The survival benefit of metastasectomy for metastatic non-clear cell renal cell carcinoma: a retrospective cohort study.

PURPOSE: The aim of this study was to explore the benefit the metastasectomy for patients with metastatic non-clear cell carcinoma (non-ccRCC). METHODS: This study enrolled 120 patients with confirmed metastatic non-ccRCC from the RCC database of our center from 2008 to 2021. Patients without metastasectomy were grouped as radical nephrectomy without metastasectomy patients. The clinical outcomes included overall survival (OS) and progression-free survival (PFS). Cox regression and Kaplan-Meier analyses were used to assess potential factors that predict clinical benefits from metastasectomy. RESULTS: A total of 100 patients received radical nephrectomy alone, while the remaining 20 patients underwent both radical nephrectomy and metastasectomy. There was no significant difference in age between the two groups. Out of 100 patients who underwent radical nephrectomy, 60 were male, and out of 20 patients who had both radical nephrectomy and metastasectomy, 12 were male. Patients who underwent systemic therapy plus radical nephrectomy and metastasectomy had significantly better PFS (27.1 vs. 14.0, p = 0.032) and OS (67.3 vs. 24.0, p = 0.043) than those who underwent systemic therapy plus radical nephrectomy alone. Furthermore, for patients without liver metastasis (n = 54), systemic therapy plus radical nephrectomy and metastasectomy improved both PFS (p = 0.028) and OS (p = 0.043). Similarly, for patients with metachronous metastasis, systemic therapy plus radical nephrectomy and metastasectomy improved both PFS (p = 0.043) and OS (p = 0.032). None of the patients experienced serious perioperative complications (Clavien-Dindo Classification ≥ III grade). CONCLUSION: Metastasectomy in patients with metastatic non-ccRCC may provide clinical benefits in terms of improved PFS and OS, especially in patients without liver metastasis and those with metachronous metastasis.

Predicting abiraterone efficacy in advanced prostate cancer: Insights from marker of proliferation Ki67.

BACKGROUND: KI67 is a well-known biomarker reflecting cell proliferation. We aim to elucidate the predictive role of KI67 in the efficacy of abiraterone for patients with advanced prostate cancer (PCa). METHODS: Clinicopathological data of 152 men with metastatic PCa, who received abiraterone therapy were retrospectively collected. The KI67 positivity was examined by immunohistochemistry using the prostate biopsy specimen. The predictive value of KI67 on the therapeutic efficacy of abiraterone was explored using Kaplan-Meier curve and Cox regression analysis. The endpoints included prostate-specific antigen (PSA) progression-free survival (PSA-PFS), radiographic PFS (rPFS), and overall survival (OS). RESULTS: In total, 85/152 (55.9%) and 67/152 (44.1%) cases, respectively, received abiraterone at metastatic hormone-sensitive (mHSPC) and castration-resistant PCa (mCRPC) stage. The median KI67 positivity was 20% (interquartile range: 10%-30%). Overall, KI67 rate was not correlated with PSA response. Notably, an elevated KI67-positive rate strongly correlated with unfavorable abiraterone efficacy, with KI67 ≥ 30% and KI67 ≥ 20% identified as the optimal cutoffs for prognosis differentiation in mHSPC (median PSA-PFS: 11.43 Mo vs. 26.43 Mo, p < 0.001; median rPFS: 16.63 Mo vs. 31.90 Mo, p = 0.003; median OS: 21.77 Mo vs. not reach, p = 0.005) and mCRPC (median PSA-PFS: 7.17 Mo vs. 12.20 Mo, p = 0.029; median rPFS: 11.67 Mo vs. 16.47 Mo, p = 0.012; median OS: 21.67 Mo vs. not reach, p = 0.073) patients, respectively. Multivariate analysis supported the independent predictive value of KI67 on abiraterone efficacy. In subgroup analysis, an elevated KI67 expression was consistently associated with unfavorable outcomes in the majority of subgroups. Furthermore, data from another cohort of 79 PCa patients with RNA information showed that those with KI67 RNA levels above the median had a significantly shorter OS than those below the median (17.71 vs. 30.72 Mo, p = 0.035). CONCLUSIONS: This study highlights KI67 positivity in prostate biopsy as a strong predictor of abiraterone efficacy in advanced PCa. These insights will assist clinicians in anticipating clinical outcomes and refining treatment decisions for PCa patients.

Prognostic significance of circulating tumor DNA in urothelial carcinoma: a systematic review and meta-analysis.

