Downregulation of SHMT2 promotes the prostate cancer proliferation and metastasis by inducing epithelial-mesenchymal transition.

Serine hydroxymethyltransferase 2 (SHMT2) is a key enzyme that regulates serine/glycine transition; however, its specific function and molecular mechanisms in tumors remain controversial. In this study, we aimed to enhance the understanding in this regard. Through in vitro and in vivo experiments, as well as data analyses using public databases, we investigated the effect of SHMT2 in prostate cancer. Our results indicated that SHMT2 acts as a prostate cancer tumor proliferation suppressor and negatively regulates the aggressive behavior of prostate cancer through activation of epithelial-mesenchymal transition. Additionally, downregulated SHMT2 expression was observed in more advanced prostate cancer phenotypes, and further analysis showed that its depletion promoted proliferation and migration in prostate cancer cell lines. Taken together, our results revealed the function of SHMT2 in prostate cancer and may potentially play a role in the exploration of new therapeutic strategies.

HOXD13 suppresses prostate cancer metastasis and BMP4-induced epithelial-mesenchymal transition by inhibiting SMAD1.

The HOX genes are a group of highly conserved Homeobox-containing genes that control the body plan organization during development. However, their contributions to tumorigenesis and tumor progression remain uncertain and controversial. Here we provided evidence of tumor-suppressive activity of HOXD13 in prostate cancer. HOXD13 depletion contributes to more aggressiveness of prostate cancer cells in vitro and in vivo. These effects were corroborated in a metastatic mice model, where we observed more bone metastatic lesions formed by prostate cancer cells with HOXD13 ablation. Mechanistically, HOXD13 prevents BMP4-induced epithelial-mesenchymal transition (EMT) by inhibiting mothers against decapentaplegic homolog 1 (SMAD1) transcription. Both bioinformation and our tissue microarray cohort data show that HOXD13 expression inversely correlated in advanced prostate cancer patient specimens. Our findings establish HOXD13 as a negative regulator of prostate cancer progression and metastasis by preventing BMP4/SMAD1 signaling, and potentially suggest new strategies for targeting metastatic prostate cancer.

Systemic immune-inflammation index predicts the combined clinical outcome after sequential therapy with abiraterone and docetaxel for metastatic castration-resistant prostate cancer patients.

OBJECTIVE: To compare the antitumor effect of abiraterone (AA) followed by docetaxel-prednisone (DP) or vice versa in metastatic castration-resistant prostate cancer (mCRPC) patients, and explored factors that might predict combined PSA-PFS, combined rPFS and OS. PATIENTS AND METHODS: We retrospectively analyzed mCRPC patients treated with sequential therapy using DP followed by AA or vice versa. Patients who had received enzalutamide or cabazitaxel were excluded. The primary outcome measure was overall survival (OS). The combined PSA progression-free survival (PSA-PFS), combined radiographic PFS (rPFS), and OS of AA-to-DP were compared to the reverse sequence using Kaplan-Meier curves with log-rank statistics. Univariable and multivariable Cox regression analyses were performed to determine prognostic factors that were associated with combined PSA-PFS, combined rPFS and OS. RESULTS: A total of 104 mCRPC patients who began treatment between 2013 and 2017 were identified: 42 were in the DP-to-AA group and 62 were in the AA-to-DP group. There was no significant difference of baseline clinical characteristics between AA-to-DP and DP-to-AA group. In addition, there was no significant difference in combined PSA-PFS (AA-to-DP: 12.5 [11.4-13.6] vs DP-to-AA: 13.2 [10.9-15.5] months [P = 0.127]), combined rPFS (AA-to-DP: 12.2 [10.9-13.4] vs DP-to-AA: 11.2 [8.9-13.5] months [P = 0.183]) and OS (AA-to-DP: 23.3 [19.7-26.9] vs DP-to-AA: 22.9 [22.1-23.7] months [P = 0.213]) between the two treatment sequences in Kaplan-Meier analysis. In multivariate Cox regression analysis, high systematic Immune-Inflammation Index (SII) level, which was calculated by P (platelet) × N (neutrophil)/L(lymphocyte), remained significant predictors of OS, combined rPFS and combined PSA-PFS. CONCLUSION: In this study, we did not observe differences in clinical outcomes based on alternative sequencing of AA and DP in mCRPC patients. The ability to tolerate side effects and patient preference may be used to determine the treatment sequencing. In addition, high pretreatment SII level is a negative independent prognosticator of survival outcomes in mCRPC with sequential therapy using DP followed by AA or vice versa, which might guide clinicians select the best treatment.

