Myeloid­derived suppressor cells: Key immunosuppressive regulators and therapeutic targets in colorectal cancer (Review).

Globally, colorectal cancer (CRC) is the third most common type of cancer. CRC has no apparent symptoms in the early stages of disease, and most patients receive a confirmed diagnosis in the middle or late disease stages. The incidence of CRC continues to increase, and the affected population tends to be younger. Therefore, determining how to achieve an early CRC diagnosis and treatment has become a top priority for prolonging patient survival. Myeloid­derived suppressor cells (MDSCs) are a group of bone marrow­derived immuno­negative regulatory cells that are divided into two subpopulations, polymorphonuclear­MDSCs and monocytic­MDSCs, based on their phenotypic similarities to neutrophils and monocytes, respectively. These cells can inhibit the immune response and promote cancer cell metastasis in the tumour microenvironment (TME). A large aggregation of MDSCs in the TME is often a marker of cancer and a poor prognosis in inflammatory diseases of the intestine (such as colonic adenoma and ulcerative colitis). In the present review, the phenotypic classification of MDSCs in the CRC microenvironment are first discussed. Then, the amplification, role and metastatic mechanism of MDSCs in the CRC TME are described, focusing on genes, gene modifications, proteins and the intestinal microenvironment. Finally, the progress in CRC­targeted therapies that aim to modulate the quantity, function and structure of MDSCs are summarized in the hope of identifying potential screening markers for CRC and improving CRC prognosis and therapeutic options.

Microbiota in colorectal cancer related to liver metastasis.

The prevalence of colorectal cancer (CRC) is increasing annually and metastasis is the principal cause of death in patients with CRC, with the liver being the most frequently affected site. Many studies have shown a strong interplay between the gut flora, particularly Fusobacterium nucleatum (F. nucleatum), Escherichia coli, and Bacteroides fragilis, and the development of gut tumors. Some strains can induce gut inflammation and produce toxins that directly harm gut epithelial cells, ultimately accelerating the onset and progression of CRC. However, little clinical evidence exists on the specific interplay between the gut microflora and colorectal cancer liver metastasis (CRLM). Some research showed the existence of viable F. nucleatum in distant metastasis of CRC. Subsequently, gut microbiota products, such as lipopolysaccharides, sodium butyrate, and protein cathepsin K, were also found to affect the development of CRC. This article summarizes the mechanism and research status of the interplay between gut microflora and CRLM, discusses the importance of gut microflora in the treatment of CRLM, and proposes a new approach to understanding the mechanism of CRLM and potential treatments for the microbiome. It is anticipated that the gut microbiota will be a formidable therapeutic and prophylactic tool for treating and preventing CRLM.

Silica-induced macrophage pyroptosis propels pulmonary fibrosis through coordinated activation of relaxin and osteoclast differentiation signaling to reprogram fibroblasts.

Silica nanoparticle (SiNP) exposure induces severe pulmonary inflammation and fibrosis, but the pathogenesis remains unclear, and effective therapies are currently lacking. To explore the mechanism underlying SiNPs-induced pulmonary fibrosis, we constructed in vivo silica exposure animal models and in vitro models of silica-induced macrophage pyroptosis and fibroblast transdifferentiation. We found that SiNP exposure elicits upregulation of pulmonary proteins associated with pyroptosis, including NLRP3, ASC, IL-1ß, and GSDMD, while the immunofluorescence staining co-localized NLRP3 and GSDMD with macrophage-specific biomarker F4/80 in silica-exposed lung tissues. However, the NLRP3 inhibitor MCC950 and classical anti-fibrosis drug pirfenidone (PFD) were found to be able to alleviate silica-induced collagen deposition in the lungs. In in vitro studies, we exposed the fibroblast to a conditioned medium from silica-induced pyroptotic macrophages and found enhanced expression of α-SMA, suggesting increased transdifferentiation of fibroblast to myofibroblast. In line with in vivo studies, the combined treatment of MCC950 and PFD was demonstrated to inhibit the expression of α-SMA and attenuate fibroblast transdifferentiation. Mechanistically, we adopted high throughput RNA sequencing on fibroblast with different treatments and found activated signaling of relaxin and osteoclast differentiation pathways, where the expression of the dysregulated genes in these two pathways was examined and found to be consistently altered both in vitro and in vivo. Collectively, our study demonstrates that SiNP exposure induces macrophage pyroptosis, which subsequently causes fibroblast transdifferentiation to myofibroblasts, in which the relaxin and osteoclast differentiation signaling pathways play crucial roles. These findings may provide valuable references for developing new therapies for pulmonary fibrosis.

