Francesco Soria1, Andrea Giordano1, Shahrokh F Shariat2,3,4,5,6, Paolo Gontero1. 1. Department of Surgical Sciences, Division of Urology, San Giovanni Battista Hospital, University of Studies of Torino, Turin, Italy. 2. Department of Urology, Medical University of Vienna, Vienna, Austria. 3. Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas, USA. 4. Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic. 5. Institute for Urology and Reproductive Health, I.M. Sechenov First Moscow State Medical University, Moscow, Russia. 6. Department of Urology, Weill Cornell Medical College, New York, New York, USA.
Abstract
PURPOSE OF REVIEW: The treatment of bacillus Calmette-Guérin (BCG) unresponsive disease remains a challenge for urooncologists. The search for effective conservative treatments is ongoing and several new agents have been recently tested for this purpose. The aim of this manuscript was to review the last developments in this interesting field. RECENT FINDINGS: The advent of systemic immunotherapy in the nonmuscle invasive setting promise to revolutionize the paradigm of treatment of BCG unresponsive disease. The preliminary results of the Keynote-057 trial (3 months complete response of 41% in carcinoma-in-situ patients) have led to the rapid approval of pembrolizumab from the Food and Drug Administration. Interesting results have been reported for gene therapies such as those with CG0700 and Adstiladrin, nonreplicating adenovirus able to increase the 'in situ' antitumor activity. However, larger prospective trials with longer follow-up are needed to confirm the initial findings. SUMMARY: In summary, early radical cystectomy remains the standard treatment for BCG unresponsive patients. However, in case of patients unfit for or refusing radical cystectomy, the bladder-sparing options are continuously increasing. Although BCG-reinduction (with or without interferon) and traditional intravesical chemotherapy may represent the past, the present and the future are characterized by device-assisted therapies, systemic immunotherapy, and gene therapy.
PURPOSE OF REVIEW: The treatment of bacillus Calmette-Guérin (BCG) unresponsive disease remains a challenge for urooncologists. The search for effective conservative treatments is ongoing and several new agents have been recently tested for this purpose. The aim of this manuscript was to review the last developments in this interesting field. RECENT FINDINGS: The advent of systemic immunotherapy in the nonmuscle invasive setting promise to revolutionize the paradigm of treatment of BCG unresponsive disease. The preliminary results of the Keynote-057 trial (3 months complete response of 41% in carcinoma-in-situpatients) have led to the rapid approval of pembrolizumab from the Food and Drug Administration. Interesting results have been reported for gene therapies such as those with CG0700 and Adstiladrin, nonreplicating adenovirus able to increase the 'in situ' antitumor activity. However, larger prospective trials with longer follow-up are needed to confirm the initial findings. SUMMARY: In summary, early radical cystectomy remains the standard treatment for BCG unresponsive patients. However, in case of patients unfit for or refusing radical cystectomy, the bladder-sparing options are continuously increasing. Although BCG-reinduction (with or without interferon) and traditional intravesical chemotherapy may represent the past, the present and the future are characterized by device-assisted therapies, systemic immunotherapy, and gene therapy.
Authors: Han Kyu Chae; Wook Nam; Han Gwun Kim; Sharon Lim; Byeong-Joo Noh; So Won Kim; Gil Hyun Kang; Jong Yeon Park; Dae-Woon Eom; Sung Jin Kim Journal: Front Immunol Date: 2022-05-23 Impact factor: 8.786