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.     

Neuroendocrine serum tumour markers in hormone-resistant prostate cancer

OBJECTIVE: The primary aim of the study was to assess the prevalence of elevated serum levels of neuron-specific enolase (NSE) and chromogranin A (CgA) in hormone-resistant prostate cancer (HRPC), and to evaluate these markers' prognostic significance. Secondarily we wanted to assess any change in serum levels of NSE or CgA after palliative radiotherapy. METHODS: Serum samples from patients with painful bone metastases or symptomatic pelvic tumours due to HRPC were analyzed for prostate specific antigen (PSA), NSE and CgA before and after palliative radiotherapy. RESULTS: Forty-six of 138 patients (33%) had elevated NSE before radiotherapy, while 80 (58%) had elevated CgA, without correlation between the two markers or with PSA. After radiotherapy the median NSE level was significantly reduced (p=0.004), whereas CgA (p=0.009) and PSA (p=0.019) increased. In the multivariate survival analysis, a reduced performance status, >20 bone metastases on bone scan, low hemoglobin, and pre-radiotherapy elevated NSE levels indicated a short survival. CONCLUSION: Together with known clinical parameters, NSE predicts survival in patients with HRPC. NSE could become a valuable prognostic marker in patients with this condition.     

Hormone-resistant prostate cancer with symptomatic pelvic tumours: patient survival and prognostic factors

OBJECTIVES: To determine the survival and investigate the prognostic significance of immunohistochemical variables and clinical factors in patients with hormone-resistant prostate cancer (HRPC) and symptomatic pelvic tumours, in whom preliminary observations indicated that survival exceeded the median 8-10 months of patients with HRPC and painful bone metastases. PATIENTS AND METHODS: Seventy-five patients with HRPC referred for palliative pelvic radiotherapy between 1980 and 1996 were identified. For all patients at least two prostate biopsies had been obtained, one before primary hormone treatment and at least one after clinical progression despite androgen deprivation (HRPC biopsy). Bone scans at the time of referral were assessed. The medical records were reviewed for clinical variables of possible prognostic significance. Histological grade was recorded, and prostate-specific antigen (PSA), androgen receptors (ARs), Ki-67 and p53 determined immunohistochemically. In 18 HRPC specimens the degree of AR amplification was analysed. RESULTS: Positive staining for ARs was high in the HRPC biopsies, although there was no association with AR amplification. Ki-67 positivity increased after the development of HRPC. The median (range) survival was 14 (1-141) months; age < 65 years was associated with increased survival. In a multivariate analysis the following variables remained independent prognostic factors for survival from the time of the HRPC biopsy: bone metastases (0-10 vs > 10 lesions, P < 0.001), low Ki-67 score (0 vs 1-3, P = 0.006) and low p53 positivity score (0 vs 1-3, P = 0.014) in the HRPC biopsy. CONCLUSIONS: The median survival of patients with HRPC and pelvic tumours requiring palliation seems to exceed that of patients with HRPC and dominating painful bone metastases by at least 4-6 months. Simple clinical (bone metastases) and immunohistochemical variables (Ki-67, p53) enable patients with particularly long survival times to be identified, and in whom palliative treatment needs to be improved.     

Skeletal retention of bisphosphonate (pamidronate) and its relation to the rate of bone resorption in patients with breast cancer and bone metastases.

