Biochemical markers of bone turnover in patients with localized and metastasized prostate cancer

OBJECTIVE: To evaluate and compare the value of several markers of bone turnover in different stages of prostate cancer, as bone metastases are a common feature in this disease, and for assessing bone metastases both bone formation and bone resorption markers are diagnostic. PATIENTS AND METHODS: The prospective study included 219 men, i.e. 129 undergoing radical retropubic prostatectomy (RRP) and 25 with bone metastases due to prostate cancer, and 65 with benign urological disorders who served as controls. Before any treatment the concentrations of alkaline phosphatase (ALP), osteocalcin, serum C-terminal telopeptide of type I collagen (S-CTX) and tartrate-resistant acid phosphatase type 5b (TRACP5b) were determined. RESULTS: Men undergoing RRP were divided into those with lymph node-negative, localized (pT3, 101) and lymph node-positive (28) disease, after histological examination. The controls had the lowest marker levels while patients with bone metastases due to prostate cancer had the highest levels, with significance for ALP, osteocalcin and TRACP5b. Patients with lymph node-positive cancer had significantly high serum levels of TRACP5b and ALP but not for osteocalcin and S-CTX. CONCLUSIONS: Bone turnover markers represent a new diagnostic tool in prostate cancer; the present data show that both bone resorption and bone formation are crucial for detecting bone metastases in prostate cancer. The value of bone turnover markers in high-risk patients should be evaluated in a longitudinal study.     

Serum alkaline phosphatase flare in prostate cancer accompanied by bone metastases and treated with hormonal therapy. TEKK Study Group

To clarify the roles of alkaline phosphatase (ALP) flare in prostate cancer accompanied by bone metastases and treated with hormonal therapy, we evaluated the clinicopathological character, treatment efficacy and outcome for patients with and without ALP flare. We evaluated 60 patients with newly diagnosed prostate cancer accompanied by bone metastases and treated with hormonal therapy, whose response in terms of serum prostate specific antigen (PSA) levels showed a partial response (PR) or better response. The patients were classified into two groups, an ALP flare group (13 cases) and a non-ALP flare group (47 cases). The former showed serum ALP elevation of more than double, and the latter less than double that of pretreatment levels following hormonal therapy. Patient characteristics, PSA response and outcome were compared between the two groups. Extent of disease (EOD) as grade of bone metastasis was significantly higher in the ALP flare group than in the non-flare group (p = 0.0352). Pre-treatment serum PSA levels were also significantly higher in the ALP flare group (p = 0.0010). However, there were no significant differences in pretreatment serum ALP levels. Serum PSA levels were normalized in 37 of the 47 patients (78.7%) in the non-ALP flare group compared with 6 of the 13 (46.2%) in the ALP flare group (p = 0.0211). Moreover, the period until biochemical failure was significantly shorter for the ALP flare than the non-flare group (p = 0.0027). These results suggest that prostate cancer patients with bone metastases in whom ALP flare is observed in response to hormonal therapy tend to have more extensive bone metastases, high pretreatment PSA levels, to be resistant to PSA normalization and more likely to experience biochemical failure.     

Routine bone scans in patients with prostate cancer related to serum prostate-specific antigen and alkaline phosphatase

OBJECTIVE: To evaluate the need for a bone scan as a routine staging procedure in patients with newly diagnosed prostate cancer in relation to serum prostate-specific antigen (PSA) and alkaline phosphatase (ALP) levels, and thus determine whether a reduction of the use of this staging method is possible in patients with a low probability of osseous metastasis. PATIENTS AND METHODS: The results of bone scans were related retrospectively to levels of serum PSA and ALP in 363 patients with prostate cancer newly diagnosed between 1989 and 1997. RESULTS: Of 363 consecutive patients, 111 had a positive bone scan. In 19 of 144 (13%, "missed diagnosis") patients with a PSA level of < 20 ng/mL the bone scan was positive. In 125 patients (49%, "false-positives") with a PSA level of > 20 ng/mL the bone scan was negative. A threshold level of 100 U/L for ALP gave a better balance for the number of "false-positives" and "missed diagnosis". ALP values correlated better with an abnormal bone scan than did PSA levels; ALP levels of > 90 U/L indicated a 60% chance for the presence of bone metastases. CONCLUSION: Patients with newly diagnosed and untreated prostate cancer should undergo bone scintigraphy if there is bone pain or if ALP levels are > 90 U/L. Recent reports discourage the routine use of a bone scan when the serum PSA level is <20 ng/mL. However, the present series suggests there is a greater chance of a positive bone scan in patients with low PSA levels; these findings need further confirmation.     

