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1.  Consequence of the introduction of routine FCH PET/CT imaging for patients with prostate cancer: a dual centre survey 
Radiology and Oncology  2014;48(1):20-28.
Fluorocholine(18F) (FCH) was introduced at the beginning of April 2010 in France, Slovenia and three other EU member states for the localisation of bone metastases of prostate cancer with PET. The aim of the study was to compare the evolution of diagnostic imaging in patients with prostate cancer using a new radiopharmaceutical FCH, observed in France and in Slovenia, and to quantify the consequence of the results of new imaging modality on the detection rate of abnormal metastases and recurrences of prostate cancer.
Patients and methods
In two centres (France/Slovenia), a survey of the number of nuclear medicine examinations in patients with prostate cancer was performed, covering 5 quarters of the year since the introduction of FCH. For each examination, the clinical and biological circumstances were recorded, as well as the detection of bone or soft tissue foci.
Six hundred and eighty-eight nuclear medicine examinations were performed impatients with prostate cancer. Nuclear medicine examinations were performed for therapy monitoring and follow-up in 23% of cases. The number of FCH PET/CT grew rapidly between the 1st and 5th period of the observation (+220%), while the number of bone scintigraphies (BS) and fluoride(18F) PET/CTs decreased (−42% and −23% respectively). Fluorodeoxyglucose(18F) (FDG) PET/CT remained limited to few cases of castrate-resistant or metastatic prostate cancer in Paris. The proportion of negative results was significantly lower with FCH PET/CT (14%) than with BS (49%) or fluoride(18F) PET/CT (54%). For bone metastases, the detection rate was similar, but FCH PET/CT was performed on average at lower prostate-specific antigen (PSA) levels and was less frequently doubtful (4% vs. 28% for BS). FCH PET/CT also showed foci in prostatic bed (53% of cases) or in soft tissue (35% of cases).
A rapid development of FCH PET/CT was observed in both centres and led to a higher detection rate of prostate cancer lesions.
PMCID: PMC3908843  PMID: 24587775
prostate cancer; PET/CT; fluorocholine (FCH); fluoride(18F); bone scintigraphy; indication of imaging
2.  Early outcome prediction on 18F-fluorocholine PET/CT in metastatic castration-resistant prostate cancer patients treated with abiraterone 
Oncotarget  2014;5(23):12448-12458.
Objective: We investigated the role of 18F-fluorocholine positron emission tomography/computed tomography (FCH-PET/CT) in the early evaluation of abiraterone and outcome prediction in patients with metastatic castration-resistant prostate cancer (CRPC).
Patient and methods: Forty-three patients with metastatic CRPC progressing after docetaxel received abiraterone 1,000 mg daily with prednisone 5 mg twice daily. Patients were evaluated monthly for serological PSA response and safety. FCH-PET/CT was done at baseline and after 3 to 6 weeks. Univariate and multivariate Cox regression models addressed potential predictors of progression-free survival (PFS) and overall survival (OS).
Results: Declines in PSA level of ≥50% were seen in 21 of 43 (49%) patients. Forty-two patients were evaluable for FCH-PET/CT response. FCH-PET/CT bone flare was observed in 4 of 42 (10%) evaluable patients. In univariate analysis, PSA decline and FCH-PET/CT response predicted PFS, while PSA decline and FCH-PET/CT (progression vs non progression) predicted OS. In multivariate analysis, only FCH-PET/CT (progression vs nonprogression) remained significant for PFS and OS (p = 0.022 and p = 0.027, respectively).
Conclusion: Early FCH-PET/CT can predict clinical outcome in CRPC beyond PSA response. These data support further studies on FCH-PET/CT for abiraterone monitoring and outcome prediction in patients with CRPC.
PMCID: PMC4322993  PMID: 25504434
Abiraterone; Castration-resistant prostate cancer; 18F-fluorocholine positron emission tomography; PSA; Bone flare
3.  Measurement of Circulating Cell-Free DNA in Relation to 18F-Fluorocholine PET/CT Imaging in Chemotherapy-Treated Advanced Prostate Cancer 
To examine the effects of chemotherapy on circulating cell-free DNA (cfDNA) composition in relation to investigational whole-body measurement of tumor activity by fluorine-18 fluorocholine (FCH) positron emission tomography/computed tomography (PET/CT) in hormone-refractory prostate cancer (HRPC).
Serial FCH PET/CT scans were performed in eight patients with HRPC receiving docetaxel-based chemotherapy. Corresponding serial cfDNA samples were characterized by microfluidic electrophoresis, quantified by real-time PCR, and compared with PET/CT results. Promoter methylation of two prostate cancer-associated genes, GSTP1 and RARB2, was assessed by methylation-specific PCR of bisulfite-converted cfDNA.
Plasma cfDNA concentrations increased significantly from 13.3 ng/mL at baseline to 46.8 ng/mL and 50.9 ng/mL after one and three treatment cycles, respectively (p= 0.001). GSTP1 and/or RARB2 promoter methylation was identified in all pretreatment samples. The appearance of large (200 bp–10.4 kb) cfDNA fragments was noted in posttreatment samples along with loss of methylation at GSTP1 and/or RARB2. Tumor activity on PET/CT correlated with cfDNA concentration (r=−0.50, p= 0.01). Patients meeting criteria for PET tumor response had significantly lower pretreatment cfDNA levels than those who did not (8.0 vs. 16.4 ng/mL, p= 0.03).
Chemotherapy is associated with significant changes in plasma cfDNA content and FCH PET/CT-detected tumor activity. These interrelated measures are potential candidate markers of therapeutic response in HRPC. Clin Trans Sci 2012; Volume #: 1–6
PMCID: PMC3500883  PMID: 22376260
prostate cancer; nucleic acids; epigenetics; positron emission tomography
4.  Prostate-Specific Antigen and Prostate-Specific Antigen Velocity as Threshold Indicators in 11C-Acetate PET/CTAC Scanning for Prostate Cancer Recurrence 
Clinical Nuclear Medicine  2014;39(9):777-783.
The aim of this study was to identify which patient characteristics are associated with the highest likelihood of positive findings on 11C-acetate PET/computed tomography attenuation correction (CTAC) (PET/CTAC) scan when imaging for recurrent prostate cancer.
From 2007 to 2011, 250 11C-acetate PET/CTAC scans were performed at a single institution on patients with prostate cancer recurrence after surgery, brachytherapy, or external beam radiation. Of these patients, 120 met our inclusion criteria. Logistic regression analysis was used to examine the relationship between predictability of positive findings and patients’ characteristics, such as prostate-specific antigen (PSA) level at the time of scan, PSA kinetics, Gleason score, staging, and type of treatment before scan.