Abiraterone acetate for chemotherapy-naive metastatic castration-resistant prostate cancer: a single-centre prospective study of efficacy, safety, and prognostic factors.

BACKGROUND: To evaluate the efficacy and safety of abiraterone acetate (AA) plus prednisone compared with prednisone alone in Asian patients with chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC), and to identify predictive factors. METHODS: We reviewed the medical records of 60 patients with chemotherapy-naive mCRPC at Renji Hospital who were treated with AA plus prednisone (n = 43) or prednisone alone (n = 17). All patients were assessed for prostate-specific antigen (PSA) response, PSA progression-free survival (PSA PFS), radiographic progression-free survival (rPFS), and overall survival (OS). The ability of several parameters to predict PSA PFS, rPFS, and OS was studied. RESULTS: The median follow-up time was 14.0 months (range 7.0-18.5 months), at which time 19 death events had been reported: 11 in the AA + prednisone group and 8 in the prednisone group. The AA + prednisone group had significantly longer median PSA PFS (10.3 vs 3.0 months, P < 0.001), rPFS (13.9 vs 3.9 months, P < 0.001), and OS (23.3 vs 17.5 months, P = 0.016) than the prednisone-alone group. The most frequently reported grade 3 or 4 adverse event in both the AA + prednisone and prednisone-alone groups was elevated alanine aminotransferase level in 5 of 43 patients (11.6%) and 2 of 17 patients (11.8%), respectively. No adverse events led to discontinuation of therapy. In multivariate analysis, time from androgen deprivation therapy (ADT) to castration resistance of ≤18 months was a determinant of shorter OS (P = 0.007). CONCLUSIONS: These results support the favourable safety and efficacy profile of AA for the treatment of Asian patients with chemotherapy-naive mCRPC. Longer duration of ADT response was significantly associated with longer survival.

Prognostic nutritional index predicts initial response to treatment and prognosis in metastatic castration-resistant prostate cancer patients treated with abiraterone.

OBJECTIVE: To determine if prognostic nutritional index (PNI) and its variation could predict initial response to treatment and prognosis in metastatic castration-resistant prostate cancer (mCRPC) patients treated with Abiraterone (AA). PATIENTS AND METHODS: One-hundred-twelve chemotherapy pretreated or chemotherapy-naive patients were scheduled for systemic treatment with AA. PNI levels were measured before and after one month of AA treatment. Univariate and multivariate logistic regression analyses were used to identify predictive factors of initial response to AA treatment. Univariable and Multivariable Cox regression analyses were performed to determine prognostic factors that were associated with PSA progression-free survival (PSA-PFS), radiographic PFS (rPFS) and overall survival (OS). The Harrell concordance index with variables only or combined PNI data were used to evaluate the prognostic accuracy. RESULTS: Eighty-one (72.3%) of 112 patients showed initial response to AA treatment, in which 15 experienced PSA flare during AA treatment. In multivariate logistic regression analyses, high baseline PNI level, PSA level decrease during the first month of AA treatment and PNI level elevation during the first month of AA treatment were significantly correlated with initial response to AA treatment. In multivariate Cox regression analysis, low PNI level remained significant predictors of OS, rPFS and PSA-PFS. The estimated c-index of the multivariate model for OS increased from 0.82 without PNI to 0.83 when PNI added. CONCLUSION: Independent of PSA level variation, PNI level elevation during the first month of AA treatment and high baseline PNI level were significantly correlated with initial response to AA treatment. In addition, low pretreatment PNI level is a negative independent prognosticator of survival outcomes in mCRPC treated with AA and also increases the accuracy of established prognostic model.

