External validation of the Prostate Cancer Prevention Trial and the European Randomized Study of Screening for Prostate Cancer risk calculators in a Chinese cohort

Several prediction models have been developed to estimate the outcomes of prostate biopsies. Most of these tools were designed for use with Western populations and have not been validated across different ethnic groups. Therefore, we evaluated the predictive value of the Prostate Cancer Prevention Trial （PCPT） and the European Randomized Study of Screening for Prostate Cancer （ERSPC） risk calculators in a Chinese cohort. Clinicopathological information was obtained from 495 Chinese men who had undergone extended prostate biopsies between January 2009 and March 2011. The estimated probabilities of prostate cancer and high-grade disease （Gleason 〉6） were calculated using the PCPT and ERSPC risk calculators. Overall measures, discrimination, calibration and clinical usefulness were assessed for the model evaluation. Of these patients, 28.7% were diagnosed with prostate cancer and 19.4% had high-grade disease. Compared to the PCPT model and the prostate-specific antigen （PSA） threshold of 4 ng m1-1, the ERSPC risk calculator exhibited better discriminative ability for predicting positive biopsies and high-grade disease （the area under the curve was 0.831 and 0.852, respectively, P〈O.01 for both）. Decision curve analysis also suggested the favourable clinical utility of the ERSPC calculator in the validation dataset. Both prediction models demonstrated miscalibration： the risk of prostate cancer and high-grade disease was overestimated by approximately 20% for a wide range of predicted probabilities. In conclusion, the ERSPC risk calculator outperformed both the PCPT model and the PSA threshold of 4 ng ml- z in predicting prostate cancer and high-grade disease in Chinese patients. However, the prediction tools derived from Western men significantly overestimated the probability of prostate cancer and high-grade disease compared to the outcomes of biopsies in a Chinese cohort.

Prognostic factors in Chinese patients with metastatic castration-resistant prostate cancer treated with docetaxel-based chemotherapy

This study aims to evaluate the potential value of patient characteristics in predicting overall survival （OS） in patients with metastatic castration-resistant prostate cancer （mCRPC） treated with docetaxel-based thermotherapy. A total of 115 patients with mCRPC undergoing a docetaxel q3w regimen were enrolled in this study. A survival analysis was performed using the Kaplan-Meier method. Cox proportional hazards models were used to evaluate the prognostic value of all covariates for OS. OS was also analysed after stratifying patients according to the results of multivariate analysis. The median OS for the entire cohort was 17.0 months. The multivariate analysis showed that the prostate-specific antigen doubling time （PSADT）, baseline haemoglobin （Hb） concentration, alkaline phosphatase （ALP） concentration, cycles of chemotherapy and time to castration resistance were independent prognostic factors of OS. According to the presence of PSADT 〈46.3 days and baseline ALP/〉 110 IU 1-1, all patients were divided into three risk groups： low-risk group （no risk factors）, intermediate-risk group （one risk factor） and high-risk group （two risk factors）. Median OSs for patients in low-, intermediate- and high-risk groups were 28.0 months （95% Ch 23.8-32.2）, 21.0 months （95% Ch 18.9-23.1） and 11.0 months （95% Ch 7.6-14.4）, respectively （P〈O.O01）. In conclusion, PSADT, baseline Hb concentration, ALP concentration, cycles of chemotherapy and time to castration resistance were independent prognostic factors of OS in Chinese patients with mCRPC treated with docetaxel. PSADT combined with the baseline ALP concentration could be a useful risk stratification parameter for evaluating survival outcomes.

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.

