Outcomes and Trends of Prostate Biopsy for Prostate Cancer in Chinese Men from 2003 to 2011

Background

Prostate-specific antigen (PSA) screening is growing in popularity in China, but its impact on biopsy characteristics and outcomes are poorly understood.

Objective

Our objective was to characterize prostate biopsy outcomes and trends in Chinese men over a 10-year period, since the increasing use of PSA tests.

Methods

All men (n = 1,650) who underwent prostate biopsy for PCa at Huashan Hospital, Shanghai, China from 2003–2011 were evaluated. Demographic and clinical information was collected for each patient, including age, digital rectal examination (DRE), transrectal ultrasound (prostate volume and nodule), total prostate-specific antigen (tPSA) levels and free PSA ratio (fPSA/tPSA) prior to biopsy. Prostate biopsy was performed using six cores before October 2007 or ten cores thereafter. Logistic regression and multivariate analysis were used to evaluate our data.

Results

The overall positive rate of prostate biopsy for PCa was 47% and the rate decreased significantly over the years from 74% in 2003 to 33% in 2011 (P-trend = 0.004) . Age at diagnosis was slightly increased (P-trend = 0.04) while fPSA/tPSA was significantly decreased (P-trend = 1.11×10-5). A statistically significant trend was not observed for tPSA levels, prostate volume, or proportion of positive nodule. The model including multiple demographic and clinical variables (i.e., age, DRE, tPSA, fPSA/tPSA and transrectal ultrasound results) (AUC = 0.93) statistically outperformed models that included only PSA (AUC = 0.85) or fPSA/tPSA (AUC = 0.66) to predict PCa risks (P<0.05). Similar results were observed in a subgroup of men whose tPSA levels were lower than 20 ng/mL (AUC = 0.87, vs. AUC of tPSA  = 0.62, P<0.05).

Conclusions

Detection rates of PCa and high-grade PCa among men that underwent prostate biopsy at the institution has decreased significantly in the past 10 years, likely due to increasing use of PSA tests. Predictive performance of demographic and clinical variables of PCa was excellent. These variables should be used in clinics to determine the need for prostate biopsy.     

Factors Affecting Family Satisfaction with Inpatient End-of-Life Care

Background

Little data exists addressing satisfaction with end-of-life care among hospitalized patients, as they and their family members are systematically excluded from routine satisfaction surveys. It is imperative that we closely examine patient and institution factors associated with quality end-of-life care and determine high-priority target areas for quality improvement.

Methods

Between September 1, 2010 and January 1, 2012 the Canadian Health care Evaluation Project (CANHELP) Bereavement Questionnaire was mailed to the next-of-kin of recently deceased inpatients to seek factors associated with satisfaction with end-of-life care. The primary outcome was the global rating of satisfaction. Secondary outcomes included rates of actual versus preferred location of death, associations between demographic factors and global satisfaction, and identification of targets for quality improvement.

Results

Response rate was 33% among 275 valid addresses. Overall, 67.4% of respondents were very or completely satisfied with the overall quality of care their relative received. However, 71.4% of respondents who thought their relative did not die in their preferred location favoured an out-of-hospital location of death. A common location of death was the intensive care unit (45.7%); however, this was not the preferred location of death for 47.6% of such patients. Multivariate Poisson regression analysis showed respondents who believed their relative died in their preferred location were 1.7 times more likely to be satisfied with the end-of-life care that was provided (p = 0.001). Items identified as high-priority targets for improvement included: relationships with, and characteristics of health care professionals; illness management; communication; and end-of-life decision-making.

Interpretation

Nearly three-quarters of recently deceased inpatients would have preferred an out-of-hospital death. Intensive care units were a common, but not preferred, location of in-hospital deaths. Family satisfaction with end-of-life care was strongly associated with their relative dying in their preferred location. Improved communication regarding end-of-life care preferences should be a high-priority quality improvement target.     

MicroRNA let-7c is downregulated in prostate cancer and suppresses prostate cancer growth

Purpose

Prostate cancer (PCa) is characterized by deregulated expression of several tumor suppressor or oncogenic miRNAs. The objective of this study was the identification and characterization of miR-let-7c as a potential tumor suppressor in PCa.