BACKGROUND: Circulating tumor DNA (ctDNA) has emerged as a non-invasive technique that provides valuable insights into molecular profiles and tumor disease management. This study aimed to evaluate the prognostic significance of circulating tumor DNA (ctDNA) in urothelial carcinoma (UC) through a systematic review and meta-analysis. METHODS: A comprehensive search was conducted in MEDLINE, EMBASE, and the Cochrane Library from the inception to December 2023. Studies investigating the prognostic value of ctDNA in UC were included. Hazard ratios (HRs) of disease-free survival (DFS) and overall survival (OS) were extracted. Overall meta-analysis and subgroup exploration stratified by metastatic status, ctDNA sampling time, treatment type, and detection method was performed using the R software (version 4.2.2). RESULTS: A total of sixteen studies with 1725 patients were included. Fourteen studies assessed the association between baseline ctDNA status and patient outcomes. Patients with elevated ctDNA levels exhibited significantly worse DFS (HR=6.26; 95% CI, 3.71-10.58, P<0.001) and OS (HR=4.23; 95% CI, 2.72-6.57, P<0.001) regardless of metastatic status, ctDNA sampling time, treatment type and detection methods. Six studies evaluated the prognostic value of ctDNA dynamics in UC. Patients who showed a decrease or clearance in ctDNA levels during treatment or observation demonstrated more favorable DFS (HR=0.26, 95% CI, 0.17-0.41, P<0.001) and OS (HR=0.21, 95% CI, 0.11-0.38, P<0.001) compared to those who did not. The association remained consistent across the subgroup analysis based on metastatic status and detection methods. In the immune checkpoint inhibitor-treated setting, both lower baseline ctDNA level and ctDNA decrease during the treatment were significantly associated with more favorable oncologic outcomes. Furthermore, specific gene mutations such as FGFR3 identified in ctDNA also demonstrated predictive value in UC patients. CONCLUSION: This meta-analysis demonstrates a strong association of ctDNA status and its dynamic change with survival outcomes in UC, suggesting substantial clinical utility of ctDNA testing in prognosis prediction and decision making in this setting.

Memory/active T cell activation is associated with immunotherapeutic response in fumarate hydratase-deficient renal cell carcinoma.

PURPOSE: Fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) is a rare and lethal subtype of kidney cancer. However, the optimal treatments and molecular correlates of benefits for FH-deficient RCC are currently lacking. EXPERIMENTAL DESIGN: A total of 91 patients with FH-deficient RCC from 15 medical centers between 2009 and 2022 were enrolled in this study. Genomic and bulk RNA sequencing (RNA-seq) were performed on 88 and 45 untreated FH-deficient RCCs, respectively. Single-cell RNA-seq was performed to identify biomarkers for treatment response. Main outcomes included disease-free survival (DFS) for localized patients, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) for metastatic patients. RESULTS: In the localized setting, we found that a cell cycle progression signature enabled to predict disease progression. In the metastatic setting, first-line immune checkpoint inhibitor plus tyrosine kinase inhibitor (ICI+TKI) combination therapy showed satisfactory safety and was associated with a higher ORR (43.2% vs. 5.6%), apparently superior PFS (median PFS: 17.3 vs. 9.6 months, P=0.016) and OS (median OS: not reached vs. 25.7 months, P=0.005) over TKI monotherapy. Bulk and single-cell RNA-seq data revealed an enrichment of memory and effect T cells in responders to ICI plus TKI combination therapy. Furthermore, we identified a signature of memory and effect T cells that was associated with the effectiveness of ICI plus TKI combination therapy. CONCLUSIONS: ICI plus TKI combination therapy may represent a promising treatment option for metastatic FH-deficient RCC. A memory/active T cell-derived signature is associated with the efficacy of ICI+TKI but necessitates further validation.

Genomic and Evolutionary Characterization of Concurrent Intraductal Carcinoma and Adenocarcinoma of the Prostate.

