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Background: Aberrant Wnt signaling has been implicated in prostate cancer tumorigenesis and metastasis in preclinical models but the impact of genetic alterations in Wnt signaling genes in men with advanced prostate cancer is unknown. Methods: We utilized the Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort (PROMISE) clinical-genomic database for this retrospective analysis. Patients with activating mutations in CTNNB1or RSPO2or inactivating mutations in APC, RNF43, or ZNRF3were defined as Wnt-altered, while those lacking such alterations were defined as Wnt non-altered. We compared patient characteristics and clinical outcomes as well as co-occurring genetic alterations according to Wnt alteration status. Results: Of the 1498 patients included, 193 (12.9%) were Wnt-altered. These men had a statistically significant 2-fold increased prevalence of liver and lung metastases as compared with Wnt non-altered patients at the time of initial diagnosis, (4.66% v 2.15% ; 6.22% v 3.07%), first metastatic disease diagnosis (10.88% v 5.29%; 13.99% v 6.21%), and CRPC development (11.40% v 6.36%; 12.95% v 5.29%). Wnt alterations were associated with more co-occurring alterations in RB1(10.4% v 6.2%), AR(38.9% vs 25.7%), SPOP(13.5% vs 4.1%), FOXA1(6.7% vs 2.8%), and PIK3CA(10.9% vs 5.1%). We found no significant differences in overall survival or other clinical outcomes from initial diagnosis, first metastatic disease, diagnosis of CRPC, or with AR inhibition for mCRPC between the Wnt groups. Conclusions: Wnt-altered patients with prostate cancer have a higher prevalence of visceral metastases and are enriched in RB1, AR, SPOP, FOXA1, and PIK3CAalterations. Despite these associations, Wnt alterations were not associated with worse survival or treatment outcomes in men with advanced prostate cancer.

Background: ARgene alterations can develop in response to pressure of testosterone suppression and androgen receptor targeting agents (ARTA). Despite this, the relevance of these gene alterations in the context of ARTA treatment and clinical outcomes remains unclear. Methods: Patients with castration-resistant prostate cancer (CRPC) who had undergone genomic testing and received ARTA treatment were identified in the Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort (PROMISE) database. Patients were stratified according to the timing of genomic testing relative to the first ARTA treatment (pre-/post-ARTA). Clinical outcomes such as time to progression, PSA response, and overall survival were compared based on alteration types. Results: In total, 540 CRPC patients who received ARTA and had tissue-based (n= 321) and/or blood-based (n= 244) genomic sequencing were identified. Median age was 62 years (range 39−90) at the time of the diagnosis. Majority were White (72.2%) and had metastatic disease (92.6%) at the time of the first ARTA treatment. Pre-ARTA genomic testing was available in 24.8% of the patients, and ARmutations and amplifications were observed in 8.2% and 13.1% of the patients, respectively. Further, time to progression was longer in patients with ARamplifications (25.7 months) compared to those without an ARalteration (9.6 months; p= 0.03). In the post-ARTA group (n= 406), ARmutations and ARamplifications were observed in 18.5% and 35.7% of the patients, respectively. The most common mutation in post-ARTA group was L702H(9.9%). Conclusion: In this real-world clinicogenomics database-driven study we explored the development of ARalterations and their association with ARTA treatment outcomes. Our study showed that ARamplifications are associated with longer time to progression on first ARTA treatment. Further prospective studies are needed to optimize therapeutic strategies for patients with ARalterations.

