Mathieu Rouanne1, Dean F Bajorin2, Raquibul Hannan3, Matthew D Galsky4, Stephen B Williams5, Andrea Necchi6, Padmanee Sharma7, Thomas Powles8. 1. Department of Urology, Hôpital Foch, UVSQ-Université Paris-Saclay, Suresnes, France; INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, France. Electronic address: mathieu.rouanne@gustaveroussy.fr. 2. Department of Medicine, Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 3. Department of Radiation Oncology, Harold C. Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA. 4. Division of Hematology and Oncology, Department of Medicine, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 5. Division of Urology, The University of Texas Medical Branch, Galveston, TX, USA. 6. Department of Medical Oncology, Fondazione IRCCS Instituto Nazionale dei Tumori, Milan, Italy. 7. Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 8. Experimental Cancer Medicine Centre Barts Cancer Institute, Queen Mary University of London, St Bartholomew's Hospital, London, UK.
Abstract
CONTEXT: Immune therapy has emerged as a powerful treatment of metastatic urothelial carcinoma. Over 20 ongoing studies are exploring this strategy in the neoadjuvant setting in patients with localized muscle-invasive bladder cancer. OBJECTIVE: To summarize the rationale and the clinical outcomes regarding the use of immune checkpoint blockade in the neoadjuvant setting before radical cystectomy. EVIDENCE ACQUISITION: A systematic review of the literature in the MEDLINE database was performed. The central search strategy used the terms bladder cancer, urothelial carcinoma, mice, human, immunotherapy, neoadjuvant therapy, atezolizumab, pembrolizumab, durvalumab, nivolumab, avelumab, ipilimumab, and tremelimumab. The search was limited to publications between January 2008 and February 2020. Publicly available relevant abstracts from recent meetings were also included. EVIDENCE SYNTHESIS: Phase II trials investigating neoadjuvant immune checkpoint blockade as a single agent before radical cystectomy reported a rate of pathological complete response (CR), ranging from 31% with an anti-PD-L1 monoclonal antibody (mAb) atezolizumab (n = 27/88) to 37% with anti-PD-1 mAb pembrolizumab (n = 42/114). Overall, 92% (n = 87/95) and 98% (n = 112/114) of the patients underwent radical cystectomy. Neoadjuvant immune checkpoint blockade did not delay planned surgery. Checkpoint inhibitor monotherapy was well tolerated, with no unexpected toxicity in the presurgical setting. Early phase I/II trials investigating neoadjuvant combination chemotherapy strategies with immune checkpoint blockers reported enhanced antitumor efficacy, with a pathological CR ranging from 33% to 50%. CONCLUSIONS: Although limited clinical data are available on long-term survival, neoadjuvant immune checkpoint blockade demonstrated effective antitumor efficacy for localized muscle-invasive bladder cancer. Phase III trials are currently investigating this strategy in the presurgical setting. PATIENT SUMMARY: Immunotherapy prior to surgery has been evaluated for patients with muscle-invasive bladder cancer. Although long-term survival benefit is unknown, such treatment strategy revealed a promising antitumor response rate for patients who underwent radical cystectomy. Ongoing prospective clinical trials will define the potential advantage of this approach over current cisplatin-based chemotherapeutic regimens alone or in combination.
CONTEXT: Immune therapy has emerged as a powerful treatment of metastatic urothelial carcinoma. Over 20 ongoing studies are exploring this strategy in the neoadjuvant setting in patients with localized muscle-invasive bladder cancer. OBJECTIVE: To summarize the rationale and the clinical outcomes regarding the use of immune checkpoint blockade in the neoadjuvant setting before radical cystectomy. EVIDENCE ACQUISITION: A systematic review of the literature in the MEDLINE database was performed. The central search strategy used the terms bladder cancer, urothelial carcinoma, mice, human, immunotherapy, neoadjuvant therapy, atezolizumab, pembrolizumab, durvalumab, nivolumab, avelumab, ipilimumab, and tremelimumab. The search was limited to publications between January 2008 and February 2020. Publicly available relevant abstracts from recent meetings were also included. EVIDENCE SYNTHESIS: Phase II trials investigating neoadjuvant immune checkpoint blockade as a single agent before radical cystectomy reported a rate of pathological complete response (CR), ranging from 31% with an anti-PD-L1 monoclonal antibody (mAb) atezolizumab (n = 27/88) to 37% with anti-PD-1 mAb pembrolizumab (n = 42/114). Overall, 92% (n = 87/95) and 98% (n = 112/114) of the patients underwent radical cystectomy. Neoadjuvant immune checkpoint blockade did not delay planned surgery. Checkpoint inhibitor monotherapy was well tolerated, with no unexpected toxicity in the presurgical setting. Early phase I/II trials investigating neoadjuvant combination chemotherapy strategies with immune checkpoint blockers reported enhanced antitumor efficacy, with a pathological CR ranging from 33% to 50%. CONCLUSIONS: Although limited clinical data are available on long-term survival, neoadjuvant immune checkpoint blockade demonstrated effective antitumor efficacy for localized muscle-invasive bladder cancer. Phase III trials are currently investigating this strategy in the presurgical setting. PATIENT SUMMARY: Immunotherapy prior to surgery has been evaluated for patients with muscle-invasive bladder cancer. Although long-term survival benefit is unknown, such treatment strategy revealed a promising antitumor response rate for patients who underwent radical cystectomy. Ongoing prospective clinical trials will define the potential advantage of this approach over current cisplatin-based chemotherapeutic regimens alone or in combination.
Authors: Jons W van Hattum; Ben-Max de Ruiter; Jorg R Oddens; Maarten C C M Hulshof; Theo M de Reijke; Adriaan D Bins Journal: Cancers (Basel) Date: 2021-12-22 Impact factor: 6.639
Authors: Manuel Olmos; Jacek Glajzer; Tjark-Ole Büntemeyer; Gesche Frohwitter; Jutta Ries; Markus Eckstein; Markus Hecht; Rainer Lutz; Marco Rainer Kesting; Manuel Weber Journal: Front Oncol Date: 2021-07-21 Impact factor: 6.244