Abstract
Background
Atezolizumab (ATZ) has demonstrated antitumor activity and manageable safety in previous studies of patients with metastatic platinum-resistant urothelial carcinoma. However, the response rate of Atezolizumab was modest. In the current study, we evaluated the pretreatment prognostic factors for overall survival in patients with metastatic urothelial carcinoma who have progressed after first-line chemotherapy in the Expanded-Access Program of Atezolizumab.
Patients and methods
In this study, we present a retrospective analysis of 113 patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy. Data of the patients was obtained from patient files and hospital records. Eligible patients included metastatic urothelial carcinoma patients treated with at least one course of ATZ. Univariate analysis was used to identify clinical and laboratory factors that significantly impact OS. Variables were retained for multivariate analysis if they had a statistical relationship with OS (p < 0.1), and then included a final model of p < 0.05.
Results
The median follow-up duration was 23.5 months. Of the patients, 98 (86.7%) were male and 13.3% were female. The median age was 65 years of age (37–86). In univariate analysis, primary tumor location in the upper tract, increasing absolute neutrophil count (ANC), increasing absolute lymphocyte count, neutrophil-to-lymphocyte ratio (NLR) > 3, liver metastases, baseline creatinine clearance less (GFR) than 60 ml/min, Eastern Cooperative Oncology Group (ECOG) performance status (1 ≥), and hemoglobin levels below 10 mg/dl were all the significantly associated with OS. Three of the five adverse prognostic factors according to the Bellmunt criteria were independent of short survival: liver metastases HR 3.105; 95% CI 1.673–5.761; p < (0.001), ECOG PS (1 ≥) HR 2.184; 95% CI 1.120–4.256; p = 0.022, and Hemoglobin level below 10 mg/dl HR 2.680; 95% CI 1.558–4.608; p < (0.001). In addition, NLR > 3 hazard ratio [HR] 2.092; 95% CI 1.031–4.243; p = 0.041 and GFR less than 60 ml/min HR 1.829; 95% CI 1.1–3.041; p = 0.02, maintained a significant association with OS in multivariate analysis.
Conclusions
This model confirms the Bellmunt model with the addition of NLR > 3 and GFR less than 60 ml/min and can be associated with clinical trials that use immunotherapy in patients with bladder cancer.
Similar content being viewed by others
References
Ferlay J, Soerjomataram I, Dikshit R et al (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136:E359–E386
National Cancer Institute Surveillance, Epidemiology, and End Results Program. (2019) SEER cancer statistics factsheets: Bladder cancer. https://seer.cancer.gov/statfacts/html/urinb.html. Accessed 10 Dec 2019
von der Maase H, Sengelov L, Roberts JT et al (2005) Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol 23:4602–4608
Bellmunt J, Théodore C, Demkov T et al (2009) Phase III trial of vinflunine plus best supportive care compared with best supportive care alone after a platinum-containing regimen in patients with advanced transitional cell carcinoma of the urothelial tract. J Clin Oncol 27:4454–4461
Bellmunt J, Powles T, Vogelzang NJ (2017) A review on the evolution of PD-1/PD-L1 immunotherapy for bladder cancer: the future is now. Cancer Treat Rev 54:58–67
Rosenberg JE, Hoffman-Censits J, Powles T et al (2016) Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet 387(10031):1909–1920
Powles T, Durán I, van der Heijden MS et al (2018) Atezolizumab versus chemotherapy in patients with platinum-treated locally advanced or metastatic urothelial carcinoma (IMvigor211): a multicentre, open-label, phase 3 randomised controlled trial. Lancet 391(10122):748–757
Sternberg CN, Loriot Y, James N et al (2019) Primary results from SAUL, a multinational single-arm safety study of atezolizumab therapy for locally advanced or metastatic urothelial or nonurothelial carcinoma of the urinary tract. Eur Urol 76(1):73–81
Tural D, Olmez OF, Sumbul AT et al (2020) Atezolizumab in patients with metastatic urothelial carcinoma who have progressed after first-line chemotherapy: results of real-life experience. Eur Urol Focus S2405–4569(20):30269–30278
Bellmunt J, Albanell J, Paz-Ares L et al (2002) Pretreatment prognostic factors for survival in patients with advanced urothelial tumors treated in a phase I/II trial with paclitaxel, cisplatin, and gemcitabine. Cancer 95(4):751–757
Sonpavde G, Pond GR, Rosenberg JE et al (2016) Improved 5-factor prognostic classification of patients receiving salvage systemic therapy for advanced urothelial carcinoma. J Urol 195:277–282
Tamura D, Jinnouchi N, Abe M et al (2020) Prognostic outcomes and safety in patients treated with pembrolizumab for advanced urothelial carcinoma: experience in real-world clinical practice. Int J Clin Oncol 25:899–905
Templeton AJ, McNamara MG, Šeruga B et al (2014) Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst 106(6):dju124
Yip SM, Kaiser J, Li H et al (2018) Real-world outcomes in advanced urothelial cancer and the role of neutrophil to lymphocyte ratio. Clin Genitourin Cancer 16(3):e637–e644
Schmidt A, Radtke AS, McConkey D et al (2020) Renal cell and urothelial carcinoma: biomarkers for new treatments. Am Soc Clin Oncol Ed Book 40:e197–e206
Ogihara K, Kikuchi E, Shigeta K et al (2020) The pretreatment neutrophil-to-lymphocyte ratio is a novel biomarker for predicting clinical responses to pembrolizumab in platinum-resistant metastatic urothelial carcinoma patients. Urol Oncol 38:602.e1-602.e10
Yamamoto Y, Yatsuda J, Shimokawa M et al (2020) Prognostic value of pre-treatment risk stratification and post-treatment neutrophil/lymphocyte ratio change for pembrolizumab in patients with advanced urothelial carcinoma. Int J Clin Oncol 26:169–177
Kobayashi T, Ito K, Kojima T et al (2021) Risk stratification for the prognosis of patients with chemoresistant urothelial cancer treated with pembrolizumab. Cancer Sci 112:760–773
Yasuoka S, Yuasa T, Nishimura N et al (2019) Initial experience of pembrolizumab therapy in Japanese patients with metastatic urothelial cancer. Anticancer Res 39:3887–3892
Shabto JM, Martini DJ, Liu Y et al (2020) Novel risk group stratification for metastatic urothelial cancer patients treated with immune checkpoint inhibitors. Cancer Med 9:2752–2760
Nassar AH, Mouw KW, Jegede O et al (2020) A model combining clinical and genomic factors to predict response to PD-1/PD-L1 blockade in advanced urothelial carcinoma. Br J Cancer 122:555–563
Sonpavde G, Manitz J, Gao C et al (2020) Five-factor prognostic model for survival of post-platinum patients with metastatic urothelial carcinoma receiving PD-L1 inhibitors. J Urol 204:1173–1179
Spitzer MH, Carmi Y, Reticker-Flynn NE et al (2017) Systemic immunity is required for effective cancer immunotherapy. Cell 168(3):487-502.e415
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
No conflict of interest exists in the submission of this manuscript, and manuscript is approved by all authors for publication.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Tural, D., Ölmez, Ö.F., Sümbül, A.T. et al. Prognostic factors in patients with metastatic urothelial carcinoma who have treated with Atezolizumab. Int J Clin Oncol 26, 1506–1513 (2021). https://doi.org/10.1007/s10147-021-01936-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10147-021-01936-6