In total, 68.3% of the 120 11C-acetate PET/CTAC scans were positive. The percentage of positive scans and PSA at the time of scanning and PSA velocity (PSAV) had positive correlations. The putative sensitivity and specificity were 86.6% and 65.8%, respectively, when a PSA level greater than 1.24 ng/mL was used as the threshold for scanning. The putative sensitivity and specificity were 74% and 75%, respectively, when a PSAV level greater than 1.32 ng/mL/y was used as the threshold. No significant associations were found between scan positivity and age, PSA doubling time, Gleason score, staging, or type of treatment before scanning.
This retrospective study suggests that threshold models of PSA greater than 1.24 ng/mL or PSAV greater than 1.32 ng/mL per year are independent predictors of positive findings in 11C-acetate PET/CTAC imaging of recurrent prostate cancer.
PMCID: PMC4136979  PMID: 25036021
11C-acetate PET; prostate cancer recurrence; prostate cancer imaging; PSA; 11C-choline PET
5.  Diagnostic role of fluorodeoxyglucose positron emission tomography-computed tomography in prostate cancer 
Oncology Letters  2014;7(6):2013-2018.
The role of fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET)-computed tomography (CT) in prostate cancer remains controversial due to a limited number of previous clinical investigations. The aim of the present retrospective study was to assess the diagnostic value of FDG PET-CT in prostate cancer, with an emphasis on the detection of metastatic disease. Twenty-five relevant cases of patients with newly diagnosed prostate cancer, referred for staging, or with a history of prostate cancer or recent prostate specific antigen (PSA) relapse, referred for the detection of metastatic disease, were included in the present study. None of the patients had known imaging or pathological evidence of metastatic disease prior to FDG PET-CT, however, the PSA levels had been recorded in all patients in the two months prior to FDG PET-CT imaging. Verification of the FDG PET-CT observations was made by biopsy, regional diagnostic CT and/or whole-body bone scintigraphy. The sensitivity of FDG PET-CT in identifying untreated primary lesions was only 33% (3/9). However, FDG PET-CT detected metastatic disease in six of the nine patients who underwent initial staging. Out of 16 patients with previous treatments and recent PSA relapse, FDG PET-CT successfully identified metastatic diseases in 12 and tumor recurrence within the prostatic fossa of two patients. The difference in the PSA levels was identified to be statistically significant between the FDG PET-CT-positive and -negative subgroups of the 16 restaging patients. The results indicated that FDG PET-CT is not useful for the diagnosis of prostate cancer, but may aid with the detection of metastatic disease in appropriately selected patients.
PMCID: PMC4049681  PMID: 24932281
fluorine-18 fluorodeoxyglucose positron emission tomography-computed tomography; metastasis; prostate cancer; prostate-specific antigen
6.  Serum prostate-specific antigen value adjusted for non-cancerous prostate tissue volume in patients undergoing radical prostatectomy: a new predictor of biochemical recurrence in localized or locally advanced prostate cancer 
Asian Journal of Andrology  2010;13(2):248-253.
The aim of this study was to investigate the significance of serum prostate-specific antigen (PSA) value adjusted for total tumor volume (PSA/tumor volume) and serum PSA value adjusted for non-cancerous prostate tissue volume (NCPV) (PSA/NCPV) as a predictor of pathological findings and clinical outcome after radical prostatectomy. Clinical and pathological data of 407 patients (median age: 66.5 years; range: 41.8–85.7 years) were reviewed retrospectively. The median follow-up period was 18.1 months (range: 1.0–107.8 months). Biochemical recurrence was defined as detectable PSA levels (greater than 0.2 ng ml−1) and the time of biochemical recurrence was taken to be the first time PSA became detectable. In the multivariate model, PSA/NCPV was an independent predictor of extracapsular extension and positive surgical margin (P<0.05), but PSA/tumor volume was not. Kaplan–Meier curves revealed that PSA/NCPV correlated with biochemical recurrence-free survival (P<0.001; log-rank test) but PSA/tumor volume did not (P=0.275; log-rank test). PSA/NCPV was also a significant independent prognostic factor for biochemical recurrence-free survival on multivariate Cox proportional hazard analysis (P=0.004, relative risk=2.42). Our findings suggest that PSA/NCPV is associated independently with extracapsular extension and surgical margin status and may be an independent prognostic variable of PSA recurrence after radical prostatectomy.
PMCID: PMC3739195  PMID: 21102474
prostatectomy; prostatic neoplasm; PSA; treatment outcome; tumor volume
7.  Prospective Evaluation of 18F-NaF and 18F-FDG PET/CT in Detection of Occult Metastatic Disease in Biochemical Recurrence of Prostate Cancer 
Clinical Nuclear Medicine  2012;37(7):637-643.
This study aimed to perform a prospective evaluation of 18F-NaF and 18F-FDG PET/CT in the detection of occult metastatic disease in men with prostate cancer and biochemical relapse.
Thirty-seven men with prostate-specific antigen (PSA) relapse (median, 3.2 ng/mL; range, 0.5–40.2 ng/mL) after definitive therapy for localized prostate cancer [26 radical prostatectomy (RP), 11 external beam radiation therapy] and negative conventional imaging underwent 18F-FDG and 18F-NaF PET/CT on 2 separate days within the same week. Studies were interpreted by 2 experienced radiologists in consensus for abnormal uptake suspicious for metastatic disease. The reference standard was a combination of imaging and clinical follow-up. Rank of PSA values for positive and negative PET/CT was compared using analysis of variance adjusting for primary therapy. Association between PSA and scan positivity in patients with RP was evaluated using Wilcoxon rank sum test.
Result of the 18F-FDG PET/CT scan was positive for nodal disease in 2 patients. True-positive detection rate for occult osseous metastases by 18F-NaF PET/CT was 16.2%. Median PSA levels for positive versus negative PET/CT scans were 4.4 and 2.9 ng/mL, respectively, with the difference marginally significant in prostatectomized men (P = 0.072). Percentages of patients with either 18F-NaF– or 18F-FDG–positive PET/CT in RP and external beam radiation therapy were 10% (n = 10) and undefined (n = 0) for a PSA of 2 ng/mL or less, 29% (n = 7) and 50% (n = 2) for PSA greater than 2 ng/mL but 4 ng/mL or less,60% (n = 5) and 40%(n = 5) for PSA greater than 4 ng/mL but 10 ng/mL or less, and 25% (n = 4) and 25% (n = 4) for PSA greater than 10 ng/mL, respectively.