Background: Natural killer (NK) cells are non-antigen specific innate immune cells that can be redirected to targets of interest using multiple strategies, although none are currently FDA-approved. We sought to evaluate NK cell infiltration into tumors to develop an improved understanding of which histologies may be most amenable to NK cell-based therapies currently in the developmental pipeline. Methods: DNA (targeted/whole-exome) and RNA (whole-transcriptome) sequencing was performed from tumors from 45 cancer types (N= 90,916 for all cancers and N= 3365 for prostate cancer) submitted to Caris Life Sciences. NK cell fractions and immune deconvolution were inferred from RNA-seq data using quanTIseq. Real-world overall survival (OS) and treatment status was determined and Kaplan–Meier estimates were calculated. Statistical significance was determined using X2and Mann–Whitney Utests, with corrections for multiple comparisons where appropriate. Results: In both a pan-tumor and prostate cancer (PCa) -specific setting, we demonstrated that NK cells represent a substantial proportion of the total cellular infiltrate (median range 2–9% for all tumors). Higher NK cell infiltration was associated with improved OS in 28 of 45 cancer types, including (PCa). NK cell infiltration was negatively correlated with common driver mutations and androgen receptor variants (AR-V7) in primary prostate biopsies, while positively correlated with negative immune regulators. Higher levels of NK cell infiltration were associated with patterns consistent with a compensatory anti-inflammatory response. Conclusions: Using the largest available dataset to date, we demonstrated that NK cells infiltrate a broad range of tumors, including both primary and metastatic PCa. NK cell infiltration is associated with improved PCa patient outcomes. This study demonstrates that NK cells are capable of trafficking to both primary and metastatic PCa and are a viable option for immunotherapy approaches moving forward. Future development of strategies to enhance tumor-infiltrating NK cell-mediated cytolytic activity and activation while limiting inhibitory pathways will be key.

To evaluate effect and outcomes of combination primary immunotherapy (IO) and nephrectomy for advanced renal cell carcinoma (RCC).

•Patients with advanced urothelial cancer (aUC) rechallenged with an ICI-based regimen may achieve disease control.•Rechallenge with ICI-based therapy in aUC seems feasible with manageable toxicity.•Further data are needed to optimally select patients for ICI rechallenge in aUC.

Prostate cancer (PC) rarely metastasizes to the central nervous system (CNS). In this retrospective single-institution study at a tertiary cancer center, we aimed to evaluate the clinical and genetic characteristics of advanced PC patients with CNS metastases.

•Data regarding direct oral anticoagulants (DOACs) appear safe for venous thromboembolism (VTE) treatment for patients with RCC on cabozantinib•No. of major bleeding events similar between no anticoagulant, low molecular weight heparin (LMWH) or DOAC groups.•The rate of new/recurrent VTE was similar among anticoagulant groups•Patients with a VTE had significantly worse survival than those without a VTE

•5-FU infusion has activity in far advanced prostate cancer.•5-FU at 200 mg/M2 per day by continuous infusion is well tolerated.•Options for advanced prostate cancer are limited.

Early progression on first-line (1L) platinum-based therapy or between therapy lines may be a surrogate of more aggressive disease and poor outcomes in advanced urothelial carcinoma (aUC), but its prognostic role regarding immune checkpoint inhibitor (ICI) response and survival is unclear. We hypothesized that shorter time until start of second-line (2L) ICI would be associated with worse outcomes in aUC.

Purpose: Prostate cancer is a heterogeneous disease with variable clinical outcomes. Despite numerous recent approvals of novel therapies, castration-resistant prostate cancer remains lethal. A “real-world” clinical-genomic database is urgently needed to enhance our characterization of advanced prostate cancer and further enable precision oncology. Methods: The Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort (PROMISE) is a consortium whose aims are to establish a repository of de-identified clinical and genomic patient data that are linked to patient outcomes. The consortium structure includes a (1) bio-informatics committee to standardize genomic data and provide quality control, (2) biostatistics committee to independently perform statistical analyses, (3) executive committee to review and select proposals of relevant questions for the consortium to address, (4) diversity/inclusion committee to address important clinical questions pertaining to racial disparities, and (5) patient advocacy committee to understand patient perspectives to improve patients’ quality of care. Results: The PROMISE consortium was formed by 16 academic institutions in early 2020 and a secure RedCap database was created. The first patient record was entered into the database in April 2020 and over 1000 records have been entered as of early 2021. Data entry is proceeding as planned with the goal to have over 2500 patient records by the end of 2021. Conclusions: The PROMISE consortium provides a powerful clinical-genomic platform to interrogate and address data gaps that have arisen with increased genomic testing in the clinical management of prostate cancer. The dataset incorporates data from patient populations that are often underrepresented in clinical trials, generates new hypotheses to direct further research, and addresses important clinical questions that are otherwise difficult to investigate in prospective studies.

