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 ml⁻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<0.01 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⁻¹ 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.     

F/T PSA在TPSA4～10μg/L之间的前列腺增生和前列腺癌鉴别诊断中的意义

目的：探讨总前列腺特异性抗原（TPSA）与游离前列腺特异性抗原（FPSA）的比值（F／TPSA）在TPSA4～10μg／L之间的良性前列腺增生（BPH）和前列腺癌（PC）中鉴别诊断的意义。方法：采用放免法对281例病人的TPSA和FPSA进行测定，并计算F／TPSA，其中TPSA在4～10μg／L的PC和BPH病人分别是10例和51例。结果：PC组和BPH组的TPSA分别是6．22μg／L和6．04μg／L，两组相比差异不显著（P＞0．05）；而F／TPSA比值分别是0．11和0．21，两组相比差异显著（P〈0．01）。当F／TPSA为0．15～0．20时，诊断的敏感性和特异性分别是70％～90％和88％～67％。结论：F／TPSA有助于鉴别TPSA在4～10μg／L之间的BPH和PC，具有较高的敏感性和特异性，可以减少不必要的活检，是一种较好的鉴别BPH和PC的方法。     

Focal Therapy in Prostate Cancer: International Multidisciplinary Consensus on Trial Design

Background

Focal therapy has been introduced for the treatment of localised prostate cancer (PCa). To provide the necessary data for consistent assessment, all focal therapy trials should be performed according to uniform, systematic pre- and post-treatment evaluation with well-defined end points and strict inclusion and exclusion criteria.

Objective

To obtain consensus on trial design for focal therapy in PCa.

Design, setting, and participants

A four-staged consensus project based on a modified Delphi process was conducted in which 48 experts in focal therapy of PCa participated. According to this formal consensus-building method, participants were asked to fill out an iterative sequence of questionnaires to collect data on trial design. Subsequently, a consensus meeting was held in which 13 panellists discussed acquired data, clarified the results, and defined the conclusions.

Outcome measurements and statistical analysis

A multidisciplinary board from oncologic centres worldwide reached consensus on patient selection, pretreatment assessment, evaluation of outcome, and follow-up.

Results and limitations

Inclusion criteria for candidates in focal therapy trials are patients with prostate-specific antigen <15 ng/ml, clinical stage T1c–T2a, Gleason score 3 + 3 or 3 + 4, life expectancy of >10 yr, and any prostate volume. The optimal biopsy strategy includes transrectal ultrasound-guided biopsies to be taken between 6 mo and 12 mo after treatment. The primary objective should be focal ablation of clinically significant disease with negative biopsies at 12 mo after treatment as the primary end point.

Conclusions

This consensus report provides a standard for designing a feasible focal therapy trial.

Patient summary

A variety of ablative technologies have been introduced and applied in a focal manner for the treatment of prostate cancer (PCa). In this consensus report, an international panel of experts in the field of PCa determined pre- and post-treatment work-up for focal therapy research.     

Insignificant Prostate Cancer and Active Surveillance: From Definition to Clinical Implications

Context

Due to early detection strategies, prostate cancer is diagnosed early in its natural history. It remains unclear whether all patients diagnosed with prostate cancer warrant radical treatment or may benefit from delayed intervention following active surveillance.

Objective

A systematic review of active surveillance protocols to investigate the inclusion criteria for active surveillance and the outcome of treatment.

Evidence acquisition

Medline was searched using the following terms: prostate cancer, active surveillance and expectant management for dates up to October 2008. Further studies were chosen on the basis of manual searches of reference lists and review papers.

Evidence synthesis

Numerous studies on active surveillance were identified. The recent inclusion criteria of the studies are rather similar. Keeping the short follow-up of all studies in mind, the majority of men stay on active surveillance, and the percentage of patients receiving active treatment is as high as 35% of all patients. Once a patients requires active treatment, most patients still present with curable prostate cancer. Furthermore, only few deaths due to prostate cancer have occurred.