In biochemical relapse of prostate cancer, 18F-NaF PET/CT is useful in the detection of occult osseous metastases, whereas the yield of 18F-FDG PET/CT is relatively limited. 18F-NaF PET/CT positivity tends to associate with increasing PSA level in prostatectomized men and may occur in lower PSA ranges than conventionally recognized.
PMCID: PMC3375600  PMID: 22691503
18F-NaF; 18F-FDG; prostate; cancer; PSA
8.  Early detection of prostate cancer local recurrence by urinary prostate-specific antigen 
We assessed the role of urinary prostate-specific antigen (uPSA) in the follow-up of prostate cancer after retropubic radical prostatectomy (RRP) for the early detection of local recurrences.
We recruited 50 patients previously treated for prostate cancer with RRP and who had not experienced a prostate-specific antigen (PSA) recurrence within their first postoperative year into a cross-sectional laboratory assessment and prospective 6-year longitudinal follow-up study. We defined biochemical failure as a serum PSA (sPSA) of 0.3 μg/L or greater. Patients provided blood samples and a 50-mL sample of first-voided urine. We performed Wilcoxon rank-sum and Fisher exact tests for statistical analysis.
The median sPSA was 0.13 μg/L. The median uPSA was 0.8 μg/L, and was not significantly different when comparing Gleason scores or pathological stages. Of the 50 patients, 27 initially had a nondetectable sPSA but a detectable uPSA, and 11 patients experienced sPSA failure after 6 years. Six patients had detectable sPSA and uPSA initially. Fifteen patients were negative for both sPSA and uPSA, and 13 remained sPSA-free after 6 years. The odds ratio (OR) of having sPSA failure given a positive uPSA test was 4.5 if sPSA was undetectable, but was reduced to 2.6 if sPSA was detectable. The pooled Mantel–Haenszel OR of 4.2 suggested that a detectable uPSA quadrupled the risk of recurrence, independent of whether sPSA was elevated or not. The sensitivity of uPSA for detecting future sPSA recurrences was 81% and specificity was 45%.
Urinary PSA could contribute to an early detection of local recurrences of prostate cancer after a radical prostatectomy.
PMCID: PMC2692171  PMID: 19543465
9.  New Acquisition Protocol of 18F-Choline PET/CT in Prostate Cancer Patients: Review of the Literature about Methodology and Proposal of Standardization 
BioMed Research International  2014;2014:215650.
Purpose. (1) To evaluate a new acquisition protocol of 18F-choline (FCH) PET/CT for prostate cancer patients (PC), (2) to review acquisition 18F-choline PET/CT methodology, and (3) to propose a standardized acquisition protocol on FCH PET/CT in PC patients. Materials. 100 consecutive PC patients (mean age 70.5 years, mean PSA 21.35 ng/mL) were prospectively evaluated. New protocol consisted of an early scan of the pelvis immediately after the injection of the tracer (1 bed position of 4 min) followed by a whole body scan at one 1 hour. Early and 1 hour images were compared for interfering activity and pathologic findings. Results. The overall detection rate of FCH PET/CT was 64%. The early static images of the pelvis showed absence of radioactive urine in ureters, bladder, or urethra which allowed a clean evaluation of the prostatic fossae. Uptake in the prostatic region was better visualized in the early phase in 26% (7/30) of cases. Other pelvic pathologic findings (bone and lymph nodes) were visualized in both early and late images. Conclusion. Early 18F-choline images improve visualization of abnormal uptake in prostate fossae. All pathologic pelvic deposits (prostate, lymph nodes, and bone) were visualized in both early and late images.
PMCID: PMC4119889  PMID: 25121090
10.  Fluorodeoxyglucose positron emission tomography may aid the diagnosis of aggressive primary prostate cancer: A case series study 
Oncology Letters  2013;7(2):381-386.
Recent evidence has shown that positive results may be observed for fluorodeoxyglucose-positron emission tomography (FDG-PET) in undifferentiated, biologically aggressive and metastatic tumors. The present study describes a case series of six patients with normal prostate-specific antigen (PSA) serum levels who underwent FDG-PET due to other causes. Positive PET results were observed at the prostate and the patients were subsequently diagnosed with high-risk prostate cancer. Clinical, anamnestic, laboratory and instrumental data were collected from six asymptomatic patients with total serum PSA levels of <4 ng/ml who had undergone FDG-PET due to other causes. The FDG-PET and prostate biopsy were positive for prostate cancer. All the patients were treated with radical intent. The median age was 66 years (range, 52–72 years), the median total PSA value was 2.4 ng/ml (range, 1.5–3.9 ng/ml) and the body mass index was 26.4 (range, 21.8–30.2). Three of the six patients underwent FDG-PET due to a clinical suspicion of multiple myeloma, while three patients were examined for other oncological diseases. The pathological analysis at the prostate biopsy revealed three patients with a Gleason score of 6, two with a score of 7 (4+3) and one with a score of 8 (4+4). Five of the six patients were treated by radical prostatectomy and one by radiotherapy. The pathological analysis revealed one patient of pT2a stage, three of pT2c and one of pT3b. No patients demonstrated lymph node invasion. The definitive Gleason score was 3+3 in one patient, 4+3 in one patient, 4+4 in two patients and 5+3 in one patient. Following a median follow-up time of six months (range, 1–12 months), five of the six patients underwent FDG-PET again, which revealed negative results. At the end of this study, these patients were alive without evidence of disease. By contrast, one patient demonstrated positive FDG-PET results. In conclusion, FDG-PET has been used to characterize prostate cancers in patients with apparently normal PSA levels.
PMCID: PMC3881937  PMID: 24396452
prostate cancer; cancer metabolism; positron emission tomography; high-risk prostate cancer; prostate specific antigen
11.  Cancer Screening: A Mathematical Model Relating Secreted Blood Biomarker Levels to Tumor Sizes  
PLoS Medicine  2008;5(8):e170.
Increasing efforts and financial resources are being invested in early cancer detection research. Blood assays detecting tumor biomarkers promise noninvasive and financially reasonable screening for early cancer with high potential of positive impact on patients' survival and quality of life. For novel tumor biomarkers, the actual tumor detection limits are usually unknown and there have been no studies exploring the tumor burden detection limits of blood tumor biomarkers using mathematical models. Therefore, the purpose of this study was to develop a mathematical model relating blood biomarker levels to tumor burden.