血清前列腺特异性抗原与碱性磷酸酶测定在判断前列腺癌骨转移中的价值

目的:探讨血清前列腺特异性抗原(PSA)和碱性磷酸酶(ALP)水平与前列腺癌骨转移的关系。方法:回顾性分析96例前列腺癌患者的临床资料(其中29例伴有骨转移,67例不伴有骨转移)及患者血清PSA、ALP水平和骨扫描情况。结果:骨扫描阳性患者的血清PSA和ALP平均浓度均明显高于骨扫描阴性者(P<0.01)。PSA>20μg/L时骨扫描的阳性率明显高于PSA<20μg/L时骨扫描的阳性率(P<0.01)。ALP>90 U/L时骨扫描的阳性率明显高于ALP<90 U/L时骨扫描的阳性率(P<0.01)。结论:伴有骨转移的前列腺癌患者血清PSA和ALP水平均明显高于无骨转移者。当血清PSA>20μg/L和(或)ALP>90 U/L时应行骨扫描检查。     

Pretreatment levels of urinary deoxypyridinoline as a potential marker in patients with prostate cancer with or without bone metastasis

OBJECTIVE: To assess the predictive role of the bone markers alkaline phosphatase (ALP) and urinary deoxypyridinoline (DPD), as indicators of bone turnover, at baseline in patients with prostate cancer. PATIENTS, SUBJECTS AND METHODS: Urinary DPD, serum ALP and prostate-specific antigen (PSA) were evaluated in 23 patients with benign prostatic hyperplasia (BPH), 115 with prostatic carcinoma, of whom 21 had bone metastasis, and in 16 age-matched control subjects. RESULTS: Patients with newly diagnosed prostate cancer and bone metastasis had a higher urinary excretion of DPD, and a higher serum PSA and ALP than had patients with BPH and those with prostate cancer but no metastasis. Receiver operating curve analysis for PSA, ALP and DPD showed a significant discriminating ability for positive and negative bone scans (P = 0.0684). However, from logistic regression of the combinations, only serum ALP was a significant independent predictor of bone metastasis in patients with prostate cancer. CONCLUSION: Serum ALP or urinary DPD are the best predictors of bone metastasis in patients with prostate cancer; further studies with more patients are required.     

血清骨保护素诊断前列腺癌骨转移的初步研究

目的探讨骨保护素（OPG）对前列腺癌骨转移的诊断意义。方法健康男性和前列腺增生患者各30例;对前列腺癌66例患者,分为无骨转移组（M0）36例（局限性前列腺癌30例、淋巴结转移6例）和骨转移组（M1）30例,采用ELISA法测定血清OPG浓度,结合临床资料进行统计学分析。结果M,组血清OPG浓度明显高于其他各组,差异有统计学意义（P〈0．001）。血清OPG与前列腺特异性抗原和碱性磷酸酶浓度呈正相关（r=0．427,0．277;P〈0．001）;与Gleason评分和病理分级呈正相关（r=0．331,0．344;P=0．001）。受试者工作特征（ROC）曲线分析可见,OPG的曲线下面积（AUC）较碱性磷酸酶大,对骨转移的诊断价值高。结论血清OPG对前列腺癌骨转移具有重要诊断价值。     

The potential role of prebiopsy magnetic resonance imaging combined with prostate-specific antigen density in the detection of prostate cancer

