BACKGROUND & AIMS: :The Authors report their personal experience relating to diagnostic screening for prostatic carcinoma using serum assays for specific markers of this tumour: prostatic acid phosphatase (PAP) and prostatic specific antigen (PSA). They underline the importance of high serum values of these substances, especially in tumors in an advanced state, and point out that these markers can play a role both in the diagnosis and in the follow-up of prostatic carcinoma.

背景与目标： : 作者报告了他们的个人经验，他们使用血清检测该肿瘤的特定标志物 (前列腺酸性磷酸酶 (PAP) 和前列腺特异性抗原 (PSA)) 进行前列腺癌诊断筛查。他们强调了这些物质的高血清值的重要性，尤其是在晚期肿瘤中，并指出这些标志物可以在前列腺癌的诊断和随访中发挥作用。

BACKGROUND & AIMS: :In recent years, there has been a marked increase in the number of approved therapies that increase survival of patients with castration-resistant prostate cancer. Current treatment guidelines provide therapeutic management recommendations, but these are primarily based on clinical factors such as performance status or site of metastasis (bone vs. visceral), and not on underlying molecular or cellular features of disease that may predict response. The ability to tailor treatment based on molecular or cellular features of disease could potentially reduce the occurrence of unnecessary side effects and ineffective treatments, and thereby reduce both direct and indirect medical costs. As such, it is important to identify and validate new prognostic and predictive molecular biomarkers that can be used to direct cancer treatment. This review will focus on existing and potential biomarkers in the context of castration-resistant prostate cancer management and discuss the need for continued discovery and validation of new biomarkers and biomarker panels for prostate cancer.

背景与目标： : 近年来，增加去势抵抗性前列腺癌患者生存率的批准疗法数量显着增加。当前的治疗指南提供了治疗管理建议，但这些建议主要基于临床因素，例如表现状态或转移部位 (骨与内脏)，而不是基于可能预测反应的疾病的潜在分子或细胞特征。根据疾病的分子或细胞特征定制治疗的能力可能会减少不必要的副作用和无效治疗的发生，从而减少直接和间接的医疗成本。因此，识别和验证可用于指导癌症治疗的新的预后和预测性分子生物标志物非常重要。这篇综述将重点关注去势抵抗性前列腺癌管理背景下的现有和潜在生物标志物，并讨论继续发现和验证前列腺癌新生物标志物和生物标志物的必要性。

BACKGROUND & AIMS: BACKGROUND:Major advances in our understanding of the underlying biology of prostate cancer have helped to herald a new era in the treatment of castration-resistant prostate cancer (CRPC), with 5 new agents having shown a survival advantage in the last 3 years and an impressive number of promising novel agents now entering the clinic. CONTENT:We discuss the challenges facing drug development for CRPC and strategies to meet these challenges, with a focus not only on the development of predictive and intermediate endpoint biomarkers, but also on novel hypothesis-testing, biomarker-driven clinical trial designs. SUMMARY:With several promising agents now entering the clinic, there is increasing pressure to rethink drug development for CRPC to ensure that novel agents are appropriately evaluated and that patients and resources are appropriately allocated. We envision that biomarker-driven, reiterative clinical trials will have a major impact on CRPC treatment through the testing of robust scientific hypotheses with rationally designed drugs and drug combinations administered to selected patients.

背景与目标：

BACKGROUND & AIMS: :Prostatic magnetic resonance images of 22 male volunteers less than 30 years old and with no known genito-urinary tract disease were obtained at 1.5 T. Normal anatomical features of the prostate were studied with spin-echo techniques. Different zones of the normal gland are shown by T2-weighted images: the anterior fibromuscular fascia, the central prostate, the peripheral prostate and the periurethral zone can be differentiated. The normal prostate gland is shown on T1-weighted images as a homogeneous appearance. It is important to recognize the normal zonal anatomy of the prostate since prostatic disorders arise in different anatomical zones.