Methods and Findings
Using a linear one-compartment model, the steady state between tumor biomarker secretion into and removal out of the intravascular space was calculated. Two conditions were assumed: (1) the compartment (plasma) is well-mixed and kinetically homogenous; (2) the tumor biomarker consists of a protein that is secreted by tumor cells into the extracellular fluid compartment, and a certain percentage of the secreted protein enters the intravascular space at a continuous rate. The model was applied to two pathophysiologic conditions: tumor biomarker is secreted (1) exclusively by the tumor cells or (2) by both tumor cells and healthy normal cells. To test the model, a sensitivity analysis was performed assuming variable conditions of the model parameters. The model parameters were primed on the basis of literature data for two established and well-studied tumor biomarkers (CA125 and prostate-specific antigen [PSA]). Assuming biomarker secretion by tumor cells only and 10% of the secreted tumor biomarker reaching the plasma, the calculated minimally detectable tumor sizes ranged between 0.11 mm3 and 3,610.14 mm3 for CA125 and between 0.21 mm3 and 131.51 mm3 for PSA. When biomarker secretion by healthy cells and tumor cells was assumed, the calculated tumor sizes leading to positive test results ranged between 116.7 mm3 and 1.52 × 106 mm3 for CA125 and between 27 mm3 and 3.45 × 105 mm3 for PSA. One of the limitations of the study is the absence of quantitative data available in the literature on the secreted tumor biomarker amount per cancer cell in intact whole body animal tumor models or in cancer patients. Additionally, the fraction of secreted tumor biomarkers actually reaching the plasma is unknown. Therefore, we used data from published cell culture experiments to estimate tumor cell biomarker secretion rates and assumed a wide range of secretion rates to account for their potential changes due to field effects of the tumor environment.
This study introduced a linear one-compartment mathematical model that allows estimation of minimal detectable tumor sizes based on blood tumor biomarker assays. Assuming physiological data on CA125 and PSA from the literature, the model predicted detection limits of tumors that were in qualitative agreement with the actual clinical performance of both biomarkers. The model may be helpful in future estimation of minimal detectable tumor sizes for novel proteomic biomarker assays if sufficient physiologic data for the biomarker are available. The model may address the potential and limitations of tumor biomarkers, help prioritize biomarkers, and guide investments into early cancer detection research efforts.
Sanjiv Gambhir and colleagues describe a linear one-compartment mathematical model that allows estimation of minimal detectable tumor sizes based on blood tumor biomarker assays.
Editors' Summary
Cancers—disorganized masses of cells that can occur in any tissue—develop when cells acquire genetic changes that allow them to grow uncontrollably and to spread around the body (metastasize). If a cancer (tumor) is detected when it is small, surgery can often provide a cure. Unfortunately, many cancers (particularly those deep inside the body) are not detected until they are large enough to cause pain or other symptoms by pressing against surrounding tissue. By this time, it may be impossible to remove the original tumor surgically and there may be metastases scattered around the body. In such cases, radiotherapy and chemotherapy can sometimes help, but the outlook for patients whose cancers are detected late is often poor. Consequently, researchers are trying to develop early detection tests for different types of cancer. Many tumors release specific proteins—“cancer biomarkers”—into the blood and the hope is that it might be possible to find sets of blood biomarkers that detect cancers when they are still small and thus save many lives.
Why Was This Study Done?
For most biomarkers, it is not known how the amount of protein detected in the blood relates to tumor size or how sensitive the assays for biomarkers must be to improve patient survival. In this study, the researchers develop a “linear one-compartment” mathematical model to predict how large tumors need to be before blood biomarkers can be used to detect them and test this model using published data on two established cancer biomarkers—CA125 and prostate-specific antigen (PSA). CA125 is used to monitor the progress of patients with ovarian cancer after treatment; ovarian cancer is rarely diagnosed in its early stages and only one-fourth of women with advanced disease survive for 5 y after diagnosis. PSA is used to screen for prostate cancer and has increased the detection of this cancer in its early stages when it is curable.
What Did the Researchers Do and Find?
To develop a model that relates secreted blood biomarker levels to tumor sizes, the researchers assumed that biomarkers mix evenly throughout the patient's blood, that cancer cells secrete biomarkers into the fluid that surrounds them, that 0.1%–20% of these secreted proteins enter the blood at a continuous rate, and that biomarkers are continuously removed from the blood. The researchers then used their model to calculate the smallest tumor sizes that might be detectable with these biomarkers by feeding in existing data on CA125 and on PSA, including assay detection limits and the biomarker secretion rates of cancer cells growing in dishes. When only tumor cells secreted the biomarker and 10% of the secreted biomarker reach the blood, the model predicted that ovarian tumors between 0.11 mm3 (smaller than a grain of salt) and nearly 4,000 mm3 (about the size of a cherry) would be detectable by measuring CA125 blood levels (the range was determined by varying the amount of biomarker secreted by the tumor cells and the assay sensitivity); for prostate cancer, the detectable tumor sizes ranged from similar lower size to about 130 mm3 (pea-sized). However, healthy cells often also secrete small quantities of cancer biomarkers. With this condition incorporated into the model, the estimated detectable tumor sizes (or total tumor burden including metastases) ranged between grape-sized and melon-sized for ovarian cancers and between pea-sized to about grapefruit-sized for prostate cancers.
What Do These Findings Mean?
The accuracy of the calculated tumor sizes provided by the researchers' mathematical model is limited by the lack of data on how tumors behave in the human body and by the many assumptions incorporated into the model. Nevertheless, the model predicts detection limits for ovarian and prostate cancer that broadly mirror the clinical performance of both biomarkers. Somewhat worryingly, the model also indicates that a tumor may have to be very large for blood biomarkers to reveal its presence, a result that could limit the clinical usefulness of biomarkers, especially if they are secreted not only by tumor cells but also by healthy cells. Given this finding, as more information about how biomarkers behave in the human body becomes available, this model (and more complex versions of it) should help researchers decide which biomarkers are likely to improve early cancer detection and patient outcomes.
Additional Information.
Please access these Web sites via the online version of this summary at
The US National Cancer Institute provides a brief description of what cancer is and how it develops and a fact sheet on tumor markers; it also provides information on all aspects of ovarian and prostate cancer for patients and professionals, including information on screening and testing (in English and Spanish)
The UK charity Cancerbackup also provides general information about cancer and more specific information about ovarian and prostate cancer, including the use of CA125 and PSA for screening and follow-up
The American Society of Clinical Oncology offers a wide range of information on various cancer types, including online published articles on the current status of cancer diagnosis and management from the educational book developed by the annual meeting faculty and presenters. Registration is mandatory, but information is free
PMCID: PMC2517618  PMID: 18715113
12.  Incidental uptake of 18F-fluorocholine (FCH) in the head or in the neck of patients with prostate cancer 
Radiology and Oncology  2014;48(3):228-234.