肥胖对临床局限性前列腺癌患者临床病理特征的影响

This study aimed to investigate the association between different anthropometric measures of obesity and clinicopathological characteristics in Chinese patients with clinically localized prostate cancer （PCa）. A total of 734 patients with clinically localized PCa who underwent radical prostatectomy （RP） were included in this study. Clinical and pathological data from each patient were collected. Anthropometric measures of abdominal adiposity were measured from T2-weighted sagittal Iocalisation images from magnetic resonance imaging （MRI） for 413 （56.3%） patients. Patient clinical and pathological characteristics were compared across body mass index （BMI） groups. Univariable and multivariable logistic regression models were used to address the influence of the preoperative total testosterone level and anthropometric measures of obesity on pathological outcomes. In the multivariate analysis, BMI was not significantly associated with any pathological outcomes. However, the percentage of visceral adipose tissue （VAT%） was an independent predictor of a pathological Gleason score ≥8 （P〈0.O01）, extracapsular extension （ECE; P=0.002） and seminal vesicle invasion （SVI; P=0.007）. More importantly, we found that the preoperative total testosterone level was significantly correlated with the VAT% （Pearson＇s correlation coefficient： -0.485, P〈0.001） and subcutaneous adipose tissue （SAT; Pearson＇s correlation coefficient： 0.413, P〈0.001）. In conclusion, the results of this study suggest that abdominal fat distribution, and particularly VAT%, is associated with a risk of advanced PCa. Moreover, our present study confirms a significant inverse correlation between visceral adiposity and testosterone. Further studies are warranted to elucidate the biological mechanisms underlying the relationship between abdominal adiposity and the aggressiveness of PCa.

局限进展性前列腺癌病人耻骨后前列腺癌根治术的围手术期并发症：与临床局限性前列腺癌的一个比较

Radical prostatectomy （RP） continues to be an effective surgical therapy for prostate carcinoma, particularly for organ-confined prostate cancer （PCa）. Recently, RP has also been used in the treatment of locally advanced prostate cancer. However, little research has been performed to elucidate the perioperative complications associated with RP in patients with clinically localized or locally advanced PCa. We sought to analyse the incidence of complications in these two groups after radical retropubic prostatectomy （RRP）. From June 2002 to July 2010, we reviewed 379 PCa patients who underwent RRP in our hospital. Among these cases, 196 had clinically localized PCa （Tla-T2c group 1）, and 183 had locally advanced PCa （ ≥ T3,： group 2）. The overall complication incidence was 21.9%, which was lower than other studies have reported. Perioperative complications in patients with locally advanced PCa mirror those in patients with clinically localized PCa （26.2% vs. 17.8%, P=0.91）. Our results showed that perioperative complications could not be regarded as a factor to consider in regarding RP in patients with cT3 or greater.

Human epidermal growth factor receptor type 2 protein expression in Chinese metastatic prostate cancer patients correlates with cancer specific survival and increases after exposure to hormonal therapy

Aim： To investigate human epidermal growth factor receptor type 2 （HER2） protein expression and gene amplification in Chinese metastatic prostate cancer patients and their potential value as prognostic factors. Methods： Immunohistochemistry （IHC） was performed to investigate HER2 protein expression in prostate biopsy specimens from 104 Chinese metastatic prostate cancer patients. After 3-11 months of hormonal therapy, 12 patients underwent transurethral resection of the prostate （TURP）. HER2 protein expression of TURP specimens was compared with that of the original biopsy specimens. Of these, 10 biopsy and 4 TURP specimens with HER2 IHC staining scores ≥ 2＋ were investigated for HER2 gene amplification status by fluorescent in situ hybridization （FISH）. Results： Of the 104 prostate biopsy specimens, HER2 protein expression was 0, 1＋, 2＋ and 3＋ in 49 （47.1%）, 45 （43.3%）, 8 （7.7%） and 2 （1.9%） cases, respectively. There was a significant association between HER2 expression and Gleason score （P = 0.026）. HER2 protein expression of prostate cancer tissues increased in 33.3% of patients after hormonal therapy. None of the 14 specimens with HER2 IHC scores 〉 2＋ showed HER2 gene amplification. Patients with HER2 scores 〉 2＋ had a significantly higher chance of dying from prostate cancer than those with HER2 scores of 0 （P = 0.004） and 1＋ （P = 0.034）. Multivariate Cox regression analysis showed that HER2 protein expression intensity was an independent predictor of cancer-related death （P = 0.039）. Conclusion： An HER2 IHC score 〉 2＋ should be defined as HER2 protein overexpression in prostate cancer. Overexpression of HER2 protein in cancer tissue might suggest an increased risk of dying from prostate cancer. HER2 protein expression increases in some individual patients after hormonal therapy.

