Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of urothelial cancer

Abstract

A number of immunotherapies have been developed and adopted for the treatment of urothelial cancer (encompassing cancers arising from the bladder, urethra, or renal pelvis). For these immunotherapies to positively impact patient outcomes, optimal selection of agents and treatment scheduling, especially in conjunction with existing treatment paradigms, is paramount. Immunotherapies also warrant specific and unique considerations regarding patient management, emphasizing both the prompt identification and treatment of potential toxicities. In order to address these issues, the Society for Immunotherapy of Cancer (SITC) convened a panel of experts in the field of immunotherapy for urothelial cancer. The expert panel developed this clinical practice guideline (CPG) to inform healthcare professionals on important aspects of immunotherapeutic treatment for urothelial cancer, including diagnostic testing, treatment planning, immune-related adverse events (irAEs), and patient quality of life (QOL) considerations. The evidence- and consensus-based recommendations in this CPG are intended to give guidance to cancer care providers treating patients with urothelial cancer.

Checkpoint Inhibition in Bladder Cancer: Clinical Expectations, Current Evidence, and Proposal of Future Strategies Based on a Tumor-Specific Immunobiological Approach

“…Yet, only fractions of patients are responding or responding long term [ 17 , 18 ]. For urothelial cancer, the initial excitement that checkpoint inhibition may change the management of the disease gave way to disappointment as several phase III trials failed to show improvement over chemotherapy, and clinical trials using seemingly similar immunotherapeutic agents showed inconsistent results [ 19 , 20 , 21 , 22 ]. However, there is still reason for excitement about immunotherapy’s potential, and maximizing patient benefit seems possible.…”

“…PD-L1 detection by IHC is FDA approved and has demonstrated prognostic value in some situations. However, it is mostly unsatisfactory to predict treatment efficacy with patients failing to respond despite PD-L1-positive tumors, and response is observed with patients despite the absence of PD-L1 in the TME [ 19 , 20 , 21 , 30 ].…”

“…Besides methodological limitations, including poor concordance among approved assays, differences in cut-offs, and multiple scoring systems defining PD-L1 protein expression on tumor and/or immune cells [ 19 , 20 , 29 , 31 ], the immunobiology of PD-L1 disqualifies this marker as a biomarker sufficient, by itself, for therapy response prediction and patient selection, outlined as follows:…”

“…Therefore, tumors with a high TMB are more likely to be targets for T cell attack. An association with immunotherapy response is conceivable, and some predictive capacity has been reported [ 39 ], variably across various tumor indications [ 19 , 20 , 21 ]. Yet, despite a high TMB, tumors can be resistant to the T cell response and ICI will be ineffective if the tumor is not infiltrated by T cells, if the tumor cells do not express MHC for antigen presentation [ 40 ], and/or if suppressor cells or metabolites are present in the TME that inhibit T cell activity.…”

Towards a Better Understanding of Antibody-Drug Conjugates in Urothelial Carcinoma

“…Patients with metastatic urothelial carcinoma (mUC) remain largely incurable despite responses to platinumbased chemotherapy, and more recently immune checkpoint inhibitors (ICIs) [1,2]. Antibody-drug conjugates (ADCs) have lately emerged as another promising therapeutic option in mUC (Table 1).…”