Aim:   Two-thirds of patients with a gray-zone prostate-specific antigen (PSA) level undergo unnecessary biopsy. Sensitivity is not yet sufficient to permit the use of modified PSA parameters or magnetic resonance (MR) imaging alone for prostate cancer screening. Thus, we evaluated the combination of MR imaging and PSA density (PSAD) for specificity and sensitivity.
Methods:   During the period April 2004 through March 2006, 185 patients with a PSA level of 4.0–10.0 ng/mL underwent MR imaging and transrectal ultrasonography-guided 8-core biopsy (systemic sextant biopsy of the peripheral zone plus two cores of transition zone). All MR images were interpreted prospectively by two radiologists. An image was considered positive for prostate cancer if any feature indicated a cancerous lesion. Receiver operating characteristic (ROC) curves were used to compare the usefulness of the PSA level, PSAD and PSA transitional zone density (PSATZ) for the detection of prostate cancer.
Results:   Of the 185 patients, 62 had prostate cancer. Sensitivity and specificity of the axial T2-weighted MR imaging findings for cancer detection were 79.0% and 59.4%, respectively. The area under the ROC curve was 0.590 for the PSA level, 0.718 for PSAD and 0.695 for PSATZ. MR imaging findings and PSAD were shown by multivariate analysis to be statistically significant independent predictors of prostate cancer ( P  < 0.001). With a PSAD cut-off value of 0.111, sensitivity was 96.8%, but specificity was 19.5%. Combining MR imaging findings with PSAD increased the specificity to 40% and retained 95% sensitivity.
Conclusion:   MR imaging findings combined with PSAD provide high sensitivity and improve the specificity for the early detection of prostate cancer.     

The value of γ-seminoprotein in combination with prostate specific antigen in detecting prostate cancer

BACKGROUND: The present study was undertaken to investigate the value of gamma-seminoprotein (gamma-Sm) and the gamma-Sm/prostate specific antigen (PSA) ratio in combination with serum PSA in detecting prostate cancer. METHODS: Prostate specific antigen, gamma-Sm and the gamma-Sm/PSA ratio were evaluated in 112 patients with untreated prostate cancer and 90 patients without prostate cancer who had serum PSA and gamma-Sm levels above their respective detection limits. RESULTS: When data for all of the patients were analyzed, serum PSA and gamma-Sm levels were significantly higher and the gamma-Sm/PSA ratio was significantly lower in patients with prostate cancer than patients without prostate cancer. The serum PSA and gamma-Sm levels significantly increased and the gamma-Sm/PSA ratio significantly decreased with advancing clinical stage in patients with prostate cancer. Among the patients with serum PSA levels ranging from 1.8 to 6 ng/mL, the gamma-Sm/PSA ratio was significantly lower (P < 0.05) and gamma-Sm levels were lower (P = 0.054) in the patients with prostate cancer than in those without prostate cancer, but serum PSA levels were not significantly different (P = 0.53). A receiver operating characteristic (ROC) analysis demonstrated that the areas under the ROC curves were 0.54 for PSA, 0.65 for gamma-Sm and 0.69 for the gamma-Sm/PSA ratio for prediction of prostate cancer in the PSA range from 1.8 to 6 ng/mL, although the ROC analysis suggested that the gamma-Sm/PSA ratio does not provide significant advantage over PSA in detecting prostate cancer when all of the patients were analyzed. CONCLUSIONS: These results suggest that the gamma-Sm/PSA ratio and gamma-Sm may facilitate differentiation between patients with and without prostate cancer who have intermediate PSA levels.     

Relationship between Prostate-Specific Antigen, Clinical Stage, and Degree of Bone Metastasis in Patients with Prostate Cancer: Comparison with Prostatic Acid Phosphatase and Alkaline Phosphatase

Background:
The study was designed to examine the relation of the levels of prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), and alkaline phosphatase (ALP) to clinical stage and bone metastasis in prostate cancer patients.
Methods:
Serum PSA, PAP, and ALP levels were evaluated in 272 patients with prostate cancer. The relation of the level of PSA, PAP, and ALP to clinical stage and to degree of bone metastasis were examined by a multiple comparison method using ranks. The superiority of a marker in the rate of detection of bone metastasis was evaluated with receiver operating characteristic (ROC) curves. The correlation coefficients of the order of the extent of bone metastasis with PSA, PAP, and ALP were examined with Spearman's rank order correlation coefficient test.
Results:
The levels of PSA showed significant differences among 8 pairs of clinical stages, in contrast, the levels of PAP showed significant differences among 6 pairs, and the levels of ALP showed significant differences among only 4 pairs. The area under the ROC curves of PSA, PAP, and ALP for revealing bone metastasis was 84.9%, 81.4%, and 77.3%, respectively. The correlation coefficients of the order of extent of disease (EOD) with log (PSA), log (PAP), and log (ALP) were 0.346, 0.394, and 0.618, respectively, and the levels of ALP showed the most significant differences regarding the extent of bone metastasis.
Conclusion:
PSA was the best marker for differentiating clinical stages, but showed limited reliability for stratifying the extent of bone metastasis.     

