放射性核素89Sr治疗前列腺癌骨转移疼痛的临床研究

目的:探讨晚期前列腺癌骨转移疼痛治疗的方法,评价放射性核素89Sr的疗效与安全性。方法:对15例未接受过任何放疗的晚期前列腺癌骨转移疼痛患者,经静脉注射放射核素89Sr治疗。结果:疼痛治疗的有效率为86.7%,80%患者的肿瘤标记物PSA水平较治疗前轻度下降,26.6%患者出现造血功能抑制。结论:放射性核素89Sr治疗前列腺癌骨转移疼痛较为安全、有效,可以提高患者生活质量。     

89锶治疗前列腺癌骨转移的疗效观察

目的：评价放射性核素^89锶(^89Sr)在前列腺癌骨转移中的治疗效果和不良反应。方法：观察31例前列腺癌骨转移患者使用^89Sr治疗后的止痛疗效、PSA变化、不良反应及血液学不良影响。结果：^89Sr治疗止痛总有效率为90．3％(28/31)．PSA均有下降；不良反应主要为轻度可逆性骨髓造血功能损害；^89Sr对肝肾功能及电解质无明显不良影响。结论：^89Sr治疗前列腺癌骨转移疼痛效果明显．对前列腺癌骨转移灶亦有治疗作用．是一种安全有效的方法。     

Prostate cancer and markers of bone metabolism: diagnostic,prognostic, and therapeutic implications

Knowledge of bone metastases complicating advanced prostate cancer (CaP) is increasingly relevant in patient selection for novel therapies. Current nuclear bone scintigraphy imaging has limited specificity for prostate metastases. As serum bone markers do correlate with bony lesions, they may play multiple roles in patients with advanced CaP. Currently, these markers play a role in prognostic nomograms for CaP. Recent studies suggest an expanding role for bone markers in the diagnosis and selection of patients for novel therapies. In the future, therapeutic roles for some of these marker pathways will emerge, eventually allowing greater individualization of patient care.     

Hypocalcemia in patients with prostate cancer

Summary We report a case of severe hypocalcemia in a patient with prostate cancer and extensive metastatic bone disease. The hypocalcemia in this patient was most likely on the basis of extensive accretion of calcium into the bones. We further studied 112 patients with prostate cancer, 15 of whom were discovered to be hypocalcemic on the basis of serum total calcium measurement. Fourteen of these 15 patients had bone metastases. Serum total calcium, total protein, and albumin levels were significantly lower in patients with bone metastases (n=61) than those without (n=51). Hypocalcemia could be explained on the basis of hypoalbuminemia or renal failure in these patients. Plasma ionized Ca measurements were made in 47 of the total 112 patients. Only one patient with extensive bone metastases was found to be hypocalcemic on the basis of ionized calcium measurement. Therefore, apparent hypocalcemia based on total calcium measurement is common in patients with prostate cancer (14% of all and 23% of those with bone metastases), whereas true hypocalcemia based on ionized calcium determinations is unusual.     

Elevated alkaline phosphatase velocity strongly predicts overall survival and the risk of bone metastases in castrate-resistant prostate cancer

ObjectivesIn patients with a rising prostate-specific antigen (PSA) level during treatment with androgen deprivation therapy, identification of men who progress to bone metastasis and death remains problematic. Accurate risk stratification models are needed to better predict risk for bone metastasis and death among patients with castration-resistant prostate cancer (CRPC). This study evaluates whether alkaline phosphatase (AP) kinetics predicts bone metastasis and death in patients with CRPC.Methods and materialsA retrospective cohort study of 9,547 patients who underwent treatment for prostate cancer was conducted using the Center for Prostate Disease Research Multi-center National Database. From the entire cohort, 347 were found to have CRPC and, of those, 165 had 2 or more AP measurements during follow-up. To determine the AP velocity (APV), the slope of the linear regression line of all AP values was plotted over time. Rapid APV was defined as the uppermost quartile of APV values, which was found to be ≥6.3 IU/l/y. CRPC was defined as 2 consecutive rising PSA values after achieving a PSA nadir<4 ng/ml and documented testosterone values less than 50 ng/dl. The primary study outcomes included bone metastasis–free survival (BMFS) and overall survival (OS).ResultsRapid APV and PSA doubling time (PSADT) less than 10 months were strong predictors of both BMFS and OS in a multivariable analysis. Faster PSADT was a stronger predictor for BMFS (odds ratio [OR] = 12.1, P<0.0001 vs. OR = 2.7, P = 0.011), whereas rapid APV was a stronger predictor of poorer OS (OR = 5.11, P = 0.0001 vs. OR = 3.98, P = 0.0034). In those with both a rapid APV and a faster PSADT, the odds of developing bone metastasis and death exceeded 50%.ConclusionAPV is an independent predictor of OS and BMFS in patients with CRPC. APV, in conjunction with PSA-based clinical parameters, may be used to better identify patients with CRPC who are at the highest risk of metastasis and death. These findings need validation in prospective studies.     

