Ekaterina Laukhtina1, Benjamin Pradere2, Keiichiro Mori3, Victor M Schuettfort4, Fahad Quhal5, Hadi Mostafaei6, Reza Sari Motlagh7, Abdulmajeed Aydh8, Marco Moschini9, Dmitry Enikeev10, Pierre I Karakiewicz11, Mohammad Abufaraj12, Shahrokh F Shariat13. 1. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia. 2. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, University Hospital of Tours, Tours, France. 3. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, The Jikei University School of Medicine, Tokyo, Japan. 4. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 5. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, King Fahad Specialist Hospital, Dammam, Saudi Arabia. 6. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Research Center for Evidence Based Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. 7. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Men's Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 8. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, King Faisal Medical City, Abha, Saudi Arabia. 9. Department of Urology, Luzerner Kantonsspital, Lucerne, Switzerland; Department of Urology, Institut Mutualiste Montsouris, Paris, France; Department of Urology and Division of Experimental Oncology, Urological Research Institute, Vita-Salute San Raffaele, Milano, Italy. 10. Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia. 11. Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre, Montreal, Canada. 12. Division of Urology, Department of Special Surgery, Jordan University Hospital, The University of Jordan, Amman, Jordan; The National Center for Diabetes, Endocrinology and Genetics, The University of Jordan, Amman, Jordan. 13. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia; Division of Urology, Department of Special Surgery, Jordan University Hospital, The University of Jordan, Amman, Jordan; The National Center for Diabetes, Endocrinology and Genetics, The University of Jordan, Amman, Jordan; Department of Urology, Weill Cornell Medical College, New York, NY,; Department of Urology, University of Texas Southwestern, Dallas, TX; Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic; Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria. Electronic address: shahrokh.shariat@meduniwien.ac.at.
Abstract
PURPOSE: The present systematic review aimed to identify prognostic values of blood-based biomarkers in patients treated with neoadjuvant chemotherapy (NAC) for urothelial carcinoma of the bladder (UCB). MATERIAL AND METHODS: The PubMed, Web of Science, and Scopus databases were searched in August 2020 according to the PRISMA statement. Studies were deemed eligible if they compared oncological outcomes in patients treated with NAC for UCB with and without pretreatment laboratory abnormalities. RESULTS: Overall, ten studies, including 966 patients who underwent NAC, met our eligibility criteria. Six studies provided data on pretreatment neutrophil to lymphocyte ratio (NLR) with contradicting results on its association with pathologic response (PR) and complete pathologic response (pCR); some studies reported a strong association between a high level of pretreatment NLR and worse survival outcomes. Two studies reported that higher pretreatment platelet-lymphocyte ratio (PLR) is associated with a lower likelihood of achieving PR and/or pCR, while lymphocyte count alone had the opposite association. One study reported a negative association between pretreatment blood-based myeloid-derived suppressors cells and pCR. Patients who experienced a remission have been reported to have higher level of lymphocyte subsets (CD3+, CD4+, CD57+ cells, the ratio of CD4+/CD8+) compared to those who had progression. One study found that low pretreatment blood-based human chorionic gonadotrophin b subunit (hCGβ) was associated with improved overall survival (OS). High levels of epithelial tumor markers (CA-125, CA 19-9) were also associated with worse OS and recurrence-free survival in the NAC setting. CONCLUSION: Current evidence suggests that several readily available, easy measurable blood-based biomarkers hold promise to improve our selection of UCB patients who are likely benefit from NAC. However, their role as an adjunct to established histopathologic characteristics for clinical decision-making requires further validation along the biomarker phased approach.
PURPOSE: The present systematic review aimed to identify prognostic values of blood-based biomarkers in patients treated with neoadjuvant chemotherapy (NAC) for urothelial carcinoma of the bladder (UCB). MATERIAL AND METHODS: The PubMed, Web of Science, and Scopus databases were searched in August 2020 according to the PRISMA statement. Studies were deemed eligible if they compared oncological outcomes in patients treated with NAC for UCB with and without pretreatment laboratory abnormalities. RESULTS: Overall, ten studies, including 966 patients who underwent NAC, met our eligibility criteria. Six studies provided data on pretreatment neutrophil to lymphocyte ratio (NLR) with contradicting results on its association with pathologic response (PR) and complete pathologic response (pCR); some studies reported a strong association between a high level of pretreatment NLR and worse survival outcomes. Two studies reported that higher pretreatment platelet-lymphocyte ratio (PLR) is associated with a lower likelihood of achieving PR and/or pCR, while lymphocyte count alone had the opposite association. One study reported a negative association between pretreatment blood-based myeloid-derived suppressors cells and pCR. Patients who experienced a remission have been reported to have higher level of lymphocyte subsets (CD3+, CD4+, CD57+ cells, the ratio of CD4+/CD8+) compared to those who had progression. One study found that low pretreatment blood-based human chorionic gonadotrophin b subunit (hCGβ) was associated with improved overall survival (OS). High levels of epithelial tumor markers (CA-125, CA 19-9) were also associated with worse OS and recurrence-free survival in the NAC setting. CONCLUSION: Current evidence suggests that several readily available, easy measurable blood-based biomarkers hold promise to improve our selection of UCB patients who are likely benefit from NAC. However, their role as an adjunct to established histopathologic characteristics for clinical decision-making requires further validation along the biomarker phased approach.