Influence of abiraterone acetate on neuroendocrine differentiation in chemotherapy-naive metastatic castration-resistant prostate cancer.

BACKGROUND: To determine the influence of abiraterone Acetate (AA) on neuroendocrine differentiation (NED) in patients with chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC). METHODS: We conducted an analysis in 115 chemotherapy-naïve mCRPC patients who would be treated with chemotherapy. The serum levels of chromogranin A (CgA), neurone-specific enolase (NSE) were measured in 67 mCRPC patients without AA treatment and 48 patients after the failure of AA treatment, in which these markers were also measured in 34 patients before and after 6 months of AA treatment. Comparative t-test was used to evaluate the serial changes of serum NED markers during AA treatment and univariate and multivariate analyses were performed to test the influence of AA treatment on NED. RESULTS: Serum CgA were NSE were evaluated to be above the upper limit of normal (ULN) in 56 (48.7%) and 29 (25.2%) patients before chemotherapy. In 34 patients with serial evaluation, serum CgA level of 14 patients and NSE of 14 patients increased after the failure of AA treatment. There was no significant difference of NED markers (CgA or NSE variation (P = 0.243) between at baseline and after the failure of AA treatment. Compared with the CgA elevation group in the first 6 months of AA treatment and baseline supranormal CgA group, the CgA decline group, and baseline normal CgA group has a much longer median PSA PFS (14.34 vs 10.00 months, P < 0.001, and 14.23 vs 10.30 months, P = 0.02) and rPFS, respectively (18.33 vs 11.37 months, P < 0.001, and 17.10 vs 12.07 months, P = 0.03). In logistic univariate analysis, AA treatment and its duration were not independent factors influencing NED. CONCLUSIONS: We hypothesized that AA might not significantly lead to progression of NED of mCRPC in general. Furthermore, we found there was heterogeneity in changes of NED markers in different mCRPC patients during AA treatment. Serial CgA and NSE evaluation might help clinicians guide clinical treatment of mCRPC patients.

Evaluation of expressed prostatic secretion and serum using surface-enhanced Raman spectroscopy for the noninvasive detection of prostate cancer, a preliminary study.

Surface-enhanced Raman spectroscopy (SERS) involving expressed prostatic secretion (EPS) and serum was investigated; the objective was to determine if this approach could distinguish prostate cancer from benign prostatic hyperplasia. A total of 120 SERS spectra for EPS and 96 spectra for serum were gathered from patients within a prospective contemporary biopsy cohort. Significant differences in spectra between prostate cancer and benign prostatic hyperplasia were tentatively assigned to component changes in EPS and serum samples. Principal component analysis and linear discriminate analysis were utilized to evaluate the spectral data for EPS and serum, to build diagnostic algorithms. The leave-one-out cross-validation method was used to validate the diagnostic algorithms; it revealed diagnostic sensitivities of 75% and 60%, specificities of 75% and 76.5%, and accuracies of 75% and 68% for EPS and serum, respectively. The results suggest that EPS and serum SERS analysis could be a potential tool for prostate cancer detection.

Nephron sparing surgery for a patient with a complicated solitary functioning kidney and a giant pT3 renal cell carcinoma: A case report.

A solitary functioning kidney (SFK) with renal cell carcinoma (RCC) is an imperative indication for nephron-sparing surgery (NSS). Nevertheless, a giant pT3 RCC mass (maximum diameter >20 cm) on the functioning side of a patient with SFK is extremely rare. However, whether NSS is more beneficial than radical nephrectomy (RN) in such patients is controversial. Here, we present the case of a 71-year-old female patient with a 20 cm*16 cm RCC mass in the SFK, who initially presented with hematuria and acute urinary tract obstructive anuria caused by renal calculi. The patient underwent NSS treatment after our evaluation, and the 26-month follow-up revealed that her renal function recovered to the state before the tumor formation. In addition, no relapse or metastasis was detected.