Positron emission tomography-computed tomography (PET/CT) with 18F-fluorocholine (FCH) is routinely performed in patients with prostate cancer. In this clinical context, foci of FCH uptake in the head or in the neck were considered as incidentalomas, except for those suggestive of multiple bone metastases.
In 8 patients the incidental focus corresponded to a benign tumour. The standard of truth was histology in two cases, correlative imaging with MRI in four cases, 99mTc-SestaMIBI scintigraphy, ultrasonography and biochemistry in one case and biochemistry including PTH assay in one case. The final diagnosis of benign tumours consisted in 3 pituitary adenomas, 2 meningiomas, 2 hyperfunctioning parathyroid glands and 1 thyroid adenoma.
Malignancy was proven histologically in 2 other patients: 1 papillary carcinoma of the thyroid and 1 cerebellar metastasis.
To the best of our knowledge, FCH uptake by pituitary adenomas or hyperfunctioning parathyroid glands has never been described previously. We thus discuss whether there might be a future indication for FCH PET/CT when one such tumour is already known or suspected: to detect a residual or recurrent pituitary adenoma after surgery, to guide surgery or radiotherapy of a meningioma or to localise a hyperfunctioning parathyroid gland. In these potential indications, comparative studies with reference PET tracers or with 99mTc-sestaMIBI in case of hyperparathyroidism could be undertaken.
PMCID: PMC4110078  PMID: 25177236
FCH, PET/CT; incidentaloma; meningioma; pituitary adenoma; hyperparathyroidism; thyroid adenoma
13.  False-Negative Bone Scan and Choline Pet/Ct Study in a Case of Prostate Cancer: The Pitfall of the Small Cell Prostate Carcinoma Variant 
We present a rare variant of prostate carcinoma. The patient is a 45-year-old male with elevated prostate-specific antigen levels at screening. Magnetic resonance imaging revealed hyperenhancing lesions throughout the axial skeleton. The fluorine-18 fluorocholine (FCH) positron emission tomography/computed tomography (PET/CT) scan showed no abnormal bone findings. Subsequently, a technetium-99 methydiphosphonate (Tc99m-MDP) bone scan was performed, with additional correlative single-photon emission computed tomography (SPECT)/CT imaging of the pelvis and the results were essentially normal. A percutaneous core biopsy of one of the bone lesions in L5 was performed and histology confirmed small cell (neuroendocrine) variant of prostate cancer. Our case illustrates a possible pitfall in molecular imaging of prostate carcinomas, whereby both bone scintigraphy and FCH PET/CT scans showed no definite bone lesions to correlate with marrow signal abnormalities seen on MR imaging. This highlights the need for caution in the diagnostic evaluation of prostate cancers with known small cell variants.
PMCID: PMC3555398  PMID: 23372441
Fluorocholine; positron emission tomography; prostate carcinoma; small cell cancer
14.  11C-Acetate PET/CT before Radical Prostatectomy: Nodal Staging and Treatment Failure Prediction 
Despite early detection programs, many patients with prostate cancer present with intermediate- or high-risk disease. We prospectively investigated whether 11C-acetate PET/CT predicts lymph-node (LN) metastasis and treatment failure in men planned for radical prostatectomy.
107 men with intermediate-or-high-risk localized prostate cancer with negative conventional imaging underwent PET/CT with 11C-acetate. Five underwent LN staging only and 102 LN staging and prostatectomy. PET/CT findings were correlated with pathologic nodal status. Treatment-failure-free survival (TFFS) was estimated by Kaplan-Meier method. The ability of PET/CT to predict outcomes was evaluated by multivariate Cox proportional hazards analysis.
PET/CT was positive for pelvic LN or distant metastasis in 36 of 107 patients (33.6%). LN metastasis was present histopathologically in 25 (23.4%). The sensitivity, specificity, positive- and negative-predictive values of PET/CT for detecting LN metastasis were 68.0%, 78.1%, 48.6% and 88.9% respectively. 64 patients failed: 25 with metastasis, 17 with persistent post-prostatectomy prostate specific antigen (PSA) >0.20 ng/mL, and 22 with biochemical recurrence (PSA >0.20 ng/mL after nadir) during follow-up for a median of 44.0 months. TFFS was worse in PET-positive than in PET-negative patients (p<0.0001) and in those with false-positive versus true-negative scans (p<0.01), suggesting that PET may have demonstrated nodal disease not removed surgically or identified pathologically. PET positivity independently predicted failure in preoperative (hazard ratio=3.26, p<0.0001) and postoperative (HR=3.07, p=0.0001) multivariate models.
In patients planned for or completing prostatectomy, 11C-acetate-PET/CT detects LN metastasis not identified by conventional imaging and independently predicts TTFS.
PMCID: PMC3787881  PMID: 23471311
prostatic cancer; PET; acetate; cancer staging; lymphatic metastasis
15.  Pattern of Prostate-Specific Antigen (PSA) Failure Dictates the Probability of a Positive Bone Scan in Patients With an Increasing PSA After Radical Prostatectomy 
Physicians often order periodic bone scans (BS) to check for metastases in patients with an increasing prostate-specific antigen (PSA; biochemical recurrence [BCR]) after radical prostatectomy (RP), but most scans are negative. We studied patient characteristics to build a predictive model for a positive scan.
Patients and Methods
From our prostate cancer database we identified all patients with detectable PSA after RP. We analyzed the following features at the time of each bone scan for association with a positive BS: preoperative PSA, time to BCR, pathologic findings of the RP, PSA before the BS (trigger PSA), PSA kinetics (PSA doubling time, PSA slope, and PSA velocity), and time from BCR to BS. The results were incorporated into a predictive model.
There were 414 BS performed in 239 patients with BCR and no history of androgen deprivation therapy. Only 60 (14.5%) were positive for metastases. In univariate analysis, preoperative PSA (P = .04), seminal vesicle invasion (P = .02), PSA velocity (P < .001), and trigger PSA (P < .001) predicted a positive BS. In multivariate analysis, only PSA slope (odds ratio [OR], 2.71; P = .03), PSA velocity (OR, 0.93; P = .003), and trigger PSA (OR, 1.022; P < .001) predicted a positive BS. A nomogram for predicting the bone scan result was constructed with an overfit-corrected concordance index of 0.93.
Trigger PSA, PSA velocity, and slope were associated with a positive BS. A highly discriminating nomogram can be used to select patients according to their risk for a positive scan. Omitting scans in low-risk patients could reduce substantially the number of scans ordered.