Conclusions

Active surveillance is an alternative option to immediate treatment of men with presumed insignificant prostate cancer. It seems that criteria used to identify men with low-risk prostate cancer are rather similar, and immediate treatment of men meeting these criteria may result in an unnecessary number of treatments in these highly selected patients. Data from randomised trials comparing active surveillance and active treatment will provide additional insight into outcome and follow-up strategies.     

前列腺特异抗原水平为4～10 μg/L的前列腺癌诊断对策

目的评价现有的前列腺特异抗原(PSA)修正方法对PSA在4~10μg/L的前列腺癌的诊断价值。方法选取经直肠B超引导下前列腺多点穿刺活检血PSA测值在4~10μg/L的86例患者,分析其PSAD、PSATZ、F/T比值及PSA修正方法各域值范围内,对前列腺癌诊断的敏感度及特异度。结果PSAD、PSATZ和F/T比值在各域值范围内,对诊断前列腺癌的敏感度均未超过50%,将PSAD域值设为0.18μg/L/cc时有较高的敏感度,F/T比值设为0.25时有较高的特异度,而PSATZ在各域值范围内对前列腺癌的敏感度及特异度无显著优势。结论PSA修正方法不能有效提高国人血PSA4~10μg/L的前列腺癌检出率;当PSAD超过0.18μg/L应建议患者作前列腺穿刺活检,F/T比值小于0.25则应增加穿刺点。     

Prostate-Specific Antigen Velocity for Early Detection of Prostate Cancer: Result from a Large,Representative, Population-based Cohort

Background

It has been suggested that changes in prostate-specific antigen (PSA) over time (ie, PSA velocity [PSAV]) aid prostate cancer detection. Some guidelines do incorporate PSAV cut points as an indication for biopsy.

Objective

To evaluate whether PSAV enhances prediction of biopsy outcome in a large, representative, population-based cohort.

Design, setting, and participants

There were 2742 screening-arm participants with PSA <3 ng/ml at initial screening in the European Randomized Study of Screening for Prostate Cancer in Rotterdam, Netherlands, or Göteborg, Sweden, and who were subsequently biopsied during rounds 2–6 due to elevated PSA.

Measurements

Total, free, and intact PSA and human kallikrein 2 were measured for 1–6 screening rounds at intervals of 2 or 4 yr. We created logistic regression models to predict prostate cancer based on age and PSA, with or without free-to-total PSA ratio (%fPSA). PSAV was added to each model and any enhancement in predictive accuracy assessed by area under the curve (AUC).

Results and limitations

PSAV led to small enhancements in predictive accuracy (AUC of 0.569 vs 0.531; 0.626 vs 0.609 if %fPSA was included), although not for high-grade disease. The enhancement depended on modeling a nonlinear relationship between PSAV and cancer. There was no benefit if we excluded men with higher velocities, which were associated with lower risk. These results apply to men in a screening program with elevated PSA; men with prior negative biopsy were not evaluated in this study.

Conclusions

In men with PSA of about ≥3 ng/ml, we found little justification for formal calculation of PSAV or for use of PSAV cut points to determine biopsy. Informal assessment of PSAV will likely aid clinical judgment, such as a sudden rise in PSA suggesting prostatitis, which could be further evaluated before biopsy.     

Prostate carcinoma in liver transplant recipients: Think about it!

