Advertisement

Survival Outcomes in Neoadjuvant Chemotherapy for High-grade Upper Tract Urothelial Carcinoma: A Nationally Representative Analysis

Published:September 03, 2020DOI:https://doi.org/10.1016/j.urology.2020.06.108

      Abstract

      Objective

      To assess the impact of neoadjuvant chemotherapy (NAC) on survival outcomes in a contemporary cohort of patients with in upper tract urothelial carcinoma (UTUC).

      Methods

      The National Cancer Database was queried from 2004 to 2015 to identify subjects who underwent nephroureterectomy for UTUC. Kaplan-Meier method with log-rank test was performed to compare all-cause mortality between patients who received preoperative chemotherapy to those who did not at each pathologic (p) TNM stage group: T1-4N0, N+, and M+ disease. Associations for all-cause mortality were identified using an adjusted Cox regression analysis.

      Results

      A total of 10,315 chemoeligible subjects were included in the analysis. A total of 296 (2.9%) of patients received NAC prior to NU. Kaplan-Meier survival curves of the entire cohort demonstrated an overall survival advantage associated with administration of NAC (P = .017). Stratified by clinical staging, subjects with nonorgan-confined tumors had improved overall survival outcomes with NAC administration (P = .012). On multivariate analysis there was a statistically significant improvement in overall survival between in patients who received NAC. Of patients in the preoperative chemotherapy group who had clinically nonorgan-confined disease, 27.1% had organ-confined disease at time of surgery compared to 1.4% of those who underwent surgery as initial therapy.

