不同治疗方案与局部晚期前列腺癌患者前列腺特异性抗原进展及生存状况的Meta分析

目的 应用Meta分析探讨不同治疗方案对局部晚期前列腺癌前列腺特异性抗原(PSA)进展及生存状况的影响. 方法制订原始文献的纳入标准、剔除标准及检索策略.以优势比(OR)及其95%可信区间(95%CI)为效应尺度,应用Meta分析固定效应模型和随机效应模型对有关治疗局部晚期前列腺癌不同方案的纳入文献进行综合定量评价. 结果 符合纳入标准的8篇文献进入Meta分析,共3826例.5篇为前列腺根治性切除术(RP)联合辅助治疗与单纯用RP或不用RP进行比较,以PSA进展率为评价指标,合并后的OR值为0.86,95%CI为0.48～1.56;3篇为RP联合激素治疗与单纯用RP或不用RP进行比较,以疾病特异性死亡率为评价指标,合并后的OR值为0.72,95%CJ为0.51～1.02. 结论 RP联合辅助治疗可以显著减少局部晚期前列腺癌患者术后PSA进展,对疾病特异性死亡率却无显著影响.     

Adding multiparametric MRI to the MSKCC and Partin nomograms for primary prostate cancer: Improving local tumor staging?

Introduction and objectives

As a single diagnostic modality, multiparametric MRI (mpMRI) has imperfect accuracy to detect locally advanced prostate cancer (T-stages 3-4). In this study we evaluate if combining mpMRI with preoperative nomograms (Memorial Sloan Kettering Cancer Center [MSKCC] and Partin) improves the prediction of locally advanced tumors.

Combined tests of prostate specific antigen and testosterone will improve diagnosis and monitoring the progression of prostate cancer

Prostate-specific antigen (PSA) testing has been widely used to screen men for prostate cancer (PCa) and to monitor PCa progression. However, more studies have shown that around 15% of men with low or normal PSA levels have PCa. In this study, we aimed to investigate the relationship of androgen and PSA levels and to better understand the reason that some PCa patients have low serum PSA values. The in vitro data demonstrated that cultured LNCaP cells ceased to produce PSA after androgen withdrawal and resumed PSA production after androgen was re-added. The in vivo experiment results showed that 48% of PCa xenografts carrying mice have serum PSA level lower than 4 ng ml⁻¹. The serum PSA levels increased significantly with rises in testosterone (T) levels 1 week after T pellet implantation. These data indicated that the androgen is a key factor controlling the production of PSA. Low serum PSA levels in mice with PCa xenografts are associated with low serum T levels. Raising serum T levels in tumor caring mice will also significantly increase serum PSA level. This may have clinical implications when screening PSA in men, who have occult PCa.     

Immunoperoxidase staining of carcinoembryonic antigen in urinary bladder cancer

Summary An immunoperoxidase study of the presence of carcinoembryonic antigen (CEA) in primary cancers of the urinary bladder, metastases to the bladder, non-malignant diseased bladder, and normal bladder tissues revealed that approximately 10 percent of the urothelial carcinomas (transitional cell and squamous cell types) contained detectable quantities of this antigen. The other tissues were devoid of stainable CEA. It thus appears that the incidence of positive CEA by immunoperoxidase staining of formalin-fixed, paraffin-embedded tumour tissue sections is much less than the frequency of blood or urinary CEA elevations in patients with urothelial cancer.     

Mass screening of prostate cancer in a Chinese population：the relationship between pathological features of prostate cancer and serum prostate specific antigen

Aim: To investigate the pathological features of the prostate biopsy through mass screening for prostate cancer in a Chinese cohort and their association with serum prostate specific antigen (PSA). Methods: A total of 12027 Chinese men in Changchun were screened for prostate cancer by means of the serum total prostate specific antigen tPSA test (by Elisa assay). Transrectal ultrasound-guided systematic six-sextant biopsies were performed on those whose serum tPSA value was > 4.0 ng/mL and those who had obstructive symptoms (despite their tPSA value) and were subject to subsequent pathological analysis with the aid of the statistic software SPSS 10.0 (SPSS. Inc., Chicago. USA). Results: Of the 12027 cases, 158 (including 137 patients whose serum tPSA values were 4.0 ng/mL and 21 patients [serum tPSA < 4.0 ng/mL] who had obstructive symptoms) undertook prostate biopsy. Of the 158 biopsies, 41 cases of prostatic carcinoma were found (25.9 %, 41/158). The moderately differentiated carcinoma and poorly differentiated carcinoma accounted for 61% and 34%, respectively. A significant linear positive correlation between the serum tPSA and the Gleason scores in the 41 cases of prostatic carcinoma (r = 0.312, P < 0.01) was established. A significant linear positive correlation between the serum tPSA value of the 41 prostatic carcinoma and the positive counts of carcinoma in sextant biopsies was established (r = 0.406, P < 0.01), indicating a significant linear relationship between serum tPSA and the size of tumor. Conclusion: This study was the first to conduct mass screening for prostate cancer by testing for serum tPSA values and the first to investigate the pathological features of prostate cancer in a cohort of Chinese men. Our results reveal that the moderately differentiated carcinoma is the most common type of prostate cancer. This study also has shown that the serum tPSA value in prostate cancer is associated with the Gleason score and the size of tumor.     