Intraductal carcinoma of the prostate (IDC-P) is a lethal prostate cancer subtype that generally coexists with invasive high-grade prostate acinar adenocarcinoma (PAC) but exhibits distinct biological features compared with concomitant adenocarcinoma. In this study, we performed whole-exome, RNA, and DNA-methylation sequencing of IDC-P, concurrent invasive high-grade PAC lesions, and adjacent normal prostate tissues isolated from 22 radical prostatectomy specimens. Three evolutionary patterns of concurrent IDC-P and PAC were identified: early divergent, late divergent, and clonally distant. In contrast to those with a late divergent evolutionary pattern, tumors with clonally distant and early divergent evolutionary patterns showed higher genomic, epigenomic, transcriptional, and pathologic heterogeneity between IDC-P and PAC. Compared with coexisting PAC, IDC-P displayed increased expression of adverse prognosis-associated genes. Survival analysis based on an independent cohort of 505 patients with metastatic prostate cancer revealed that IDC-P carriers with lower risk International Society of Urological Pathology (ISUP) grade 1-4 adenocarcinoma displayed a castration-resistant free survival as poor as those with the highest risk ISUP grade 5 tumors that lacked concurrent IDC-P. Furthermore, IDC-P exhibited robust cell-cycle progression and androgen receptor activities, characterized by an enrichment of cellular proliferation-associated master regulators and genes involved in intratumoral androgen biosynthesis. Overall, this study provides a molecular groundwork for the aggressive behavior of IDC-P and could help identify potential strategies to improve treatment of IDC-P. SIGNIFICANCE: The genomic, transcriptomic, and epigenomic characterization of concurrent intraductal carcinoma and adenocarcinoma of the prostate deepens the biological understanding of this lethal disease and provides a genetic basis for developing targeted therapies.

The mutational pattern of homologous recombination repair genes in urothelial carcinoma and its correlation with immunotherapeutic response.

BACKGROUND: The mutational pattern of homologous recombination repair (HRR)-associated gene alterations in Chinese urothelial carcinoma (UC) necessitates comprehensive sequencing efforts, and the clinical implications of HRR gene mutations in UC remain to be elucidated. MATERIALS AND METHODS: We delineated the mutational landscape of 343 Chinese UC patients from West China Hospital and 822 patients from The Cancer Genome Atlas (TCGA) using next-generation sequencing (NGS). Data from 182 metastatic UC patients from MSK-IMPACT cohort were used to assess the association between HRR mutations and immunotherapy efficacy. Comprehensive transcriptomic analysis was performed to explore the impact of HRR mutations on tumor immune microenvironment. RESULTS: Among Chinese UC patients, 34% harbored HRR gene mutations, with BRCA2, ATM, BRCA1, CDK12, and RAD51C being the most prevalently mutated genes. Mutational signatures contributing to UC differed between patients with and without HRR mutations. Signature 22 for exposure to aristolochic acid was only observed in Chinese UC patients. The presence of HRR mutations was correlated with higher tumor mutational burden, neoantigen burden, and PD-L1 expression. Importantly, patients with HRR mutations exhibited significantly improved prognosis following immunotherapy compared to those without HRR mutations. CONCLUSIONS: Our findings provide valuable insights into the genomic landscape of Chinese UC patients and underscore the molecular rationale for utilizing immunotherapy in UC patients with HRR mutations.

Retraction to the prognostic value of the pretreatment lung immune prognostic index in patients with metastatic hormone-sensitive and castration-resistant prostate cancer.

[This retracts the article DOI: 10.21037/atm-22-4318.].

Mutations in epigenetic regulator KMT2C detected by liquid biopsy are associated with worse survival in prostate cancer patients.

Background: KMT2 (lysine methyltransferase) family enzymes are epigenetic regulators that activate gene transcription. KMT2C is mainly involved in enhancer-associated H3K4me1, and is also one of the top mutated genes in cancer (6.6% in pan-cancer). Currently, the clinical significance of KMT2C mutations in prostate cancer is understudied. Methods: We included 221 prostate cancer patients diagnosed between 2014 and 2021 in West China Hospital of Sichuan University with cell-free DNA-based liquid biopsy test results in this study. We investigated the association between KMT2C mutations, other mutations, and pathways. Furthermore, we evaluated the prognostic value of KMT2C mutations, measured by overall survival (OS) and castration resistance-free survival (CRFS). Also, we explored the prognostic value of KMT2C mutations in different patient subgroups. Lastly, we investigated the predictive value of KMT2C mutations in individuals receiving conventional combined anti-androgen blockade (CAB) and abiraterone (ABI) as measured by PSA progression-free survival (PSA-PFS). Results: The KMT2C mutation rate in this cohort is 7.24% (16/221). KMT2C-mutated patients showed worse survival than KMT2C-wild type (WT) patients regarding both CRFS and OS (CRFS: mutated: 9.9 vs. WT: 22.0 months, p = 0.015; OS: mutated: 71.9 vs. WT 137.4 months, p = 0.012). KMT2C mutations were also an independent risk factor in OS [hazard ratio: 3.815 (1.461, 9.96), p = 0.006] in multivariate analyses. Additionally, we explored the association of KMT2C mutations with other genes. This showed that KMT2C mutations were associated with Serine/Threonine-Protein Kinase 11 (STK11, p = 0.004) and Catenin Beta 1 (CTNNB1, p = 0.008) mutations. In the CAB treatment, KMT2C-mutated patients had a significantly shorter PSA-PFS compared to KMT2C-WT patients. (PSA-PFS: mutated: 9.9 vs. WT: 17.6 months, p = 0.014). Moreover, KMT2C mutations could effectively predict shorter PSA-PFS in 10 out of 23 subgroups and exhibited a strong trend in the remaining subgroups. Conclusions: KMT2C-mutated patients showed worse survival compared to KMT2C-WT patients in terms of both CRFS and OS, and KMT2C mutations were associated with STK11 and CTNNB1 mutations. Furthermore, KMT2C mutations indicated rapid progression during CAB therapy and could serve as a potential biomarker to predict therapeutic response in prostate cancer.

