Mathieu Roumiguié1, Eva Compérat2, Léonor Chaltiel3, François Xavier Nouhaud4,5, Gregory Verhoest6, Alexandra Masson-Lecomte7, Pierre Colin8, François Audenet9, Nadine Houédé10, Stéphane Larré11, Evanguelos Xylinas12, Serge Brunelle13, Jeanne Piana-Thomassin14, Juliette Cotte15, Géraldine Pignot16, Yann Neuzillet17, Morgan Rouprêt18. 1. Department of Urology, Institut Universitaire du Cancer de Toulouse Oncopole, Rangueil University Hospital, 31059, Toulouse, France. roumiguie_mathieu@yahoo.fr. 2. GRC n°5, PREDICTIVE ONCO-URO, AP-HP Service de Pathology, Tenon Hospital, Sorbonne University, 75020, Paris, France. 3. Biostatistics Unit, Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse, France. 4. Urology Department, Rouen University Hospital, Rouen, France. 5. UNIROUEN, IRON Group, Rouen University Hospital, Normandy University, Rouen, France. 6. Department of Urology, Rennes University Hospital, Rennes, France. 7. Urology Department, Saint-Louis Hospital, Paris-Diderot University, 75010, Paris, France. 8. Urology Department, Hôpital privé de la Louvière, 59042, Lille, France. 9. Urology Department, Georges Pompidou European Hospital, University Paris Descartes, AP-HP, 75015, Paris, France. 10. Department of Medical Oncology, CHU Caremeau, Montpellier University, 30029, Nimes, France. 11. Urology Department, CHU de Reims, 51100, Reims, France. 12. Urology Department, Bichat-Claude Bernard Hospital, Paris Descartes University, AP-HP, 75018, Paris, France. 13. Department of Radiology, Institut Paoli-Calmettes, 13009, Marseille, France. 14. Department of Pathology, Institut Paoli-Calmettes, 13009, Marseille, France. 15. Urology Department, GRC n°5, PREDICTIVE ONCO-URO, AP-HP, Hôpital Pitié-Salpêtrière, Sorbonne University, 75013, Paris, France. 16. Department of Surgical Oncology 2, Institut Paoli-Calmettes, 13009, Marseille, France. 17. Urology Department, Foch Hospital, Versailles-Saint-Quentin-en-Yvelines University, 92150, Suresnes, France. 18. Urology Department, GRC n°5, PREDICTIVE ONCO-URO, AP-HP, Hôpital Pitié-Salpêtrière, Sorbonne University, 75013, Paris, France. mroupret@gmail.com.
Abstract
PURPOSE: To assess the association between PD-L1 expression and disease-free survival (DFS) in High-Risk Non-Muscle Invasive Bladder Cancer (HR-NMIBC) patients treated with intravesical Bacillus Calmette-Guerin (BCG) instillations (IBI). METHODS: Retrospective study in five French centres between 2001 and 2015. Participants were 140 patients with histologically confirmed HR-NMIBC. All patients received induction and maintenance IBI. Pathological stage/grade, concomitant carcinoma in situ, lesion number and tumour size were recorded. CD3, CD8 and PD-L1 expression in tumour cells and in T cells in the tumour microenvironment (TME) was determined immunohistochemically. Median follow-up was 54.2 months. The primary outcome measure was DFS. Univariable and multivariable analyses were performed using the log rank test and Cox proportional hazards model. RESULTS: Of the 140 NMIBC, 52 (37.1%) were Ta, 88 (62.9%) were T1 and 100% were high grade. Median number of maintenance IBI was six (range 1-30). Twenty-five (17.9%) patients had recurrence/progression. In multivariable analysis, age (HR 1.07 [95% CI 1.02-1.13], p = 0.009), PD-L1 expression in tumour cells (HR per 10 units = 1.96 [95% CI 1.28-3.00], p = 0.02) and CD3/CD8 ratio (HR per 10 units = 3.38 [95% CI 1.61-7.11], p = 0.01) were significantly associated with DFS. However, using the cut-off corresponding for each PD-L1 antibodies, PD-L1 + status was not associated with DFS. CONCLUSION: Despite an association between PD-L1 expression and BCG failure in HR-NMIBC, the PD-L1 + status was not a prognostic factor in the response of BCG. Moreover, we confirmed the key role played by the IC within the microenvironment in BCG treatment. These findings highlighted the rationale to combine BCG and PD-L1/PD-1 antibodies in early bladder cancer.
PURPOSE: To assess the association between PD-L1 expression and disease-free survival (DFS) in High-Risk Non-Muscle Invasive Bladder Cancer (HR-NMIBC) patients treated with intravesical Bacillus Calmette-Guerin (BCG) instillations (IBI). METHODS: Retrospective study in five French centres between 2001 and 2015. Participants were 140 patients with histologically confirmed HR-NMIBC. All patients received induction and maintenance IBI. Pathological stage/grade, concomitant carcinoma in situ, lesion number and tumour size were recorded. CD3, CD8 and PD-L1 expression in tumour cells and in T cells in the tumour microenvironment (TME) was determined immunohistochemically. Median follow-up was 54.2 months. The primary outcome measure was DFS. Univariable and multivariable analyses were performed using the log rank test and Cox proportional hazards model. RESULTS: Of the 140 NMIBC, 52 (37.1%) were Ta, 88 (62.9%) were T1 and 100% were high grade. Median number of maintenance IBI was six (range 1-30). Twenty-five (17.9%) patients had recurrence/progression. In multivariable analysis, age (HR 1.07 [95% CI 1.02-1.13], p = 0.009), PD-L1 expression in tumour cells (HR per 10 units = 1.96 [95% CI 1.28-3.00], p = 0.02) and CD3/CD8 ratio (HR per 10 units = 3.38 [95% CI 1.61-7.11], p = 0.01) were significantly associated with DFS. However, using the cut-off corresponding for each PD-L1 antibodies, PD-L1 + status was not associated with DFS. CONCLUSION: Despite an association between PD-L1 expression and BCG failure in HR-NMIBC, the PD-L1 + status was not a prognostic factor in the response of BCG. Moreover, we confirmed the key role played by the IC within the microenvironment in BCG treatment. These findings highlighted the rationale to combine BCG and PD-L1/PD-1 antibodies in early bladder cancer.
Authors: Stephen Chenard; Chelsea Jackson; Thiago Vidotto; Lina Chen; Céline Hardy; Tamara Jamaspishvilli; David Berman; D Robert Siemens; Madhuri Koti Journal: Eur Urol Open Sci Date: 2021-06-03