BACKGROUND: Immune checkpoint inhibitors (ICI) have emerged as active therapies in the management of advanced RCC. While multiple studies have shown clinical activity of ICIs in clear cell histologies, the evidence to support their use in non-clear cell (ncc) subtypes is based on smaller prospective trials and retrospective analyses.OBJECTIVE: The objective of this review is to summarize the clinical outcomes of ICI-based therapies in ncc-subtypes and in tumors with sarcomatoid/rhabdoid features.METHODS: We performed a systematic literature search using PubMed, Google Scholar and ASCO databases. The keywords “renal cell cancer” and “immune checkpoint inhibitors” and equivalents were used and all original publications between July 2016 and July 2021 were included.RESULTS: We included a total of 14 publications, including two clinical trials and 12 case series. The most frequent histologies were papillary (up to 75-100%), unclassified (up to 34%) and chromophobe (up to 28%). ICI monotherapy showed some activity in both 1st and 2nd line with response rates up to 27%. ICI combination regimens yielded better activity than ICI monotherapy but, overall, a heterogeneous efficacy was noted across histologies. Overall, outcomes of ICIs were superior in tumors with sarcomatoid/rhabdoid features.CONCLUSION: The observed activity of ICI-based therapies was heterogeneous. Combination regimens, papillary subtype and sarcomatoid/rhabdoid features were associated with higher responses. These findings might help treatment decisions and require further validation.

Immune checkpoint inhibitors (ICI) have emerged as active therapies in the management of advanced RCC. While multiple studies have shown clinical activity of ICIs in clear cell histologies, the evidence to support their use in non-clear cell (ncc) subtypes is based on smaller prospective trials and retrospective analyses. The objective of this review is to summarize the clinical outcomes of ICI-based therapies in ncc-subtypes and in tumors with sarcomatoid/rhabdoid features. We performed a systematic literature search using PubMed, Google Scholar and ASCO databases. The keywords “renal cell cancer” and “immune checkpoint inhibitors” and equivalents were used and all original publications between July 2016 and July 2021 were included. We included a total of 14 publications, including two clinical trials and 12 case series. The most frequent histologies were papillary (up to 75-100%), unclassified (up to 34%) and chromophobe (up to 28%). ICI monotherapy showed some activity in both 1st and 2nd line with response rates up to 27%. ICI combination regimens yielded better activity than ICI monotherapy but, overall, a heterogeneous efficacy was noted across histologies. Overall, outcomes of ICIs were superior in tumors with sarcomatoid/rhabdoid features. The observed activity of ICI-based therapies was heterogeneous. Combination regimens, papillary subtype and sarcomatoid/rhabdoid features were associated with higher responses. These findings might help treatment decisions and require further validation.