Plasma osteopontin in comparison with bone markers as indicator of bone metastasis and survival outcome in patients with prostate cancer

BACKGROUND: The study was undertaken to evaluate the diagnostic and prognostic value of plasma osteopontin (OPN) in comparison to bone markers as well as the relationships between the markers and clinico-pathological factors in prostate cancer (PCa) patients. METHODS: OPN and the bone markers carboxyterminal-telopeptide of type I collagen, bone-specific alkaline phosphatase (bALP), and aminoterminal-propeptide of type I procollagen (PINP) were measured in 90 PCa patients with and without bone metastases, 35 patients with benign prostatic hyperplasia, and 29 healthy men. RESULTS: OPN and bone markers were significantly elevated in patients with bone metastases compared to the other groups. Significant correlations were found between all four-bone markers (r(s) = 0.43-0.79, all P < 0.01). OPN correlated with tumor grade (r(s) = 0.23, P < 0.05). In receiver-operating characteristics (ROC) analyses, OPN and bone markers were effective in distinguishing PCa patients with and without bone metastases showing areas under the curve (AUC) between 0.80 and 0.88 (all P < 0.001). OPN had an AUC of 0.85 that increased in combination with bALP up to 0.93 providing at the point with the highest diagnostic accuracy both a sensitivity and specificity of about 90%. Kaplan-Meier analyses and Cox proportional hazards regression models showed decreased survival of patients with high OPN and bone marker levels, while only high OPN and PINP were independent negative prognostic factors for PCa-related death. CONCLUSIONS: OPN alone or in combination with bone markers is useful as diagnostic marker in the detection of bone metastases and as prognosticator in the survival prediction in PCa patients.     

Results of laparoscopic pelvic lymphadenectomy in patients at high risk for nodal metastases from prostate cancer

Background: Laparoscopic pelvic lymphadenectomy (LPLND) can be performed safely and with minimal morbidity in the staging of prostate cancer. Its utility in evaluating patients at high risk for metastatic disease before primarily nonsurgical treatment modalities was evaluated. Methods: Twenty-four consecutive patients who underwent LPLND between June 1993 and July 1996 were studied. These patients were considered poor surgical candidates based on several risk factors, as follows: elevation of serum PSA >20 in 19 patients (79%); elevation of serum acid phosphatase in 4 patients (17%); digital rectal examination findings indicative of extraprostatic extension or seminal vesical involvement in 14 patients (58%); and poorly differentiated tumors on prostate biopsy in 19 patients (79%). Nineteen patients (79%) had two or more of these risk factors. Median PSA for the entire series of patients was 35.2 ng/mL (range 7.9 to 133 ng/mL), and median Gleason score was 7 (range 5 to 9). Preoperative CT or MRI was negative for pelvic lymph node metastases in 17 of 23 patients (79%), and bone scan was negative in all 24 patients. Results: Unilateral (n=2) or bilateral (n=22) LPLND was performed in all patients. Six patients (25%) had lymph node metastases detected laparoscopically. Five of the six patients had palpable extraprostatic extension (T3a/b) or invasion of a seminal vesical (T3c), and in four of these patients the site of the metastatic lymph nodes was ipsilateral to the palpable prostate abnormality. None of the risk factors was independently predictive of lymph node metastases within this series of patients. An average of 10.8±6.5 lymph nodes was removed at a mean operative time of 174±10 minutes for patients undergoing bilateral LPLND. Estimated blood loss was minimal for 20 of 22 patients (92%) undergoing LPLND alone, and there were no complications requiring open exploration. Mean postoperative hospital stay was 1.2±0.5 days for patients undergoing LPLND alone. Conclusions: LPLND can be used efficiently to identify patients with nodal metastases from select high-risk patients. This, in turn, can exclude such patients from noncurative local and regional therapy. Presented at the 50th Annual Cancer Symposium of The Society of Surgical Oncology, Chicago, Illinois, March 20–23, 1997.     