Experimental Design

Levels of expression of miR-let-7c were examined in human PCa cell lines and tissues using qRT-PCR and in situ hybridization. Let-7c was overexpressed or suppressed to assess the effects on the growth of human PCa cell lines. Lentiviral-mediated re-expression of let-7c was utilized to assess the effects on human PCa xenografts.

Results

We identified miR-let-7c as a potential tumor suppressor in PCa. Expression of let-7c is downregulated in castration-resistant prostate cancer (CRPC) cells. Overexpression of let-7c decreased while downregulation of let-7c increased cell proliferation, clonogenicity and anchorage-independent growth of PCa cells in vitro. Suppression of let-7c expression enhanced the ability of androgen-sensitive PCa cells to grow in androgen-deprived conditions in vitro. Reconstitution of Let-7c by lentiviral-mediated intratumoral delivery significantly reduced tumor burden in xenografts of human PCa cells. Furthermore, let-7c expression is downregulated in clinical PCa specimens compared to their matched benign tissues, while the expression of Lin28, a master regulator of let-7 miRNA processing, is upregulated in clinical PCa specimens.

Conclusions

These results demonstrate that microRNA let-7c is downregulated in PCa and functions as a tumor suppressor, and is a potential therapeutic target for PCa.     

Development of a Nuclear Morphometric Signature for Prostate Cancer Risk in Negative Biopsies

Background

Our objective was to develop and validate a multi-feature nuclear score based on image analysis of direct DNA staining, and to test its association with field effects and subsequent detection of prostate cancer (PCa) in benign biopsies.

Methods

Tissue sections from 39 prostatectomies were Feulgen-stained and digitally scanned (400×), providing maps of DNA content per pixel. PCa and benign epithelial nuclei were randomly selected for measurement of 52 basic morphometric features. Logistic regression models discriminating benign from PCa nuclei, and benign from malignant nuclear populations, were built and cross-validated by AUC analysis. Nuclear populations were randomly collected <1 mm or >5 mm from cancer foci, and from cancer-free prostates, HGPIN, and PCa Gleason grade 3–5. Nuclei also were collected from negative biopsy subjects who had a subsequent diagnosis of PCa and age-matched cancer-free controls (20 pairs).

Results

A multi-feature nuclear score discriminated cancer from benign cell populations with AUCs of 0.91 and 0.79, respectively, in training and validation sets of patients. In prostatectomy samples, both nuclear- and population-level models revealed cancer-like features in benign nuclei adjacent to PCa, compared to nuclei that were more distant or from PCa-free glands. In negative biopsies, a validated model with 5 variance features yielded significantly higher scores in cases than controls (P = 0.026).

Conclusions

A multifeature nuclear morphometric score, obtained by automated digital analysis, was validated for discrimination of benign from cancer nuclei. This score demonstrated field effects in benign epithelial nuclei at varying distance from PCa lesions, and was associated with subsequent PCa detection in negative biopsies.

Impact

This nuclear score shows promise as a risk predictor among men with negative biopsies and as an intermediate biomarker in Phase II chemoprevention trials. The results also suggest that subvisual disturbances in nuclear structure precede the development of pre-neoplastic lesions.     

Proteomic Profiling of Exosomes Leads to the Identification of Novel Biomarkers for Prostate Cancer

Background

Current markers for prostate cancer, such as PSA lack specificity. Therefore, novel biomarkers are needed. Unfortunately, the complexity of body fluids often hampers biomarker discovery. An attractive alternative approach is the isolation of small vesicles, i.e. exosomes, ∼100 nm, which contain proteins that are specific to the tissue from which they are derived and therefore can be considered as treasure chests for disease-specific biomarker discovery.

Materials and Methods

Exosomes were isolated from 2 immortalized primary prostate epithelial cells (PNT2C2 and RWPE-1) and 2 PCa cell lines (PC346C and VCaP) by ultracentrifugation. After tryptic digestion, proteomic analyses utilized a nanoLC coupled with an LTQ-Orbitrap operated in tandem MS (MS/MS) mode. Accurate Mass and Time (AMT) tag approach was employed for peptide identification and quantitation. Candidate biomarkers were validated by Western blotting and Immunohistochemistry.