Genomic and transcriptomic features between primary and paired metastatic fumarate hydratase-deficient renal cell carcinoma.

BACKGROUND: Fumarate hydratase-deficient renal cell carcinoma (FH-RCC) is a rare highly aggressive subtype of kidney cancer for which the distinct genomic, transcriptomic, and evolutionary relationships between metastatic and primary lesions are still unclear. METHODS: In this study, whole-exome, RNA-seq, and DNA methylation sequencing were performed on primary-metastatic paired specimens from 19 FH-RCC cases, including 23 primary and 35 matched metastatic lesions. Phylogenetic and clonal evolutionary analyses were used to investigate the evolutionary characteristics of FH-RCC. Transcriptomic analyses, immunohistochemistry, and multiple immunofluorescence experiments were performed to identify the tumor microenvironmental features of metastatic lesions. RESULTS: Paired primary and metastatic lesions generally showed similar characteristics of tumor mutation burden, tumor neoantigen burden, microsatellite instability score, CNV burden, and genome instability index. Notably, we identified an FH-mutated founding MRCA (the most recent common ancestor) clone that dominated the early evolutionary trajectories in FH-RCC. Although both primary and metastatic lesions manifested high immunogenicity, metastatic lesions exhibited higher enrichment of T effector cells and immune-related chemokines, together with upregulation of PD-L1, TIGIT, and BTLA. In addition, we found that concurrent NF2 mutation may be associated with bone metastasis and upregulation of cell cycle signature in metastatic lesions. Furthermore, although in FH-RCC metastatic lesions in general shared similar CpG island methylator phenotype with primary lesions, we found metastatic lesions displaying hypomethylated chemokine and immune checkpoints related genomic loci. CONCLUSIONS: Overall, our study demonstrated the genomic, epigenomic, and transcriptomic features of metastatic lesions in FH-RCC and revealed their early evolutionary trajectory. These results provided multi-omics evidence portraying the progression of FH-RCC.

Primary renal mucinous adenocarcinoma masquerading as a giant renal cyst: a case report.

Mucinous adenocarcinoma of the kidney is rarely reported in the literature. We present a previously unreported mucinous adenocarcinoma arising from the renal parenchyma. A 55-year-old male patient with no complaints showed a large cystic hypodense lesion in the upper left kidney on contrast-enhanced computed tomography (CT) scan. A left renal cyst was initially considered, and a partial nephrectomy (PN) was performed. During the operation, a large amount of jelly-like mucus and bean-curd-like necrotic tissue was found in the focus. The pathological diagnosis was mucinous adenocarcinoma, and further systemic examination revealed no clinical evidence of primary disease elsewhere. Then the patient underwent left radical nephrectomy (RN), and the cystic lesion was found in the renal parenchyma, while neither the collecting system nor the ureters were involved. Postoperative sequential chemotherapy and radiotherapy were administered, and no signs of disease recurrence were observed over 30 months of follow-up. Based on a literature review, we summarize the lesion with rarity and the associated dilemma in preoperative diagnosis and treatment. Given the high degree of malignancy, a careful history analysis accompanied by dynamic observation of imaging and tumor markers is recommended for the diagnosis of the disease. Comprehensive treatment based on surgery may improve its clinical outcomes.

The prognostic value of the pretreatment lung immune prognostic index in patients with metastatic hormone-sensitive and castration-resistant prostate cancer.