背景与目标： : 在1.5 T时获得了22名30岁以下且没有已知生殖泌尿道疾病的男性志愿者的前列腺磁共振图像。使用自旋回波技术研究了前列腺的正常解剖特征。T2-weighted图像显示了正常腺体的不同区域: 可以区分前纤维肌筋膜，中央前列腺，外周前列腺和尿道周围区域。正常前列腺在T1-weighted图像上显示为均匀外观。重要的是要认识到前列腺的正常区域解剖结构，因为前列腺疾病发生在不同的解剖区域。

BACKGROUND & AIMS: :Terminally differentiated rhabdomyoblasts are common after or during therapy for rhabdomyosarcoma (RMS). Case reports have suggested that their presence after therapy does not indicate a poor prognosis, but significance and relationship to outcome has not been systematically studied. Management of patients with this finding can cause confusion. Slides and pathology reports from 44 patients with bladder/prostate RMS treated on Fourth Intergroup Rhabdomyosarcoma Study were examined by a pathologist experienced in RMS, and findings compared with institutional reports. Details regarding patient characteristics, outcome, and management were reviewed. Outcome of patients with various pathologic findings was assessed. One of 10 patients with only mature rhabdomyoblasts at their last procedure recurred, versus 4 of 17 patients with viable tumor and 2 of 17 patients with no viable tumor and no rhabdomyoblasts. Sixteen of 42 cases reviewed had results differing from our review. Mature rhabdomyoblasts are a discrete entity which may not be predictive of recurrence, but should be evaluated by a pathologist experienced with this entity. The presence of mature rhabdomyoblasts at the end of therapy for bladder/prostate RMS does not justify radical surgery. Sequential biopsies are subject to sampling error and should only be performed in the context of protocol-directed therapy to avoid unnecessary radical surgeries.

背景与目标： : 在横纹肌肉瘤 (RMS) 治疗后或治疗期间，晚期分化的横纹肌母细胞很常见。病例报告表明，治疗后它们的存在并不表明预后不良，但尚未系统地研究其意义和与结果的关系。对有此发现的患者进行管理可能会引起混乱。由RMS经验丰富的病理学家检查了在第四组间横纹肌肉瘤研究中接受治疗的44例膀胱/前列腺RMS患者的载玻片和病理报告，并将发现与机构报告进行了比较。回顾了有关患者特征，结果和管理的详细信息。评估了具有各种病理发现的患者的结局。最后一次手术中只有成熟横纹肌母细胞的10例患者中有1例复发，而17例有存活肿瘤的患者中有4例复发，而17例没有存活肿瘤且没有横纹肌母细胞的患者中有2例复发。在审查的42例病例中，有16例的结果与我们的审查不同。成熟的横纹肌母细胞是一个离散的实体，可能无法预测复发，但应由具有该实体经验的病理学家进行评估。膀胱/前列腺RMS治疗结束时存在成熟的横纹肌母细胞并不能证明根治性手术是合理的。顺序活检可能会出现采样误差，并且只能在方案指导的治疗中进行，以避免不必要的根治性手术。

BACKGROUND & AIMS: BACKGROUND:In a large number of studies a positive family history is documented as one of the main risk factors for the development of prostate cancer. In a US population an association between early-onset prostate cancer among familial patients and a more differentiated tumour was shown. The aim of this study was to compare clinical parameters between sporadic and familial or hereditary patients with an age at diagnosis < or =55 years. MATERIAL AND METHODS:The clinical data of prostate cancer patients with an age at diagnosis < or =55 years and who were recruited between July 1999 and the end of June 2004 to the database "familial prostate cancer in Germany" were analysed. The following data were documented for all patients: PSA at diagnosis, histopathological stage, grading, Gleason score and progression-free survival. RESULTS:The clinical data of 685 patients could be completed: 222 (32.4%) had one first-degree relative with prostate cancer, 48 of whom (7.0%) were hereditary; 463 (67.6%) were sporadic. The median age at diagnosis in the hereditary patients was 51.6 (41-55) years, in the familial patients 51.1 (35-55) years and in the sporadic patients 52.0 (38-55) years. The median follow-up was 24 months in hereditary, 36 months in familial and 35 months in sporadic patients. An initial curative therapy with radical prostatectomy or radiotherapy/brachytherapy was planned in 657/685 (95.9%) of the patients. There were no clear differences regarding PSA at diagnosis, the postoperative parameters (organ-confined disease, lymph node involvement, Gleason score, grading) and the progression-free survival in sporadic and familial or hereditary patients. CONCLUSIONS:Patients with an age at diagnosis < or =55 years have a positive family history more often than all prostate cancer patients in Germany. No association could be shown between pathohistological stage or clinical course and a positive family history in patients with an age at diagnosis < or =55 years.