CXCL16 promotes tumor metastasis by regulating angiogenesis in the tumor micro-environment of BRAF V600E mutant colorectal cancer.

Patients of colorectal cancer (CRC) with BRAF V600E mutation obtain poor prognosis. This study aimed to explore the role and mechanism of BRAF V600E mutation in angiogenesis of tumor micro-environment (TME). It has been reported that CXCL16 expression in TME is closely related to BRAF mutation. Clinicopathological features of CRC with BRAF V600E mutant or wild type were collected in this study. Immunohistochemistry (IHC) assays were conducted to test the expressions of vascular endothelial growth factor (VEGF), CD31 and CXCL16. ROC curve was used to determine the optimal cut off values of CXCL16. A total of 680 patients including 141 BRAF V600E type and 679 wild type were included. BRAF V600E mutant tumors were presented with significant worse clinicopathological features and a shorter overall survival (OS) than wild-type. Besides, chemokines CXCL16 was up-regulated in BRAF V600E mutant tissues and was associated with poorer prognosis. In addition, VEGF levels and vascular endothelial cell density was significantly increased in BRAF mutation. At last, CXCL16 was positively correlated with VEGF expression and vascular endothelial cell density. In conclusion, BRAF V600E mutations may promote metastasis of CRC by regulating CXCL16 expression and promoting angiogenesis in the TME.

Metagenomic Analysis of Intratumoral Microbiome Linking to Response to Neoadjuvant Chemoradiotherapy in Rectal Cancer.

PURPOSE: To assess taxonomic and functional characteristics of tumor-bearing microbiota and its association with response to neoadjuvant chemoradiation therapy (nCRT) in patients with locally advanced rectal cancer. METHODS AND MATERIALS: We performed metagenomic sequencing of biopsy tumoral tissues from 73 patients with locally advanced rectal cancer before nCRT. Patients were classified into poor responders (PR) and good responders (GR) according to response to nCRT. Subsequent investigation of network alteration, key community, microbial biomarkers, and function related to nCRT responses were carried out. RESULTS: The network-driven analysis systematically revealed 2 co-occurring bacteria modules that exhibited opposite relationship with rectal cancer radiosensitivity. In the 2 modules, prominent alteration of global graph properties and community structure was observed between networks of PR and GR group. By quantifying changes in between-group association patterns and abundances, a total of 115 discriminative biomarker species linked to nCRT response were found, and 35 microbial variables were selected to establish the optimal randomForest classifier for nCRT response prediction. It yielded an area under the curve value of 85.5% (95% CI, 73.3%-97.8%) in the training cohort and 88.4% (95% CI, 77.5%-99.4%) in the validation cohort. In a comprehensive consideration, 5 key bacteria showed high relevance with inducing resistance to nCRT, including Streptococcus equinus, Schaalia odontolytica, Clostridium hylemonae, Blautia producta, and Pseudomonas azotoformans. One key hub including several butyrate-formation bacteria involving with driving network alteration from GR to PR indicate that microbiota-derived butyrate may also be involved in reducing the antitumor effects of nCRT, especially Coprococcus. The functional analysis of metagenome linked the nitrate and sulfate-sulfur assimilation, histidine catabolic process, and resistance to cephamycin to the reduced therapeutic response. It also linked to leucine degradation, isoleucine biosynthesis, taurine, and hypotaurine metabolism to the improved response to nCRT. CONCLUSIONS: Our data offer novel potential microbial factors and shared metagenome function linked to resistance to nCRT.

Using a stacked ensemble learning framework to predict modulators of protein-protein interactions.