A comparative performance analysis of total prostate-specific antigen, percentage free prostate-specific antigen, prostate-specific antigen velocity and urinary prostate cancer gene 3 in the first, second and third repeat prostate biopsy

Study Type – Diagnostic (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Although non‐recommended PSA testing has been reported in men younger than 40 years of age, there are few recognized data on PSA in younger American men, particularly younger African‐American men, to provide age‐ and race‐specific references. Using data from an existing large study of young, male members of the US military, aged 28–36 years, the present study provides PSA reference distributions for young Caucasian‐American men (median = 0.56, 95th percentile = 1.42, range: <0.01–3.34 ng/mL) and African‐American men (median = 0.64, 95th percentile = 1.89, range: 0.12–6.45 ng/mL). Previous estimates from the literature are also summarized.

OBJECTIVE

• ? To provide race‐specific prostate‐specific antigen (PSA) reference distributions for young men less than 40 years of age who might have undergone non‐recommended PSA testing because of their family history of prostate cancer or inadvertently as part of a standard panel of tests.

MATERIALS AND METHODS

• ? We used data from a large existing study of young, male Caucasian‐ and African‐American members of the US military with stored serum in the Department of Defense serum repository.
• ? As part of this previous study, we selected a random sample of 373 Caucasian‐ and 366 African‐American men aged 28–36 years with an archived serum specimen collected for standard military purposes from 2004 to 2006.
• ? We measured serum total PSA concentration in this specimen using the Beckman Coulter Access Hybritech PSA assay.

RESULTS

• ? The PSA level ranged from <0.01 to 3.34 ng/mL among Caucasian‐American men, with a median of 0.56 ng/mL and a 95th percentile of 1.42 ng/mL.
• ? The PSA level ranged from 0.12 to 6.45 ng/mL among African‐American men, with a median of 0.64 ng/mL and 95th percentile of 1.89 ng/mL.
• ? The PSA level was significantly higher in African‐ than in Caucasian‐American men (P= 0.001).

CONCLUSION

• ? The PSA estimates, together with those summarized from the literature, provide age‐ and race‐specific PSA reference distributions for young men who might have undergone non‐recommended PSA testing.
• ? Comparisons by race could also begin to inform the timing of divergence of prostate cancer risk by race.

     

Usefulness of prostate-specific antigen velocity in screening for prostate cancer

BACKGROUND: The cut-off value of prostate-specific antigen velocity (PSAV) was investigated in relation to the initial prostate-specific antigen (PSA) value in subjects with initial values of 1.0-4.0 ng/mL, and the usefulness and limitations of PSAV as a screening test for prostate cancer were examined. METHODS: In this study, 4883 men who underwent mass screening for prostate cancer two or more times between 1987 and 1998 and had initial PSA levels of 1.0-4.0 ng/mL were investigated. The subjects ranged in age from 42 to 96 years (mean: 68.0 +/- 6.6 years). The cut-off value of PSAV was set at 0.1-1.5 ng/mL per year, and the sensitivity, specificity, efficiency and positive predictive value (PPV) of PSAV for detecting prostate cancer were determined according to the initial PSA value. A similar examination of the average PSAV was carried out in 2888 subjects with three or more visits for mass screening for prostate cancer. RESULTS: The diagnostic efficiency of PSAV was optimal with cut-off values of 0.3 and 0.75 ng/mL per year in those subjects with initial PSA levels of 1.0-1.9 and 2.0-4.0 ng/mL, respectively, but the PPV was low at 1.8% in subjects with initial PSA levels of 1.0-1.9 ng/mL. When the cutoff value of PSAV was set at 1.2 ng/mL per year in individuals with initial PSA levels of 1.0-1.9 ng/mL, the PPV increased to 7.3% and the sensitivity was 40%. The diagnostic efficiency of the average PSAV was optimal at the cut-off values of 0.2 and 0.4 ng/mL per year in subjects with initial PSA levels of 1.0-1.9 and 2.0-4.0 ng/mL, respectively, but the PPV was low at 2.2% in the subjects with initial PSA values of 1.0-1.9 ng/mL. When the cut-off value of PSAV was set at 0.75 ng/mL per year in individuals with initial PSA levels of 1.0-1.9 ng/mL, the PPV was 9.8% and the sensitivity was 46%. CONCLUSION: It is possible to improve the diagnostic accuracy of prostate cancer screening using the cut-off value of PSAV and average PSAV in subjects with initial PSA levels of 1.0-4.0 ng/mL. The cut-off values of PSAV should be set at 1.2 and 0.75 ng/mL per year in individuals with initial PSA levels of 1.0-1.9 and 2.0-4.0 ng/mL, respectively. The cut-off values of the average PSAV should be set at 0.75 and 0.4 ng/mL per year in individuals with initial PSA levels of 1.0-1.9 and 2.0-4.0 ng/mL, respectively.     

