Does Magnetic Resonance Imaging of the Spine Have a Role in the Staging of Prostate Cancer?

AimsMagnetic resonance imaging (MRI) is an effective method for evaluating the spine in patients with a high risk of metastatic disease. The aim of this study was to compare MRI spine with radionuclide bone scan in detecting spinal metastases for staging prostate cancer patients.Materials and methodsA cohort of 99 patients with locally advanced prostate cancer at high risk of skeletal metastasis (prostate-specific antigen > 10 ng/ml, composite Gleason score ≥ 8) or equivocal findings on bone scan were included in the retrospective study, and their MRI spine and bone scans were analysed.ResultsTen patients were detected to have definite spinal metastasis by bone scan, whereas 12 patients had definite skeletal metastasis by MRI spine. Compared with the ‘gold standard’, derived from clinical and radiological follow-up, the sensitivities for radionuclide bone scan and that for MRI spine for detecting skeletal metastasis were 71.4 and 85.7%, respectively (P = 0.023), whereas the specificities were 96.5 and 97.7%, respectively (P = 0.95). Of the 34 individual metastatic lesions in the spine, 15 were concordantly positive on both scans, whereas five lesions were positive only by bone scan and 11 positive only by MRI. The addition of MRI spine in the staging for prostate cancer resulted in a change of stage and management plan in seven (7%) patients.ConclusionMRI spine has comparable specificity and slightly better sensitivity than bone scan to detect spinal metastasis from prostate cancer.     

前列腺癌骨转移患者89SrCl2治疗后血清E-选择素浓度的变化

目的:观察前列腺癌骨转移患者89SrCl2治疗后血清E-选择素浓度的变化,了解核素治疗是否减少参与肿瘤细胞转移过程的细胞粘附分子-内皮细胞选择素(E-选择素)的表达.方法:23例经99Tcm-MDP骨扫描证实存在多发性骨转移的雄激素非依赖性前列腺癌患者,进行89SrCl2治疗,于治疗时、治疗后2、4、6、8个月测定患者血清E-选择素浓度,其中8例于初次治疗后8个月时接受第二次治疗.同时测定患者血清前列腺特异抗原(PSA),10例健康体检者作为对照.结果:前列腺癌多发性骨转移患者的血清E-选择素浓度在89SrCl2治疗后明显降低,治疗前后的血清E-选择素和PSA浓度之间不存在明显相关性.结论:89SrCl2可以抑制E-选择素的表达,这种作用可能为放射性核素抑制恶性肿瘤骨转移的机制之一.     

Monitoring therapeutic response in skeletal metastases using dual-energy x-ray absorptiometry: a prospective feasibility study in breast cancer patients

Response to systemic therapy in breast cancer patients with lytic skeletal metastases manifests as a shift from increased bone resorption to new bone formation. We hypothesized that dual-energy x-ray absorptiometry (DXA) could be used to prospectively quantitate changes in bone mineral density (BMD) in metastatic skeletal lesions in breast cancer patients receiving systemic therapy. Nine metastatic breast cancer patients with one or more assessable lytic skeletal metastases receiving systemic therapy were prospectively evaluated with DXA, skeletal radiographs, computed tomography (CT), and radionuclide bone scans at baseline (t = 0 months, 2 months, and 6 months). The median (range) percentage change in BMD in skeletal lesions among patients responding to systemic therapy was 10.7% (0.1-21.85), 5.0% (-1.3-23.8), and 16.7% (-2.0-50.8) at 0-2, 2-6, and 0-6 months, respectively. Changes in BMD between 0-2, and 0-6 months were significant (Wilcoxin signed rank test; p = 0.013 and p = 0.017, respectively). The percentage change in BMD skeletal lesions between 0-2 and 2-6 months correlated with the changes imaged on skeletal x-rays (Spearman rank order correlation coefficient [Rs] = 0.511, p = 0.011) and CTs (Rs = 0.416, p = 0.046) but less so with bone scans (Rs = 0.293, p = 0.189). It is technically feasible to use DXA to prospectively monitor changes in lytic skeletal metastases in breast cancer patients receiving systemic therapy. The BMD of skeletal metastases increases in patients responding to treatment and was significantly correlated with the changes imaged on skeletal x-rays and CTs. Additional studies of DXA to evaluate response in skeletal metastasis are warranted.     