Identifying small molecule protein-protein interaction modulators (PPIMs) is a highly promising and meaningful research direction for drug discovery, cancer treatment, and other fields. In this study, we developed a stacking ensemble computational framework, SELPPI, based on a genetic algorithm and tree-based machine learning method for effectively predicting new modulators targeting protein-protein interactions. More specifically, extremely randomized trees (ExtraTrees), adaptive boosting (AdaBoost), random forest (RF), cascade forest, light gradient boosting machine (LightGBM), and extreme gradient boosting (XGBoost) were used as basic learners. Seven types of chemical descriptors were taken as the input characteristic parameters. Primary predictions were obtained with each basic learner-descriptor pair. Then, the 6 methods mentioned above were used as meta learners and trained on the primary prediction in turn. The most efficient method was utilized as the meta learner. Finally, the genetic algorithm was used to select the optimal primary prediction output as the input of the meta learner for secondary prediction to obtain the final result. We systematically evaluated our model on the pdCSM-PPI datasets. To our knowledge, our model outperformed all existing models, which demonstrates its great power.

Agromyces cavernae sp. nov., a novel member of the genus Agromyces isolated from a karstic cave in Shaoguan.

A novel actinobacterial strain, designated SYSU K20354T, was isolated from a soil sample collected from a karst cave in Shaoguan city, Guangdong province, southern China. The taxonomic position of the strain was investigated using a polyphasic approach. Cells of the strain were aerobic, Gram-stain-positive and non-motile. On the basis of 16S rRNA gene sequence similarities and phylogenetic analysis, strain SYSU K20354T was most closely related to Agromyces humatus JCM 14319T, and shared the highest sequence identity of 98.3 % based on NCBI database. In addition, 2,4-diaminobutyric acid was the diagnostic diamino acid in cell-wall peptidoglycan. The whole-cell sugars were galactose, glucose, mannose and ribose. The major isoprenoid quinone was MK-12, while the major fatty acids (>10 %) were iso-C16 : 0, anteiso-C15 : 0 and anteiso-C17 : 0. The polar lipids contained diphosphatidylglycerol, phosphatidylglycerol, three unknown glycolipids, three unknown phospholipids and two unknown lipids. The draft genome size of strain SYSU K20354T was 3.96 Mbp with G+C content of 69.7 mol%. Furthermore, the average nucleotide identity and digital DNA-DNA hybridization values between strain SYSU K20354T and A. humatus JCM 14319T were 90.3 and 55.6 %, respectively. On the basis of phenotypic, genotypic and phylogenetic data, strain SYSU K20354T represents a novel species of the genus Agromyces, for which the name Agromyces cavernae sp. nov. is proposed. The type strain is SYSU K20354T (=KCTC 49499T= CGMCC 4.7691T).

Capillary Gas Chromatographic Separation Performances of a Tetraphenyl Porphyrin Stationary Phase.

Tetraphenyl porphyrin (TPP) has enormous potential for use as gas chromatography stationary phases because it has a distinctive extended π-π conjugated coplanar structure and a range of interesting properties such as a good solubility in dichloromethane, high melting point, and good thermal stability. In this work, a TPP column was successfully prepared using a static method. The column was nonpolar and had a high efficiency. The chromatographic selectivity of the TPP column was assessed. The TPP column showed superiority retention and higher resolution for alicyclic, aromatic molecules through ring matching and π-π stacking interaction comparable to HP-5MS column. The unique mechanisms through which the TPP column retained polychlorinated biphenyls allowed the peak pair of 2,2',5-trichlorobiphenyl and 4,4'-dichlorobiphenyl to be resolved better on the TPP column than the HP-5MS column. The TPP column was thermally stable even at 260°C for 2 h and gave results of a high degree of precision (run-to-run and column-to-column) with relative standard deviations <0.05% and <4.96%, respectively. The results indicated that porphyrin derivatives will be useful gas chromatography stationary phases.

Stereotactic body radiotherapy in combination with non-frontline PD-1 inhibitors and targeted agents in metastatic renal cell carcinoma.