背景与目标：

BACKGROUND & AIMS: :This paper reevaluates the recently reported excess mortality following transurethral resection of the prostate (TURP) for benign hypertrophy as compared with traditional open resection (OPEN). We studied survival through linkage of hospital discharge data with mortality data for the entire male population of Denmark (1977-85). For a maximum of 10.5 years 38,067 prostatectomy patients were followed. Adjusting for age and health status before surgery, TURP patients were subject to significantly higher levels of mortality than OPEN patients (RR = 1.19, 95% confidence interval (1.15-1.24). The extent to which this difference is attributable to the surgical intervention itself remains an open question. The two groups of patients are quite different with regard to age and preoperative health status, and available data may not be sufficient to control such differences through statistical analysis. On the other hand, the difference in mortality persisted over calendar time, even during periods when the pattern of utilization for the two procedures changed significantly (constant RR = 1.19, adjusting for age and comorbidity). The most important causes of death among Danish TURP patients differ from the causes suggested on the basis of previously reported Canadian data. The current evidence is thus ambiguous with regard to hypothetical biologic mechanisms behind the excess mortality over TURP patients. Further investigations are needed to evaluate the safety and effectiveness of prostate surgery.

背景与目标： : 本文重新评估了最近报道的经尿道前列腺切除术 (TURP) 与传统开腹切除术 (open) 相比，良性肥大的死亡率。我们通过将丹麦 (1977-85) 的整个男性人口的出院数据与死亡率数据联系起来研究了生存率。对38,067名前列腺切除术患者进行了最长10.5年的随访。调整手术前的年龄和健康状况，TURP患者的死亡率明显高于开放患者 (RR = 1.19，95% 置信区间 (1.15-1.24)。这种差异归因于手术干预本身的程度仍然是一个悬而未决的问题。两组患者在年龄和术前健康状况方面存在很大差异，并且可用的数据可能不足以通过统计分析来控制这种差异。另一方面，死亡率的差异在日历期间持续存在，即使在两种程序的使用模式发生显著变化的时期 (恒定RR = 1.19，调整年龄和合并症)。丹麦TURP患者中最重要的死亡原因不同于先前报告的加拿大数据所提出的原因。因此，目前的证据对于TURP患者死亡率过高背后的假想生物学机制是不明确的。需要进一步的研究来评估安全性和前列腺手术的有效性。

BACKGROUND & AIMS: BACKGROUND:Androgen regulation and prostate-specific expression of targeted genes in transgenic mice can be controlled by a small DNA fragment of the probasin (PB) promoter (-426 to +28 base pairs, bp). Although the small PB fragment was sufficient to direct prostate-specific expression, the low levels of transgene expression suggested that important upstream regulatory sequences were missing.

METHODS:To enhance transgene expression, a large fragment of the PB promoter (LPB, -11,500 to +28 bp) was isolated, linked to the bacterial chloramphenicol acetyl transferase (CAT) gene, and microinjected into CD1 mouse oocytes to generate transgenic mouse lines.

RESULTS:As shown by the immunohistochemical studies, CAT gene expression was restricted to the prostatic epithelial cells in a tissue-specific manner. High levels of CAT gene expression were observed in two of the six LPB-CAT transgenic lines. In Line 1, developmental regulation of LPB-CAT was detected early, from 1 to 4 weeks of age, with the activity of CAT increasing from 3 to 40,936 dpm/min/mg protein. Upon sexual maturation and elevated serum androgen levels (7 weeks of age), a further 18-fold rise in CAT activity occurred. Hormone ablation by castration in mature mice dramatically reduced transgene expression, whereas treatment with androgens returned LPB-CAT expression to precastration levels. In contrast, treatment with glucocorticoids had no significant effect on CAT gene expression. Zinc treatment of the castrated animals also increased LPB-CAT expression three- to four-fold in two prostatic lobes.

CONCLUSIONS:This study demonstrates that important regulatory DNA sequences located in the LPB fragment contribute to tissue-specific expression and greatly increase levels of transgene expression induced by androgens and zinc.