PMCID: PMC1850929  PMID: 15774789
16.  Distinct ERG rearrangement prevalence in prostate cancer: higher frequency in young age and in low PSA prostate cancer 
The TMPRSS2-ERG gene fusion resulting in ERG overexpression has been found in around 50% of prostate cancers (PCa) and is a very early event in tumorigenesis. Most studies have reported on selected surgical cohorts with inconsistent results. We hypothesized that ERG gene rearrangements impact tumor development and investigated the frequency of ERG overexpression in the context of clinicopathological tumor characteristics.
ERG overexpression (ERG+ or ERG-) was determined by immunohistochemistry (IHC) in 1039 radical prostatectomy (RP) tumors and association with PSA, D'Amico risk score, histopathology, biochemical recurrence, body mass index and age of PCa cases was analyzed.
ERG+ was associated with younger age at diagnosis (P<0.0001), lower serum PSA (P=0.002) and lower prostate volume (PV) (P=0.001). It was most frequent in the youngest age quartile (⩽55 years, 63.9% ERG+) and decreased constantly with increasing age to 40.8% in the oldest age quartile (⩾67 years, P<0.0001). In the PSA range <4 ng ml−1 the frequency of ERG positivity was 60.2% compared with 47.5 and 49.1% in the PSA ranges 4–10 and ⩾10 ng ml−1, respectively. In the first age quartile, ERG+ patients had lower median serum PSA and fPSA% and smaller PV. In the highest age quartile tumor volume (TV) was increased. Similar differences were observed in the low PSA range. Multivariate analysis identified the first age quartile as a predictor for ERG status (odds ratios (OR) 2.05, P=0.007). No association was found with the D'Amico progression risk score and with biochemical tumor recurrence.
ERG+ tumors manifest clinically at lower PSA levels and their prevalence is age dependent. This suggests acceleration of tumor development by ERG overexpression that results in earlier tumor detection in young patients. Long-term results are warranted to determine the impact of ERG overexpression on disease outcome.
PMCID: PMC3655380  PMID: 23381693
age; ERG frequency distribution; ERG overexpression; early-onset prostate cancer; PSA screening
17.  PSA mass as a marker of prostate cancer progression after radical prostatectomy 
Obese patients with prostate cancer may have lower preoperative PSA concentration due to hemodilution. Lower PSA concentration may falsely affect assessing the risk of progression after radical prostatectomy (RP). The aim of this study was to determine preoperative PSA mass as the absolute amount of PSA protein secreted into circulation, and evaluation of its usefulness in prediction of biochemical recurrence after RP.
177 patients after RP due to prostate cancer were included in the study. On the basis of formulas, PSA mass was calculated {PSA mass [μg] = (weight [kg])0.425 × (height [cm])0.72 × 0.007184 × 1.670 × PSA concentration [ng/ml]}. Patients were divided into 3 groups according to increasing values of PSA mass. The following features were assessed and compared between these groups (χ-square test): pathologic stage T3, nodal metastases, positive surgical margins, biochemical and local recurrence and the rate of death. Cancer-specific survival was assessed depending on PSA mass (Kaplan-Meier curves with log rank test). The usefulness of PSA mass in prediction of biochemical recurrence was compared with PSA concentration (logistic regression with ROC curves).
Pathologic stage T3, nodal metastases, positive surgical margins and progression were more common in patients with higher levels of PSA mass (p<0.01). Cancer-specific survival was significantly shorter in patients with elevated values of PSA mass (p=0.02). Preoperative PSA mass was a more sensitive predictor of biochemical recurrence than was PSA concentration (p=0.04).
The preoperative PSA mass is a better predictor of biochemical recurrence after RP than PSA concentration.
PMCID: PMC3524695  PMID: 21278686
hemodilution; obesity; prostate cancer; PSA mass; radical prostatectomy
18.  Long-term Outcomes of Radical Prostatectomy With Multimodal Adjuvant Therapy in Men With a Preoperative Serum Prostate-Specific Antigen Level ≥50 ng/mL 
Cancer  2008;113(7):1544-1551.
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.
This study included 236 men with preoperative serum PSA values ≥50 ng/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.
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.
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.
PMCID: PMC2789388  PMID: 18680171
androgen deprivation therapy; external beam radiotherapy; prostate cancer; prostate-specific antigen; radical prostatectomy
19.  The use of early postoperative prostate-specific antigen to stratify risk in patients with positive surgical margins after radical prostatectomy 
BMC Urology  2014;14(1):79.
It is well recognized that the presence of positive surgical margins (PSM) after radical prostatectomy (RP) adversely affects cancer specific outcomes and recent evidence from randomized trials supports the use of adjuvant radiotherapy in these cases. However, not all of the patients with PSM develop disease recurrence and the policy of adjuvant radiation could result in considerable over-treatment. We investigated the ability of early postoperative prostate specific antigen (PSA) and PSA decline rates to stratify the risk of disease progression during the first weeks after the surgery thereby allowing adequate time for planning eventual adjuvant therapy.
We studied 116 consecutive patients with the finding of PSM after RP for localized prostate cancer between 2001 and 2012. No patients were treated with radiation or hormonal therapy. An intensive postoperative PSA monitoring using ultrasensitive assay started first at day 14 after the surgery, then at day 30, 60, 90 and 180, and subsequently in 3 monthly intervals. Biochemical recurrence (BCR) presented the failure of surgical treatment and it was defined as PSA ≥0.2 ng/ml. The ability of PSA decline parameters to predict BCR was assessed using Cox regression model and area under the curve (AUC) calculation.
Overall 55 (47%) patients experienced BCR during median follow-up of 31.4 months (range 6–69). Preoperative PSA, pathologic Gleason sum and pathologic grade failed to reveal any association with observation of BCR. Postoperative PSA levels achieved significant predictive accuracy already on day 30 (AUC 0.74). PSA >0.073 ng/ml at day 30 increased significantly the risk of BCR (HR 4.35, p < 0.001). Predictive accuracy was significantly exceeded on day 60 (AUC 0.84; p < 0.001), while further enhancements on day 90 (AUC 0.84) and 180 (AUC 0.91) were not significant.
The level of ultrasensitive PSA yields valuable information about the prostatectomy outcome already at the first month after the surgery and should aid risk stratification in patients with PSM. Patients not likely to experience subsequent disease progression may be spared the toxicity of immediate adjuvant radiotherapy.