BACKGROUND: Radiotherapy may work synergistically with immunotherapy and targeted agents. We aimed to assess the safety and outcomes of stereotactic body radiotherapy (SBRT) plus non-first-line programmed death-1 (PD-1) inhibitors and targeted agents (TA) in metastatic renal cell carcinoma (mRCC). METHODS: We retrospectively reviewed 74 patients treated with non-first-line PD-1 inhibitors plus TA in non-first-line setting. Survival outcomes were calculated from the anti-PD-1 treatment using the Kaplan-Meier method. Univariate and multivariate analyses were performed by Cox proportional hazards models. RESULTS: Thirty-two (43.2%) patients received anti-PD-1/TA therapy alone (anti-PD-1/TA alone group), and 42 (56.8%) received SBRT in addition (anti-PD-1/TA + SBRT group). The median duration of first-line therapy was 8.6 months. Patients in the anti-PD-1/TA + SBRT group had significantly longer overall survival (OS) (38.5 vs 15.4 months; P = 0.022). On multivariate analysis, oligometastasis, ECOG performance status 0-1, anti-PD-1/TA + SBRT, and duration of first-line therapy ≥ 8.6 months were predictors for OS. The addition of SBRT was associated with improved OS in patients with clear-cell type (HR 0.19; 95% CI 0.07-0.55; P = 0.002) and duration of first-line therapy ≥ 8.6 months (HR 0.22; 95% CI 0.06-0.88; P = 0.032). Grade ≥ 3 toxicities occurred in 23 patients (54.8%) in the anti-PD-1/TA + SBRT group, and in 21 patients (65.6%) in the anti-PD-1/TA alone group. CONCLUSIONS: Incorporating SBRT into anti-PD-1/TA therapy is safe and tolerable. Further investigation is needed, particularly in patients with clear-cell histology and a longer duration of response to first-line antiangiogenic therapy.

ReRF-Pred: predicting amyloidogenic regions of proteins based on their pseudo amino acid composition and tripeptide composition.

BACKGROUND: Amyloids are insoluble fibrillar aggregates that are highly associated with complex human diseases, such as Alzheimer's disease, Parkinson's disease, and type II diabetes. Recently, many studies reported that some specific regions of amino acid sequences may be responsible for the amyloidosis of proteins. It has become very important for elucidating the mechanism of amyloids that identifying the amyloidogenic regions. Accordingly, several computational methods have been put forward to discover amyloidogenic regions. The majority of these methods predicted amyloidogenic regions based on the physicochemical properties of amino acids. In fact, position, order, and correlation of amino acids may also influence the amyloidosis of proteins, which should be also considered in detecting amyloidogenic regions. RESULTS: To address this problem, we proposed a novel machine-learning approach for predicting amyloidogenic regions, called ReRF-Pred. Firstly, the pseudo amino acid composition (PseAAC) was exploited to characterize physicochemical properties and correlation of amino acids. Secondly, tripeptides composition (TPC) was employed to represent the order and position of amino acids. To improve the distinguishability of TPC, all possible tripeptides were analyzed by the binomial distribution method, and only those which have significantly different distribution between positive and negative samples remained. Finally, all samples were characterized by PseAAC and TPC of their amino acid sequence, and a random forest-based amyloidogenic regions predictor was trained on these samples. It was proved by validation experiments that the feature set consisted of PseAAC and TPC is the most distinguishable one for detecting amyloidosis. Meanwhile, random forest is superior to other concerned classifiers on almost all metrics. To validate the effectiveness of our model, ReRF-Pred is compared with a series of gold-standard methods on two datasets: Pep-251 and Reg33. The results suggested our method has the best overall performance and makes significant improvements in discovering amyloidogenic regions. CONCLUSIONS: The advantages of our method are mainly attributed to that PseAAC and TPC can describe the differences between amyloids and other proteins successfully. The ReRF-Pred server can be accessed at http://106.12.83.135:8080/ReRF-Pred/.

Surface Depletion Effects in Bromide-Ligated Colloidal Cadmium Selenide Nanoplatelets: Toward Efficient Emission at High Temperature.