Squalene Epoxidase Metabolic Dependency Is a Targetable Vulnerability in Castration-Resistant Prostate Cancer.

Considering the dismal prognosis of castration-resistant prostate cancer (CRPC), it is critical to identify novel therapeutic targets in this disease. Malignant cells have metabolic dependencies distinct from their healthy counterparts, resulting in therapeutic vulnerabilities. Although PTEN and TP53 are the most frequently comutated or codeleted driver genes in lethal CRPC, the metabolic dependencies underlying PTEN/p53 deficiency-driven CRPC for therapeutic intervention remain largely elusive. In this study, PTEN/p53 deficient tumors were determined to be reliant on cholesterol metabolism. Moreover, PTEN/p53 deficiency transcriptionally upregulated squalene epoxidase (SQLE) via activation of sterol regulatory element-binding protein 2 (SREBP2). In addition, PTEN deficiency enhanced the protein stability of SQLE by inhibiting the PI3K/Akt/GSK3ß-mediated proteasomal pathway. Consequently, SQLE increased cholesterol biosynthesis to facilitate tumor cell growth and survival. Pharmacologic blockade of SQLE with FR194738 profoundly suppressed the invasive program of CRPC. Collectively, these results demonstrate a synergistic relationship between SQLE and PTEN/p53 deficiency in CRPC development and progression. Therefore, pharmacologic interventions targeting SQLE may hold promise for the treatment of patients with CRPC. SIGNIFICANCE: This study reveals PTEN and p53 deficiency confers a dependence on SQLE-mediated cholesterol metabolism, providing insights for new therapeutic strategies for treating castration-resistant prostate cancer.

Immune infiltration phenotypes of prostate adenocarcinoma and their clinical implications.

BACKGROUND: Tumor-infiltrating immune cells participate in the initiation and progression of prostate adenocarcinoma (PRAD). However, it is not fully known how immune infiltration affects the development of PRAD and its clinical presentation. METHODS: Herein, we investigated the immune infiltration phenotypes in PRAD based on transcriptome profiles, methylation profiles, somatic mutation, and copy number variations. We also developed an immune prognostic model (IPM) to identify unfavorable prognosis. To verify this model, immunohistochemistry staining was performed on a cohort of PRAD samples. Moreover, we constructed a nomogram to assess the survival of PRAD incorporating immune infiltration and other clinical features. RESULTS: We categorized PRAD patients into high and low-level clusters based on immune infiltration phenotypes. The patients in the high-level clusters had worse survival than their low-level counterparts. Gene set enrichment analysis indicated that both anti- and pro-tumor terms were enriched in high-level cluster. Moreover, we identified a positive correlation between anti- and pro-tumor immune cells in PRAD microenvironment. Notably, Somatic mutation analysis showed patients in high-level cluster had a higher somatic mutation burden of KMT2D, HSPA8, CHD7, and MAP1A. In addition, we developed an IPM with robust predictive ability. The model can distinguish high-risk PRAD patients with poor prognosis from low-risk PRAD patients in both training and another three independent validation datasets. Besides, we constructed a nomogram incorporating Gleason score, pathological T stage, and IPM for the prognosis prediction of PRAD patients, which displayed robust predictive ability and might contribute to clinical practice. CONCLUSION: Our work illustrated the immune infiltration phenotypes strongly related to the poor prognosis of PRAD patients, and highlighted the potential of the IPM to identify unfavorable tumor features.

SUMOylation controls the binding of hexokinase 2 to mitochondria and protects against prostate cancer tumorigenesis.