ObjectivesTo analyze retrospectively our series of prostate cancer (PC) in liver transplant recipients (LTRs) given an increase in frequency in an aging recipient population when no studies were reported in literature.MethodsWe conducted a retrospective analysis of LTRs in a single institution. After liver transplantation, all patients were followed up in our institution with an annual digital rectal examination by a urologist and prostate-specific antigen measurement after the age of 50 years.ResultsBetween 1995 and 2013, among 361 male LTRs, 12 (3.3%) had PC. The mean age at diagnosis was 62.8 years, and the time lapse between liver transplantation and diagnosis was 55.7 months. The median initial prostate-specific antigen level was 7.4 ng/ml. In total, 9 patients underwent radical prostatectomy. Histological findings showed 5 pT2 and 4 pT3 cancers. A patient showed invasion in the lymph nodes and was treated with hormonotherapy. Another patient had a biochemical recurrence at 10 months and underwent salvage radiotherapy. After 32.9 months of follow-up, no other patients showed any recurrence. Moreover, 1 patient was treated by radiohormonotherapy for high-risk PC with no recurrence at 65 months, and 1 patient was treated with high-intensity focal ultrasound. There was 1 patient with metastatic disease who received hormonotherapy and died 5 months after diagnosis.ConclusionOur incidence of intermediate- and high-risk PCs in LTRs was slightly higher than in the general population. In the absence of any recommendations, individual screening should be proposed to LTRs. The treatment of choice remains surgery or radiotherapy to ensure a good carcinologic control.     

Transperineal prostate biopsy: a review of technique

As the second most diagnosed cancer worldwide, prostate cancer is confirmed via tissue biopsy. Given the large number of prostate biopsies performed each year, the technique should be as accurate and safe as possible for the patient’s well-being. Transrectal ultrasound guided prostate biopsy (TRUS-biopsy) is most offered worldwide. Transperineal biopsy (TPP-biopsy), on the other hand, has been gaining popularity due to its superior sensitivity and lower rate of sepsis. This article offers a review of the brachytherapy grid technique used to perform a TPP-biopsy, as well as a discussion of possible variations in the procedure. TPP-biopsy is typically performed under general anaesthesia with patient in lithotomy. Through the perineum, cores of tissue are taken systematically, with or without targeting, under US guidance. Different fusion techniques (cognition, MRI-US fusion software, MRI in-bore) can be used to target pre-identified lesions on MRI. The sampling can be done either by free hand or using a brachytherapy grid. Robotic assisted prostate biopsy is also available on the market as an alternative. In recent years, there has been accumulating evidence showing that it is safe and feasible to perform TPPB under local anaesthesia. This may improve the uptake of TPPB as the preferred biopsy technique for prostate cancer.     

血清PSA、f-PSAR与前列腺重量相关性研究

目的：探讨前列腺增生症（ＢＰＨ）人群中前列腺重量（ＰＷ）与血清前列划抗原（ＰＳＡ）、血清液离前腺特异抗原百分率（ｆ－ＰＳＡＲ）的相关性,方法：术前测定１４６例ＢＰＨ患者血清ＰＳＡ〈其中５１例测定了血清游离前列腺特异抗原值,对血清ＰＳＡ〉１０μｇ／Ｌ患者行前列腺穿刺活检以排除前列腺癌,术后对前列腺手术标本进行称重,并按〈２５ｇ,２５￣５０ｇ、５１￣７５ｇ、〉７５ｇ分为４组,均经病理证实为ＢＰＨ,对忾     

Age-Specific Risk of Incident Prostate Cancer and Risk of Death from Prostate Cancer Defined by the Number of Affected Family Members

Background

The thorough assessment of familial prostate cancer (PCa) risk is as important as ever to provide a basis for clinical counselling and screening recommendations.

Objective

Our aim was to determine the age-specific risks of PCa and the risk of death from PCa according to the number and the age of affected first-degree relatives.

Design, setting, and participants

The nationwide Swedish Family-Cancer Database includes a record of >11.8 million individuals and their cancers from 1958 to 2006. All men from the database with identified parents (>3.9 million individuals) were followed between 1961 and 2006. The study included 26 651 PCa patients, of whom 5623 were familial.

Measurements

The age-specific hazard ratios (HRs) of PCa and the HRs of death from PCa were calculated according to the number and age of affected fathers and brothers.

Results and limitations

The HRs of PCa diagnosis increased with the number of affected relatives and decreased with increasing age. The highest HRs were observed for men <65 yr of age with three affected brothers (HR: approximately 23) and the lowest for men between 65 and 74 yr of age with an affected father (HR: approximately 1.8). The HRs increased with decreasing paternal or fraternal diagnostic age. The pattern of the risk of death from familial PCa was similar to the incidence data.