Bisphosphonate pharmacokinetics may affect individual responses. Skeletal retention of pamidronate infused monthly to patients with bone metastases was highly variable (12-98%) and did not diminish with time, showing the capacity of the skeleton to retain large amounts of bisphosphonate. Relationships between skeletal retention of pamidronate and rate of bone resorption are complex and depend on previous treatment and the total amount of retained bisphosphonate. INTRODUCTION: Bisphosphonates (BPs) given intravenously every 3-4 weeks are effective in the management of metastatic bone disease from breast cancer, but responses among patients vary, and it is not known whether current dose and dose intervals are appropriate for an individual patient. An influence of pharmacokinetics of BPs on antiresorptive action may contribute to this variation in response. To test this hypothesis, we determined the skeletal retention of intravenous pamidronate and its association to the rate of bone resorption in patients with bone metastases from breast cancer. MATERIALS AND METHODS: In a cross-sectional study, 24-h urinary excretion of pamidronate and the biochemical marker of bone resorption N-terminal telopeptide of type 1 collagen and serum alkaline phosphatase were measured in 40 patients with bone metastases from breast cancer at the beginning, after 3-6 months, and after 1 year of treatment with intravenous pamidronate 90 mg every 3-4 weeks. RESULTS AND CONCLUSIONS: Skeletal retention (dose--amount excreted into urine) 2 days after infusion varied between 12% and 98% (mean, 62%) of the administered dose, but there were no differences in retention between patients receiving pamidronate for the first time or after 3-6 months or after 1 year of treatment. Retention of pamidronate was related to the prevalent rate of bone turnover in previously untreated patients, whereas no such relationship was found in previously treated patients. Rate of bone resorption after treatment seemed to be related to the amount of pamidronate retained. During 1 year of treatment, retention of pamidronate remained constant, indicating no saturation of skeletal binding sites with treatment. The variability in retention among individual patients can be attributed to the number of available binding sites. This is related, however, to bone turnover only before the start of treatment. The apparent relationships between skeletal retention and antiresorptive effect could have implications for the design of optimal therapeutic regimens with BPs in patients with bone metastases from breast cancer.     

The serum level of the amino-terminal propeptide of type I procollagen is a sensitive marker for prostate cancer metastasis to bone

OBJECTIVE: To assess the level of a bone-formation marker, the amino-terminal propeptide of type I procollagen (PINP), for its utility in indicating bone metastasis in patients with prostate cancer. PATIENTS AND METHODS: Several bone formation markers, i.e. PINP, the carboxy-terminal propeptide of type I procollagen (PICP), bone-specific alkaline phosphatase (BALP), and bone Gla protein (BGP), a bone resorption marker (pyridinoline cross-linked carboxy-terminal telopeptide, ICTP), and prostate specific antigen (PSA) were measured in 40 patients without and 25 patients with bone metastasis. No patient had undergone previous treatment, except for six who developed bone metastasis while undergoing hormone therapy. RESULTS: All markers except BGP were significantly higher in patients with bone metastasis than in those without. The levels of PINP correlated best with the extent of disease, although the levels of PSA, BALP and ICTP also correlated well. While PINP had the largest area under the receiver-operator characteristic curve, PSA, BALP and ICTP also produced useful curves. CONCLUSION: The bone formation marker PINP seems to be useful for discriminating patients with and without bone metastasis. PINP may help in the early and accurate diagnosis of bone metastasis in such patients.     

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。     

The patient with hormone-refractory prostate cancer: determining who, when, and how to treat

Hormone-refractory prostate cancer (HRPC) encompasses a wide spectrum of patients, including patients with prostate-specific antigen (PSA)--only disease, those with increasing PSA levels yet stable metastatic disease, and those with increasing PSA levels and objective evidence of progressive metastases. Unfortunately, with the historical lack of effective therapy in this population, the oncologist is faced with few data with which to make difficult clinical decisions. Although our understanding of the biology of androgen independence continues to improve, and our fund of potential therapeutic agents has widened, multiple trial-specific and patient-specific obstacles have contributed to the difficulty in demonstrating clear benefit to therapy. Herein, we will review the biology of androgen-independent prostate cancer, the historical impediments to clinical trials in this population, and the reasons to treat, or not to treat, the patient with HRPC.     

Serial markers of bone turnover in men with metastatic prostate cancer treated with zoledronic Acid for detection of bone metastases progression