Addition of radiotherapy to long-term androgen deprivation in locally advanced prostate cancer: an open randomised phase 3 trial

Background

Radiotherapy combined with androgen-deprivation therapy (ADT) is superior to radiotherapy alone in localised prostate cancer; however, data comparing ADT alone are somewhat limited.

Objective

To compare 3-yr ADT plus radiotherapy with ADT alone in locally advanced prostate cancer patients.

Design, setting, and participants

A multicentre randomised open controlled phase 3 trial in 264 histologically confirmed T3–4 or pT3N0M0 prostate cancer patients randomised from March 2000 to December 2003.

Intervention

ADT (11.25 mg subcutaneous depot injection of leuprorelin every 3 mo for 3 yr) plus external-beam radiotherapy or ADT alone. Flutamide (750 g/d) was administered for 1 mo.

Outcome measurements and statistical analysis

The primary objective was 5 yr progression-free survival (PFS) according to clinical or biologic criteria, using the American Society for Therapeutic Radiology and Oncology (ASTRO) and the newer (Phoenix) definition (nadir plus 2 ng/ml), by intention to treat. Secondary objectives included time to locoregional recurrence and distant metastases, and overall and disease-specific survival. Our Analyses: intent-to-treat analysis, multivariate analyses using a Cox model with a 5% threshold from univariate analysis, and Kaplan-Meier estimates.

Results and limitations

ADT alone was administered to 130 patients and combined therapy to 133. With a median follow-up of 67 mo, 5-yr PFS was 60.9% for combined therapy versus 8.5% with ADT alone (ASTRO; p < 0.0001), and 64.7% versus 15.4%, respectively, for Phoenix (p < 0.0011). Locoregional progression was reported in 9.8% of combined-therapy patients versus 29.2% with ADT alone (p < 0.0001) and metastatic progression in 3.0% versus 10.8%, respectively (p < 0.018). Overall survival was 71.4% with combined therapy versus 71.5% with ADT alone; disease-specific survival was 93.2% versus 86.2%. Limitations included the relatively small population and a relatively short follow-up period.

Conclusions

Combined therapy strongly favoured improved PFS, locoregional control, and metastasis-free survival. Longer follow-up is needed to assess the potential survival impact.     

Application of the Epstein criteria for prediction of clinically insignificant prostate cancer in Korean men

Study Type – Prognosis (case series)
Level of Evidence 4

OBJECTIVE

To investigate the rate of pathologically confirmed unfavourable prostate cancers among Korean men who fulfilled the contemporary Epstein criteria for clinically insignificant prostate cancer.

PATIENTS AND METHODS

This was a retrospective study of 131 Korean men who underwent radical prostatectomy (RP) for clinically insignificant prostate cancer as defined by contemporary Epstein criteria. We assessed the percentage of unfavourable prostate cancer (pathological Gleason sum ≥7 and/or extraprostatic extension [EPE]) among these men and tried to identify useful predictors for such unfavourable tumour profiles using uni‐ and multivariate analyses.

RESULTS

Among 131 men with clinically insignificant prostate cancer, 40 (30.5%) had pathological Gleason ≥7 tumours after RP. Of these 40 men, four (3.1%) also had EPE on examination of RP specimen. All those who did not have Gleason score upgrading after RP had organ‐confined disease from examination of RP specimen. Overall, 40 (30.5%) of the 131 men who fulfilled the contemporary Epstein criteria for clinically insignificant prostate cancer before RP had pathologically unfavourable disease. Among our patients, no significant preoperative predictor of pathologically unfavourable disease was identified using uni‐ and multivariate analyses.

CONCLUSION

Our results showed that a significant proportion of contemporary Korean patients who meet all the conditions of the contemporary Epstein criteria for prediction of clinically insignificant prostate cancer might actually harbour prostate cancer with unfavourable pathological features. Such findings should be considered when treatment options are contemplated based upon the Epstein criteria among Asian patients.