      Conclusion

      In a contemporary cohort of subjects who underwent nephroureterectomy for UTUC, administration of NAC in patients with high-grade nonorgan-confined disease led to higher rates of pathologic downstaging and was associated with improved overall survival.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Urology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Siegel RL
        • Miller KD
        • Jemal A
        Cancer statistics, 2019.
        CA Cancer J Clin. 2019; 69: 7-34https://doi.org/10.3322/caac.21551
        • Lucca I
        • Leow JJ
        • Shariat SF
        • Chang SL
        Diagnosis and management of upper tract urothelial carcinoma.
        Hematol Oncol Clin North Am. 2015; 29 (ix): 271-288https://doi.org/10.1016/j.hoc.2014.10.003
        • Roupret M
        • Babjuk M
        • Comperat E
        • et al.
        European Association of Urology guidelines on upper urinary tract urothelial carcinoma: 2017 update.
        Eur Urol. 2018; 73: 111-122https://doi.org/10.1016/j.eururo.2017.07.036
        • Green DA
        • Rink M
        • Xylinas E
        • et al.
        Urothelial carcinoma of the bladder and the upper tract: disparate twins.
        J Urol. 2013; 189: 1214-1221https://doi.org/10.1016/j.juro.2012.05.079
        • Leow JJ
        • Martin-Doyle W
        • Fay AP
        • Choueiri TK
        • Chang SL
        • Bellmunt J
        A systematic review and meta-analysis of adjuvant and neoadjuvant chemotherapy for upper tract urothelial carcinoma.
        Eur Urol. 2014; 66: 529-541https://doi.org/10.1016/j.eururo.2014.03.003
        • Siefker-Radtke AO
        • Dinney CP
        • Shen Y
        • et al.
        A phase 2 clinical trial of sequential neoadjuvant chemotherapy with ifosfamide, doxorubicin, and gemcitabine followed by cisplatin, gemcitabine, and ifosfamide in locally advanced urothelial cancer: final results.
        Cancer. 2013; 119: 540-547https://doi.org/10.1002/cncr.27751
        • Deyo RA
        • Cherkin DC
        • Ciol MA
        Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases.
        J Clin Epidemiol. 1992; 45: 613-619
        • Chakiryan N
        • Martinez A
        • Gao L
        • et al.
        Optimizing the sequence of chemotherapy for upper tract urothelial carcinoma with clinically positive regional lymph nodes.
        J Urol. 2019; 202: 76-82https://doi.org/10.1097/JU.0000000000000172
        • Hafner C
        • Knuechel R
        • Zanardo L
        • et al.
        Evidence for oligoclonality and tumor spread by intraluminal seeding in multifocal urothelial carcinomas of the upper and lower urinary tract.
        Oncogene. 2001; 20: 4910-4915https://doi.org/10.1038/sj.onc.1204671
        • Gayed BA
        • Thoreson GR
        • Margulis V
        The role of systemic chemotherapy in management of upper tract urothelial cancer.
        Curr Urol Rep. 2013; 14: 94-101https://doi.org/10.1007/s11934-013-0307-z
        • Audenet F
        • Isharwal S
        • Cha EK
        • et al.
        Clonal relatedness and mutational differences between upper tract and bladder urothelial carcinoma.
        Clin Cancer Res. 2019; 25: 967-976https://doi.org/10.1158/1078-0432.CCR-18-2039
        • Sfakianos JP
        • Cha EK
        • Iyer G
        • et al.
        Genomic characterization of upper tract urothelial carcinoma.
        Eur Urol. 2015; 68: 970-977https://doi.org/10.1016/j.eururo.2015.07.039
        • Kitamura H
        • Igarashi M
        • Tanaka T
        • et al.
        A role for preoperative systemic chemotherapy in node-positive upper tract urothelial carcinoma treated with radical nephroureterectomy.
        Jpn J Clin Oncol. 2012; 42: 1192-1196https://doi.org/10.1093/jjco/hys166
        • Rajput MZ
        • Kamat AM
        • Clavell-Hernandez J
        • et al.
        Perioperative outcomes of laparoscopic radical nephroureterectomy and regional lymphadenectomy in patients with upper urinary tract urothelial carcinoma after neoadjuvant chemotherapy.
        Urology. 2011; 78: 61-67https://doi.org/10.1016/j.urology.2011.01.002
        • Lane BR
        • Smith AK
        • Larson BT
        • et al.
        Chronic kidney disease after nephroureterectomy for upper tract urothelial carcinoma and implications for the administration of perioperative chemotherapy.
        Cancer. 2010; 116: 2967-2973https://doi.org/10.1002/cncr.25043
        • Kaag MG
        • O'Malley RL
        • O'Malley P
        • et al.
        Changes in renal function following nephroureterectomy may affect the use of perioperative chemotherapy.
        Eur Urol. 2010; 58: 581-587https://doi.org/10.1016/j.eururo.2010.06.029
        • Kubota Y
        • Hatakeyama S
        • Tanaka T
        • et al.
        Oncological outcomes of neoadjuvant chemotherapy in patients with locally advanced upper tract urothelial carcinoma: a multicenter study.
        Oncotarget. 2017; 8: 101500-101508https://doi.org/10.18632/oncotarget.21551
        • Cohen A
        • Kuchta K
        • Park S
        Neoadjuvant and adjuvant chemotherapy use in upper tract urothelial carcinoma.
        Urol Oncol. 2017; 35: 322-327https://doi.org/10.1016/j.urolonc.2016.11.018
        • Margulis V
        • Shariat SF
        • Matin SF
        • et al.
        Outcomes of radical nephroureterectomy: a series from the Upper Tract Urothelial Carcinoma Collaboration.
        Cancer. 2009; 115: 1224-1233https://doi.org/10.1002/cncr.24135
        • Matin SF
        • Margulis V
        • Kamat A
        • et al.
        Incidence of downstaging and complete remission after neoadjuvant chemotherapy for high-risk upper tract transitional cell carcinoma.
        Cancer. 2010; 116: 3127-3134https://doi.org/10.1002/cncr.25050
        • Igawa M
        • Urakami S
        • Shiina H
        • et al.
        Neoadjuvant chemotherapy for locally advanced urothelial cancer of the upper urinary tract.
        Urol Int. 1995; 55: 74-77https://doi.org/10.1159/000282755
        • Kobayashi K
        • Saito T
        • Kitamura Y
        • et al.
        Effect of preoperative chemotherapy on survival of patients with upper urinary tract urothelial carcinoma clinically involving regional lymph nodes.
        Int J Urol. 2016; 23: 153-158https://doi.org/10.1111/iju.13010
        • Almassi N
        • Gao T
        • Lee B
        • et al.
        Impact of neoadjuvant chemotherapy on pathologic response in patients with upper tract urothelial carcinoma undergoing extirpative surgery.
        Clin Genitourin Cancer. 2018; 16: e1237-e1242https://doi.org/10.1016/j.clgc.2018.08.003
        • Kim DK
        • Lee JY
        • Kim JW
        • Hah YS
        • Cho KS
        Effect of neoadjuvant chemotherapy on locally advanced upper tract urothelial carcinoma: a systematic review and meta-analysis.
        Crit Rev Oncol Hematol. 2019; 135: 59-65https://doi.org/10.1016/j.critrevonc.2019.01.019