Background: The lung immune prognostic index (LIPI) was first reported to predict the effectiveness of immune checkpoint inhibitors in patients with metastatic non-small cell lung cancer and there are no studies investigating the predictive value of LIPI for patients with PCa. This study explores the prognostic value of the LIPI in patients with metastatic hormone-sensitive prostate cancer (mHSPC) and metastatic castration-resistant prostate cancer (mCRPC). Methods: Data from 502 patients with mHSPC primarily treated with maximal androgen blockade (MAB; 89% of patients received MAB) and 158 patients with mCRPC who received abiraterone were retrospectively analyzed. All cases were classified into LIPI-good, LIPI-intermediate, and LIPI-poor groups based on their LIPI score as calculated with the derived neutrophil-to-lymphocyte ratio and lactate dehydrogenase level. The potential for LIPI to be used in predicting mCRPC-free survival (CFS), prostate-specific antigen (PSA) response, PSA-progression-free survival (PSA-PFS), and overall survival (OS) was analyzed. A propensity score matching (PSM) methodology was performed to balance the baseline factors of the different groups. Results: In the mHSPC cohort, patients of the LIPI-good (mCFS: 25.7 months; mOS: 93.3 months), LIPI-intermediate (mCFS: 14.8 months; mOS: 51.9 months), and LIPI-poor group (mCFS: 6.8 months; mOS: 18.5 months) had sequentially worse clinical outcomes (P<0.001 for all pairwise comparisons). The results remained consistent after PSM. Multivariate Cox regression further confirmed that LIPI was an independent predictor of survival outcomes. Subgroup analysis verified that LIPI was associated with an unfavorable prognosis in all subgroups except for cases with visceral metastases or those receiving abiraterone or docetaxel. As for patients with mCRPC receiving abiraterone, LIPI was also an indicator of poor prognosis. Specifically, cases in the LIPI-good, LIPI-intermediate, and LIPI-poor groups had a ladder-shaped worse PSA response [71.4% (50/70) vs. 56.5% (39/69) vs. 36.8% (7/19); P=0.015], PSA-PFS (14.9 vs. 9.3 vs. 3.1 months; P<0.001), and OS (14.6 vs. 32.3 vs. 53.4 months; P<0.001). The results were robust even after PSM. Multivariate Cox regression confirmed that LIPI was an independent prognosticator of PSA-PFS and OS in patients with mCRPC treated with abiraterone. Conclusions: This study demonstrated that the baseline LIPI was a significant prognostic biomarker for patients with both mHSPC and mCRPC and could potentially facilitate risk classification and clinical decision-making.

Adipose-derived stem cells show hepatic differentiation potential and therapeutic effect in rats with acute liver failure.

Hepatocyte transplantation contributes to the repair of liver damage, but hepatocyte resources are limited, making it difficult for this to become a routine treatment. Previous studies have confirmed that mesenchymal stem cells (MSCs) can be induced to differentiate into hepatocyte-like cells (HLCs) by adding different cytokine combinations in vitro, and they then play some roles of hepatocytes. Our previous studies found that the differentiation ability of stem cells is closely related to the origin of the tissue. To identify the mesenchymal stem cells that are most suitable for hepatic differentiation and the treatment of liver failure, we use a three-phase induction process in which human adipose-derived stem cells (hADSCs) and umbilical cord mesenchymal stem cells (hUCMSCs) are induced to differentiate towards HLCs in vitro, and rats with acute liver failure (ALF) induced by D-gal are cured by MSCs and MSC-derived HLCs (MSCs-HLC), respectively. We find that hADSCs are stronger than hUCMSCs in hepatic differentiation ability, and they have a better curative effect when using hADSCs-HLC or jointly using hADSCs and hADSCs-HLC, which has positive significance for hepatocyte regeneration, recovery of liver function and reduction of systemic inflammatory reaction, finally improving the survival rate of rats with acute liver failure.

Safety and efficacy associated with single-fraction high-dose-rate brachytherapy in localized prostate cancer: a systematic review and meta-analysis.