骨代谢标志物在乳腺癌骨质疏松中的评估价值

目的探究骨代谢标志物在乳腺癌骨质疏松中的诊断价值。方法选取2014年6月至2017年6月在我院住院接受治疗的182例乳腺癌骨质疏松患者为本次研究的研究对象,对本研究对象的骨代谢标志物BALP以及uNTx水平进行检测,统计并对比治疗前后乳腺癌骨质疏松患者骨代谢标志物的变化情况,采用单因素分析方法及多元线性回归分析方法分析影响乳腺癌骨质疏松患者骨代谢标志物水平的因素。结果乳腺癌骨质疏松患者骨代谢标志物BALP以及uNTx水平明显高于正常水平(P0.05),治疗后两者水平均明显低于治疗前(P0.05);单因素分析显示,骨代谢标志物BALP以及uNTx水平与患者骨转移数目呈正相关(P0.05),与骨痛程度无明显联系(P0.05);多元线性回归分析,骨代谢标记物和骨转移数目是影响患者近期疗效的相关因素。结论骨代谢标志物水平与骨质疏松有着密切联系,可作为乳腺癌骨质疏松的理想诊断指标,且该指标相对于影像学检查反应敏感性更强。     

Correlation between BMD and bone scintigraphy in patients with prostate cancer

OBJECTIVE: Bone metastasis is a major cause of morbidity in prostatic cancer. Therefore, detecting and monitoring bone lesions are crucial for treatment of prostatic carcinoma. We aimed to evaluate total body bone mineral density and regional bone mineral density in patients with prostate cancer with and without metastases, and to compare them with bone scintigraphy. METHODS: Fifty-four patients with prostatic carcinoma and 20 healthy subjects were investigated with bone scintigraphy and dual-energy X-ray absorptiometry. The bone scintigraphic findings were classified as normal (score 0: n = 22), abnormal but not typical for metastases (score 1: n = 18), and typical pattern of metastases (score 2: n = 14). RESULTS: The patients with bone metastases prostate cancer had significantly higher total bone mineral density and regional bone mineral density of trunk and pelvis than healthy controls and prostate cancer patients without bone metastases. There was a significant positive correlation between bone scan score and total bone mineral density and regional bone mineral density of trunk and pelvis (r = 0.328, P < 0.05, r = 0.60, P < 0.001, r = 0.480, P < 0.001, respectively). CONCLUSION: Our results show that patients of prostate cancer with bone metastases have increased bone mineral density (BMD) in the pelvis and trunk, possibly because of a predominance of osteoblastic over osteolytic metastases demonstrated by Tc-99m MDP bone scan.     

Brain metastases: a rare initial presentation of prostate cancer

Although brain metastases are common in cancer patients, carcinoma of the prostate rarely metastasizes to the brain. Cerebral metastases as an initial clinical presentation of prostate carcinoma are extremely rare. We report a patient, who presented with confusion and behavioral changes. Cranial magnetic resonance imaging revealed a large right temporal lobe lesion. The pathological diagnosis of the tumor was consistent with metastatic prostate carcinoma. Further evaluation revealed widespread bony metastases by technetium 99 bone scan and high level of prostate-specific antigen.     

The effect of combined androgen blockade on bone turnover and bone mineral density in men with prostate cancer

Summary Our study and previous reports suggest that castration results in increased bone turnover and lowered BMD and that these changes might be attenuated by anti-androgens, such as BL and EMP. Introduction Recent studies have shown that castration for PC decreases bone mineral density (BMD), while estrogen therapy or bicalutamide (BL) monotherapy maintains BMD. However, the effect of combined androgen blockade (CAB) on bone turnover is not well studied. Methods A total of 204 men were evaluated in the study (control group: n = 56, castration group: n = 102, ‘CAB with BL’ group: n = 22, ‘CAB with estramustine phosphate (EMP)’ group: n = 24). We measured steroid hormone levels, BMD (measured at one-third distal radius), bone turnover markers (levels of urinary N-telopeptide cross links of type 1 collagen (u-NTx) and deoxypyridinoline (u-DPD), serum concentrations of osteocalcin (OC)) in order to assess differences between groups. Results The BMD % Z score of the castration group was significantly lower than that of the control group or the ‘CAB with EMP’ group (90.6% vs. 95.5%, 98.6%; p < 0.042, p < 0.044, respectively). Levels of u-NTx, u-DPD, OC of the castration group were the highest followed by the control group, then the ‘CAB with BL’ group and the ‘CAB with EMP’ group. Conclusions Our study and previous reports suggests that castration results in increased bone turnover and lowered BMD and that these changes might be attenuated by anti-androgens, such as BL and EMP.     

