 46%; cN2, 44%; cN3 10%), the majority underwent combined chemotherapy and RC (NAC, 418; AC, 591; RC, 567; CRT, 392; CT, 1068; NT, 205). Overall survival did not differ between NAC and AC, but both had improved survival compared to RC. All other treatment groups had worse survival outcomes compared to NAC. Down-staging to pT0 (adjusted odds ratio = 26.39) and pN0 (adjusted odds ratio = 6.88) was higher for NAC than RC. Utilization of NAC has increased, AC and RC has declined, and CRT and NT is unchanged.

      CONCLUSION

      Combined chemotherapy and RC demonstrates best survival outcomes for N+ BC, with complete pathologic response to pT0N0 after NAC associated with a 5-year overall survival rate of ∼85%. However, there is no significant difference between NAC and AC. CRT is associated with worse oncologic outcomes compared to RC with perioperative chemotherapy, but improved survival compared to RC or CT.
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      References

        • Siegel RL
        • Miller KD
        • Jemal A
        Cancer statistics, 2019.
        CA Cancer J Clin. 2019; 69: 7-34https://doi.org/10.3322/caac.21551
        • Galsky MD
        • Stensland K
        • Sfakianos JP
        • et al.
        Comparative effectiveness of treatment strategies for bladder cancer with clinical evidence of regional lymph node involvement.
        J Clin Oncol. 2016; 34: 2627-2635https://doi.org/10.1200/JCO.2016.67.5033
        • Power NE
        • Kassouf W
        • Bell D
        • et al.
        Natural history of pT3-4 or node positive bladder cancer treated with radical cystectomy and no neoadjuvant chemotherapy in a contemporary North-American multi-institutional cohort.
        J Can Urol Assoc. 2012; 6: 217-223https://doi.org/10.5489/cuaj.11012
        • Stein BJP
        • Lieskovsky G
        • Cote R
        • et al.
        Radical cystectomy in the treatment of invasive bladder cancer : long-term results in 1,054 patients.
        J Clin Oncol. 2011; 19: 666-675
        • Türkölmez K
        • Tokgöz H
        • Reşorlu B
        • Köse K
        • Bedük Y
        Muscle-invasive bladder cancer: predictive factors and prognostic difference between primary and progressive tumors.
        Urology. 2007; 70: 477-481https://doi.org/10.1016/j.urology.2007.05.008
        • Vale CL
        Neoadjuvant chemotherapy in invasive bladder cancer: update of a systematic review and meta-analysis of individual patient data.
        Eur Urol. 2005; 48: 202-205https://doi.org/10.1016/j.eururo.2005.04.006
        • Bellmunt J
        • Von Der Maase H
        • Mead GM
        • et al.
        Randomized phase III study comparing paclitaxel/cisplatin/ gemcitabine and gemcitabine/cisplatin in patients with locally advanced or metastatic urothelial cancer without prior systemic therapy: EORTC intergroup study 30987.
        J Clin Oncol. 2012; 30: 1107-1113https://doi.org/10.1200/JCO.2011.38.6979
        • von der Maase H
        • Hansen SW
        • Roberts JT
        • et al.
        Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study.
        Lancet. 2000; 17: 3068-3077
        • Grossman HB
        • Natale RB
        • Tangen CM
        • et al.
        Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer.
        N Engl J Med. 2003; 349: 859-866https://doi.org/10.1056/NEJMoa022148
      1. National Comprehensive Cancer Network. Bladder cancer. Version 1.2020. https://www.nccn.org/professionals/physician_gls/pdf/bladder.pdfAccessed December 12, 2019.