PMCID: PMC4195911  PMID: 25277310
Prostate specific antigen; Radical prostatectomy; Surgical margins; Adjuvant radiotherapy
20.  The diagnostic value of PET/CT imaging with the 68Ga-labelled PSMA ligand HBED-CC in the diagnosis of recurrent prostate cancer 
Since the introduction of positron emission tomography (PET) imaging with 68Ga-PSMA-HBED-CC (=68Ga-DKFZ-PSMA-11), this method has been regarded as a significant step forward in the diagnosis of recurrent prostate cancer (PCa). However, published data exist for small patient cohorts only. The aim of this evaluation was to analyse the diagnostic value of 68Ga-PSMA-ligand PET/CT in a large cohort and the influence of several possibly interacting variables.
We performed a retrospective analysis in 319 patients who underwent 68Ga-PSMA-ligand PET/CT from 2011 to 2014. Potential influences of several factors such as prostate-specific antigen (PSA) level and doubling time (DT), Gleason score (GSC), androgen deprivation therapy (ADT), age and amount of injected tracer were evaluated. Histological verification was performed in 42 patients after the 68Ga-PSMA-ligand PET/CT. Tracer uptake was measured in 901 representative tumour lesions.
In 82.8 % of the patients at least one lesion indicative of PCa was detected. Tumor-detection was positively associated with PSA level and ADT. GSC and PSA-DT were not associated with tumor-detection. The average maximum standardized uptake value (SUVmax) of tumour lesions was 13.3 ± 14.6 (0.7–122.5). Amongst lesions investigated by histology, 30 were false-negative in 4 different patients, and all other lesions (n = 416) were true-positive or true-negative. A lesion-based analysis of sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) revealed values of 76.6 %, 100 %, 91.4 % and 100 %. A patient-based analysis revealed a sensitivity of 88.1 %. Of 116 patients available for follow-up, 50 received local therapy after 68Ga-PSMA-ligand PET/CT.
68Ga-PSMA-ligand PET/CT can detect recurrent PCa in a high number of patients. In addition, the radiotracer is highly specific for PCa. Tumour detection is positively associated with PSA and ADT. 68Ga-PSMA-ligand PET/CT can help delay systemic therapy of PCa.
Electronic supplementary material
The online version of this article (doi:10.1007/s00259-014-2949-6) contains supplementary material, which is available to authorized users.
PMCID: PMC4315487  PMID: 25411132
Prostate cancer; PET/CT; Positron emission tomography; PSMA; FMCH; FECH
21.  Sensitivity and specificity of PET/CT regarding the detection of lymph node metastases in prostate cancer recurrence 
SpringerPlus  2014;3:340.
The aim of the study is to assess the efficacy of choline PET/CT regarding the detection of lymph node (LN) metastases in recurrent prostate cancer (PCa).
49 patients with a biochemical recurrence of PCa (PSA >0.2 ng/ml) were included in the study. All patients were selected for further diagnostics with a choline-PET/CT. All patients underwent salvage extended lymphadenectomy. The PET/CT result and the histological findings were analyzed regarding the specificity and sensitivity and with respect to the localization of the metastases. The detection rate of LN metastases was analyzed with respect to interdependencies between the pre-PET/CT PSA-value as well as the role of prior ADT.
41 out of 49 (83.6%) patients showed positive PET/CT results. Positive LNs were found in 27 out of 49 patients (55.1%). 48.9% of the PET-CT-findings proved true positive, 36.7% were found to be false positive. 8.1% proved true negative and 8.1% false negative. This results in a specificity of 22.7% and a sensitivity of 85.1%. Out of the true positive PET/CT scans, 61.9% were not congruent regarding the localization of positive LNs. In patients with PSA [greater than or equal to] 5 ng/ml, the sensitivity of the PET/CT result was 93.7%, while specificity was 0%. In 24 patients who underwent ADT prior to the PET/CT diagnostics, the sensitivity was 84.6% and specificity 9.0%.
The reliability of PET/CT imaging for detection of LN metastases is limited by a high false-positive rate. The influence of ADT further diminishes the PET/CT reliability. Sensitivity of the PET/CT is highest in patients with a PSA of [greater than or equal to] 5 ng/ml. Based on our results, we propose the following conclusions: 1. There is no well-established diagnostic alternative to Choline-PET/CT Scan. Therefore this method may continue to be performed in patients with BCR. 2. It is not sufficient to remove only those LNs that show up in the PET/CT. 3. Salvage extended lymphadenectomy should follow a predefined template (e.g. the “Kiel template”) and not just the PET/CT scan results.
PMCID: PMC4096858  PMID: 25045614
Prostate cancer recurrence; Detection of lymph node metastases; PET CT scan
22.  Ultrasensitive Prostate Specific Antigen Assay Following Laparoscopic Radical Prostatectomy – An Outcome Measure for Defining the Learning Curve 
Radical retropubic prostatectomy (RRP) performed laparoscopically is a popular treatment with curative intent for organ-confined prostate cancer. After surgery, prostate specific antigen (PSA) levels drop to low levels which can be measured with ultrasensitive assays. This has been described in the literature for open RRP but not for laparoscopic RRP. This paper describes PSA changes in the first 300 consecutive patients undergoing non-robotic laparoscopic RRP by a single surgeon.
To use ultrasensitive PSA (uPSA) assays to measure a PSA nadir in patients having laparoscopic radical prostatectomy below levels recorded by standard assays. The aim was to use uPSA nadir at 3 months' post-prostatectomy as an early surrogate end-point of oncological outcome. In so doing, laparoscopic oncological outcomes could then be compared with published results from other open radical prostatectomy series with similar end-points. Furthermore, this end-point could be used in the assessment of the surgeon's learning curve.
Prospective, comprehensive, demographic, clinical, biochemical and operative data were collected from all patients undergoing non-robotic laparoscopic RRP. We present data from the first 300 consecutive patients undergoing laparoscopic RRP by a single surgeon. uPSA was measured every 3 months post surgery.
Median follow-up was 29 months (minimum 3 months). The likelihood of reaching a uPSA of ≤ 0.01 ng/ml at 3 months is 73% for the first 100 patients. This is statistically lower when compared with 83% (P < 0.05) for the second 100 patients and 80% for the third 100 patients (P < 0.05). Overall, 84% of patients with pT2 disease and 66% patients with pT3 disease had a uPSA of ≤ 0.01 ng/ml at 3 months. Pre-operative PSA, PSA density and Gleason score were not correlated with outcome as determined by a uPSA of ≤ 0.01 ng/ml at 3 months. Positive margins correlate with outcome as determined by a uPSA of ≤ 0.01 ng/ml at 3 months but operative time and tumour volume do not (P < 0.05). Attempt at nerve sparing had no adverse effect on achieving a uPSA of ≤ 0.01 ng/ml at 3 months.
uPSA can be used as an early end-point in the analysis of oncological outcomes after radical prostatectomy. It is one of many measures that can be used in calculating a surgeon's learning curve for laparoscopic radical prostatectomy and in bench-marking performance. With experience, a surgeon can achieve in excess of an 80% chance of obtaining a uPSA nadir of ≤ 0.01 ng/ml at 3 months after laparoscopic RRP for a British population. This is equivalent to most published open series.