ABSTRACTObjectivesThe burden of nonalcoholic fatty liver disease (NAFLD) is increasing, with an estimated prevalence in Europe of 20–30%. Although most patients present with simple steatosis, some progress to advanced fibrosis, cirrhosis, and hepatocellular carcinoma. Definite diagnosis and staging require liver biopsy, which is not feasible given the high prevalence of NAFLD. As such, several noninvasive tools have been formulated. However, to date, none have been validated in the Portuguese population. The aim of this study was to determine the diagnostic accuracy of the aspartate aminotransferase to platelet ratio (APRI), the BMI, AST/ALT ratio and Diabetes (BARD), the FIB-4 Index (FIB-4), the Hepamet fibrosis score (HFS), and the NAFLD fibrosis score (NFS) in a Portuguese population.MethodsA retrospective review of liver biopsies from two hospital centers was performed. Patients with NAFLD and no decompensated cirrhosis, liver cancer, or terminal illness were included. APRI, BARD, FIB-4, HFS, and NFS were calculated for each patient.ResultsA total of 121 individuals were included, of which 21.5% had advanced fibrosis (F ≥ 3). There was a moderate or high correlation between most tools. The negative predictive factor (NPV) and area under receiver operating curve (AUROC) were 89.9% and 0.80 for APRI, 91.8% and 0.84 for BARD, 95.7% and 0.88 for FIB-4, 96.4% and 0.88 for HFS, and 93.0% and 0.86 for NFS, respectively.ConclusionThe tools analyzed had excellent performance (AUROC ≥ 0.80) and were adequate for ruling out advanced fibrosis (NPV ≥ 89.9%) in a Portuguese population. As such, they are adequate for use in clinical practice or as a part of referral and follow-up programs wherever this population is treated.AbbreviationsAPRI – aspartate aminotransferase to platelet ratio, ALT – alanine aminotransferase, AST – aspartate aminotransferase, BARD – BMI, AST/ALT ratio and Diabetes, BMI – body mass index, FIB-4 – FIB-4 index, HCC – hepatocellular carcinoma, HFS – Hepamet fibrosis score, HOMA-IR – homeostatic model assessment for insulin resistance, IQR – interquartile range, MAFLD – metabolic associated fatty liver disease, NAFLD – nonalcoholic fatty liver disease, NASH – nonalcoholic steatohepatitis, NFS – NAFLD fibrosis score, OMIC – genomics, transcriptomics, proteomics, and metabolomics, T2DM – type 2 diabetes mellitus

Microsatellite Instability (MSI) and Tumor Mutational Burden (TMB) are associated with immune checkpoint inhibitor (ICI) efficacy. We examined the association between TMB and MSI status with survival in patients with urothelial carcinoma (UC) treated with ICI.

Immune checkpoint inhibitors (ICI) improve overall survival (OS) in patients with locally advanced, unresectable, or metastatic urothelial carcinoma (aUC), but response rates can be modest. We compared outcomes between patients with and without prior intravesical Bacillus Calmette-Guerin (BCG), who received ICI for aUC, hypothesizing that prior intravesical BCG would be associated with worse outcomes.

BACKGROUND: Metastatic and unresectable non-clear cell renal cell carcinoma comprises more than a quarter of kidney cancers but does not have standardized treatment. Non-clear renal carcinoma consists of a variety of diverse histologic subtypes, including papillary, chromophobe, collecting duct, translocation, and medullary histologies, many of which carry a poor prognosis. Many prospective clinical trials exclude these kidney cancers, and for most clinical trials of non-clear cell renal cell carcinoma, only a small number of patients are enrolled.OBJECTIVE: To perform a systematic review of recently published and currently enrolling prospective clinical trials for advanced non-clear cell renal cell carcinoma.METHODS: A systematic search of Pubmed and MEDLINE (Ovid) was conducted as per PRISMA guidelines to identify recent prospective clinical trials in non-clear cell renal cell carcinoma. To ensure a thorough search, terms not only included non-clear cell renal carcinoma but also molecular subtypes. A review of currently enrolling clinical trials was conducted on Clinicaltrials.gov and the EU Clinical Trials Register as well.RESULTS: A total of 33 prospective clinical trials with published results and 10 currently enrolling clinicals trials were identified. About half (48.5%) of these studies were reported in 2020 or 2021, and 36.4% were in the first-line setting. Treatments investigated in these trials included mTOR inhibitors, VEGF-and MET-targeted tyrosine kinase inhibitors, immune checkpoint inhibitors, and combinatorial strategies. Outcomes from these data revealed a wide range of response rate and progression free survival, favoring TKIs and immune checkpoint inhibitors -based combination regimens.CONCLUSIONS: Novel targeted therapies and immunotherapies have changed the landscape of treatment for advanced non-clear cell renal cell carcinoma. Combination regimens may provide even further clinical benefit and warrant further investigation in larger, randomized prospective clinical trials.