Preoperative serum acid phosphatase and alkaline phosphatase are not predictors of pathological stage and prostate-specific antigen failure after radical prostatectomy

OBJECTIVE: To examine the utility and prognostic significance of enzymatic serum acid phosphatase (total acid phosphatase, TAP, and prostatic fraction of acid phosphatase, PFAP) and alkaline phosphatase (ALP) for staging, grading and outcome of patients who underwent radical retropubic prostatectomy (RRP) after the introduction of prostate-specific antigen (PSA) testing. PATIENTS AND METHODS: In all, 180 consecutive patients with clinically localized prostate cancer who underwent RRP with standard obturator lymph-node dissection between 1 January 1990 and 31 December 1995 were evaluated. Levels of TAP of > 5.4 IU/L, PFAP of > 1.2 IU/L and ALP of > 120 IU/L were classified as abnormally high. The relationship between abnormally high values and prostate cancer stage, grade and time to recurrence after RRP were calculated. The median follow-up was 86 months (approximately 7 years). RESULTS: Of the 180 patients, information about preoperative TAP, PFAP and ALP were available in 164, 163 and 154, respectively; TAP was abnormal in seven (4%), PFAP in 33 (20%) and ALP in only 13 (8%). None of the markers examined was associated with any variables of disease severity, as measured by pathological stage, Gleason score, perineural invasion, capsular penetration, positive margins, seminal vesicle involvement, and lymph node involvement. Abnormal TAP, PFAP or ALP were not associated with recurrence (P = 0.96, 0.45 and 0.41, respectively). In contrast, a PSA level of > 4 ng/mL was predictive of recurrence after RRP (P < 0.001). In the sample overall, 25 (14%) of the patients had recurrence and only one died from prostate cancer. CONCLUSIONS: Preoperative enzymatic serum TAP, PFAP and ALP levels are not predictors of the severity of disease or PSA disease-free recurrence after RRP.     

Prediction of extraprostatic extension by prostate specific antigen velocity, endorectal MRI, and biopsy Gleason score in clinically localized prostate cancer

Objectives:   To investigate the clinical value of prostate specific antigen velocity (PSAV) in predicting the extraprostatic extension of clinically localized prostate cancer.
Methods:   One hundred and three patients who underwent radical prostatectomy for clinically localized prostate cancer were included in the analysis. The correlation between preoperative parameters, including PSA-based parameters, clinical stage, and histological biopsy findings, and the pathological findings were analyzed. Logistic regression analysis was performed to identify a significant set of independent predictors for the local extent of the disease.
Results:   Sixty-four (60.2%) patients had organ confined prostate cancer and 39 (39.8%) patients had extraprostatic cancer. The biopsy Gleason score, PSA, PSA density, PSA density of the transition zone, and PSAV were significantly higher in the patients with extraprostatic cancer than in those with organ confined cancer. Multivariate logistic regression analysis indicated that the biopsy Gleason score, endorectal magnetic resonance imaging findings, and PSAV were significant predictors of extraprostatic cancer ( P  < 0.01). Probability curves for extraprostatic cancer were generated using these three preoperative parameters.
Conclusions:   The combination of PSAV, endorectal magnetic resonance imaging findings, and biopsy Gleason score can provide additional information for selecting appropriate candidates for radical prostatectomy.     

血清ICTP与TRACP 5b联合检测在乳腺癌骨转移诊断中的价值

目的:探讨溶骨性骨代谢标志物血Ⅰ型胶原交联羧基末端肽(ICTP)和血抗酒石酸酸性磷酸酶5b(TRACP 5b)的检测对诊断乳腺癌骨转移的价值.方法:用ELISA法测定78例乳腺癌患者及40例乳腺良性肿瘤患者血清ICTP和TRACP 5b水平,比较两者水平在骨转移、非骨转移乳腺癌患者及良性乳腺肿瘤患者中的差异及其相关性.结果:乳腺癌骨转移患者血清ICTP和TRACP 5b水平均明显高于无骨转移及乳腺良性肿瘤患者(均P＜0.001),而后两者间无统计学差异(均P＞0.05).乳腺癌患者血清ICTP与TRACP 5b浓度表达呈正相关(r=0.63,P＜0.01).血清ICTP和TRACP诊断乳腺癌骨转移的敏感性、特异性和准确性分别为55.3％,92.5％,81.4％和84.2％,83.8％,83.9％,两者联合检测分别为94.7％,81.3％,85.6％.结论:血清ICTP和TRACP 5b对乳腺癌骨转移的诊断均有重要价值,两者联合检测有助于提高诊断的敏感性和准确性.     