The colloidal semiconductor nanoplatelet (NPL) with broad ligand-semiconductor interface is an ideal system for surface science investigation, but the study regarding depletion effects in NPLs remains lacking. Herein we explore such effects in colloidal CdSe NPLs through Br ligation. Apart from improved brightness and red-shifted optical features, we also experimentally observed abnormal negative thermal quenching phenomena in bromide-ligated CdSe NPLs over 200 K under a cryogenic environment and up to 383 K under an ambient environment, which was absent in pristine NPLs. We speculate that the surface depletion effect shall account for these anomalous phenomena due to the susceptibility of the surface depletion region on photoexcited carrier concentration and surface condition. The existence of the depletion layer in NPLs is also validated quantitatively with k·p simulation. Besides offering an alternative explanation on the red-shifted optical properties of CdSe NPLs by Br-ligation, our findings pave the new route toward solution-processed NPLs-based optoelectronics with boosted thermal resistance.

Metastasis-directed stereotactic body radiotherapy for oligometastatic renal cell carcinoma: extent of tumor burden eradicated by radiotherapy.

PURPOSE: We aimed to explore whether complete eradication of tumor burden with stereotactic body radiotherapy (SBRT) would affect the outcomes of oligometastatic renal cell carcinoma (RCC). MATERIALS AND METHODS: Patients diagnosed with extracranial oligometastatic RCC (no more than five metastases) between 2007 and 2019 were reviewed. Those without nephrectomy were excluded. SBRT to all, some and no lesions were defined as complete, incomplete, and no SBRT. Progression-free survival (PFS) and cancer-specific survival (CSS) were analyzed using Kaplan-Meier method, Cox regression model and the Fine and Gray method. RESULT: A total of 101 patients were included, 51.5% of whom had < 3 metastases. Forty (39.6%) patients received complete SBRT, and 61 (60.4%) received no or incomplete SBRT. The 1-year LC rate was 97.3%. The complete SBRT group had significantly longer PFS (26.0 vs 18.8 months; p = 0.043) and CSS (not reached vs. 55.3 months; p = 0.012) compared with the no or incomplete SBRT group. In multivariate analysis, ECOG 0-1 (HR 0.389, 95% CI 0.167-0.906, p = 0.029) and complete SBRT were prognostic factors for CSS (HR 0.307, 95% CI 0.108-0.876, p = 0.027). Complete SBRT was associated with improved CSS in the subgroups of patients with age < 55 years, ECOG 0-1, clear-cell histology, IMDC intermediate/poor risk, metachronous metastasis, and < 3 lesions. CONCLUSION: Complete eradication of tumor burden with SBRT was associated with better survival in patients with oligometastatic RCC. The recommendation of SBRT to all lesions should be individualized.

Screening and identification of hub genes in bladder cancer by bioinformatics analysis and KIF11 is a potential prognostic biomarker.

Bladder cancer (BC) is the ninth most common lethal malignancy worldwide. Great efforts have been devoted to clarify the pathogenesis of BC, but the underlying molecular mechanisms remain unclear. To screen for the genes associated with the progression and carcinogenesis of BC, three datasets were obtained from the Gene Expression Omnibus. A total of 37 tumor and 16 non-cancerous samples were analyzed to identify differentially expressed genes (DEGs). Subsequently, 141 genes were identified, including 55 upregulated and 86 downregulated genes. The protein-protein interaction network was established using the Search Tool for Retrieval of Interacting Genes database. Hub gene identification and module analysis were performed using Cytoscape software. Hierarchical clustering of hub genes was conducted using the University of California, Santa Cruz Cancer Genomics Browser. Among the hub genes, kinesin family member 11 (KIF11) was identified as one of the most significant prognostic biomarkers among all the candidates. The Kaplan Meier Plotter database was used for survival analysis of KIF11. The expression profile of KIF11 was analyzed using the ONCOMINE database. The expression levels of KIF11 in BC samples and bladder cells were measured using reverse transcription-quantitative pCR, immunohistochemistry and western blotting. In summary, KIF11 was significantly upregulated in BC and might act as a potential prognostic biomarker. The present identification of DEGs and hub genes in BC may provide novel insight for investigating the molecular mechanisms of BC.