Bone turnover markers and bone mineral density response with risedronate therapy: Relationship with fracture risk and patient adherence

Surrogate markers of fracture risk—bone turnover markers (BTMs) and bone mineral density (BMD)—can be used to monitor treatment response. We assessed whether changes in these markers greater than the least significant change (LSC) were associated with fracture risk reduction and greater adherence. This secondary analysis of the Improving Measurements of Persistence on ACtonel Treatment (IMPACT) study—a multinational prospective, open‐label, cluster‐randomized study of postmenopausal women on oral risedronate 5 mg/d for 52 weeks—assessed adherence by electronic monitors. Urinary N‐terminal cross‐linked telopeptide of type 1 collagen (uNTX) and serum C‐terminal cross‐linked telopeptide of type 1 collagen (sCTX) levels were assessed at baseline and weeks 10 and 22, and BMD at baseline and week 52. Fractures were recorded as adverse events. In 2302 women, responses beyond LSC in BTMs (uNTX and sCTX) and BMD (spine only) were associated with a reduced risk of nonvertebral fractures (NVFs) and all fractures. NVF incidence was about 50% lower in patients with 30% or more of uNTX reduction at week 22 (1.6%) than in those with less than 30% reduction (3.2%, p = .015). NVFs also were reduced in patients with more than 3% spine BMD increase at 52 weeks than those with 3% or less. Responses greater than LSC in BTMs and BMD were associated with greater adherence, but there was no association between adherence and fracture outcomes at 52 weeks. Changes greater than the LSC in BTMs and BMD reflect better treatment adherence, were associated with fracture risk reduction, and identify differences in individual responsiveness to risedronate. © 2011 American Society for Bone and Mineral Research.     

Bone mineral density and bone turnover markers in children with chronic renal failure

Bone mineral density (BMD) at lumbar spine (L₂-L₄) was measured by dual-energy X-ray absorptiometry (DEXA) in 21 children with predialysis chronic renal failure (CRF) and 44 children with end-stage renal failure (ESRF) on regular hemodialysis. BMD results were expressed as Z-scores. Osteopenia was documented in 13 predialysis patients (61.9%) and 26 patients (59.1%) with ESRF. No significant correlation was observed between Z-scores and the duration of CRF or estimated creatinine clearance. In osteopenic children there was a negative correlation between Z-scores and serum phosphorus (r=–0.61, P=0.004), intact parathyroid hormone (iPTH) (r=–0.47, P=0.03), and bone-specific alkaline phosphatase (r=–0.52, P=0.02) and a positive correlation with total calcium (r=0.41, P=0.07) and 25-hydroxycholecalciferol (r=0.53, P=0.02). Osteopenic children who had iPTH values 200 pg/ml were more osteopenic than those who had lower iPTH levels (P=0.006). In conclusion, osteopenia, assessed by DEXA, is frequent in children with CRF. It occurs early irrespective of the duration or the severity of CRF. In children with ESRF the degree of osteopenia is correlated with laboratory markers of renal osteodystrophy and patients with biochemical findings of secondary hyperparathyroidism are more osteopenic than the others.     

Bone turnover markers in postmenopausal breast cancer treated with fulvestrant – A pilot study

BackgroundTamoxifen has a protective effect on bone metabolism in breast cancer; aromatase inhibitors deleterious and that of fulvestrant is unknown.MethodsFourteen locally advanced breast cancers with clinical benefit on fulvestrant (250 mg/month) as first-line primary endocrine therapy had sequential serum bone-specific alkaline phosphatase (BAP), N-terminal propeptide of procollagen type 1 (PINP) and C-terminal telopeptide (CTX) at 0, 1, 6, 12, and 18 months. Mean percentage changes (95% CI) were calculated.ResultsChanges from baseline at 1, 6, 12, and 18 months with BAP (3.9–46.8 ng/ml) were +1.5 (?9.8 to +12.9), +2.2 (?22.1 to +26.6), +17.6 (?12.4 to +47.6), +10.8 (?29.9 to +51.7); with PINP (20.6–82.1 ng/ml) were +3.4 (?12.0 to 19.0), +18.8 (?36.7 to +74.2), +47.5 (?21.4 to 116.3), +33.3 (?49.5 to +116.1) and with CTX (0.14–1.35 ng/ml) were +30.8 (0.1 to +61.6), +13.9 (?22.3 to +50.2), +42.9 (?12.7 to +98.5), +45.2 (?28.3 to +118.8).ConclusionsLong-term (18 months) stability of bone markers may be exploited by using fulvestrant earlier in sequence of endocrine therapies particularly in adjuvant setting in those with pre-existing decreased bone mass.     