背景与目标： 背景 : 转基因小鼠中靶向基因的雄激素调节和前列腺特异性表达可以由probasin (PB) 启动子的小DNA片段 (-426至 + 28个碱基对，bp) 控制。尽管小的PB片段足以指导前列腺特异性表达，但低水平的转基因表达表明重要的上游调控序列缺失。
方法 : 为了增强转基因表达，PB启动子的大片段 (LPB，-分离出11,500至28 bp)，与细菌氯霉素乙酰转移酶 (CAT) 基因连接，并将其微注射到CD1小鼠卵母细胞中，以生成转基因小鼠品系。
结果 : 如免疫组织化学研究所示，CAT基因表达以组织特异性方式限制在前列腺上皮细胞中。在六个LPB-CAT转基因品系中的两个中观察到高水平的CAT基因表达。在第1行中，从1至4周龄早期检测到LPB-CAT的发育调节，CAT的活性从3 dpm/min/mg增加到40,936 dpm/min/mg蛋白。性成熟和血清雄激素水平升高 (7周龄) 后，CAT活性进一步增加了18倍。成熟小鼠中去势的激素消融显着降低了转基因表达，而雄激素治疗使LPB-CAT表达恢复到去势前水平。相反，糖皮质激素治疗对CAT基因表达没有显着影响。Cast割动物的锌治疗还使两个前列腺叶中的LPB-CAT表达增加了三到四倍。
结论 : 这项研究表明，位于LPB片段中的重要调控DNA序列有助于组织特异性表达，并大大提高了雄激素和锌诱导的转基因表达水平。

BACKGROUND & AIMS: BACKGROUND:The majority of patients receive HT after biochemical progression despite primary therapy of prostate cancer with curative intent. It is difficult to differentiate at a low rise in PSA level, e.g.,

BACKGROUND & AIMS: BACKGROUND:The purpose of this study was to determine the distribution of radioiodinated estramustine (RI-EMP) and a radioiodinated antibody against estramustine binding protein (RI-EMBP-AB) in mice. METHODS:RI-EMP and RI-EMBP-AB were injected in male mice intravenously, and the activities of tissue samples were measured 1-31 hr from the injection. Pure iodine-125 (RI) was used as a control. RESULTS:RI-EMP accumulated in the prostate, which contained 2.6% of injected activity (ID) per gram tissue at 7 hr. The liver had an activity of 21.4% ID/g at 1 hr, which decreased as RI-EMP was secreted in bile. The lung contained 2.3% ID/g at 7 hr, and it retained the activity longer than the prostate. RI-EMBP-AB accumulated in the prostate: The activity was 2.9% ID/g at 7 hr. The gallbladder contained 6.5% ID/g at 7 hr. CONCLUSIONS:Due to its cytotoxic and radiosensitizing properties, RI-EMP can possibly be used for treating prostate cancer and other tumors.

背景与目标：

BACKGROUND & AIMS: Since loss of heterozygosity on 8p22-p21.3 has been found frequently in prostate cancer, the status of a candidate tumor suppressor gene named PRLTS gene, recently cloned from the same region in some human malignancies, was examined in the present study. DNAs were isolated from 69 Japanese prostate cancer patients (37 localized and 32 cancer-death cases). Loss of heterozygosity at this gene locus was observed in 15 of 36 (42%) localized prostate cancer patients and 22 of 32 (69%) cancer-death patients. One cancer-death patient had a missense mutation, ACG-->ATG (Thr-->Met) at codon 64 in metastatic tumor tissues of pelvic lymph node and liver, and these tissues showed loss of the homologous allele, indicating that "two-hit" mutation of the PRLTS gene had occurred in this case. The others did not show any mutation, regardless of the presence or absence of loss of heterozygosity. Although loss of heterozygosity at the PRLTS gene locus is a relatively common abnormality, mutation of this gene is rare in prostate cancer.

背景与目标： 由于在前列腺癌中经常发现8p22-p21.3上杂合性的丧失，因此在本研究中检查了最近从某些人类恶性肿瘤的同一区域克隆的候选肿瘤抑制基因PRLTS基因的状态。从69例日本前列腺癌患者 (37例局部和32例癌症死亡病例) 中分离出dna。在36名 (42% 名) 局部前列腺癌患者中的15名和32名 (69% 名) 癌症死亡患者中的22名中观察到该基因位点的杂合性丧失。一名癌症死亡患者在盆腔淋巴结和肝脏的转移性肿瘤组织中出现错义突变，ACG -->ATG (Thr -->Met) 密码子64，这些组织显示同源等位基因丢失，表明在这种情况下发生了PRLTS基因的 “两次命中” 突变。其他人没有显示任何突变，无论是否存在杂合性丧失。尽管PRLTS基因位点杂合性缺失是一种相对常见的异常，但该基因的突变在前列腺癌中很少见。