Cytoreductive radiotherapy combined with abiraterone in metastatic castration-resistance prostate cancer: a single center experience.

BACKGROUND: To investigate the potential benefit of cytoreductive radiotherapy (cRT) in metastatic castration-resistant prostate cancer (mCRPC) patients receiving abiraterone. METHODS: From February 2014 to February 2019, 149 mCRPC patients treated with abiraterone were identified. Patients receiving cRT before abiraterone failure (AbiRT group) were matched by one-to-two propensity score to patients without cRT before abiraterone failure (non-AbiRT group). RESULTS: The median follow-up was 23.5 months. Thirty patients (20.1%) were in the AbiRT group, whereas 119 patients (79.9%) were in the non-AbiRT group. The 2-year OS of patients managed by AbiRT and non-AbiRT were 89.5% and 73.5%, respectively (P = 0.0003). On multivariate analysis, only AbiRT (HR 0.17; 95% CI 0.05-0.58; P = 0.004) and prognostic index (HR 2.71; 95% CI 1.37-5.35; P = 0.004) were significant factors. After matching, AbiRT continued to be associated with improved OS (median OS not reached vs. 44.0 months, P = 0.009). Subgroup analysis revealed that patients aged ≤ 65 years (HR 0.09; 95% CI 0.01-0.65; P = 0.018), PSA ≤ 20 ng/mL (HR 0.29; 95% CI 0.09-0.99; P = 0.048), chemotherapy-naïve upon abiraterone treatment (HR 0.20; 95% CI 0.06-0.66; P = 0.008) and in intermediate prognosis groups by COU-AA-301 prognostic index (HR 0.13; 95% CI 0.03-0.57; P = 0.007) had improved OS with AbiRT. CONCLUSIONS: cRT before resistance to abiraterone may improve survival in selected mCRPC patients: age ≤ 65 years old, chemotherapy-naïve, with a relatively low PSA level at the diagnosis of mCRPC and intermediate prognosis.

Study of Complex Optical Constants of Neat Cadmium Selenide Nanoplatelets Thin Films by Spectroscopic Ellipsometry.

Knowledge of tunability of complex optical constants of colloidal CdSe nanoplatelets (NPLs) thin films is essential for accurate modeling and design of NPL-containing optoelectronic devices. Here, dielectric functions, complex optical conductivities, and absorption coefficients of a series of CdSe NPL films with a varying number of atomic layers were investigated in a combination of spectroscopic ellipsometry techniques and transmittance measurements over a broad spectral range. Fine electronic structures were deciphered from the dielectric functions. Oscillator strengths at the lowest exciton resonance up to 0.62 for a series of CdSe NPL films were also determined. From our results, increasing the number of monolayers was found to boost the complex optical constants and the amplitude of the coupling strength of the fundamental exciton state mainly due to higher inorganic volume filling factors and pronounced surface passivation. Our work gives insights into both the interpretation and improvements of performance of CdSe NPL-based photoelectronic applications.

Circular RNA circGSK3B Promotes Cell Proliferation, Migration, and Invasion by Sponging miR-1265 and Regulating CAB39 Expression in Hepatocellular Carcinoma.

Circular RNAs (circRNAs) have important regulatory roles in the development of various cancers. However, the biological functions and potential molecular mechanisms of circRNAs in hepatocellular carcinoma (HCC) are still unclear. In this study, we investigated the role of a new circRNA-circGSK3B (hsa_circ_0003763) and its molecular mechanism in HCC. We found that circGSK3B was highly expressed in HCC tissues and HCC cell lines. Additionally, the expression level of circGSK3B significantly correlated with HCC tumor size and vascular invasion. Functionally, we confirmed that circGSK3B can promote the proliferation, migration, and invasion of HCC cells in vivo and in vitro. In terms of mechanism, we demonstrated that circGSK3B acts as a miR-1265 sponge, positively regulates the target gene CAB39, and promotes the reprogramming of glutamine metabolism, thereby promoting the progression of HCC. Finally, the classic RNA binding protein QKI was observed to participate in the biogenesis of circGSK3B. In summary, we proved that the circGSK3B-miR-1265-CAB39 axis can promote the proliferation, migration, invasion of HCC cells, indicating that circGSKB may serve as a promising diagnostic and prognostic marker in HCC.