总前列腺特异抗原、游离前列腺特异抗原、碱性磷酸酶和Gleason评分联合检测对前列腺癌骨转移的预测价值

探讨总前列腺特异抗原（tPSA）、游离前列腺特异抗原（fPSA）、碱性磷酸酶（ALP）和Gleason评分与前列腺癌骨转移的关系,评价联合检测对前列腺癌骨转移的预测价值。 方法 回顾性分析2015年1月1日至2018年11月1日在本院临床诊断为良性前列腺增生或前列腺癌的患者（tPSA>10 ng/mL）以及健康体检人群的临床资料,其中前列腺癌患者又经核素骨显像分为骨转移组和非骨转移组;共收集304例完整病例进行分析,其中前列腺癌骨转移组48例(15.8%）,前列腺癌未发生骨转移组116例（38.2%）,良性前列腺增生组56例（18.4%）,健康对照组84例（27.6%）。检测分析所有患者的tPSA 、fPSA、ALP值及Gleason评分。结果 任意两组之间的tPSA、fPSA比较,差异均有统计学意义（P<0.05）;前列腺癌骨转移组的ALP均高于其他三组,差异均有统计学意义（P<0.05）;前列腺癌骨转移组的Gleason评分高于非骨转移组,差异有统计学意义（P<0.05）,对不同分化程度的前列腺癌患者骨转移率进行比较,发现低风险组的骨转移率明显低于中高风险组（P<0.05）。单指标tPSA、fPSA和ALP预测前列腺癌骨转移时,绘制ROC曲线下面积分别为0.664、0.700和0.783,其cut off值分别为57.47 ng/mL、8.44 ng/mL、85.47 U/L;三项指标联合检测时发现tPSA+fPSA+ALP的特异度和阳性预测值分别达86.20%和64.40%,高于单指标和两项指标联合检测。结论 对于怀疑有骨转移的前列腺癌患者,不宜单独用血清前列腺特异性抗原（PSA）浓度来判断骨转移,应联合tPSA、fPSA、ALP三者及Gleason评分对前列腺癌患者发生骨转移风险的预测。     

Changes in tumor markers following cryosurgery of prostate carcinoma

Cryosurgery is performed in poor risk cases of prostate carcinoma with dysuria. This modality has been reported to reduce the metastatic lesion postoperatively in cases of prostate carcinoma accompanied by metastasis and is employed as an adjuvant therapy of prostate carcinoma. However, many cases are already at an advanced stage and have undergone other therapeutic modalities and as a result the exact role of cryosurgery in prostate carcinoma is not clear. The present investigation was undertaken to clarify the effectiveness of cryosurgery in prostate carcinoma. The patients consisted of 21 untreated cases of histologically confirmed prostate carcinoma admitted our hospital during the 5-year period from December, 1982 to December, 1987, in all of whom treatment by cryosurgery alone was indicated, i.e., up stage B, and in whom changes in prostate carcinoma tumor markers, alkaline phosphatase (ALP), acid phosphatase (ACP), prostatic ACP detected enzymatically (PACP), and by radioimmunoassay (PAP), gamma-seminoprotein (gamma-Sm), and prostate specific antigen (PSA) were measured. During the same period, changes in tumor makers in 11 cases of prostate hypertrophy treated by transurethral resection of prostate (TUR-P) were also examined. The tumor markers were measured prior to cryosurgery and 1, 3, 7 and 14 days postoperatively as well as at 1, 3 and 6 months. Following TUR-P, in the cases of prostate hypertrophy, no postoperative changes in ALP, ACP or PACP were observed but there was elevation of PAP and gamma-Sm at day 1 and elevation of PSA until day 3, but none of these were statistically significant differences.(ABSTRACT TRUNCATED AT 250 WORDS)     

MRI of the skeleton in prostate cancer staging

OBJECTIVE: To explore the value of MRI in the detection of bone metastases in newly diagnosed prostate cancer. MATERIAL AND METHODS: MRI examinations of the axial skeleton in 76 patients with newly diagnosed prostate cancer were reviewed, and the relation of these findings to the serum level of prostate specific antigen (PSA) was examined. RESULTS: MRI indicated bone metastases in 26/76 patients (34%) in the entire study group, in 4/24 (17%) with serum PSA <20 ng/ml and in 22/52 (42%) with serum PSA >20 ng/ml. CONCLUSIONS: These results suggest that MRI is a more sensitive indicator of suspected bone metastases than bone scintigraphy in the low range of serum PSA, but less sensitive in the high range. Further studies of MRI and bone scintigraphy in parallel in patients with serum PSA <20 ng/ml are needed to elucidate their relative value in the staging of patients with prostate cancer.     