OBJECTIVES: This study assessed the usefulness of serial measurements of bone turnover markers in men with metastatic prostate cancer treated with zoledronic acid to detect disease progression. METHODS: Serum measurements of total alkaline phosphatase (tALP), bone-specific alkaline phosphatase (bALP), cross-linked N-terminal (NTx) and cross-linked C-terminal (CTx) telopeptides of type I collagen, amino-terminal procollagen propeptides of type I collagen (PINP), C-terminal telopeptides of type I collagen (ICTP), and prostate-specific antigen (PSA) were performed in 77 prostate cancer patients suffering from bone metastases and treated with zoledronic acid up to 15 mo. Fifty patients were with and 27 patients without objective evidence of metastatic bone progression during the administration of zoledronic acid. RESULTS: The baseline bone marker concentrations were not significantly different between the groups. After administration of zoledronic acid all bone markers except of ICTP decreased compared with baseline. CTx showed the greatest decrease. In patients with metastatic bone progression PINP, tALP, bALP, and ICTP were significantly higher at weeks 24, 36, 48, and 60 after starting treatment with zoledronic acid compared with patients without progression. In addition to the information of prostate-specific antigen as a monitoring parameter, the bone formation marker showed a better distinction between patients with and without disease progression. CONCLUSIONS: Selected bone turnover markers provide valuable information regarding progression of bone metastasis in men with metastatic prostate cancer under bisphosphonate therapy. The clinical impact should be confirmed in prospective randomised studies.     

Chemotherapy for the Treatment of Hormone-Refractory Prostate Cancer

Men with metastatic prostate cancer treated with androgen ablation therapy respond rapidly and often dramatically, with improvement in bone pain, regression of soft tissue metastases, and decreases in serum prostate-specific antigen (PSA) levels. Unfortunately, few treatment options are available to men with advanced prostate cancer in whom disease progresses after hormonal therapy. The combination of mitoxantrone with a corticosteroid is effective palliative therapy for bone pain; however, it is not associated with an improvement in overall survival. Recent studies have focused on the proteins that regulate apoptosis as a target for the treatment of hormone-refractory prostate cancer (HRPC). Agents that inhibit microtubule-associated proteins, such as estramustine, and agents known to phosphorylate Bcl-2, such as the taxanes, demonstrate high activity in HRPC. Estramustine-based regimens are commonly used for the treatment of men with HRPC. Results of phases I and II clinical trials evaluating the taxanes as single agents and combined with estramustine have demonstrated significant activity in terms of response rate, decrease in PSA level, and improvement of bone pain. Moreover, although completion of phase III trials is awaited, survival data with estramustine-taxane combinations appear promising in phase II trials.     

The role of bisphosphonates in hormone-refractory prostate cancer

Men with advanced prostate cancer are at high risk for developing bone metastases, which result in clinically significant skeletal morbidity. Treatments that prevent skeletal complications in these patients could considerably improve their quality of life. Therefore, this paper reviews the role of bisphosphonates in the treatment of hormone-refractory prostate cancer (HRPC). Published studies were identified through MEDLINE searches, review of bibliographies of relevant articles, and review of abstracts from scientific meetings. Metastatic bone disease in men with HRPC results in skeletal complications such as pathologic fractures, spinal cord compression, and debilitating bone pain. First- and second-generation bisphosphonates, clodronate and pamidronate, had transient palliative effects that were not durable and did not prevent skeletal events in these patients. A small open-label study of ibandronate demonstrated significant reductions in pain, but these results have not been confirmed in a larger, randomized, controlled trial. To date, zoledronic acid is the only bisphosphonate that has demonstrated a statistically significant reduction in skeletal morbidity in this patient population. In a large, multicenter, randomized, placebo-controlled trial, treatment of men with HRPC and bone metastases with zoledronic acid significantly reduced skeletal-related events and provided a durable reduction of bone pain over 24 months compared with placebo. Zoledronic acid is the only bisphosphonate that has demonstrated efficacy for preventing skeletal complications in patients with HRPC and bone metastases. Therefore, initiation of zoledronic acid therapy should be considered to prevent skeletal morbidity and improve the quality of life of these patients.     

Use of bone turnover marker, pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP), in the assessment and monitoring of bone metastasis in prostate cancer

BACKGROUND: We investigated whether a new marker of bone turnover, pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP), could be useful in the assessment of bone metastasis and in monitoring of the response to treatment in patients with prostate cancer with bone metastasis. METHODS: In all, 58 patients with prostate cancer (25 with bone metastasis and 33 without bone metastasis) and 52 patients with benign prostate hypertrophy who were treated between June 1994-August 1997 were included in this study. All patients were newly diagnosed. RESULTS: Serum ICTP levels in patients with prostate cancer with bone metastasis were significantly higher than those in patients with prostate cancer without bone metastasis (P<0.0001) or with benign prostate hypertrophy (P<0.0001). No significant differences were observed in serum ICTP levels between patients with prostate cancer without bone metastasis and those with benign prostate hypertrophy. Serum ICTP levels correlated significantly with Soloway's grading system for bone scans. Serum ICTP levels in patients with bone metastasis showed a significant downward trend in response to hormonal treatment. CONCLUSIONS: The determination of serum ICTP levels is useful in the assessment of bone metastasis and in monitoring the response of bone metastasis to treatment to prostate cancer.     