Diagnostic Role of Serum Free-to-Total Prostate Specific Antigen (PSA) Ratio in Prostate Cancer with Serum Total Concentration of PSA below 4 ng/mL

Purpose: To examine the effectiveness of serum free-to-total prostate specific antigen ratio (%fPSA) forthe detection of prostate cancer (PCa) in men with different serum total PSA (tPSA) categories. Materials andMethods: From January 2010 to December 2013, a total of 225 patients with lower urinary tract symptoms(LUTS) underwent tPSA and %fPSA measurements. Histological examination with calculation of Gleasonscore and whole body bone scans were performed in identified cases of PCa. Results: PCa was diagnosed in 44(19.6%) patients and the remaining 181 patients had benign prostate disease. PCa was detected in 5 (23.8%),13 (8.7%) and 26 (47.3%) cases with tPSA level ranges ≤4 ng/ml, 4 to 10 ng/ml and >10 ng/ml, respectively. Theaverage Gleason score was 7.2±0.2. Some 6 (13.6%) out of 44 PCa patients had bone metastases. The sensitivitywas 80% and specificity was 81.3% at the cut-off %fPSA of 15% in PCa patients with a tPSA level below 4 ng/mL. A lower %fPSA was associated with PCa patients with Gleason score ≥7 than those with Gleason score≤6 (11.7±0.98 vs. 16.5±2.25%, P=0.029). No obvious relation of %fPSA to the incidence of bone metastasis wasapparent in this study. Conclusions: The clinical application of %fPSA could help to discriminate PCa frombenign prostate disease in men with a tPSA concentration below 4 ng/mL.     

Osseous metastases of breast cancer. Clinical, biochemical, radiographic, and scintigraphic evaluation of response to therapy

Serial bone scans and radiographs were assessed in 50 patients with breast cancer metastatic to bone treated with combination chemotherapy. In 34 patients evaluable nonosseous metastases were present in addition to bone lesions. Clinical and biochemical changes also were assessed serially, independent of skeletal disease. Pretherapy bone scans were more sensitive but less specific than radiographs for detection of osseous metastasis. Response to therapy in nonosseous metastasis correlated well with radiographic improvement of bone lesions (91%), but less well with changes in bone scans (57%). There was concordance between clinical and radiographic findings, suggesting progression of metastatic disease, in 81% of patients and between scan and clinical findings in 72% of them. Changes in carcinoembryonic antigen levels closely reflected clinical and radiographic changes. Serial bone radiographs are the most useful method of determining response to therapy in breast cancer metastatic to bone. The addition of scintigraphs and carcinoembryonic antigen measurements results in a highly sensitive and accurate method of response evaluation.     

全身骨显像疗效评价153 钐-EDTMP 治疗骨转移癌的疗效

目的：通过骨显像评价^153钐-EDTMP治疗骨转移癌的效果，进而证实其抑制、消除转移灶作用。方法：对182例恶性肿瘤合并骨转移病人共进行560次^153钐-EDTMP治疗，治疗前后常规行骨显像检查。结果：^153钐-EDTMP治疗后疼痛总缓解率为88．46％（161／182），12．64％（23／182）病例发生严重白细胞减低。44．51％（81／182）病例骨转移灶缩小、消失。结论：^153钐-EDTMP是通过抑制、消除骨转移灶达到止痛的。骨显像能显示治疗后骨转移灶的变化。     

Long-term outcomes of radical prostatectomy with multimodal adjuvant therapy in men with a preoperative serum prostate-specific antigen level > or =50 ng/mL

BACKGROUND.

The authors evaluated the long‐term outcomes of men with prostate cancer and very high (≥50 ng/mL) preoperative serum prostate‐specific antigen (PSA) values that were treated with radical prostatectomy.

METHODS.