Serum alkaline phosphatase changes predict survival independent of PSA changes in men with castration-resistant prostate cancer and bone metastasis receiving chemotherapy

ObjectivesThe association of a change in serum alkaline phosphatase (ALP) with overall survival OS in men with metastatic castration-resistant prostate cancer (CRPC) receiving chemotherapy is unknown. We evaluated the association of changes in ALP within 90 days with OS in men with CRPC and bone metastases treated with docetaxel or mitoxantrone in the TAX327 trial.Materials and methodsEligible patients included those with bony metastatic disease, baseline ALP ≥ 120 u/L (upper limit of normal) and ≥2 post-therapy measurements of ALP available. Survival was estimated using the Kaplan-Meier method and prognostic potential of change in ALP was evaluated using Cox proportional hazards regression. Surrogacy was calculated by the Likelihood Reduction Factor.Results601 patients met the eligibility criteria. By day 90, 159 patients had ALP normalization (<120 u/L) and 442 patients did not normalize. Normalization of ALP remained prognostic for OS after adjusting for PSA decline ≥ 30% by day 90 (HR 0.79, 95% CI = 0.65–0.97, P = 0.022). Increase in ALP remained prognostic for OS when adjusting for PSA increase ≥ 50% by day 90 (HR 1.69, 95% CI = 1.33–2.14, P < 0.001). ALP changes did not meet criteria for surrogacy for OS.ConclusionsFor men with CRPC, bone metastasis and high baseline ALP receiving docetaxel or mitoxantrone chemotherapy, normalization of ALP by day 90 was predictive of better survival independent of ≥30% PSA declines. An increase in ALP by day 90 was also predictive of poor survival independent of ≥50% PSA increase. Given the ready availability of ALP, the validation of our data is warranted.     

Pyridinoline cross-linked carboxyterminal telopeptide of type I collagen as a useful marker for monitoring metastatic bone activity in men with prostate cancer

PURPOSE: We investigated the clinical usefulness of measuring the serum concentrations of pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) and carboxyterminal propeptide of type I procollagen (PICP) as markers for monitoring metastatic bone activity in patients with prostate cancer. MATERIALS AND METHODS: Serum levels of ICTP, PICP, alkaline phosphatase, prostatic acid phosphatase and prostate specific antigen (PSA) were analyzed in 104 untreated patients with prostate cancer, including 62 with and 42 without bone metastasis. Serial measurements of ICTP, PICP and PSA were performed during hormonal therapy in 35 of 62 prostate cancer patients with bone metastasis. RESULTS: Serum levels of all markers except prostatic acid phosphatase were significantly higher with than without bone metastasis. The median values of each marker increased according to the extent of bone metastasis. Serial ICTP, PICP and PSA in 19 patients with a partial response or no change in bone scans demonstrated a downward trend after treatment, while in 16 with progression they showed an upward trend after treatment. The rate of detecting bone metastasis and progression using ICTP were highest compared with other markers based on the percent clinical effectiveness and receiver operating characteristic curves. CONCLUSIONS: Measuring serum ICTP may be useful for detecting bone metastasis and prostate cancer progression, and may augment PSA and bone scan monitoring of metastatic bone activity.     