多西紫杉醇治疗激素难治性前列腺癌的研究

目的研究多西紫杉醇3周方案治疗激素难治性前列腺癌的疗效、毒副反应。方法对HRPC患者进行3周方案化疗：多西紫杉醇75mg／m2（第一天）,泼尼松5mg,口服hid,21d为一周期。反应严重的患者之后的给药剂量改为70mg／m2。观察患者的前列腺特异性抗原水平、病灶的变化、毒副反应。结果12例患者经治疗后PSA均有下降,5例PSA下降〉50％。治疗前后PSA中位数分别为28和18,两者比较有统计学差异。复查MRI中2例出现病灶减小。所有患者骨扫描未见新发灶,骨痛的患者中50％有不同程度缓解。主要的副反应为骨髓抑制。结论多西紫杉醇3周方案对于我国HRPC患者的疗效是肯定的,但毒副反应对化疗进程影响很大,本研究建议将不能耐受的患者药物剂量降为70mg／m2。     

Rationale for the use of bisphosphonates in osteoblastic and osteolytic bone lesions

Various primary malignancies develop bone metastases, and the resultant skeletal complications cause significant morbidity/mortality in advanced cancer patients. Bone lesions associated with metastases are traditionally classified radiologically as either osteolytic or osteoblastic, and both types of lesions are associated with elevated levels of specific bone resorption markers. Some common aspects in the pathophysiology of bone lesions have prompted speculation that treatments for osteolytic metastases might also be effective for predominantly osteoblastic metastases, such as in prostate cancer. Potent osteoclast activity inhibitors, bisphosphonates have been successful in the treatment of osteolytic tumor bone disease. Zoledronic acid is the first bisphosphonate shown to have a direct clinical benefit in the treatment of osteoblastic bone metastases, reducing the number and rate of skeletal events in prostate cancer patients with metastatic bone disease. Moreover, the shorter, more convenient infusion time and similar safety profile of 4 mg zoledronic acid compared with 90 mg pamidronate presently make zoledronic acid the preferred therapy for treatment of bone metastases in patients with all types of advanced malignancy.     

PSA和SPECT骨显像在前列腺癌诊断治疗中的意义

目的：研究PSA、SPECT骨显像在前列腺癌诊断及治疗中的临床意义。方法：对100例经临床确诊的前列腺癌患者全部行血清PSA测定及全身骨显像。结果：发生骨转移的患者为81％,PSA≥20tμg／I．的患者发生骨转移的为60％。结论：血清PSA与骨显像联检对前列腺癌临床诊断、疗效观察及预后判定具有重要的指导意义。     

Role of Chemotherapy in Nonmetastatic Hormone-Refractory Prostate Cancer

ContextDocetaxel chemotherapy has become the standard first-line treatment for metastatic hormone-refractory prostate cancer (HRPC). Nowadays, one of the goals of research is to determine optimal management strategies for different patient populations with prostate cancer.ObjectiveBecause the utility of docetaxel in patients with nonmetastatic HRPC has not yet been evaluated, one of the most challenging questions is to define the role of chemotherapy in nonmetastatic HRPC.Evidence acquisitionIn a recently published subset analysis of TAX-327, a multivariate prognostic model incorporating prostate-specific antigen (PSA) kinetics has been developed to predict survival at 1, 2, and 5 yr in men with metastatic HRPC treated with chemotherapy. This novel model includes PSA doubling time (PSA DT), baseline pain, baseline PSA level, age, type of progression at baseline (measurable disease or bone scan compared with PSA only), presence of liver metastases, and the number of metastatic disease sites.Evidence synthesisThe authors found a statistically significantly better overall survival in patients with PSA ≤114 ng/ml and PSA DT >55 d. Patients with a PSA DT of <55 d had a worse prognosis than patients with a longer PSA DT.ConclusionsBased on these findings, it seems clear nowadays that evaluation of PSA kinetics can help us to delineate the potential benefits of the early indication of chemotherapy. It could be hypothesized that docetaxel-based chemotherapy could have a role in those patients with nonmetastatic HRPC who have a very short PSA DT.     