Impact of Time to Castration Resistance on Cytoreductive Radiotherapy in Metastatic Castration-Resistant Prostate Cancer.

BACKGROUND: The role of local radiotherapy in metastatic castration-resistant prostate cancer (mCRPC) remains undefined. This study aimed to identify the value of local radiotherapy and potential candidates for mCRPC. METHODS: A total of 215 patients with mCRPC treated with or without cytoreductive radiotherapy (CRT) between June 2011 and February 2019 were analyzed. Overall survival (OS) was calculated from the onset of mCRPC. The receiver-operating characteristic (ROC) curve was used to find the cutoff point for time to castration resistance (TCR). RESULTS: One-hundred and fifty-five (72.1%) patients received abiraterone after mCRPC, and 54 (25.1%) patients received CRT. The median TCR was 14.9 months. After a median follow-up of 31.7 months, the median OS was 33.3 months. The Eastern Cooperative Oncology Group (ECOG) performance scores 0-1, oligometastases, abiraterone after mCRPC, CRT, and TCR ≥9 months were independent prognostic factors for better OS. Stratified analyses showed improved survival when CRT was applied to patients treated with abiraterone (HR 0.44; 95% CI 0.23-0.83; P = 0.012) and TCR ≥9 months (HR 0.39; 95% CI 0.21-0.74; P = 0.004). The percentage of PSA response after radiotherapy was higher in patients with TCR ≥9 months compared to those with TCR <9 months. No grade 3 or worse adverse events after radiotherapy were reported. CONCLUSIONS: ECOG performance score, oligometastases, abiraterone application, TCR and CRT were independent prognostic factors for OS in patients with mCRPC. Patients with a short duration of response to primary androgen deprivation therapy were less likely to benefit from CRT.

Survival Outcomes and Prognostic Analysis Following Greater Cytoreductive Radiotherapy in Patients With Metastatic Prostate Cancer.

Purpose: To assess the survival outcomes of patients with metastatic prostate cancer (mPCa) who undergo greater cytoreductive radiotherapy in a real-world clinical practice and determine their prognostic factors. Methods: We performed a retrospective study of 160 patients with mPCa who underwent cytoreductive radiotherapy between 2009 and 2018 at a single institution. The degree of the cytoreductive burden was calculated for each patient. Overall survival (OS) was calculated from the date of detection of metastases. Variables associated with prostate-specific antigen (PSA) response and OS were evaluated via univariate and multivariate analyses. Results: The median follow-up period was 47.2 months. The median OS was 42.3 months with a 5-year OS rate of 37.9%. The PSA levels of 90 patients (56.7%) decline by > 50% after radiotherapy. The 5-year OS rates of patients who underwent total, major, and minor cytoreductive radiotherapy were 53.4, 38.2, 17.6%, respectively; the corresponding median OS intervals were 62.5, 41.0, and 24.4 months, respectively (P < 0.001). A greater extent of cytoreduction (P < 0.05), lower PSA at radiotherapy initiation [hazard ratio 0.51, 95% confidence interval [CI] 0.33-0.78; P = 0.002] and better PSA response [hazard ratio 0.47, 95% CI 0.30-0.72; P < 0.001] were independent factors associated with superior OS. A high metastatic burden (as defined in the CHAARTED trial) was the only independent predictor of a poorer PSA response (odds ratio 0.36, 95% CI 0.19-0.69; P = 0.002). Grade 2 late gastrointestinal and genitourinary toxicities were observed in 3 and 2 patients, respectively, and only 1 patient had grade 3 late gastrointestinal toxicity. Conclusion: Cytoreductive radiotherapy is effective and safe in select patients with mPCa. Greater cytoreduction, together with lower PSA at radiotherapy initiation and improved PSA response are favorable prognostic factors. Further studies are needed to confirm our findings.