Metastatic and unresectable non-clear cell renal cell carcinoma comprises more than a quarter of kidney cancers but does not have standardized treatment. Non-clear renal carcinoma consists of a variety of diverse histologic subtypes, including papillary, chromophobe, collecting duct, translocation, and medullary histologies, many of which carry a poor prognosis. Many prospective clinical trials exclude these kidney cancers, and for most clinical trials of non-clear cell renal cell carcinoma, only a small number of patients are enrolled. To perform a systematic review of recently published and currently enrolling prospective clinical trials for advanced non-clear cell renal cell carcinoma. A systematic search of Pubmed and MEDLINE (Ovid) was conducted as per PRISMA guidelines to identify recent prospective clinical trials in non-clear cell renal cell carcinoma. To ensure a thorough search, terms not only included non-clear cell renal carcinoma but also molecular subtypes. A review of currently enrolling clinical trials was conducted on Clinicaltrials.gov and the EU Clinical Trials Register as well. A total of 33 prospective clinical trials with published results and 10 currently enrolling clinicals trials were identified. About half (48.5%) of these studies were reported in 2020 or 2021, and 36.4% were in the first-line setting. Treatments investigated in these trials included mTOR inhibitors, VEGF-and MET-targeted tyrosine kinase inhibitors, immune checkpoint inhibitors, and combinatorial strategies. Outcomes from these data revealed a wide range of response rate and progression free survival, favoring TKIs and immune checkpoint inhibitors -based combination regimens. Novel targeted therapies and immunotherapies have changed the landscape of treatment for advanced non-clear cell renal cell carcinoma. Combination regimens may provide even further clinical benefit and warrant further investigation in larger, randomized prospective clinical trials.

TFE3-rearranged renal cell carcinoma (rRCC) is a rare subtype of renal cell carcinomas belonging to the MiT family translocation RCC. To further elucidate the co-alterations that occur along with TFE3fusions in rRCC, we characterized the genomic, transcriptional, and immune landscapes in comparison to clear cell (ccRCC) and papillary renal cell carcinoma (pRCC). Next-generation sequencing of RNA (whole transcriptome) and DNA (592-gene panel or whole exome) for rRCC (N = 20), pRCC (N = 20), and ccRCC samples (N = 392) was performed. Patients with rRCC were significantly younger and more frequently female (median 44.5 years, 75.0% female) as compared with patients with pRCC (68.5 years, 25.0% female; P< .05) and ccRCC (62.0 years, 27.8% female; P< .05). A total of 8 unique fusion partners were observed, including a novel fusion with SRRM2::TFE3in 2 patients. ccRCC exhibited significantly higher mutation rates of VHL(0% rRCC, 0% pRCC, 78.7% ccRCC; P< .05) and PBMR1(0% rRCC, 5.0% pRCC, 49.4% ccRCC; P< .05). The genomic landscapes of rRCC were sparse with no mutations occurring with a prevalence higher than 10% other than pTERT(18.2% rRCC, 0% pRCC, 9.2% ccRCC). rRCC were associated with significantly less M1 macrophages (0.8%) as compared with pRCC (1.4%) and ccRCC (2.7%) (P< .05), suggesting a cold tumor-immune microenvironment. However, rRCC were more commonly PD-L1+ (rRCC 50%, pRCC 19.0%, ccRCC 12.2%; P< .05). Gene set enrichment analysis showed that rRCC are enriched in genes related to oxidative phosphorylation when compared with both ccRCC and pRCC. Despite having a colder tumor-immune microenvironment than pRCC and ccRCC, increased PDL1+ rates in rRCC suggest a potential benefit from immune checkpoint inhibitor therapy.