Implications of circulating chromogranin A in prostate cancer

OBJECTIVE: To evaluate whether measurement of circulating chromogranin A (CgA) levels provides clinicopathological and prognostic information in prostate cancer. MATERIAL AND METHODS: Plasma CgA levels were measured in 57 patients with histologically confirmed prostate cancer (stage B or less, n=22; stage C, n=10; stage D1, n=2; hormone-naive D2, n=12; hormone-refractory D2, n=11) and in 22 with undetected prostate cancer using an enzyme-linked immunoabsorbent assay. RESULTS: Median plasma CgA levels were significantly higher in patients with prostate cancer than in those with undetected cancer (p=0.0271). Higher stage (p<0.0001) and higher grade (p=0.0412) tumours were also significantly associated with higher plasma CgA levels. Above-normal CgA levels were also detected in 4/27 patients (15%) who underwent radical prostatectomy. Postoperative clinical failure was not reported in the prostatectomy patients; however, prostate-specific antigen (PSA) failure was reported in 44% of patients after a median follow-up period of 20.3 months. Multivariate analysis revealed that the pathological stage of the tumour was the only independent predictive variable for postoperative PSA failure (p=0.0494). Preoperative plasma CgA levels had no impact on postoperative PSA failure in the subgroup (prostatectomy patients). Elevated plasma CgA levels were associated with a poor survival prognosis in patients with stage D2 prostate cancer after a median follow-up period of 22.5 months (p=0.0416). CONCLUSIONS: It was demonstrated in this study that plasma CgA levels in prostate cancer increase with the severity of the disease, especially for progressive hormone-refractory prostate cancer (HRPC), after hormone therapy. Although this cross-sectional study involved only a small number of patients, we believe that plasma CgA levels may effectively predict HRPC status and prognosis in metastatic cases.     

Clinical outcome of maximum androgen blockade using flutamide as second-line hormonal therapy for hormone-refractory prostate cancer

OBJECTIVES: To investigate the efficacy of maximum androgen blockade (MAB) using flutamide as second-line hormonal therapy for advanced hormone-refractory prostate cancer (HRPC). PATIENTS AND METHODS: The study included 55 patients with HRPC who were treated with MAB using flutamide (375 mg daily) as second-line hormonal therapy. All patients had previously received bicalutamide combined with either surgical or medical castration as first-line hormonal therapy, which failed. The effect of the second-line therapy was evaluated by serum prostate-specific antigen (PSA) level alone, and the response defined as a decrease of >50% from the baseline PSA at the start of second-line therapy. RESULTS: On initiating second-line hormonal therapy there was a reduction in the PSA level in 25 of the 55 patients (45%), among whom 12 (22%) were regarded as responders, while the PSA level continued to increase in the remaining 30 (55%). The median (range) duration of the PSA response was 6 (1-13) months. During the observation period there were no severe side-effects from the second-line MAB therapy. Patients without bone metastases or whose disease progressed >1 year after first-line therapy had a significantly higher incidence of PSA response to second-line therapy, despite no significant effect of other factors examined on the PSA response to second-line therapy. Furthermore, the cause-specific survival in responders to second-line therapy was significantly better than that in nonresponders; however, multivariate analysis showed that no factors, including response to second-line therapy, could be used as independent predictors of cause-specific survival. CONCLUSIONS: MAB using flutamide as second-line hormonal therapy can give a comparatively favourable PSA response with no severe side-effects; therefore, this therapy may be suitable for patients with HRPC after primary MAB using bicalutamide has failed, particularly in those with no bone metastases or whose disease has progressed for >1 year after first-line therapy.     

