Prostate-specific antigen half-life： a new predictor of progression- free survival and overall survival in Chinese prostate cancer patients

We investigated the potential value of prostate-specific antigen half-life （PSAHL） and decreasing velocity （PSAVd） to predict progression-free survival （PFS） and overall survival （OS） in Chinese patients with prostate cancer. A total of 153 patients treated with hormonal therapy were included in the study. Of these, 78 patients progressed to hormone- refractory prostate cancer （HRPC） and 24 patients died by the end of follow-up. PSAHL was defined as the time during which prostate-specific antigen （PSA） concentration became half of the initial value during the first hormonal therapy. PSAVd reflected the decreasing velocity of PSA during the first hormonal therapy. PFS was defined as the interval from the beginning of hormonal therapy to HRPC. Cox proportional hazards regression analysis was used to evaluate whether PSAHL and PSAVd were significantly associated with PFS and OS. The median PSAHL and PSAVd were 0.50 months and 33.8 ng mL^-1 per month. The median PFS and OS were 22.7 months （95% confidence interval [CI], 22.0-29.6 months） and 43.5 months （95% CI, 37.9-48.4 months）, respectively. On univariate and multivariate analysis, long PSAHL （〉 0.5 months）, metastatic disease, high biopsy Gleason scores （〉 8） and high nadir PSA （〉 0.4 ng mL^-1） were all found to be significantly associated with short PFS. Long PSAHL, high nadir PSA and short PSA doubling time （PSADT 〈 2.0 months） were significantly associated with short OS. There were no significant relationships between PSAVd and either PFS or OS. Thus, PSAHL is a promising new independent predictor of survival. Patients with long PSAHL were identified as those at high risk for a relatively short PFS and OS.

Comparison of two adjuvant hormone therapy regimens in patients with high-risk localized prostate cancer after radical prostatectomy, primary results of study CU 1005

The role of adjuvant hormonal therapy and optimized regimens for high-risk localized prostate cancer after radical prostatectomy remains controversial. Herein, the clinical trial CU 1005 prospectively evaluated two regimens of maximum androgen blockage or bicalutamide 150 mg daily as immediate adjuvant therapy for high-risk localized prostate cancer. Overall, 209 consecutive patients were recruited in this study, 107 of whom received 9 months of adjuvant maximum androgen blockage, whereas 102 received 9 months of adjuvant bicalutamide 150 mg. The median postoperative follow-up time was 27.0 months. The primary endpoint was biochemical recurrence. Of the 209 patients, 59 patients developed biochemical recurrence. There was no difference between the two groups with respect to clinical characteristics, including age, pretreatment prostate-specific antigen, Gleason score, surgical margin status, or pathological stages. The maximum androgen blockage group experienced longer biochemical recurrence-free survival （P = 0.004） compared with the bicalutamide 150 mg group. Side-effects in the two groups were similar and could be moderately tolerated in all patients. In conclusion, immediate, 9-month maximum androgen blockage should be considered as an alternative to bicalutamide 150 mg as adjuvant treatment for high-risk localized prostate cancer patients after radical prostatectomy.

Serum lipid profiles： novel biomarkers predicting advanced prostate cancer in patients receiving radical prostatectomy

This study aimed to evaluate the role of serum lipid profiles as novel biomarkers in predicting pathological characteristics of prostate cancer （PCa）. We retrospectively analyzed 322 consecutive patients with clinically localized PCa receiving radical prostatectomy （RP） and extended pelvic lymphadenectomy. Unconditional logistic regression was used to estimate the prostatectomy Gleason score （pGS）, pathological stage and lymph node involvement （LNI） in RP specimens. Preoperative prostate-specific antigen （PSA） levels, biopsy GS （bGS）, and preoperative tumor, node, metastasis staging were used as basic variables to predict postoperative pathological characteristics. Preoperative serum lipid profiles were introduced as potential predictors. A receiver operating characteristic （ROC） curve was used to determine predictive efficacy. Significant differences in pathological characteristics were observed among patients with normal and abnormal total cholesterol （TC）, triglyceride （TG）, and low-density lipoprotein （LDL） levels, with the exception of pGS in the TG group. Multivariable regression analysis revealed that the odds ratio for high levels of TC for LNI compared with normal TC levels was 6.386 （95% confidence interval [Cl] 1.510-27.010）, 3.270 （95% CI. 1.470-7.278） for high levels of TG for pT3-4 disease, and 2.670 （95% Ch 1.134-6.287） for high levels of LDL for pGS. The area under the ROC curve of the models with dyslipidemia was larger than that in models without dyslipidemia, in predicting pathological characteristics. Abnormal TC, TG, and LDL levels are significantly associated with postoperative pathological status in PCa patients. Together with preoperative PSA levels, bGS, and clinical stage, dyslipidemia is more accurate in predicting pathological characteristics.

Large-Scale Proteomics Data Reveal Integrated Prognosis-Related Protein Signatures and Role of SMAD4 and RAD50 in Prognosis and Immune Infiltrations of Prostate Cancer Microenvironment

As prostate cancer(PCa)is one of the most commonly diagnosed cancer worldwide,identifying potential prognostic bio-markers is crucial.In this study,the survival information,gene expression,and protein expression data of 344 PCa cases were collected from the Cancer Proteome Atlas(TCPA)and the Cancer Genome Atlas(TCGA)to investigate the potential prognostic biomarkers.The integrated prognosis-related proteins(IPRPs)model was constructed based on the risk score of each patients using machine-learning algorithm.IPRPs model suggested that Elevated RAD50 expression(p=0.016)and down-regulated SMAD4 expression(p=0.017)were significantly correlated with unfavorable outcomes for PCa patients.Immunohistochemical(IHC)staining and western blot(WB)analysis revealed significant differential expression of SMAD4 and RAD50 protein between tumor and normal tissues in validation cohort.According to the overall IHC score,patients with low SMAD4(p<0.0001)expression and high RAD50 expression(p=0.0001)were significantly correlated with poor outcomes.Besides,expression of SMAD4 showed significantly negative correlation with most immune checkpoint molecules,and the low SMAD4 expression group exhibited significantly high levels of LAG3(p<0.05),TGFβ(p<0.001),and PD-L1(p<0.05)compared with the high SMAD4 expression group in the validation cohort.Patients with low SMAD4 expression had significantly higher infiltration of memory B cells(p=0.002),CD8+T cells(p<0.001),regulatory T cells(p=0.006),M2-type macrophages(p<0.001),and significantly lower infiltration of naïve B cells(p=0.002),plasma cells(p<0.001),resting memory CD4+T cells(p<0.001)and eosinophils(p=0.045).Candidate proteins were mainly involved in antigen processing and presentation,stem cell differentiation,and type I interferon pathways.