Human hexokinase 2 is an essential regulator of glycolysis that couples metabolic and proliferative activities in cancer cells. The binding of hexokinase 2 to the outer membrane of mitochondria is critical for its oncogenic activity. However, the regulation of hexokinase 2 binding to mitochondria remains unclear. Here, we report that SUMOylation regulates the binding of hexokinase 2 to mitochondria. We find that hexokinase 2 can be SUMOylated at K315 and K492. SUMO-specific protease SENP1 mediates the de-SUMOylation of hexokinase 2. SUMO-defective hexokinase 2 preferably binds to mitochondria and enhances both glucose consumption and lactate production and decreases mitochondrial respiration in parallel. This metabolic reprogramming supports prostate cancer cell proliferation and protects cells from chemotherapy-induced cell apoptosis. Moreover, we demonstrate an inverse relationship between SENP1-hexokinase 2 axis and chemotherapy response in prostate cancer samples. Our data provide evidence for a previously uncovered posttranslational modification of hexokinase 2 in cancer cells, suggesting a potentially actionable strategy for preventing chemotherapy resistance in prostate cancer.

Glucose limitation activates AMPK coupled SENP1-Sirt3 signalling in mitochondria for T cell memory development.

Metabolic programming and mitochondrial dynamics along with T cell differentiation affect T cell fate and memory development; however, how to control metabolic reprogramming and mitochondrial dynamics in T cell memory development is unclear. Here, we provide evidence that the SUMO protease SENP1 promotes T cell memory development via Sirt3 deSUMOylation. SENP1-Sirt3 signalling augments the deacetylase activity of Sirt3, promoting both OXPHOS and mitochondrial fusion. Mechanistically, SENP1 activates Sirt3 deacetylase activity in T cell mitochondria, leading to reduction of the acetylation of mitochondrial metalloprotease YME1L1. Consequently, deacetylation of YME1L1 suppresses its activity on OPA1 cleavage to facilitate mitochondrial fusion, which results in T cell survival and promotes T cell memory development. We also show that the glycolytic intermediate fructose-1,6-bisphosphate (FBP) as a negative regulator suppresses AMPK-mediated activation of the SENP1-Sirt3 axis and reduces memory development. Moreover, glucose limitation reduces FBP production and activates AMPK during T cell memory development. These data show that glucose limitation activates AMPK and the subsequent SENP1-Sirt3 signalling for T cell memory development.

Cell cycle progression score improves risk stratification in prostate cancer patients with adverse pathology after radical prostatectomy.

OBJECTIVE: To assess the use of the cell cycle progression (CCP) score versus actual risk stratification practice in making treatment decisions for prostate cancer patients with locally adverse pathology after radical prostatectomy (RP). PATIENTS AND METHODS: Men with adverse pathologic features, pT3 or positive surgical margins who underwent RP in 2010-2014 at Renji hospital were retrospectively analyzed. The primary outcome was biochemical recurrence (BCR) after RP. RNA was quantified from paraffin-embedded RP specimens. The CCP score was calculated as average expression of 31 CCP genes, normalized to 15 housekeeper genes. The prognostic utility of the CCP score was assessed using Kaplan-Meier analysis and multivariable Cox proportional hazards model. RESULTS: Among the 100 men identified, 5-year BCR-free survival for the low- (< 0), intermediate- (0-1) and high- (> 1) CCP score groups was 89.3%, 38.8%, and 12.9%, respectively. In multivariable models adjusting for clinical and pathological variables with the cancer of the prostate risk assessment post-surgical (CAPRA-S) score, both continuous CCP score [hazard ratio (HR) 1.373 per unit score, 95% confidence interval (CI) 1.006-1.874; p = 0.046) and the categorized CCP score (p < 0.001)were independent predictors of BCR. CONCLUSIONS: The present study provides insights into the role the CCP score plays in risk stratification of this cohort and in determining candidacy for deferred secondary treatment. From our perspective, the CCP score allows better stratification and can help identifying patients at lower risk of disease recurrence who could benefit from a wait-and-see policy.

Insulinoma-associated protein 1 is a novel sensitive and specific marker for small cell carcinoma of the prostate.