Function of PCA3 in prostate tissue and clinical research progress on developing a PCA3 score

Prostate cancer gene 3 （PCA3, also known as DD3） is a new biomarker that could improve the accuracy of prostate cancer diagnosis. It is a great biomarker with fairly high specificity and sensitivity. The incidence of prostate cancer is rising steadily in most countries. The commonly used prostate-specific antigen （PSA） test once gave people hope for early diagnosis of prostate cancer. However, the low specificity of the PSA test has resulted in a large number of unnecessary biopsies and overtreatment. During the past decade, many new prostate cancer biomarkers have been found. Among these, PCA3 is the most promising. Due to its great performance in distinguishing prostate cancer from other prostate conditions, PCA3 could likely be applied for early diagnosis of prostate cancer, patient follow-up, prognosis prediction, and targeted therapy. After years of research, we have obtained some knowledge about the sequence of PCA3 gene. We have also determined the relationship between PCA3 and the proliferation of prostate cancer cells and learned some information about how PCA3 affects tumor-related genes and proteins. A PCA3 score has been created, and it has been used in a variety of studies. Some researchers have even applied PCA3 to targeted therapy and obtained a good effect in vitro. This review describes the current state of research, and explores the future prospects for PCA3.

Lumboperitoneal shunts for the treatment of post-traumatic hydrocephalus

Objective: To assess the effectiveness and safety of lumboperitoneal shunt for treatment of post-traumatic hydrocephalus(PTH).Methods: A retrospective analysis of medical records of patients with lumboperitoneal shunts admitted in Shanghai Tenth People's Hospital from January 2014 to March 2017 was done.Experience with lumboperitoneal shunt placement for PTH was reviewed.The diagnosis of PTH was based on ventricular enlargement with the Evans' index(EI>0.3) before shunt implantation.Patients were evaluated for improvements in Glasgow Coma Scale(GCS), Glasgow Outcome Scale(GOS), and EI after shunt placement.Results: Totally, the study included 34 PTH patients with the average age of 49.32 years(range: 9–67 years).The average follow-up period was(3.9±3.5) months.Before lumboperitoneal shunt, the GOS score was(4±1), the GCS score was(8.53±3.38), and the EI score was(0.40±0.08).After shunt implantation, the GOS score was(3±1), the GCS score was(10.29±3.15), and the EI score was(0.34±0.13), respectively(P<0.05).Before lumboperitoneal shunt, 24(70.58%) patients had a GOS score of 4(vegetative state), and 10(29.42%) patients had a GOS score of 3(severe disabled).After lumboperitoneal shunt, 18(52.94%) patients had improvement in GOS(11 patients improve from GOS 4 to GOS 3, 5 patients from GOS 3 to GOS 2 and 2 patients from GOS 3 to GOS 1), 22(64.71%) patients achieved improvement in their GCS(14 patients GCS improvements ≥2 and 8 patients GCS improvement=1), 21(61.76%) patients had EI improvement(18 patients with EI<0.3).There was no complication in this study.Conclusion: Lumboperitoneal shunt placement is safe and effective for PTH, and serious complications are not observed.

External validation of nomograms for predicting cancer-specific mortality in penile cancer patients treated with definitive surgery

Using a population-based cancer registry,Thuret et al.developed 3 nomograms for estimating cancerspecific mortality in men with penile squamous cell carcinoma.In the initial cohort,only 23.0% of the patients were treated with inguinal lymphadenectomy and had pN stage.To generalize the prediction models in clinical practice,we evaluated the performance of the 3 nomograms in a series of penile cancer patients who were treated with definitive surgery.Clinicopathologic information was obtained from 160 M0 penile cancer patients who underwent primary tumor excision and regional lymphadenectomy between 1990 and 2008.The predicted probabilities of cancer-specific mortality were calculated from 3 nomograms that were based on different disease stage definitions and tumor grade.Discrimination,calibration,and clinical usefulness were assessed to compare model performance.The discrimination ability was similar in nomograms using the TNM classification or American Joint Committee on Cancer staging(Harrell's concordance index = 0.817 and 0.832,respectively),whereas it was inferior for the Surveillance,Epidemiology and End Results staging(Harrell's concordance index = 0.728).Better agreement with the observed cancer-specific mortality was shown for the model consisting of TNM classification and tumor grade,which also achieved favorable clinical net benefit,with a threshold probability in the range of 0 to 42%.The nomogram consisting of TNM classification and tumor grading was shown to have better performance for predicting cancer-specific mortality in penile cancer patients who underwent definitive surgery.Our data support the integration of this model in decision-making and trial design.