PMCID: PMC2758435  PMID: 19409146
Laparoscopic radical prostatectomy; Ultrasensitive prostate specific antigen assay; Learning curve
23.  Prostate cancer detection rate in patients with fluctuating prostate-specific antigen levels on the repeat prostate biopsy 
Prostate International  2014;2(1):26-30.
To evaluate whether the risk of prostate cancer was different according to the pattern of fluctuation in prostate-specific antigen (PSA) levels in patients undergoing repeat transrectal ultrasound-guided prostate biopsy (TRUS-Bx).
From March 2003 to December 2012, 492 patients underwent repeat TRUS-Bx. The patients were stratified into 3 groups based on the PSA fluctuation pattern: group 1 (continuous elevation of PSA, n=169), group 2 (PSA fluctuation with PSA velocity [PSAV]≥1.0 ng/mL/yr, n=123), and group 3 (PSA fluctuation with PSAV<1.0 ng/mL/yr, n=200).
Prostate cancer was detected in 112 of 492 patients (22.8%) in the repeat biopsy set. According to the PSA fluctuation pattern, prostate cancer detection rates at repeat TRUS-Bx were 29.6% (50/169) for patients with continuously increasing PSA, 30.1% (37/123) for PSA fluctuation with PSAV ≥1.0 ng/mL/yr, and 12.5% (25/200) for PSA fluctuation with PSAV <1.0 ng/mL/yr. Multivariate analysis showed that PSA fluctuation pattern and high grade prostatic intraepithelial neoplasia at initial TRUS-Bx were the predictive parameters for positive repeat biopsies. Among the 96 patients (85.7%) who underwent radical prostatectomy, no significant differences in pathologic outcomes were found according to the PSA fluctuation pattern.
The current study shows that the risk of prostate cancer at repeat TRUS-Bx was higher in men with a fluctuating PSA level and PSAV≥1.0 ng/mL/yr than in those with a fluctuating PSA level and PSAV<1.0 ng/mL/yr.
PMCID: PMC3970986  PMID: 24693531
Prostate-specific antigen; Prostatic neoplasms; Biopsy; Needles
24.  Risk assessment for biochemical recurrence prior to radical prostatectomy: significant enhancement contributed by human glandular kallikrein 2 (hk2) and free prostate specific antigen (PSA) in men with moderate PSA-elevation in serum 
Most models to predict biochemical recurrence (BCR) of prostate cancer use pretreatment serum prostate-specific antigen (PSA), clinical stage and prostate biopsy Gleason grade. We investigated whether human glandular kallikrein 2 (hK2) and free prostate-specific antigen (fPSA) measured in pretreatment serum enhance prediction. We retrospectively measured total PSA (tPSA), fPSA and hK2 in preoperative serum samples from 461 men with localized prostate cancer treated with radical prostatectomy between 1999 and 2001. We developed a regression model to predict BCR using preoperative tPSA, clinical stage and biopsy Gleason grade. We then compared the predictive accuracy of this “base” model with a model with fPSA and hK2 as additional predictors. BCR was observed in 90 patients (20%), including 48 patients with a pretreatment tPSA ≤ 14 ng/ml (13%), and 28 patients (10%) with a pretreatment tPSA ≤ 10 ng/ml. Overall, the predictive accuracy of the base model (bootstrap-corrected concordance index of 0.813) was not improved after the addition of fPSA or hK2 (0.818). However, for men with moderate tPSA-elevation (tPSA ≤ 10 ng/ml), addition of fPSA and hK2 data increased predictive accuracy (from a base model concordance index of 0.756–0.815, p = 0.005). The improvement in accuracy was not sensitive to the threshold for “moderately elevated” PSA. For patients with a moderate tPSA-elevation (tPSA ≤ 10 ng/ml), which closely corresponds to concurrent disease demographics, BCR-prediction was enhanced when fPSA and hK2 were added to the conventional model. Measurements of fPSA and hK2 improve on our ability to counsel patients prior to treatment as to their risk of BCR.
PMCID: PMC1950472  PMID: 16152616
prostate cancer; biochemical recurrence; PSA; hK2; free PSA; radical prostatectomy
25.  Positive resection margins may not reflect the true margin in patients undergoing radical prostatectomy 
Oncology Letters  2014;8(5):2237-2242.
The aim of the present study was to evaluate the hypothesis that a positive resection margin (RM1) of an excised specimen may not reflect the true margin in patients that have undergone radical prostatectomy (RP). Between September 2003 and March 2011, 370 Japanese patients underwent an antegrade RP at the National Kyushu Cancer Center (Fukuoka, Japan), however, 95 of these patients were excluded from the study due to a history of receiving hormonal therapy or insufficient preoperative clinical data. The incidence of biochemical failure (BCF) was evaluated using multivariate analysis, which revealed that the preoperative prostate-specific antigen (PSA) level, pathological tumor stage, RP Gleason score and a PSA nadir <0.008 ng/ml were significant predictors (P=0.0065, 0.0006, 0.0002 and <0.0001, respectively). By contrast, an RM1 was not found to be a significant predictor of BCF, while the parameter with the highest hazard ratio (HR) was a PSA nadir <0.008 ng/ml (HR, 10.055; 95% confidence interval, 5.005–20.200). From the 56 cases that were RM1, 41 cases (73.2%) exhibited a PSA nadir <0.008 ng/ml. There were 42 cases (75.0%) in which only one site was identified to be RM1; among these cases, no significant difference was observed between a PSA level <0.008 ng/ml and a PSA level ≥0.008 ng/ml at the RM1 site (apex, P=0.1460; base, P=0.1384; anterior, P=0.3870; and posterolateral, P=0.5040). There were 14 cases (25.0%) in which multiple sites were RM1; these cases were classified by the number of sites that were RM1 (one vs. multiple) and no significant difference was observed between a PSA level <0.008 ng/ml and a PSA level ≥0.008 ng/ml (P=0.6090). Based on these results, an RM1 of an excised specimen may not reflect the true margin in patients that are treated with RP, specifically in cases where the PSA level is identified to decrease to below the postoperative measurement threshold value (PSA nadir <0.008 ng/ml).
PMCID: PMC4186613  PMID: 25295112
prostate cancer; surgical margin; radical prostatectomy; ultrasensitive prostate-specific antigen; prostate-specific antigen nadir

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