Failing to achieve a nadir prostate-specific antigen after combined androgen blockade: Predictive factors

Objectives:   To determine the optimal cut-off of a nadir prostate-specific antigen (PSA) for prediction of progression within 24 months after combined androgen blockade (CAB) and to analyze predictive factors of failing to achieve the nadir PSA.
Methods:   We retrospectively reviewed the medical records of 343 patients with prostate cancer treated with CAB from 2000 to 2005. We determined the nadir PSA level that predicts progression to hormone refractory prostate cancer (HRPC) at 24 months after CAB. Predictive factors for failing to achieve a determined nadir PSA were analyzed.
Results:   Mean age was 74.0 years. Mean follow up was 42.1 month. Seventy-seven patients experienced progression to HRPC. A nadir PSA of 1.0 ng/mL predicts progression to HRPC at 24 months. Predictive factors for failing to achieve a nadir PSA of 1.0 ng/mL or less include pretreatment PSA, percentage positive biopsy core, Gleason score, serum hemoglobin, stage, and extent of bone metastasis in univariate analysis. Pretreatment PSA (>50 ng/mL) and serum hemoglobin (<12 g/dL) were significant factors to predict failing to achieve a nadir PSA of 1.0 ng/mL or less in logistic regression analysis.
Conclusions:   A nadir PSA of 1.0 ng/mL can predict progression to HRPC after CAB. Pretreatment PSA and serum hemoglobin are significant predictors of failing to achieve a nadir PSA of 1.0 ng/mL or less.     

Effects of combined androgen blockade on bone metabolism and density in men with locally advanced prostate cancer

Objective: To investigate whether combined androgen blockade (CAB) produces any adverse effects on bone metabolism and mineral density in patients with locally advanced prostate cancer.Materials and methods: The study group consisted of 17 stage T4 prostate cancer patients treated with CAB and had no evidence of bone metastasis on bone scintigraphy. The mean duration of CAB and final total prostate specific antigen (PSA) level at the time of study were found at 28.5 ± 15.9 (6–58) months and 0.39 ± 0.5 (0.1–2) ngml, respectively. Twenty age and socioeconomically matched benign prostate hyperplasia (BPH) patients were taken as the control group. Both groups were compared with regard to lumbar bone mineral density (LBD), femur bone mineral density (FBD) and serum parameters of bone metabolism namely calcium (Ca), phosphate (P), magnesium (Mg) and alkaline phosphatase (ALP). Bone mineral density was measured with dual energy x-ray absorptiometry.Results: The mean FBD, LBD and serum Ca, P, Mg and ALP measurement of the patients treated with CAB were 0.85 ± 0.1 g/cm², 1.16 ± 0.2 g/cm², 9.1 ± 0.3 mg/dl, 3.6 ± 0.6 mg/dl, 1.95 ± 0.14 mg/dl, 187.5 ± 61 mg/dl, respectively. No significant difference was found between patients subjected to CAB and the age matched controls in any of the studied parameters namely age, FBD, LBD, Ca, Mg and ALP except serum phosphate. Serum phosphate levels were significantly (p =0.001) higher in patients treated with CAB suggesting a minor effect of CAB on bone metabolism.Conclusion: No convincing evidence was found about the detrimental effect of CAB on bone mineral density and metabolism in a highly selected group of patients with advanced prostate cancer without bone metastases.     

An elevated serum miR-141 level in patients with bone-metastatic prostate cancer is correlated with more bone lesions

The skeleton is the most common metastatic organ in patients with prostate cancer (PCa). Non-invasive biomarkers that can facilitate the detection and monitoring of bone metastases are highly desirable. We designed this study to assess the expression patterns of serum miR-141 in patients with bone-metastatic PCa. Serum samples were collected to measure the miR-141 level in 56 patients, including six with benign prostatic hyperplasia (BPH), 20 with localized PCa and 30 with bone-metastatic PCa (10 with hormone-naive PCa, 10 with hormone-sensitive PCa and 10 with hormone-refractory PCa). A bone scan was performed for each patient with PCa to assess the number of bone lesions. The quantification of serum miR-141 levels was assayed by specific TaqMan qRT-PCR. The results showed that serum miR-141 levels were elevated in patients with bone metastasis (P<0.001). There was no statistically significant difference in the serum miR-141 levels between patients with BPH and patients with localized PCa. Using Kendall''s bivariate correlation test, both the Gleason score and the number of bone-metastatic lesions were found to correlate with serum miR-141 levels (P=0.012 and P<0.001, respectively). The serum miR-141 level was found to be positively correlated with alkaline phosphatase (ALP) level in patients with skeletal metastasis, using Pearson''s bivariate correlation test. No relationship was found between the serum miR-141 level and the serum prostate-specific antigen (PSA) level. We concluded that serum miR-141 levels are elevated in patients with bone-metastatic PCa and that patients with higher levels of serum miR-141 developed more bone lesions. Furthermore, serum miR-141 levels are correlated with serum ALP levels but not serum PSA levels.