        • Herr HW
        • Donat SM
        Outcome of patients with grossly node positive bladder cancer after pelvic lymph node dissection and radical cystectomy.
        J Urol. 2001; 165: 62-64https://doi.org/10.1097/00005392-200101000-00015
        • Zhang S
        • Yu Y
        • Zhang Y
        • Qu W
        • Li J
        Radiotherapy in muscle-invasive bladder cancer : the latest research progress and clinical application.
        Am J Cancer Res. 2015; 5 (doi. ISSN:2156-6976/ajcr0003611): 854-868
        • Herr HW
        • Dotan Z
        • Donat SM
        • Bajorin DF
        Defining optimal therapy for muscle invasive bladder cancer.
        J Urol. 2007; 177: 437-443https://doi.org/10.1016/j.juro.2006.09.027
        • Petrelli F
        • Coinu A
        • Cabiddu M
        • Ghilardi M
        • Vavassori I
        • Barni S
        Correlation of pathologic complete response with survival after neoadjuvant chemotherapy in bladder cancer treated with cystectomy: a meta-analysis.
        Eur Urol. 2013; 65: 1-8https://doi.org/10.1016/j.eururo.2013.06.049
        • Hermans TJN
        • Fransen van de Putte EE
        • Horenblas S
        • et al.
        Pathological downstaging and survival after induction chemotherapy and radical cystectomy for clinically node-positive bladder cancer—results of a nationwide population-based study.
        Eur J Cancer. 2016; 69: 1-8https://doi.org/10.1016/j.ejca.2016.09.015
        • Matsubara N
        • Mukai H
        • Naito Y
        • Nezu M
        • Itoh K
        Comparison between neoadjuvant and adjuvant gemcitabine plus cisplatin chemotherapy for muscle-invasive bladder cancer.
        Asia Pac J Clin Oncol. 2013; 9: 310-317https://doi.org/10.1111/ajco.12017
        • Leow JJ
        • Martin-Doyle W
        • Rajagopal PS
        • et al.
        Adjuvant chemotherapy for invasive bladder cancer: a 2013 updated systematic review and meta-analysis of randomized trials.
        Eur Urol. 2014; 66: 42-54https://doi.org/10.1016/j.eururo.2013.08.033
        • Haque W
        • Verma V
        • Butler EB
        • Teh BS
        Chemotherapy versus chemoradiation for node-positive bladder cancer: practice patterns and outcomes from the national cancer data base.
        Bl Cancer. 2017; 3: 283-291https://doi.org/10.3233/BLC-170137
        • Milowsky MI
        • Bryan Rumble R
        • Booth CM
        • et al.
        Guideline on muscle-invasive and metastatic bladder cancer (European Association of Urology guideline): American Society of Clinical Oncology clinical practice guideline endorsement.
        J Clin Oncol. 2016; 34: 1945-1952https://doi.org/10.1200/JCO.2015.65.9797
        • Raj G V.
        • Karavadia S
        • Schlomer B
        • et al.
        Contemporary use of perioperative cisplatin-based chemotherapy in patients with muscle-invasive bladder cancer.
        Cancer. 2011; 117: 276-282https://doi.org/10.1002/cncr.25429
        • Feifer A
        • Taylor JM
        • Shouery M
        • et al.
        Multi-institutional quality-of-care initiative for nonmetastatic, muscle-invasive, transitional cell carcinoma of the bladder: phase I.
        J Clin Oncol. 2011; 29
        • Smith AB
        • Deal AM
        • Woods ME
        • et al.
        Muscle-invasive bladder cancer: evaluating treatment and survival in the national cancer data base.
        BJU Int. 2014; 114: 719-726https://doi.org/10.1111/bju.12601
        • Gray PJ
        • Fedewa SA
        • Shipley WU
        • Efstathiou JA
        • Zietman AL
        • Virgo KS
        Utilization of potentially curative therapies for muscle invasive bladder cancer: Results from the national cancer data base.
        Int J Radiat Oncol Biol Phys. 2012; 84: S119https://doi.org/10.1016/j.eururo.2012.11.015
        • Nielsen ME
        • Smith AB
        • Meyer AM
        • et al.
        Trends in stage-specific incidence rates for urothelial carcinoma of the bladder in the United States: 1988 to 2006.
        Cancer. 2014; 120: 86-95https://doi.org/10.1002/cncr.28397
      2. Donat SM, Shabsigh A, Savage C, et al. Potential impact of postoperative early complications on the timing of adjuvant chemotherapy in patients undergoing radical cystectomy : a high-volume tertiary cancer center experience. 2008;55:177-186. doi:10.1016/j.eururo.2008.07.018

        • Kates M
        • Whalen MJ
        • Badalato GM
        • McKiernan JM
        The effect of race and gender on the surgical management of the small renal mass.
        Urol Oncol Semin Orig Investig. 2013; 31: 1794-1799https://doi.org/10.1016/j.urolonc.2012.05.005
        • Ellis L
        • Canchola AJ
        • Spiegel D
        • Ladabaum U
        • Haile R
        • Gomez SL
        Racial and ethnic disparities in cancer survival: the contribution of tumor, sociodemographic, institutional, and neighborhood characteristics.
        J Clin Oncol. 2018; 36: 25-33https://doi.org/10.1200/JCO.2017.74.2049
        • Sui W
        • Lim EA
        • Decastro GJ
        • Mckiernan JM
        Use of adjuvant chemotherapy in patients with advanced bladder cancer after neoadjuvant chemotherapy.
        Bl Cancer. 2017; 3: 181-189https://doi.org/10.3233/BLC-170107
        • Seisen T
        • Jamzadeh A
        • Leow JJ
        • et al.
        Adjuvant chemotherapy vs observation for patients with adverse pathologic features at radical cystectomy previously treated with neoadjuvant chemotherapy.
        JAMA Oncol. 2018; 4: 225-229https://doi.org/10.1001/jamaoncol.2017.2374
        • Fahmy NM
        • Mahmud S
        • Aprikian AG
        Delay in the surgical treatment of bladder cancer and survival: systematic review of the literature.
        Eur Urol. 2006; 50: 1176-1182https://doi.org/10.1016/j.eururo.2006.05.046