This study included 236 men with preoperative serum PSA values ≥50ng/mL who underwent radical retropubic prostatectomy between 1987 and 2004. For comparison, the study cohort was divided into 2 groups: patients with PSA levels between 50 and 99 ng/mL and patients with PSA levels ≥100 ng/mL. Biochemical recurrence was defined as a single postoperative serum PSA value of 0.4 ng/mL or greater. Systemic disease progression was defined as the development of a local recurrence or systemic metastases, and any death resulting from prostate cancer or its treatment was defined as a cancer‐specific mortality.

RESULTS.

Biochemical recurrence‐free survival rates in the groups of patients with a PSA level 50 to 99 ng/mL and ≥100 ng/mL were 43% and 36% at 10 years, respectively. Systemic progression‐free survival rates in the PSA 50 to 99 ng/mL and PSA ≥100 ng/mL groups were 83% and 74% at 10 years, respectively. Estimated overall cancer‐specific survival was 87% at 10 years.

CONCLUSIONS.

Patients with prostate cancer and a serum PSA level ≥50 ng/mL have very high‐risk prostate cancer that carries a high likelihood of being pathologically advanced. Although the probability of realizing long‐term survival in these high‐risk patients is less than in patients with more favorable disease, 10‐year survival outcomes remain excellent and argue for aggressive management of these cases. Cancer 2008. © 2008 American Cancer Society.     

全身骨显像疗效评价^153钐-EDTMP治疗骨转移癌的疗效

目的：通过骨显像评价^153钐-EDTMP治疗骨转移癌的效果，进而证实其抑制、消除转移灶作用。方法：对182例恶性肿瘤合并骨转移病人共进行560次^153钐-EDTMP治疗，治疗前后常规行骨显像检查。结果：^153钐-EDTMP治疗后疼痛总缓解率为88．46％（161／182），12．64％（23／182）病例发生严重白细胞减低。44．51％（81／182）病例骨转移灶缩小、消失。结论：^153钐-EDTMP是通过抑制、消除骨转移灶达到止痛的。骨显像能显示治疗后骨转移灶的变化。     

The role of bisphosphonates in the treatment of prostate cancer: recommendations from an expert panel

In this study, we provide consensus guidelines for the use of bisphosphonates in men with prostate cancer. To this end, an expert panel composed of urologists, medical oncologists, radiation oncologists, and endocrinologists met to review current clinical evidence for the use of bisphosphonates in patients with different stages of prostate cancer to derive consensus recommendations. Physicians should be proactive in monitoring bone loss in patients receiving long-term androgen-deprivation therapy for prostate cancer. Further study is needed before recommending the routine use of bisphosphonates in men with nonmetastatic prostate cancer. However, if a patient has clinically significant bone loss, use of a bisphosphonate to prevent further compromise of bone integrity should be strongly considered, regardless of hormonal and metastatic status. Bone scans are the preferred method for the identification of bone metastases. In patients with hormonerefractory prostate cancer and bone metastases, zoledronic acid is the only bisphosphonate indicated for the prevention of skeletal complications. In conclusion, patients with prostate cancer are at high risk for skeletal morbidity. Bisphosphonates have been shown to prevent cancer treatment-induced bone loss in men receiving androgen-deprivation therapy as well as skeletal complications in men with bone metastases. However, further study of the use of bisphosphonates across the clinical spectrum of prostate cancer is needed.     

A case of castration-refractory prostate cancer showing marked decrease of serum PSA level after zoledronic acid treatment with estramustine phosphate and prednisolone

A 66-year-old man was referred to our outpatient clinic for an elevated serum prostatic-specific antigen (PSA 4,319 ng/ mL). Magnetic resonance imaging (MRI) showed multiple metastatic lesions in the bones. The patient had received androgen deprivation therapy, but six months after treatment, he was diagnosed as having prostate cancer refractory to hormones. Combined treatment with docetaxel (DOC 30 mg/m2/week )and estramustine phosphate (EMP 560 mg/day) was initiated as first-line chemotherapy, but the treatment was discontinued because of side effects. Then, treatment with zoledronic acid was started(4 mg/4 weeks)and the PSA level decreased dramatically from 457.2 ng/mL to 5.5 ng/mL. Seven months after the diagnosis of CRPC, MRI showed a decrease ofbone metastases, and the PSA levels continued to decrease, eventually reaching 0.3 ng/mL. Zoledronic acid appears to not only show efficacy in preventing skeletal-related events, but has a potential antitumor effect in patients with metastatic CRPC.     