Conclusions

The present results should guide clinical counselling and demonstrate the vast increases in risk when multiple first-degree relatives are affected.     

保留神经血管束的耻骨后前列腺癌根治术的疗效观察

目的：小结开展保留神经血管束的耻骨后前列腺癌根治术（RRP）的经验和教训。方法：对40例穿刺活检证实的前列腺癌患者行RRP，术前采用新辅助治疗，术中采用保护尿道膜部括约肌和前列腺侧旁神经血管束，并在重建膀胱颈部粘膜充分外翻后的后壁行折叠缝合1针。间断、无张力行残留尿道和外翻的膀胱颈缝合。结果：经3～78个月随访，全部患者排尿通畅，无肿瘤复发；除2例发生轻度尿失禁外，余38例在6个月内均恢复尿控能力。结论：充分做好耻骨后前列腺癌根治术前的准备工作，有利于手术操作；术中保护好尿道膜部括约肌和前列腺侧旁神经血管束，在充分外翻膀胱粘膜的重建膀胱颈后壁折叠缝合，能减少前列腺癌根治术后尿失禁的发生。     

Early Detection of Prostate Cancer: European Association of Urology Recommendation

Background

The recommendations and the updated EAU guidelines consider early detection of PCa with the purpose of reducing PCa-related mortality and the development of advanced or metastatic disease.

Objective

This paper presents the recommendations of the European Association of Urology (EAU) for early detection of prostate cancer (PCa) in men without evidence of PCa-related symptoms.

Evidence acquisition

The working panel conducted a systematic literature review and meta-analysis of prospective and retrospective clinical studies on baseline prostate-specific antigen (PSA) and early detection of PCa and on PCa screening published between 1990 and 2013 using Cochrane Reviews, Embase, and Medline search strategies.

Evidence synthesis

The level of evidence and grade of recommendation were analysed according to the principles of evidence-based medicine. The current strategy of the EAU recommends that (1) early detection of PCa reduces PCa-related mortality; (2) early detection of PCa reduces the risk of being diagnosed and developing advanced and metastatic PCa; (3) a baseline serum PSA level should be obtained at 40–45 yr of age; (4) intervals for early detection of PCa should be adapted to the baseline PSA serum concentration; (5) early detection should be offered to men with a life expectancy ≥10 yr; and (6) in the future, multivariable clinical risk-prediction tools need to be integrated into the decision-making process.

Conclusions

A baseline serum PSA should be offered to all men 40–45 yr of age to initiate a risk-adapted follow-up approach with the purpose of reducing PCa mortality and the incidence of advanced and metastatic PCa. In the future, the development and application of multivariable risk-prediction tools will be necessary to prevent over diagnosis and over treatment.     

Prostate Abscess: A Rare Complication of Brachytherapy for Prostate Cancer

Brachytherapy involves the therapeutic implantation of a radio-active seed source into, or close to, prostate cancer.We report the rare case of a 76-year-old man who presented with a prostate abscess after months of intractable pelvic pain following prostate cancer treatment with iodine- 125 brachytherapy.Despite multiple investigations, the diagnosis was made only once the abscess discharged exudate per-urethra.     

Prostate cancer in the elderly patient

Although malignant tumours occur at all ages, cancer disproportionately strikes individuals in the age group 65 years and older. The increasing statistical life expectancy of men together with the introduction of prostate specific antigen (PSA) as a screening tool have both contributed to a rising number of elderly men with a diagnosis of prostate cancer. Age is generally considered to be a key prognostic factor in terms of therapeutic decision making, perhaps as important as PSA level and Gleason score. Even in men over 70 years, treatment without curative intent may deprive frail patients of years of life. When considering local treatment, strong consideration should be given to radical surgery. Modern radical prostatectomy is associated with low perioperative morbidity, excellent clinical outcomes as well as long term disease control. Besides, overdiagnosis has led to the concept of expectant management for screening-detected small-volume, low grade disease, with intention of providing therapy for those men experiencing disease progression.