Prostate Cancer Liver Metastasis: An Ominous Metastatic Site in Need of Distinct Management Strategies.

Prostate cancer liver metastasis (PCLM), seen in upwards of 25% of metastatic castration-resistant PC (mCRPC) patients, is the most lethal site of mCRPC with a median overall survival of 10-14 months. Despite its ominous prognosis and anticipated rise in incidence due to longer survival with contemporary therapy, PCLM is understudied. This review aims to summarize the existing literature regarding the risk factors associated with the development of PCLM, and to identify areas warranting further research. A literature search was conducted through Ovid MEDLINE from 2000 to March 2023. Relevant subject headings and text words were used to capture the following concepts: "Prostatic Neoplasms", "Liver Neoplasms", and "Neoplasm Metastasis". Citation searching identified additional manuscripts. Forty-one studies were retained for detailed analysis. The clinical risk factors for visceral/liver metastasis included <70 years, ≥T3 tumor, N1 nodal stage, de novo metastasis, PSA >20 ng/mL, and a Gleason score >8. Additional risk factors comprised elevated serum AST, LDH or ALP, decreased Hb, genetic markers like RB1 and PTEN loss, PIK3CB and MYC amplification, as well as numerous PC treatments either acting directly or indirectly through inducing liver injury. Further research regarding predictive factors, early detection strategies, and targeted therapies for PCLM are critical for improving patient outcomes.

Managing Metastatic Renal Cell Carcinoma after Progression on Immunotherapy.

Treatment of metastatic renal cell carcinoma (mRCC) after first-line immune checkpoint inhibitors (ICIs) lacks standardization, with limited evidence from small trials and retrospective data. Vascular endothelial growth factor receptor (VEGFR) inhibition through tyrosine kinase inhibitors (TKIs) is the most widely adopted second-line treatment. Encouraging results have been seen with VEGFR-TKIs in the second-line after exposure to an ICI-based combination, achieving a response rate of 30%, and 75% of patients achieving disease control. Rechallenge with ICI alone seems safe but has limited clinical benefit. Promising regimens with combination therapies and novel drugs are being evaluated in phase 3 trials.

Role of PD-1 Inhibitors in the Treatment of Esophagogastric Adenocarcinoma: Patient Selection and Reported Outcomes.

Esophagogastric cancers are aggressive malignancies, with poor prognosis despite current standard-of-care therapies. PD-1 inhibitors are a newer class of antitumor agents with the potential to improve outcomes among appropriately selected patients. This review provides an overview of the key trials that have guided the use of PD-1 and PD-L1 inhibitors in the refractory and first-line settings. We highlight recent studies investigating the role of genomic classification in predicting therapeutic activity of PD-1 inhibitors. In addition, there is a discussion of the use of different scoring systems and criteria to determine PD-L1 positivity, the impact on the therapeutic use of immune checkpoint inhibition with anti-PD-1 agents, and the controversies in current methods of PD-L1 testing and their implications in patient selection for anti-PD-1 therapy.

The Gut Microbiome and Metastatic Renal Cell Carcinoma.

The introduction of targeted therapy (TT) and immuno-oncology (IO) agents have revolutionized the treatment of metastatic renal cell carcinoma (mRCC). However, despite the significant improvements in survival and clinical response yielded by these agents, a significant percentage of patients still experience progressive disease. Evidence now suggests that microorganisms living in the gut (i.e., the gut microbiome) could be used as a biomarker for response and may also have utility in increasing response to these treatments. In this review, we present an overview of the role of the gut microbiome in cancer and its potential implications in the treatment of mRCC.

A Systematic Review and Meta-Analysis of the Role of Immune Checkpoint Inhibitors (ICI) as Adjuvant Treatment for Localized High-Risk Muscle-Invasive Urothelial Carcinoma (MIUC).

Nivolumab, a PD-1 ICI has been recently approved for the adjuvant treatment of high-risk MIUC patients. However, conflicting data from another randomized controlled trial (RCT) with atezolizumab makes the benefit of this treatment uncertain. We performed a systematic review and study-level meta-analysis to evaluate the benefit in terms of disease-free survival (DFS) with ICI adjuvant treatment for patients with high-risk MIUC. Considering the Preferred Reporting Items for Systematic Review statement, a systematic search was performed in PUBMED/MEDLINE, Scopus and EMBASE up to October 30, 2021. The statistical analysis was performed by RevMan 5.4 software in intention-to-treat (ITT) population and in predetermined subgroups. Two RCTRCT, with a total of 1518 patients, met the inclusion criteria. Systemic immunotherapy was atezolizumab for 406 patients and nivolumab for 353 patients. In the ITT population there was a nonsignificant benefit with the systemic adjuvant immunotherapy (HR:0.79, 95% CI 0.62-1.00; z = 2.00) but with high heterogeneity (I2 = 65%). Regarding the subgroups, there was no benefit in PD-L1 negative (HR:0.81, 95% CI 0.70-1.00; z = 1.96, I2 = 0%) and in non-neoadjuvant chemotherapy (HR:0.95, 95% CI 0.78-1.15; z = 0.56, I2 = 0%). Adjuvant treatment with ICI to patients with high-risk MIUC reveals a nonsignificant impact in DFS. The lack of clinical benefit was demonstrated in all subgroups. These data reinforce the need for a careful selection of patients before offering this approach in daily practice.

EGFR-RAD51 fusion in lung adenocarcinoma with systemic and intracranial response to osimertinib: A case report and review of the literature.

Comprehensive next-generation sequencing panels are leading to detection of rare gene fusion events. EFGR-RAD51 fusion is a rare oncogenic finding and clinical data for management of this condition is scarce. We report a widely metastatic non-small cell lung cancer in a never-smoker young male patient with sustained near-complete systemic and intracranial response to osimertinib, a third-generation EGFR tyrosine-kinase inhibitor (TKI). We also review the available data of other TKIs in this scenario and underscore the role of comprehensive molecular testing for NSCLC.

Hepatocellular Carcinoma Immunotherapy.

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and the third leading cause of cancer-related death worldwide. Single-agent anti-PD-1 immune checkpoint inhibitors (ICIs) demonstrated promising efficacy in early-phase trials, a finding that was not confirmed in phase III studies. The combination of atezolizumab (an anti-PD-L1 ICI) with bevacizumab (an anti-VEGF antibody) was approved as first-line therapy in 2020, however, with significant improvement in response rate, progression-free survival, and overall survival in comparison with the previous standard of care, sorafenib. Numerous ongoing clinical trials are assessing ICIs in combination with each other or with targeted agents, and also in earlier stages with local therapies. This review summarizes the latest concepts in the use of ICIs for the management of HCC.