Percentage of the positive area of bone metastasis is an independent predictor of disease death in advanced prostate cancer

We addressed in this study whether quantifying the extent of disease on bone scans can predict the disease death of patients with advanced prostate cancer using computer-assisted image analysis. Pretreatment radionuclide bone scans were reviewed in 56 patients with bone metastases from prostate cancer, and the percentage of the positive area on a bone scan (%PABS) was quantified automatically using a personal computer with the NIH Image program for estimation of the accurate extent of metastatic bone lesions on a bone scan. The significance of the %PABS as well as the other known prognostic factors was evaluated using univariate and multivariate Cox proportional hazards analysis. In univariate regression analysis, the %PABS (P=0.0155), serum alkaline phosphatase (P=0.0272), the tumour grade based on biopsy (P=0.044) and the number of bone lesions on bone scans (P=0.0388) were well associated with disease-specific survival. In multivariate analysis, the %PABS (P=0.0155, relative risk ratio 2.603), but not the other factors, was the independent predictor of the disease death. These results suggest that the %PABS is a novel parameter for predicting the prognosis of patients with advanced prostatic cancer.     

Detection of bone marrow involvement in patients with cancer

Current methods for the study of bone marrow to evaluate possible primary or metastatic cancers are reviewed. Bone marrow biopsy, radionuclide scan, computed tomography and magnetic resonance imaging (MRI) are analyzed with regard to their clinical usefulness at the time of diagnosis and during the course of the disease. Bone marrow biopsy is still the examination of choice not only in hematologic malignancies but also for tumors that metastasize into the marrow. Radionuclide scans are indicated for screening for skeletal metastases, except for those from thyroid carcinoma and multiple myeloma. Computed tomography is useful for cortical bone evaluation. MRI shows a high sensitivity in finding occult sites of disease in the marrow but its use has been restricted by high cost and limited availability. However, the future of MRI in bone marrow evaluation seems assured. MRI is already the method of choice for diagnosis of multiple myeloma, when radiography is negative, and for quantitative evaluation of lymphoma when a crucial therapeutic decision (i.e. bone marrow transplantation) must be made. Finally, methods are being developed that will enhance the sensitivity and specificity of MRI studies of bone marrow.     

Osteocalcin as a Biological Marker in the Therapeutic Management of Breast Cancer Bone Metastases

Circulating osteocalcin (BGP), the major noncollagenous bone protein, is elevated in patients with certain metabolic bone disease while its behavior in cancer patients, particularly those with bone metastases, is unclear. We measured circulating BGP in 37 healthy females, in 13 female patients with benign breast disease, and in a group of 51 cancer patients (breast, lung, prostate, and bladder) with and without bone metastases, before and after 4'-epidoxorubicin (4'-Epidx) therapy (4'-Epidx 120 mg/m² every 3 weeks). Under basal conditions, mean BGP levels of all of these subjects fell within the normal range of 2.0-5.0 ng/ml (mean SD, 4.8 1.0 ng/ml). In cancer patients without bone metastases BGP levels measured before and after 4'-Epidx therapy were not significantly different (4.4 versus 4.6 ng/ml). Only in breast cancer patients with multiple bone metastases was circulating BGP higher after the onset of antiblastic treatment and through the entire course of therapy, accompanied by bone pain remission and regression of bone lesions (BGP = 6.7 1.3 ng/ml). Thus an increase in BGP concentration can be considered as a biological marker of recovered osteoblast activity during therapeutically induced stabilization or regression of skeletal metastatic lesions.     

Response in bone turnover markers during therapy predicts overall survival in patients with metastatic prostate cancer: analysis of three clinical trials

Background:

The bone-forming metastases of prostate cancer result from complex stromal–epithelial interactions within the tumour microenvironment. Autocrine–paracrine signalling pathways between prostate cancer epithelial cells, osteoblasts, and osteoclasts stimulate aberrant bone remodelling, and the activity of these three cell populations can be quantitatively measured using prostate-specific antigen (PSA), bone-specific alkaline phosphatase (BAP) and urine N-telopeptide (uNTx), respectively. The purpose of the present study was to test the hypothesis that serial measurements of BAP and uNTx during therapy would facilitate monitoring of disease activity and predict the overall survival (OS) in patients with metastatic prostate cancer receiving therapy.