The correct diagnosis of small cell carcinoma (SCC) of the prostate is critical because of its aggressive behavior and poor prognosis. The histopathologic diagnosis could be challenging without neuroendocrine markers, which currently has limitations. Insulinoma-associated protein 1 (INSM1), a zinc-finger transcription factor, is considered to play an important role in the development of several neuroendocrine precursor cells. Its diagnosis value has only recently been evaluated. In this study, we analyzed the expression of INSM in three high-throughput RNA sequencing data sets and performed INSM1 immunohistochemistry on a large series of prostatic SCCs and non-neuroendocrine prostate tissues. To validate its possible utility as a diagnostic marker, the performance of chromogranin and synaptophysin was used for comparison. We found INSM1 mRNA is up-regulated in neuroendocrine prostate carcinoma samples from the published data sets. The results were verified by the immunohistochemistry performance. INSM1 was positive in 92.3% of prostatic SCCs, compared with 53.8% positive for chromogranin, and 84.6% positive for synaptophysin. INSM1 was also stained all of the mixed SCC-acinar adenocarcinomas and metastatic SCCs progression from acinar adenocarcinoma. Only 3.4% of benign prostate tissues and 4.0% of prostate adenocarcinomas were INSM1 positive. Our data suggest that INSM1 is a novel sensitive and specific marker for detection of SCC of the prostate. Application of INSM1 in clinical pathologic diagnosis will be valuable.

Management of prostate cancer patients with locally adverse pathologic features after radical prostatectomy: feasibility of active surveillance for cases with Gleason grade 3 + 4 = 7.

PURPOSE: To evaluate the ability of the new Gleason grade groups (GGGs) to stratify risk in prostate cancer patients with locally adverse pathologic features after radical prostatectomy (RP) thereby allowing more accurate assessment for planning eventual adjuvant therapy. PATIENTS AND METHODS: Data on 172 patients with locally adverse pathologic features (including seminal vesicle invasion, extracapsular extension, or positive surgical margins) who had been treated with wait and see policy after RP were retrospectively analyzed for biochemical recurrence (BCR)-free survival. Kaplan-Meier survival analysis and Cox proportional hazard regression models were used to test the association between the GGGs and BCR. Finally, concordance indices of different grading classifications were calculated to evaluate the predictive accuracy for biochemical failure after RP. RESULTS: The five-year BCR-free survival rates were 71.2, 66.9, 25.7, 17.4, and 8.3 % for GGG 1-5 assessed on surgical specimens (p < 0.001, log-rank test). In the two-way log-rank test, men with prostatectomy GGG 2 had a lower progression risk relative to GGG 3 (p = 0.001), though similar risk as GGG 1 (p = 0.105). In multivariate Cox regression analysis, specimen GGG ≥3 and early postoperative PSA ≥0.1 ng/ml were independent risk factors for biochemical failure (p < 0.001). In addition, GGGs had higher predictive accuracy compared with the alternate classification system (improvement in concordance index by 0.036-0.141). CONCLUSIONS: For the appropriate patient, depending on age, physical condition, early postoperative PSA, patient desire, etc., could be a candidate for wait and see policy with specimen GGG 2 disease, so to distinguish this from GGG 3 may facilitate discussions at the point of treatment decision making.

Prostate transitional zone volume-based nomogram for predicting prostate cancer and high progression prostate cancer in a real-world population.

PURPOSE: To evaluate and compare the efficacy of prostate volume (PV), transitional zone volume (TZV), and prostate volume index (PVI, the ratio of TZV to peripheral zone volume) in the identification of men at risk of prostate cancer (PCa) and high-progression PCa (HPPCa) at the initial biopsy (IBX) in a real-world population. METHODS: From Jul 2014 to Aug 2016, data on 1144 patients who had undergone the initial prostate biopsies were prospectively collected and analyzed. Univariate and multivariate logistic regression analyses were performed to identify the independent predictors for PCa and HPPCa. Based on independent predictors, nomogram models were developed and internally validated to assess a man's risk of harboring PCa and HPPCa. RESULTS: The detection rates of PCa and HPPCa were 43.09% (493/1144) and 39.16% (448/1144), respectively. In the multivariate analyses, age, PSA, TZV, DRE, and TRUS instead of PV or PVI were independent predictors for PCa and HPPCa, percent free PSA was independent predictor for PCa not for HPPCa. Such independent predictors were finally included in the nomogram models. The AUCs of TZV-based nomogram models were 87.0% for PCa and 87.7% for HPPCa, which were higher than that of PSA alone or other predictive models. CONCLUSIONS: TZV is a better predictive biomarker than PV or PVI for PCa and HPPCa, we recommend adding TZV but not PV or PVI to the nomogram models to improve the predictive accuracy of PCa and HPPCa at IBX.