BACKGROUND & AIMS: :Intraductal carcinoma of the prostate is a marker of aggressive disease. However, intraductal carcinoma exists on a morphologic continuum with high-grade prostatic intraepithelial neoplasia (PIN) and distinguishing intraductal carcinoma from PIN is a common diagnostic dilemma with significant clinical implications. We evaluated whether immunostains for PTEN and ERG can sensitively identify intraductal carcinoma and accurately distinguish it from high-grade PIN. A combined immunostain for PTEN, ERG, p63 and CK903 was developed and validated. Radical prostatectomy specimens with lesions meeting criteria for intraductal carcinoma (n=45), intraductal cribriform proliferations falling short of intraductal carcinoma (n=15), and PIN lesions (n=39) were retrospectively identified and assessed for PTEN and ERG. Cytoplasmic PTEN loss was identified in 84% (38/45) of the intraductal carcinoma and 100% (15/15) of intraductal cribriform proliferation cases. In contrast, cytoplasmic PTEN loss was never observed in PIN (0/39; P<0.0001). Of the 53 cases of intraductal carcinoma or intraductal cribriform proliferation with cytoplasmic PTEN loss, it was homogeneously lost in 42 cases (79%). Weak, focal nuclear positivity for PTEN was retained in 31 of these 42 cases (74%). ERG expression was identified in 58% (26/45) of intraductal carcinoma and 67% (10/15) of intraductal cribriform proliferations compared with 13% (5/39) of PIN. Concordance between the PTEN/ERG status of the intraductal carcinoma lesions and the concurrent invasive carcinoma was high (>95% and P<0.0001 for each), and substantially less for PIN and the concurrent invasive tumor (83% for PTEN and 67% for ERG; P=NS for each). Cytoplasmic PTEN loss occurs in the majority of intraductal carcinoma and intraductal cribriform proliferation cases. Cytoplasmic PTEN loss was never observed in PIN (100% specificity). Our study identifies PTEN loss as a potentially useful marker to distinguish intraductal carcinoma from PIN and provides a plausible molecular explanation for why intraductal carcinoma is associated with poor prognosis.

背景与目标： : 前列腺导管内癌是侵袭性疾病的标志。然而，导管内癌存在于高度前列腺上皮内瘤变 (PIN) 的形态连续体上，将导管内癌与PIN区分开是一个常见的诊断难题，具有重要的临床意义。我们评估了PTEN和ERG的免疫染色是否可以敏感地识别导管内癌并将其与高级别PIN区分开。开发并验证了PTEN，ERG，p63和CK903的联合免疫染色。回顾性鉴定了符合导管内癌 (n = 45)，导管内筛状增生低于导管内癌 (n = 15) 和PIN病变 (n = 39) 的前列腺癌根治术标本，并评估了PTEN和ERG。在导管内癌的84% (38/45) 和导管内筛状增殖病例的100% (15/15) 中发现了细胞质PTEN丢失。相反，在PIN中从未观察到细胞质PTEN丢失 (0/39; P<0.0001)。53例导管内癌或导管内筛状增生伴细胞质PTEN丢失，42例 (79%) 均匀丢失。在这42例中，有31例 (74% 例) 保留了PTEN的弱局灶性核阳性。与PIN的13% (5/39) 相比，在导管内癌的58% (26/45) 和导管内筛状增生的67% (10/15) 中鉴定了ERG表达。导管内癌病变与并发浸润性癌的PTEN/ERG状态之间的一致性较高 (每个均> 95% 且P<0.0001)，而PIN与并发浸润性肿瘤的一致性较小 (PTEN 83%，ERG 67%; P = NS)。细胞质PTEN丢失发生在大多数导管内癌和导管内筛状增生病例中。在PIN中从未观察到细胞质PTEN丢失 (100% 特异性)。我们的研究确定PTEN丢失是区分导管内癌和PIN的潜在有用标记，并为为什么导管内癌与不良预后相关提供了合理的分子解释。

