Prognostic and Predictive Factors in Advanced Urothelial Carcinoma Treated with Immune Checkpoint Inhibitors: A Review of the Current Evidence

Abstract

In recent years, the treatment landscape of urothelial carcinoma has significantly changed due to the introduction of immune checkpoint inhibitors (ICIs), which are the standard of care for second-line treatment and first-line platinum-ineligible patients with advanced disease. Despite the overall survival improvement, only a minority of patients benefit from this immunotherapy. Therefore, there is an unmet need to identify prognostic and predictive biomarkers or models to select patients who will benefit from ICIs, especially in view of novel therapeutic agents. This review describes the prognostic and predictive role, and clinical readiness, of clinical and tumour factors, including new molecular classes, tumour mutational burden, mutational signatures, circulating tumour DNA, programmed death-ligand 1, inflammatory indices and clinical characteristics for patients with urothelial cancer treated with ICIs. A classification of these factors according to the levels of evidence and grades of recommendation currently indicates both a prognostic and predictive value for ctDNA and a prognostic relevance only for concomitant medications and patients’ characteristics.

Current Advances in Immune Checkpoint Inhibition and Clinical Genomics in Upper Tract Urothelial Carcinoma: State of the Art

“…Blood-based evaluation, using ct-DNA, of genomic signatures may present a further opportunity to develop response biomarkers for available therapeutic armamentarium options. In UCs, proof-of-concept data documented that ctDNA is detectable in plasma and urine, and could be a prognostic factor [ 48 , 49 , 50 , 51 ]. Liquid biopsy could represent a cost-effective and minimally invasive method for biomarker identification and patient stratification.…”

Urological Cancer Panorama in the Second Year of the COVID-19 Pandemic

“…Two out of seven papers in this section are reviews. Rebuzzi et al [18] evaluate the prognostic and predictive factors of advanced urothelial carcinoma treated with immune checkpoints inhibitors (ICIs), with the intention to identify biomarkers to select the patients at higher chances of responding to ICI treatment that may merit further prospective investigation. Their main conclusions are that current evidence on the predictive and prognostic value of PD-L1 expression is limited by the different assays used for each anti-PD1 or anti-PD-L1 agent in the clinical trials evaluated, and thereof their clinical value remains inconclusive.…”

“…On the other hand, the authors position towards the value of sequencing of the tumor fraction of the cell-free DNA (ctDNA) is an interesting method to detect residual disease and anticipate disease relapse after treatment using different biomarkers that include FGFR3, XPD, HER2, and TMB. What is more, the serial monitoring of ctDNA as a tumor tissue surrogate could be of value to stratify metastatic urothelial carcinoma and could act as a treatment response marker [18,19].…”

Change in Splenic Volume as a Surrogate Marker for Immunotherapy Response in Patients with Advanced Urothelial and Renal Cell Carcinoma—Evaluation of a Novel Approach of Fully Automated Artificial Intelligence Based Splenic Segmentation

“…Until today, the PD-1, as well as the PD-L1 expression, has not proven to be a robust biomarker for therapy response in aUC and aRCC. Besides multiple prognostic models, no relevant radiological surrogate markers exist to detect early IO response in these patients [ 3 , 4 ].…”

“…In summary, there is a rapidly changing therapeutic landscape in the treatment of aUC and aRCC that is leading to significant improvements in patient outcomes [ 8 ]. However, there is still an urgent need for simple and feasible prognostic tools to detect early responses to IO treatments [ 3 , 4 ]. Since IO as described has taken an important place in the treatment of aUC and aRCC in recent years, we aimed to investigate both tumour identities separately in our study in order to make a new, innovative, scientific contribution to the treatment of genitourinary cancer.…”