Methods:

Radionuclide bone scan, PSA, BAP, and uNTx data were retrospectively analysed from three clinical trials in patients with metastatic prostate cancer conducted at our institution. Qualitative changes in bone scans and quantitative changes in PSA, BAP, and uNTx concentrations during therapy were correlated with OS.

Results:

Baseline levels of BAP, but not PSA, were prognostic for OS in both androgen-dependent and castrate-resistant disease. A reduction in PSA, BAP, uNTx, or BAP/uNTx on therapy was predictive of improved OS in both patient groups. Conversely, an increase in PSA, or BAP on therapy was predictive of worse OS in both patient groups. Baseline number of lesions and response on bone scan during therapy were neither prognostic nor predictive of OS in either patient group.

Conclusion:

These observations support the concept that serial measurements of bone turnover metabolites during therapy function as clinically informative predictive biomarkers in patients with advanced prostate cancer and skeletal metastases. PSA measurements and bone scans remain essential to monitor the overall disease activity and determine the anatomic distribution of skeletal metastases.     

Magnetic resonance imaging in the detection of skeletal metastases in patients with breast cancer

Eighty-four patients with breast cancer at high risk of bone metastases were investigated with magnetic resonance imaging (MRI) of the thoracolumbar spine. Of 58 patients with normal limited skeletal surveys (LSS) and bone scans (BS), 4 (7%) had MR images compatible with malignant infiltration. Fourteen patients had abnormal bone scans with normal or non-diagnostic plain films; 7 of these patients (50%) had MR images compatible with malignant infiltration. Twelve patients had single or multiple wedge collapses of uncertain aetiology on plain film; MR demonstrated metastatic disease as the cause of wedge collapse in 7 (58%). MRI may define a group of patients with extra-osseous relapse who have occult metastatic disease. Although the detection rate in patients with primary breast cancer is low (4/45), MRI is of value in determining the cause of wedge collapse in postmenopausal women with breast cancer and may elucidate the cause of an abnormal bone scan with normal or non-diagnostic plain films.     

Prognostic Risk Classification for Biochemical Relapse-Free Survival in Oligometastatic Recurrent Prostate Cancer Determined by Choline PET

BackgroundCholine positron emission tomography/computed tomography (PET/CT) is a new imaging technique for the detection of oligometastatic (OM) prostate cancer. The aim of this study was to evaluate the outcomes after initial OM diagnoses; treatment, particularly metastasis-directed therapy (MDT); and determine risk groups.Patients and MethodsThis multi-center, retrospective study included patients with hormone-sensitive biological relapse after local treatment with curative intent and with fewer than six choline PET/CT metastases. The primary endpoint was biochemical relapse-free survival (bRFS). Risk groups were based on prostate-specific antigen (PSA) ≥ 0.8 ng/mL and metastatic sites at OM cancer diagnosis.ResultsBetween October 2012 and December 2016, 177 patients were included, with a median follow-up of 49.02 months. The median bRFS was 39.74 months. In multivariate analyses, bone metastases and PSA ≥ 0.8 ng/mL were associated with worse bRFS. Four risk groups (I to IV; hazard ratio [HR], 5.92; 95% confidence interval [CI], 1.32-26.61) were observed, with median bRFS not reached for group I (PSA < 0.8 ng/mL; node metastasis [M1a]), a 40.00-month bRFS for group II (PSA ≥ 0.8 ng/mL; M1a), 29.97-month bRFS for group III (bone metastasis [M1b], whatever the PSA level); and 22.70-month bRFS for group IV (PSA > 0.8 ng/mL and visceral metastasis [M1c]). MDT plus androgen deprivation therapy (ADT) improved bRFS over MDT alone (48.36 vs. 34.16 months; HR, 2.12; 95% CI, 1.38-3.26), particularly for group II (HR, 2.09; 95% CI, 1.09-4.00), and reached a limit of significance for group III (HR, ;3.79 95% CI, 0.88- 16.38).ConclusionPrognostic group classifications were confirmed: PSA < 0.8 ng/mL and M1a showed a better outcome than patients with M1c and PSA ≥ 0.8 ng/mL. These results could facilitate patient selection for prospective clinical trials in OM prostate cancer.     