OBJECTIVE: Although single-fraction high-dose-rate brachytherapy (SFHDR) for localized prostate cancer has been tried in clinical trials, relevant medical evidence is currently lacking. It is necessary to systematically analyze the safety and efficacy of SFHDR. METHODS: Comprehensive and systematic searches for eligible studies were performed in PubMed, Embase, and the Cochrane Library databases. The primary endpoints included safety and efficacy, represented by toxic effects and biochemical recurrence-free survival (bRFS), respectively. The proportion rates were used as the effect measure for each study and were presented with corresponding 95% confidence intervals (CI) and related 95% prediction interval (PI). Restricted maximum-likelihood estimator (REML) and the Hartung-Knapp method were used in the meta-analysis. RESULTS: Twenty-five studies met the inclusion criteria for quantitative analysis, including 1440 patients. The median age of patients was 66.9 years old (62-73 years old) and the median follow-up was 47.5 months (12-75 months). The estimates of cumulative occurrence for severe gastrointestinal (GI) and genitourinary (GU) toxic effects were 0.1% (95% CI 0-0.2%) and 0.4% (95% CI 0-1.2%), and for grade 2 toxic effects were 1.6% (95% CI 0.1-4.7%) and 17.1% (95% CI 5.4-33.5%), respectively. The estimate of 3­year bRFS was 87.5% (95% CI 84.4-90.3%) and 71.0% (95% CI 63.0-78.3%) for 5­year bRFS. The pooled bRFS rates for low-risk patients were 99.0% (95% CI 85.2-100.0%) at 3 years and 80.9% (95% CI 75.4-85.9%) at 5 years, and the risk group was found to be statistically correlated with bRFS (3-year bRFS, P < 0.01; 5­year bRFS, P = 0.04). CONCLUSION: SFHDR is associated with favorable tolerability and suboptimal clinical benefit in patients with localized prostate cancer. Ongoing and planned high-quality prospective studies are necessary to verify its safety and efficacy.

Multidisciplinary Team (MDT) Discussion Improves Overall Survival Outcomes for Metastatic Renal Cell Carcinoma Patients.

Purpose: Multidisciplinary team (MDT) discussion is a widely used model to manage patients diagnosed with cancer. However, there has been no direct evidence to prove its effect on the prognosis of metastatic renal cell carcinoma (mRCC) patients, so this study explored the impact of MDT discussion on mRCC patient survival. Methods: The clinical data of 269 mRCC patients were retrospectively collected from 2012 to 2021. The cases were grouped into the MDT and non-MDT groups, then subgroup analysis was performed according to different histology types, as well as exploring the role of MDT in patients who have undergone multiple-line therapy. Overall survival (OS) and progression free survival (PFS) were set as the study endpoint. Results: Approximately half (48.0%, 129/269) of the patients were in the MDT group, with univariable survival analyses showing these patients had remarkably longer median OS (MDT group: 73.7 months; non-MDT group: 33.2 months, hazard ratio (HR): 0.423 (0.288, 0.622), p<0.001) and longer median PFS (MDT group: 16.9 months, non-MDT group: 12.7 months, HR: 0.722 (0.542, 0.962), p=0.026). Furthermore, MDT management resulted in longer survival for both ccRCC and non-ccRCC subgroups. Patients in the MDT group were more likely to receive multi-line therapy (MDT group: 79/129, 61.2% vs non-MDT group: 56/140, 40.0%, p<0.001), and within this patient group, MDT management still resulted in longer OS (MDT group: 94.0 months; non-MDT group: 43.5 months, p=0.009). Conclusion: MDT is associated with prolonged overall survival in mRCC independent of histology, ensuring that patients receive better management and precise treatment.

Neuroendocrine differentiation predicts the therapeutic efficacy of abiraterone and docetaxel as first-line therapy in metastatic castration-resistant prostate cancer.

PURPOSE: We aim to explore the predictive value of neuroendocrine differentiation (NED) in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving abiraterone or docetaxel as first-line therapy. METHODS: We retrospectively analyzed data of 262 mCRPC patients receiving abiraterone or docetaxel as first-line mCRPC treatment. NED was evaluated using prostate biopsy samples at the time of mCRPC by immunohistochemical staining. Kaplan-Meier curves and Cox regression were used to assess the association between NED and treatment outcomes including PSA progression-free survival (PSA-PFS), radiographic progression-free survival (rPFS), and overall survival (OS). RESULTS: NED was confirmed in 100/262 (38.2%) mCRPC patients, with 76/100 (76.0%) and 24/100 (24.0%) men harboring NED < 10% and NED ≥ 10%, respectively. 203/262 (77.5%) and 59/262 (22.5%) patients received abiraterone and docetaxel, respectively. In abiraterone treatment, NED was associated with a significantly shorter median PSA-PFS (mPSA-PFS, 7.5 vs. 10.3-Mo, P < 0.001), median rPFS (mrPFS, 15.9 vs. 19.5-Mo, P = 0.010), and median OS (mOS, 23.2 vs. 34.3-Mo, P = 0.014)). Likewise, for mCRPC patients receiving docetaxel, the positive detection of NED also predicted shorter mPSA-PFS (3.8 vs. 5.9-Mo, P = 0.052), mrPFS (8.4 vs. 20.4-Mo, P = 0.016) and mOS (13.6 vs. 29.0-Mo, P = 0.033). The adverse prognostic trait of NED is consistent in most subgroups. Additionally, patients' survival outcomes deteriorated as the NED proportion grew in both therapies. After propensity score matching, NED-positive patients showed comparable prognosis in abiraterone and docetaxel therapy. CONCLUSION: For mCRPC patients receiving abiraterone or docetaxel, NED and its proportion were critical predictive factors. NED detection at mCRPC might aid in predicting patients' outcomes and optimizing treatment decisions.