BACKGROUND & AIMS: Importance:Prostate cancer is the most common cancer diagnosis made in men with more than 160 000 new cases each year in the United States. Although it often has an indolent course, prostate cancer remains the third-leading cause of cancer death in men. Observations:When prostate cancer is suspected, tissue biopsy remains the standard of care for diagnosis. However, the identification and characterization of the disease have become increasingly precise through improved risk stratification and advances in magnetic resonance and functional imaging, as well as from the emergence of biomarkers. Multiple management options now exist for men diagnosed with prostate cancer. Active surveillance (the serial monitoring for disease progression with the intent to cure) appears to be safe and has become the preferred approach for men with less-aggressive prostate cancer, particularly those with a prostate-specific antigen level of less than 10 ng/mL and Gleason score 3 + 3 tumors. Surgery and radiation continue to be curative treatments for localized disease but have adverse effects such as urinary symptoms and sexual dysfunction that can negatively affect quality of life. For metastatic disease, chemotherapy as initial treatment now appears to extend survival compared with androgen deprivation therapy alone. New vaccines, hormonal therapeutics, and bone-targeting agents have demonstrated efficacy in men with metastatic prostate cancer resistant to traditional hormonal therapy. Conclusions and Relevance:Advances in the diagnosis and treatment of prostate cancer have improved the ability to stratify patients by risk and allowed clinicians to recommend therapy based on cancer prognosis and patient preference. Initial treatment with chemotherapy can improve survival compared with androgen deprivation therapy. Abiraterone, enzalutamide, and other agents can improve outcomes in men with metastatic prostate cancer resistant to traditional hormonal therapy.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:Monocarboxylate transporter 2 (MCT2) is a transmembrane protein involved in the transport of monocarboxylates such as pyruvate and lactate. In a previous study we described overexpression of MCT2 in prostate carcinoma raising the hypothesis of using MCT2 as a possible biomarker in prostate cancer. With the present study we aimed to compare the pattern of expression of MCT2 and alpha-methylacyl-CoA racemase (AMACR), in prostate carcinoma, PIN lesions, non-neoplastic prostate tissue, and normal prostate and compare their sensitivity and specificity. Also, we wanted to evaluate the value of using MCT2 in combination with AMACR and the negative markers 34βE12 or p63 to detect prostate cancer. METHODS:A total of 349 cases, including prostate carcinoma, non-neoplastic prostate tissue and PIN lesions, from radical prostatectomies were examined by immunohistochemistry for AMACR, MCT2, p63, and 34βE12, using tissue microarrays (TMAs). Normal prostate from radical cystoprostatectomy was also studied. RESULTS:Our study revealed that MCT2, similarly to AMACR, was consistently expressed in prostate cancer regardless of the Gleason score. In combination with AMACR and p63 or 34βE12, MCT2 helped to improve the diagnosis of prostate carcinoma. Also, overexpression of MCT2 as well as AMACR in PIN lesions may indicate the involvement of these two proteins in prostate cancer initiation. CONCLUSIONS:We provided evidence for the presence of MCT2 in prostate cancer, selectively labeling malignant glands. Importantly, assessment of MCT2 together with AMACR, along with the negative markers, highly increases the accuracy in prostate cancer diagnosis.

背景与目标：

BACKGROUND & AIMS: :A total of 1200 patients had undergone I-125 prostate brachytherapy (BXT) in our centre. We present prospective outcome data for the first 400 treated patients. Data were analysed from a prospective database of 400 consecutive patients treated with permanent prostate BXT between March 1999 and December 2003. Patients were stratified into low (49%), intermediate (36%) and high (15%) risk as defined by the Memorial Sloan-Kettering Prognostic Index. Patients received 145 Gy BXT alone (41%), BXT with 3 months neoadjuvant androgen deprivation (NAAD) (39%), 45 Gy external beam radiotherapy (EBRT) with 110 Gy BXT (3%) or a combination of NAAD, 45 Gy EBRT and 110 Gy BXT (17%). Biochemical relapse-free survival (bRFS) and prostate-specific antigen (PSA) nadirs were analysed for treatment received in each risk group. Median follow-up was 54 months (range, 38-96 months) with a mean patient age of 63 years. Prostate cancer-specific survival was 99.5%. Twenty-eight patients (7%) experienced biochemical failure according to the 2006 Radiation Therapy Oncology Group-American Society for Therapeutic Radiology and Oncology (RTOG-ASTRO) Phoenix Consensus definition (PSA nadir plus >or=2 ng ml(-1)): nine low-, fourteen intermediate- and five high-risk patients. When stratified by treatment group for low-, intermediate- and high-risk groups, the 5-year actuarial bRFS was 98, 89 and 100% for BXT; 91, 87 and 88% for NAAD and BXT; 100, 80 and 100% for EBRT and BXT; and 100, 92 and 88% for NAAD, EBRT and BXT, respectively. Overall 4- and 5-year PSA