BACKGROUND: Over the past decade, immune checkpoint inhibitors (ICIs) have increasingly become the standard of care for various advanced malignancies, including metastatic clear cell renal cell carcinoma (mccRCC). Most ICIs currently used in clinical practice inhibit the interaction between the programmed cell death protein-1 (PD-1) and programmed death ligand-1 (PD-L1) complex. A deeper understanding of this interaction and PD-L1 expression in tumors has led to more effective therapies in the treatment of advanced cancers, but the debate regarding the utility of PD-L1 as a biomarker continues.OBJECTIVE: We aimed to systematically evaluate the role of PD-L1 in mccRCC in terms of expression and treatment implications.METHODS: Following PRISMA guidelines, we performed a systematic literature search using PubMed and Embase through August 31, 2020. Titles and abstracts were screened to identify articles for full-text review. A hand search was also performed using Google Scholar and the bibliography to relevant studies.RESULTS: A total of 26 articles were identified, and relevant data were extracted and organized. The available information regarding PD-L1 expression in mccRCC from both prospective clinical trials and retrospective studies were summarized. We discussed the utility of PD-L1 as a predictive and prognostic biomarker in mccRCC, its association with other potential biomarkers, and the pattern and level of expression of PD-L1 in primary versus metastatic tumors.CONCLUSIONS: Although significant progress has been made, much more remains to be learned regarding the differences between PD-L1+ and PD-L1- ccRCC tumors, in terms of both the underlying biology and clinical responses to immunotherapy and other agents.

Over the past decade, immune checkpoint inhibitors (ICIs) have increasingly become the standard of care for various advanced malignancies, including metastatic clear cell renal cell carcinoma (mccRCC). Most ICIs currently used in clinical practice inhibit the interaction between the programmed cell death protein-1 (PD-1) and programmed death ligand-1 (PD-L1) complex. A deeper understanding of this interaction and PD-L1 expression in tumors has led to more effective therapies in the treatment of advanced cancers, but the debate regarding the utility of PD-L1 as a biomarker continues. We aimed to systematically evaluate the role of PD-L1 in mccRCC in terms of expression and treatment implications. Following PRISMA guidelines, we performed a systematic literature search using PubMed and Embase through August 31, 2020. Titles and abstracts were screened to identify articles for full-text review. A hand search was also performed using Google Scholar and the bibliography to relevant studies. A total of 26 articles were identified, and relevant data were extracted and organized. The available information regarding PD-L1 expression in mccRCC from both prospective clinical trials and retrospective studies were summarized. We discussed the utility of PD-L1 as a predictive and prognostic biomarker in mccRCC, its association with other potential biomarkers, and the pattern and level of expression of PD-L1 in primary versus metastatic tumors. Although significant progress has been made, much more remains to be learned regarding the differences between PD-L1+ and PD-L1- ccRCC tumors, in terms of both the underlying biology and clinical responses to immunotherapy and other agents.

Prostate-specific antigen screening is controversial. In 2008, the United States Preventive Services Task Force recommended against screening men aged ≥ 75 years, and in 2012, expanded this to include all men. The impact of these changes continues to unfold. We hypothesized that these screening changes could delay the diagnosis of advanced prostate cancer.

Cell-free circulating DNA (cfDNA) can be used for noninvasive profiling of tumor genomic aberrations. We hypothesized that molecular alterations may inform prognostication in advanced urothelial carcinoma (aUC). We evaluated 124 aUC patients who underwent cfDNA analysis using a 73-gene sequencing panel (Guardant360). The association of molecular alterations and clinical factors with overall survival (OS) and failure-free-survival (FFS) was evaluated using the Kaplan-Meier method and Cox proportional-hazards regression. The median age was 72yr, and 65 patients (52.4%) received prior therapy with platinum, 21 (17.1%) with a taxane, and ten (8.1%) with a PD-1/PD-L1 inhibitor. At least one genomic alteration was detected in 112 patients (90.3%). The median number of alterations per sample was four (range 0–80). Commonly altered genes included TP53(54.8%), PIK3CA(24.2%), ARID1A(22.6%), ERBB2(19.4%), EGFR(16.1%), NF1(13.7%), RB1(12.9%), FGFR3(11.3%), BRAF(10.5%), BRCA1(10.5%), and RAF1(8.9%). BRCA1and RAF1alterations were associated with worse OS (hazard ratio [HR] 2.48; p=0.07; HR 4.87; p=0.007) and FFS (HR 2.35; p=0.016; HR 2.40; p=0.047). Poor Eastern Cooperative Oncology Group performance status and the presence of visceral metastasis were associated with shorter OS; genomic evolution was observed. In conclusion, cfDNA molecular alterations were detected in most aUC patients. BRCA1and RAF1alterations were negatively prognostic, supporting further evaluation of DNA damage response and RAF kinase inhibitors.