Identifying the critical activated carbon properties affecting the adsorption of effluent organic matter from bio-treated coking wastewater.

Activated carbon is widely used to remove effluent organic matter (EfOM) from bio-treated coking wastewater. However, the critical carbon properties affecting adsorption performance are still unclear. Nine commercial powdered activated carbons (PACs) with different pore structures, surface functional groups, and surface charges were used to adsorb EfOM from bio-treated coking wastewater, which was fractionated according to their molecular weight (MW) and hydrophobicity. Good correlations were observed between the adsorption of biopolymers (MW > 20,000 Da, 7 %) and macropore volume (>50 nm), as well as between the adsorption of humics (MW = 1000 ~ Da, 36 %) and mesopore volume (2-50 nm), suggesting that the adsorption sites of EfOM depended on their molecular size. Higher isoelectric points and fewer acidic groups promoted the adsorption of the most negatively charged hydrophobic acids (HPOA, 39.5 %). According to variation partitioning analysis (VPA), mesopore-macropore greatly contributed to the adsorption capacities of EfOM (71.3 %), whereas the sum of phenolic hydroxyl and carboxyl (26.3 %) and isoelectric point (12.2 %) affected the normalized adsorption capacities of EfOM. In conclusion, PAC with a higher mesopore volume, fewer acidic groups, and a higher isoelectric point was desirable for removing EfOM from bio-treated coking wastewater. This study provides guidance for the selection of PAC for the removal of EfOM from bio-treated coking wastewater.

Delta Radiomics Model Predicts Lesion-Level Responses to Tyrosine Kinase Inhibitors in Patients with Advanced Renal Cell Carcinoma: A Preliminary Result.

BACKGROUND: This study aimed to develop and internally validate computed tomography (CT)-based radiomic models to predict the lesion-level short-term response to tyrosine kinase inhibitors (TKIs) in patients with advanced renal cell carcinoma (RCC). METHODS: This retrospective study included consecutive patients with RCC that were treated using TKIs as the first-line treatment. Radiomic features were extracted from noncontrast (NC) and arterial-phase (AP) CT images. The model performance was assessed using the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA). RESULTS: A total of 36 patients with 131 measurable lesions were enrolled (training: validation = 91: 40). The model with five delta features achieved the best discrimination capability with AUC values of 0.940 (95% CI, 0.890‒0.990) in the training cohort and 0.916 (95% CI, 0.828‒1.000) in the validation cohort. Only the delta model was well calibrated. The DCA showed that the net benefit of the delta model was greater than that of the other radiomic models, as well as that of the treat-all and treat-none criteria. CONCLUSIONS: Models based on CT delta radiomic features may help predict the short-term response to TKIs in patients with advanced RCC and aid in lesion stratification for potential treatments.

The safety of radium-223 combined with new-generation hormonal agents in bone metastatic castration-resistant prostate cancer: a systematic review and network meta-analysis.

