Highlights
- •Site-specific success rates for pembrolizumab treatments were as follows: primary tumors: 67%, lymph node: 70%, lung: 44%, liver: 40%, and peritoneal metastasis: 56% in patients with urothelial carcinoma.
- •Changes in NLR, ie, NLR kinetics, following pembrolizumab treatment were a predictor of the response to pembrolizumab, notably in lymph node metastases in patients with urothelial carcinoma.
- •NLR kinetics was also a predictor for overall mortality following pembrolizumab, independent of performance status and liver metastasis.
Abstract
Introduction
Since tumors in different human organs may have different tumor microenvironments,
we evaluate time-course changes in all tumor locations after pembrolizumab treatment
in urothelial carcinoma (UC) to examine the differences in efficacy of pembrolizumab
per organ. Further, we uncover the usefulness of inflammatory markers such as neutrophil-to-lymphocyte
ratio (NLR), CRP, and kinetics of these markers to predict pembrolizumab success and
relation to overall survival (OS) in UC.
Patients and Methods
A total of 115 cancerous lesions from 44 UC patients were measurable based on RECIST
1.1 criteria. The serum CRP and NLR levels were measured at baseline prior to pembrolizumab
treatment and at least every 3 weeks just prior to pembrolizumab administration.
Results
Site-specific success (ie, patients with CR/PR/SD by RESIST 1.1) rates for pembrolizumab
treatments were as follows: primary tumors: 67%, lymph node: 70%, lung: 44%, liver:
40%, and peritoneal metastasis: 56%. Focusing on the major metastasis sites, lymph
nodes and lungs, we examined the relationships between NLR, CRP, or that kinetics
and pembrolizumab success. In lymph nodes, both early NLR kinetics (P = .005) and CRP kinetics (P = .035) was a predictor for pembrolizumab success. On the other hand, none of 4 was
not in lung metastases. Regarding to the mortality, the multivariate analysis revealed
that early NLR kinetics was a prognostic biomarker for OS among the 4, independent
of performance status and liver metastasis.
Conclusion
We revealed that site-specific pembrolizumab success in UC. Early NLR kinetics was
a predictor for lymph node pembrolizumab success and OS in our cohorts.
Keywords
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References
- Pembrolizumab as second-line therapy for advanced urothelial carcinoma.N Engl J Med. 2017; 376: 1015-1026
- Randomized phase III KEYNOTE-045 trial of pembrolizumab versus paclitaxel, docetaxel, or vinflunine in recurrent advanced urothelial cancer: results of >2 years of follow-up.Ann Oncol. 2019; 30: 970-976
- The future of immune checkpoint therapy.Science. 2015; 348: 56-61
- Organ-specific tumor response to pembrolizumab in advanced urothelial carcinoma after platinum-based chemotherapy.Onco Targets Ther. 2021; 14: 1981-1988
- Tumor infiltrating lymphocytes in lymph node metastases of stage III melanoma correspond to response and survival in nine patients treated with ipilimumab at the time of stage IV disease.Cancer Immunol Immunother. 2018; 67: 39-45
- The liver works as a school to educate regulatory immune cells.Cell Mol Immunol. 2013; 10: 292-302
- Safety, activity, and immune correlates of anti-PD-1 antibody in cancer.N Engl J Med. 2012; 366: 2443-2454
- Tumor mutational burden and response rate to PD-1 inhibition.N Engl J Med. 2017; 377: 2500-2501
- Clinical impact of sarcopenia and inflammatory/nutritional markers in patients with unresectable metastatic urothelial carcinoma treated with pembrolizumab.Diagnostics (Basel). 2020; 10: E310
- Impact of C−reactive protein flare−response on oncological outcomes in patients with metastatic renal cell carcinoma treated with nivolumab.J Immunother Cancer. 2021; 9e001564
- A model combining clinical and genomic factors to predict response to PD-1/PD-L1 blockade in advanced urothelial carcinoma.Br J Cancer. 2020; 122: 555-563
- Impact of C-reactive protein kinetics on survival of patients with advanced urothelial carcinoma treated by second-line chemotherapy with gemcitabine, etoposide and cisplatin.BJU Int. 2012; 110: 1478-1484
- Real-world outcomes of nivolumab in patients with unresectable hepatocellular carcinoma in an endemic area of hepatitis B virus infection.Front Oncol. 2020; 10: 1043
- Organ-specific response to nivolumab in patients with non-small cell lung cancer (NSCLC).Cancer Immunol Immunother. 2018; 67: 1825-1832
- Site-specific response patterns, pseudoprogression, and acquired resistance in patients with melanoma treated with ipilimumab combined with anti-PD-1 therapy.Cancer. 2020; 126: 86-97
- Pre-treatment neutrophil-to-lymphocyte ratio as predictor of adverse outcomes in patients undergoing radical cystectomy for urothelial carcinoma of the bladder.Br J Cancer. 2014; 111: 444-451
- High neutrophil-to-lymphocyte ratio predicts worse overall survival in patients with advanced/metastatic urothelial bladder cancer.Int J Urol. 2018; 25: 232-238
- European association of urology guidelines on upper urinary tract urothelial carcinoma: 2020 update.Eur Urol. 2021; 79: 62-79
- 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. 2020; 38: 602.e1-602.e10
- Cost-effectiveness of pembrolizumab in second-line advanced bladder cancer.Eur Urol. 2018; 74: 57-62
Article info
Publication history
Published online: September 01, 2022
Accepted:
August 3,
2022
Received in revised form:
August 1,
2022
Received:
January 12,
2022
Identification
Copyright
© 2022 Elsevier Inc. All rights reserved.
