Abstract
Patients with muscle-infiltrating bladder cancer (MIBC) present a high risk of postoperative recurrence and death from metastatic urothelial cancer despite surgical resection. Before the use of peri-operative chemotherapy, about half (52%) of patients undergoing radical cystectomy had had a relapse of tumor disease within 5 years of surgery. However, when peri-operative cisplatin-based chemotherapy is added to radical cystectomy for patients with MIBC it provides limited benefit in terms of survival, disease recurrence and development of metastases, at the expense of toxic effects. In fact, a significant proportion of patients still recurs and die to metastatic disease. Given the success of immune-oncological drugs in metastatic urothelial cancer, several trials started to test them in patients with non-metastatic MIBC either in neo-adjuvant and adjuvant setting. The preliminary results of these studies in neo-adjuvant setting are showing great promise, confirming the potential benefits of immunotherapy also in patients with non-metastatic MIBC. The aim of this review is to present an overview of developments happening on the introduction of immunotherapy in peri-operative setting in non-metastatic urothelial cancer. Moreover, an analysis of the critical issues regarding how best customize the delivery of immunotherapy to optimize efficacy and minimize the adverse effects, with particular focus on potential prognostic and predictive molecular biomarkers, is done.
Highlights
The urothelial carcinoma of the urinary tract is one of the most prevalent cancer in the world and the urinary bladder is the most frequent pathologic site of occurrence [1].Approximately 30% of patients with bladder cancer have a muscle-infiltrating bladder cancer (MIBC), namely pT2 or more according to TNM staging [2]
The prognostic value of pathologic complete response (pCR) is meaningful because several studies have correlated the degree of pathologic response with survival after radical cystectomy (RC) and the achievement of pCR indicates the best chance of long-term survival
On the one hand this study showed that patients harboring squamous-cell carcinoma or lymphoepithelioma-like variant feature had a higher pCR rate compared with other predominant variant histology (VH), but on the other hand it observed that PD-L1 combined positive score and tumor mutation burden (TMB) are the key response predictors irrespective of the histological subtypes
Summary
The urothelial carcinoma of the urinary tract is one of the most prevalent cancer in the world and the urinary bladder is the most frequent pathologic site of occurrence [1].Approximately 30% of patients with bladder cancer have a MIBC, namely pT2 or more according to TNM staging [2]. 50% of patients were ineligible to receive cisplatin for pre-existing comorbidity (such as kidney failure with a creatinine clearance less than 60 mL/min; hearing loss of grade 2 or more; impaired performance status; neuropathy of grade 2 or higher; cardiac dysfunction) while the remaining 30% refused the treatment [10]. These cisplatin-unfit patients could be treated with carboplatin and gemcitabine, but there are no literature data to support this strategy
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