About one-third of advanced renal cell carcinoma (RCC) patients have bone metastases, which subsequently leads to the development of skeletal-related events (SREs), broadly defined to include surgery and radiation to bone, bone pain, pathological fracture, spinal cord compression, or hypercalcemia. The cumulative impact of SREs in RCC has not been well studied. SREs increase morbidity and mortality of RCC patients, although many interventions do significantly reduce their rates of development and improve prognosis. We performed a systematic review from the existing literature in PubMed from January 2002 through September 2019 and summarized the body of evidence regarding the development, prevention, prognosis and treatment of SREs in advanced RCC patients.

About one-third of advanced renal cell carcinoma (RCC) patients have bone metastases, which subsequently leads to the development of skeletal-related events (SREs), broadly defined to include surgery and radiation to bone, bone pain, pathological fracture, spinal cord compression, or hypercalcemia. The cumulative impact of SREs in RCC has not been well studied. SREs increase morbidity and mortality of RCC patients, although many interventions do significantly reduce their rates of development and improve prognosis. We performed a systematic review from the existing literature in PubMed from January 2002 through September 2019 and summarized the body of evidence regarding the development, prevention, prognosis and treatment of SREs in advanced RCC patients.

Circulating tumor DNA (ctDNA), which can be assessed by liquid biopsy, can provide valuable genomic information that may affect treatment response in prostate cancer. The aim of this study was to characterize TP53mutations and treatment history in prostate cancer.

For mild adverse events (AEs), continue cancer therapy and provide symptomatic/supplementary treatment. For more severe AEs, hold cancer therapy temporarily, restarting either at the same or at a reduced dose when the AE resolves. For all AEs, apply symptomatic treatment before holding or stopping cancer therapy, and carefully consider the potential clinical benefit of cancer therapy before discontinuation.

ABSTRACTRenal cell carcinoma (RCC), especially clear cell RCC, is generally considered an immunotherapy-responsive cancer. Recently, the prognosis for patients with locally advanced and metastatic RCC has significantly improved with the regulatory approvals of anti-PD-1/PD-L1/CTLA-4 immune checkpoint inhibitor (ICI)-based regimens. Yet in most cases, RCC will remain initially unresponsive to treatment or will develop resistance over time. Hence, there remains an unmet need to understand what leads to ICI resistance and to develop novel immune and nonimmune treatments to enhance the response to ICIs. In this review, we highlight recently published studies and the latest clinical studies investigating the next generation of immune approaches to locally advanced and metastatic RCC beyond traditional ICIs. These trials include cytokines, gut microbiota-based therapies, novel immune checkpoint agents, vaccines, and chimeric antigen receptor T cells. These agents are being evaluated as monotherapy or in combination with traditional ICIs and will hopefully provide improved outcomes to patients with RCC soon.

The mammalian target of rapamycin (mTOR) pathway is up-regulated in prostate cancer (PCa). We evaluated the tumor tissue expression of downstream mTOR targets in patients with intermediate- and high-risk (IR/HR) PCa and their ability to predict outcome after radical prostatectomy (RP).

Treatment of metastatic castration-resistant prostate cancer (mCRPC) has evolved significantly during the past decade, and the preferred combination and/or sequence of these treatments remains controversial. In this retrospective study, we explored clinical and pathologic factors that could predict response to consecutive treatment with enzalutamide (ENZA) after disease progression (PD) on abiraterone acetate and prednisone (AA/P).