The effectiveness of the TAX 327 nomogram in predicting overall survival in Chinese patients with metastatic castration-resistant prostate cancer

Based on the results of TAX 327, a nomogram was developed to predict the overall survival of metastatic castration-resistant prostate cancer （mCRPC） after first-line chemotherapy. The nomogram, however, has not been validated in an independent dataset, especially in a series out of clinical trials. Thus, the objective of the current study was to validate the TAX 327 nomogram in a community setting in China. A total of 146 patients with mCRPC who received first-line chemotherapy （docetaxel or mitoxantrone） were identified. Because clinical trials are limited in China's Mainland, those patients did not receive investigational treatment after the failure of first-line chemotherapy. The predicted overall survival rate was calculated from the TAX 327 nomogram. The validity of the model was assessed with discrimination, calibration and decision curve analysis. The median survival of the cohort was 21 months （docetaxel） and 19 months （mitoxantrone） at last follow-up. The predictive c-index of the TAX 327 nomogram was 0.66 （95% CI： 0.54-0.70）. The calibration plot demonstrated that the 2-year survival rate was underestimated by the nomogram. Decision curve analysis showed a net benefit of the nomogram at a threshold probability greater than 30%. In conclusion, the present validation study did not confirm the predictive value of the TAX 327 nomogram in a contemporary community series of men in China, and further studies with a large sample size to develop or validate nomograms for predicting survival and selecting therapies in advanced prostate cancer are necessary.

The prognostic factors of effective ketoconazole treatment for metastatic castration-resistant prostate cancer： who can benefit from ketoconazole therapy？

We investigated the prognostic value of some variables of effective ketoconazole treatment for metastatic castration-resistant prostate cancer （mCRPC）. In total, 163 patients with mCRPC were eligible, receiving ketoconazole 200-400 mg three times daily with replacement doses of prednisone. Progression-free survival （PFS） was calculated from the beginning of the ketoconazole therapy to the onset of disease progression. The prognostic value of different variables for PFS was assessed by Cox regression analysis. The median PFS was 2.6 months （0.5-8.6 months） for these patients. The serum testosterone level changed during therapy, which decreased when the prostate-specific antigen （PSA） declined; the serum testosterone level increased as the levels of PSA relapsed. The median PFS values for patients associated with different factors were the following： 1.4 and 3.5 months for a nadir PSA of ≥ 0.2 and 〈0.2 ng ml- 1, respectively （hazard rate （HR）=4.767, P〈0.001）; 3.1 and 1.6 months for a baseline testosterone of ≥0.1 and 〈0.1 ng m1-1, respectively （HR=2.865, P=0.012）; 2.8 and 1.9 months for a baseline haemoglobin of ≥ 120 and 〈120 g 1-1, respectively （HR= 1.605, P〈0.001）; and 3.0 and 1.9 months for a PSA doubling time （PSADT） of ≥ 2.0 and 〈2.0 months, respectively （HR= 1.454, P=-0.017）. A risk model was constructed according to the four factors that divided patients into three subgroups of low risk （0-1 factors）, moderate risk （2 factors） and high risk （3-4 factors） with PFS values of 3.6, 3.0 and 1.4 months, respectively （HR=1.619, P〈0.001）. A nadir PSA of ≥0.2 ng m1-1, a baseline testosterone of 〈0.1 ng m1-1, a baseline haemoglobin of 〈 120 g I- 1 and a PSADT of 〈2 months were associated with a poor PFS. This risk model could provide evidence to predict the survival benefit of ketoconazole therapy.