Risk Factors for the Development of Bone Metastases in Prostate Cancer

ObjectivesBone health of men with prostate cancer is threatened throughout the disease course. The majority of patients with advanced prostate cancer will develop bone metastases that can undermine skeletal integrity and result in skeletal complications including pathologic fractures, spinal cord compression, and palliative radiotherapy to bone. The early identification of patients who are at a high risk for bone metastases may enable earlier identification and treatment of bone lesions, thereby preserving patients’ independence throughout the disease course.MethodsCurrent guidelines for bone health maintenance were reviewed and PubMed key word searches performed to identify risk factors for the development of bone metastases in patients with prostate cancer. Additionally, guidelines and consensus recommendations were reviewed to identify bone health issues and their management in patients with early prostate cancer.ResultsCurrent prostate cancer monitoring guidelines recommend bone scans at initial diagnosis for patients with prostate-specific antigen (PSA) levels >20 ng/ml and in patients with chronic bone pain or fractures. Multiple studies have concluded that high baseline PSA levels, rising PSA despite androgen-deprivation therapy (ADT), and high PSA velocity are risk factors for the development of bone metastasis in patients with prostate cancer. In patients with early prostate cancer, bone loss is an emerging concern, and bisphosphonates have been demonstrated to prevent bone loss from ADT. Use of risk factors such as PSA kinetics may optimize screening and enable earlier identification of bone metastases.ConclusionsMonitoring bone mineral density may allow for better preservation of skeletal health in patients undergoing ADT.     

Prostate-specific antigen doubling time and survival in patients with advanced metastatic prostate cancer

The relation between tumor kinetics and disease progression in patients with hormone-refractory prostate cancer (HRPC) has not been well described. Biochemical recurrence of prostate cancer is characterized by detectable prostate-specific antigen (PSA) levels after treatment and occurs in approximately 30% of patients after therapy for apparent localized disease. An increase in PSA almost always occurs before clinical evidence of disease. The ability to identify early biochemical failure in patients to assess disease aggressiveness and guide changes in treatment needs to be examined. We examined serial PSA data from 249 patients with metastatic disease to assess PSA doubling time (PSADT) in hormone-naive prostate cancer (HNPC) and HRPC states. In a subset of patients, the relation of PSADT to Gleason score and survival was studied. PSADT decreased from 37.5 +/- 4.5 weeks to 15.6 +/- 1.6 weeks (mean +/- SEM) in patients with HNPC versus HRPC. In this small study, PSADT did not correlate with Gleason score, survival from start of hormonal treatment, length of time receiving hormone therapy, or survival in the HRPC state. The decrease in PSADT with disease state may help provide insight into understanding the biology of late-stage disease.     

Prediction of bone metastases by combination of tartrate-resistant acid phosphatase, alkaline phosphatase and prostate specific antigen in patients with prostate cancer

Objective:   The clinical value of serum tartrate-resistant acid phosphatase (TRACP), prostate specific antigen (PSA), alkaline phosphatase (ALP), and prostatic acid phosphatase (PACP) for the prediction of bone metastases in prostate cancer were investigated.
Methods:   TRACP, PACP, ALP, and PSA serum levels were measured in 215 patients with prostate cancer, including 160 without and 55 with bone metastases. Correlation of serum marker levels with bone metastases was assessed using receiver operating characteristics (ROC) analysis. Sensitivity, specificity, accuracy, positive and negative predictive values were calculated for each serum marker. Multivariate stepwise logistic regression analysis was used to identify independent predictors for the presence of bone metastasis.
Results:   Mean serum TRACP, PACP, ALP, and PSA levels were significantly elevated in patients with bone metastases compared with those without ( P  < 0.05). PSA and PACP levels increased significantly with clinical stage of the disease, whereas TRACP and ALP levels only increased significantly in stage D2. Serum TRACP levels correlated significantly with extent of disease on bone scans. ROC analyses showed no significant differences in area under the curve for these markers. Logistic regression analysis demonstrated that PSA, ALP, and TRACP were significant predictors of bone metastasis. Predicted and observed risks of bone metastasis were well correlated when TRACP, ALP, and PSA were combined and bone scan could have been omitted in 70% of patients by assessing these three markers.
Conclusions:   Serum TRACP can be considered a useful predictor of bone metastases in prostate cancer. A combination of TRACP, ALP, and PSA can obviate the need for a bone scan in 70% of cases.