Serum Pre-Albumin Predicts the Clinical Outcome in Metastatic Castration-Resistant Prostate Cancer Patients Treated With Abiraterone.

Objective To determine the prognostic utility of serum pre-albumin in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone (AA). Patients and Methods 112 chemotherapy pretreated or chemotherapy-naive patients were scheduled for systemic treatment with AA. Serum pre-albumin levels were measured before and after 3 months of AA treatment. Univariate and multivariate analyses were performed to determine prognostic factors that were associated with PSA progression-free survival (PSA-PFS), radiographic PFS (rPFS) and overall survival (OS). The Harrell concordance index with variables only or combined pre-albumin data were used to evaluate the prognostic accuracy. Results The group of patients with baseline pre-albumin value ≥20mg/dL had a longer OS, PSA-PFS, rPFS than those with pre-albumin value <20mg/dL. Based on the values of pre-albumin before and after 3 months of AA treatment, we divided these patients into 4 groups: high-high, high-low, low-high and low-low group. High- high group showed a significantly better OS, PSA-PFS, rPFS than other 3 groups. In multivariate analysis, low pre-albumin level remained significant predictors of OS (HR, 13.2; P<0.001), rPFS (HR, 3.7; P=0.003) and PSA-PFS (HR, 8.7; P<0.001). The estimated c-index of the multivariate model for OS increased from 0.814 without pre-albumin to 0.845 when pre-albumin added. Conclusion Low pretreatment serum pre-albumin is a negative independent prognosticator of survival outcomes in mCRPC treated with AA and also increases the accuracy of established prognostic model. Serial pre-albumin evaluation might help clinicians guide clinical treatment of mCRPC patients.

Albumin and Fibrinogen Combined Prognostic Grade Predicts Prognosis of Patients with Prostate Cancer.

Background: The nutritional status and systemic inflammation are thought to be associated with outcome in multiple types of cancer. The objective of this study was to determine the prognostic value of pretreatment albumin and fibrinogen combined prognostic grade (AFPG) in prostate cancer (PCa). Methods: 462 prostate cancer patients who had undergone androgen deprivation therapy (ADT) as first-line therapy at four cencters were retrospectively analyzed. The serum albumin levels and plasma fibrinogen levels were measured at the time of diagnosis. The AFPG was calculated according to albumin and fibrinogen levels dichotomized by optimal cut-off values or clinical reference values. Univariate and multivariate cox regression analyses were performed to determine the associations of AFPG with progression-free survival (PFS), cancer-specific survival (CSS) and overall survival (OS). Prognostic accuracy was evaluated with the Harrell concordance index. Results: Multivariate analyses identified AFPG as an independent prognostic indicator for PFS, CSS and OS (each p < 0.01). According to optimal cut-off values, the addition of AFPG to the final models improved predictive accuracy for PFS, CSS and OS compared with the clinicopathological base models, which included Gleason score and incidence of metastasis. Moreover, AFPG according to optimal cut-off values was a better prognostic predictor than albumin levels alone or fibrinogen levels alone or AFPG according to clinical reference values. Conclusion: Decreased AFPG could predict a significantly poor prognosis in patients with PCa. Thus, we recommend adding AFPG according to optimal cut-off values to traditional prognostic model to improve the predictive accuracy.