原发性肺癌患者治疗前后放射性核素骨显像的应用价值

目的 探讨核素骨显像在原发性肺癌患者治疗前帮助确定治疗方案及治疗后定期随访的应用价值.方法 对810例原发性肺癌患者在治疗前进行了核素骨显像,对其中采用手术治疗的492例患者术后2年进行了核素骨显像随访,非手术治疗的318例患者中,治疗前无骨转移的142例患者治疗后进行了2年的核素骨显像随访.结果 在810例肺癌患者治疗前共检出骨转移179例,占22.1%,其中多发性骨转移157例,单发性骨转移22例,骨转移灶绝大多数分布于胸部、脊柱及骨盆.手术后2年内检出骨转移57例.非手术治疗且治疗前无骨转移的142例患者在2年内新检出骨转移患者79例.结论核素骨显像在肺癌治疗前可帮助疾病分期及确定治疗方案.手术治疗后定期骨显像有助于早期发现骨转移及确定相应治疗方案,应作为检查骨转移的首选方法.其他方法治疗后骨显像随访,可能有助于对患者预后的判断.     

血清PSA及fPSA/tPSA比值在前列腺癌骨转移诊断中的价值

目的:通过分析前列腺癌患者血清中前列腺癌特异性抗原（PSA）浓度和游离前列腺特异性抗原（fPSA）/总前列腺特异性抗原（tPSA）与骨转移的关系,探讨血清PSA和fPSA/tPSA在诊断前列腺癌骨转移中的价值。方法:采用电化学发光法检测74例前列腺癌患者血清中的fPSA、tPSA浓度并计算fPSA/tPSA,并对所有前列腺癌患者进行全身骨扫描显像。结果:74例前列腺癌患者当中无骨转移的29例,有骨转移的45例,分别占前列腺癌患者的39.2％和60.8％。在发生骨转移的前列腺癌患者当中单一病灶的有5例,占11.1%,其中3例转移灶在骨盆,2例在椎体;转移灶为两处的有3例,占6.7%;三处或三处以上转移的有37例,占82.2%。从骨转移发生的部位来看,椎体转移的最多,有35例;其次为骨盆转移,有31例;发生肋骨转移的有28例;四肢骨转移的有9例;其它部位转移的有2例。前列腺癌骨转移组和无骨转移组的PSA和fPSA/tPSA分别为（57.68±38.67） ng/ml、0.14±0.08和（21.61±17.87） ng/ml、0.25±0.09,差异均有统计学意义（P<0.05）。结论:前列腺癌骨转移以多发病灶为主,且病灶主要发生在脊柱和骨盆。前列腺癌患者随血清PSA浓度的升高,fPSA/tPSA比值降低,发生骨转移的比例增高,当PSA>20.00 ng/ml或fPSA/tPSA≤0.15时,诊断前列腺癌骨转移的灵敏度和特异度较高。     

Bone scintigrams: their clinical usefulness in patients with breast carcinoma.

A comparison of bone scintigrams and roentgenographic skeletal surveys, obtained on 170 patients with breast carcinoma, was made to evaluate the diagnostic efficacy of these techniques in detecting metastatic bone lesions. The bone scans were abnormal in 81 patients, while the roentgenograms were abnormal in only 51. In 34 of the 81 (42%) patients with abnormal bone scans, there was no radiographic evidence of a benign lesion to account for the increased ratiotracer uptake; and the abnormalities noted on the bone scans were proven to be bony metastases on follow-up examinations. In the remaining 47 patients with positive bone scintigrams, both the scans and the roentgenograms were abnormal; however, in 23 patients the bone scan demonstrated significantly more lesions than what the roentgenograms had revealed. This study confirms that bone scan is superior to roentgen surveys in detecting skeletal metastases in patients with breast carcinoma. It was noted that the metastatic lesions can be visualized on the scans earlier than they are apparent on the X-rays by a mean interval of 4 months.