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.     

Renal toxicity following zoledronic acid reversed with ibandronate in a prostate cancer patient with bone metastases

Bisphosphonates are a standard treatment for metastatic bone disease, although agents vary in their potential for renal toxicity. This case report describes the reversal of zoledronic acid-induced renal toxicity by switching treatment to ibandronate in a patient with hormone-refractory prostate cancer and bone metastases.     

89锶、唑来膦酸及99锝-亚甲基二膦酸盐治疗老年前列腺癌骨转移的临床观察

［摘要］ 目的 观察和比较89Sr、唑来膦酸及99锝-亚甲基二膦酸盐（云克）在老年前列腺癌骨转移患者治疗中的临床价值。方法 回顾性分析2017年01月至2018年01月我科收治的老年前列腺癌骨转移患者，分为89Sr治疗组、唑来膦酸治疗组及云克治疗组。比较三组患者治疗后骨痛缓解、骨转移灶控制及不良反应情况，并行统计学分析。结果 本研究共纳入53例患者，镇痛疗效：89Sr组较唑来膦酸组、云克组治疗早期止痛效果好，差异有统计学意义（P<0.05），但治疗6个月后差异减小，12个月后三组间差异无明显统计学意义（P>0.05）。89Sr组及唑来膦酸组对重度疼痛组缓解优于中度疼痛组，无明显统计学差异（P>0.05），云克组对重度疼痛组缓解明显差于中度疼痛组，有统计学差异（P<0.05）。转移灶疗效：89Sr组较唑来膦酸组、云克组治疗效果好，但无明显统计学差异。骨转移灶数目，89Sr组及唑来膦酸组、云克组对≥10组的治疗效果优于<10组，但均无明显统计学差异。不良反应：89Sr的骨髓抑制、唑来膦酸的发热反应，较另两种药物有明显统计学差异（P<0.05），其余不良反应无明显统计学差异（P>0.05）。结论 89Sr、唑来膦酸、云克均有较好的缓解骨痛、控制骨进展作用。89Sr针对老年患者，易出现骨髓抑制，需密切随访。云克不良反应少，连续长期静脉输液，增加老年患者的痛苦。唑来膦酸易出现发热，但给予对症后可缓解。     

Oncological validation of bone turnover markers c-terminal telopeptide of type I collagen (1CTP) and peptides n-terminal propeptide of type I procollagen (P1NP) in patients with prostate cancer and bone metastases

BackgroundBone formation markers c-terminal telopeptide of type I collagen (1CTP) and peptides n-terminal propeptide of type I procollagen (P1NP) were reported to be increased in patients with prostate cancer (PC) and bone metastases. The objective of the presented study was to investigate the utility of serum 1CTP and P1NP values in the diagnosis of bone metastases and in predicting oncological outcome in patients with PC.MethodsIn total, serum samples of 186 patients were included retrospectively including 53 (28.50%) benign prostatic hyperplasia (BPH) patients and 133 (71.50%) PC-patients. The group of patients with PC consisted of 58 patients with non-metastatic PC (cM0) (43.61%) and 70 (52.63%) patients with bone metastases (cM1b). Serum 1CTP and P1NP were measured by radioimmunoassay (RIA). Results were compared to clinical variables including oncologic follow-up data by univariate and multivariate analyses.ResultsMedian 1CTP concentrations were significantly higher in patients with PC compared to the BPH group [5.08 (range, 1.73–158.00) vs. 4.00 (range, 2.18–34.19) µg/L, P=0.019]. However, no significant difference of P1NP levels could be shown for these groups. With median values of 6.04 (1.73–158.00) and 3.91 µg/L (2.04–34.51) for 1CTP and 48.60 (9.12–1,074.37) and 33.90 (8.72–149.30) for P1NP both markers were altered in cM1b patients compared to cM0 patients (P=0.001 each). Furthermore, cancer-specific survival (CSS) and overall survival (OS) were significantly shorter in cM1b patients with higher 1CTP concentrations (P=0.037 and P=0.019, respectively), whereas no associations of P1NP and outcomes were observed.ConclusionsThe present study confirms that increased levels of 1CTP and P1NP concentrations are associated with presence of metastatic disease in the bone. Moreover, these markers are able to predict clinical course in PC patients with bone metastases. The potential use of these markers for treatment selection in advanced PC remains to be determined.     

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.