Patients with bone metastatic castration-resistant prostate cancer (mCRPC) might benefit from radium-223 (223Ra) combined with new-generation hormonal agents (NHAs) in terms of survival and quality of life (QoL). However, the safety of combination therapies remains unclear. Therefore, we aimed to perform a network meta-analysis by reviewing the literature about the combination of 223Ra with abiraterone acetate plus prednisone (AAP) or enzalutamide and to evaluate the safety of combination therapy in bone mCRPC patients. Ultimately, ten studies (2835 patients) were selected, including four randomized controlled trials (RCTs), five retrospective cohort studies, and one single-arm study. Overall, there was no difference in the incidence of fracture between the 223Ra+NHA combination group and the 223Ra monotherapy group (odds ratio [OR]: 1.46, 95% confidence interval [CI]: 0.91-2.34, P = 0.66), but the incidences in both the 223Ra+NHA combination group (OR: 3.22, 95% CI: 2.24-4.63, P < 0.01) and the 223Ra monotherapy group (OR: 2.24, 95% CI: 1.23-4.08, P < 0.01) were higher than that in the NHA monotherapy group. However, in the meta-analysis involving only RCTs, there was no difference between the 223Ra monotherapy group and the NHA monotherapy group (OR: 1.14, 95% CI: 0.22-5.95, P = 0.88), while the difference between the 223Ra+NHA combination group and the NHA monotherapy group remained significant (OR: 3.22, 95% CI: 2.24-4.63, P < 0.01). Symptomatic skeletal events (SSEs), SSE-free survival (SSE-FS), all grades of common adverse events (AEs), and ≥grade 3 AEs among all groups did not show any significant difference. Our results indicate that the combination of 223Ra with NHAs was well tolerated in bone mCRPC patients compared to 223Ra monotherapy, even though the incidence of fracture was higher in patients who received 223Ra than that among those who received NHA monotherapy. More evidence is needed to explore the safety and efficiency of 223Ra combination therapies.

Regional location of lymph node metastases predicts survival in patients with de novo metastatic prostate cancer.

To report the regional locations of metastases and to estimate the prognostic value of the pattern of regional metastases in men with metastatic hormone-sensitive prostate cancer (mHSPC), we retrospectively analyzed 870 mHSPC patients between November 28, 2009, and February 4, 2021, from West China Hospital in Chengdu, China. The patients were initially classified into 5 subgroups according to metastatic patterns as follows: simple bone metastases (G1), concomitant bone and regional lymph node (LN) metastases (G2), concomitant bone and nonregional LN (NRLN) metastases (G3), lung metastases (G4), and liver metastases (G5). In addition, patients in the G3 group were subclassified as G3a and G3b based on the LN metastatic plane (below or above the diaphragm, respectively). The associations of different metastatic patterns with castration-resistant prostate cancer-free survival (CFS) and overall survival (OS) were analyzed by univariate and multivariate analyses. The results showed that patients in G1 and G2 had relatively favorable clinical outcomes, patients in G3a and G4 had intermediate prognoses, and patients in G3b and G5 had the worst survival outcomes. We observed that patients in G3b had outcomes comparable to those in G5 but had a significantly worse prognosis than patients in G3a (median CFS: 8.2 months vs 14.3 months, P = 0.015; median OS: 38.1 months vs 45.8 months, P = 0.038). In conclusion, metastatic site can predict the prognosis of patients with mHSPC, and the presence of concomitant bone and NRLN metastases is a valuable prognostic factor. Furthermore, our findings indicate that the farther the NRLNs are located, the more aggressive the disease is.

The therapeutic efficacy of radical prostatectomy and external beam radiation therapy in patients with different pathological patterns of prostate cancer.

BACKGROUND: We aim to investigate the prognostic value of different pathological patterns of non-adenocarcinoma prostate cancers (PCa) in radical prostatectomy (RP) and external beam radiation therapy (EBRT). METHODS: Data of 470,258 localized PCa patients between 2004 and 2016 were collected from the Surveillance, Epidemiology, and End Results database. Propensity score matching was performed to balance the baseline characteristics of patients in different groups. Kaplan-Meier curves and Cox regression were used for survival analysis. Overall survival (OS) and cancer-specific survival (CSS) were set as endpoints. RESULTS: Totally, 1044 patients with non-adenocarcinoma patterns of PCa were included. Patients with small cell neuroendocrine carcinoma (SCNC) and neuroendocrine differentiation (NED) harbored the worst prognosis in both RP and EBRT among all pathological groups. RP exhibited superior effects to EBRT for this group of cases. Ductal carcinoma (DA) was also related to poorer survival outcomes versus PAC in both local therapies. Yet, for men with DA, both RP and EBRT still improved patients' prognosis against no local therapy (NLT), with RP being the superior modality. Cases harboring mucinous adenocarcinoma (MA) and signet ring cell carcinoma (SRCC) shared comparable clinical outcomes to men with PAC. However, for cases with MA, neither RP nor EBRT was related to better survival outcomes against NLT, while for patients with SRCC, both RP and EBRT prolonged patients' survival with similar effects. CONCLUSIONS: Our study provided a comprehensive view of the treatment effect of RP and EBRT in non-adenocarcinoma PCa patients. These findings could facilitate clinicians in making therapeutic decision-making for non-adenocarcinoma patients.