Results

Proteomic characterization resulted in the identification of 248, 233, 169, and 216 proteins by at least 2 peptides in exosomes from PNT2C2, RWPE-1, PC346C, and VCaP, respectively. Statistical analyses revealed 52 proteins differently abundant between PCa and control cells, 9 of which were more abundant in PCa. Validation by Western blotting confirmed a higher abundance of FASN, XPO1 and PDCD6IP (ALIX) in PCa exosomes.

Conclusions

Identification of exosomal proteins using high performance LC-FTMS resulted in the discovery of PDCD6IP, FASN, XPO1 and ENO1 as new candidate biomarkers for prostate cancer.     

Distinct microRNA Expression Profile in Prostate Cancer Patients with Early Clinical Failure and the Impact of let-7 as Prognostic Marker in High-Risk Prostate Cancer

Background

The identification of additional prognostic markers to improve risk stratification and to avoid overtreatment is one of the most urgent clinical needs in prostate cancer (PCa). MicroRNAs, being important regulators of gene expression, are promising biomarkers in various cancer entities, though the impact as prognostic predictors in PCa is poorly understood. The aim of this study was to identify specific miRNAs as potential prognostic markers in high-risk PCa and to validate their clinical impact.

Methodology and Principal Findings

We performed miRNA-microarray analysis in a high-risk PCa study group selected by their clinical outcome (clinical progression free survival (CPFS) vs. clinical failure (CF)). We identified seven candidate miRNAs (let-7a/b/c, miR-515-3p/5p, -181b, -146b, and -361) that showed differential expression between both groups. Further qRT-PCR analysis revealed down-regulation of members of the let-7 family in the majority of a large, well-characterized high-risk PCa cohort (n = 98). Expression of let-7a/b/and -c was correlated to clinical outcome parameters of this group. While let-7a showed no association or correlation with clinical relevant data, let-7b and let-7c were associated with CF in PCa patients and functioned partially as independent prognostic marker. Validation of the data using an independent high-risk study cohort revealed that let-7b, but not let-7c, has impact as an independent prognostic marker for BCR and CF. Furthermore, we identified HMGA1, a non-histone protein, as a new target of let-7b and found correlation of let-7b down-regulation with HMGA1 over-expression in primary PCa samples.

Conclusion

Our findings define a distinct miRNA expression profile in PCa cases with early CF and identified let-7b as prognostic biomarker in high-risk PCa. This study highlights the importance of let-7b as tumor suppressor miRNA in high-risk PCa and presents a basis to improve individual therapy for high-risk PCa patients.     

Health outcome measures in atopic dermatitis: a systematic review of trends in disease severity and quality-of-life instruments 1985-2010

Background

A number of disease-severity and quality-of-life (QoL) instruments have emerged in atopic dermatitis (AD) in the last decade.

Objectives

To identify trends in outcomes instruments used in AD clinical trials and to provide a useful summary of the dimensions and validation studies for the most commonly used measures.

Method

All randomized control trials (RCTs) from 1985 to 2010 in the treatment of AD were examined.

Results

Among the 791 RCTs reviewed, we identified 20 disease-severity and 14 QoL instruments. Of these outcomes instruments, few have been validated. SCORAD, EASI, IGA and SASSAD were the most commonly used disease-severity instruments and CDLQI, DFI, DLQI and IDQOL were the most frequently used QoL measures.

Limitations

The small number of RCTs using QoL scales makes identifying trends for QoL instruments difficult.

Conclusion

Overall, there is an increase in the use of disease-severity and QoL instruments in AD clinical trials.     

High frequency chest wall oscillation for asthma and chronic obstructive pulmonary disease exacerbations: a randomized sham-controlled clinical trial

Background

High frequency chest wall oscillation (HFCWO) is used for airway mucus clearance. The objective of this study was to evaluate the use of HFCWO early in the treatment of adults hospitalized for acute asthma or chronic obstructive pulmonary disease (COPD).

Methods

Randomized, multi-center, double-masked phase II clinical trial of active or sham treatment initiated within 24 hours of hospital admission for acute asthma or COPD at four academic medical centers. Patients received active or sham treatment for 15 minutes three times a day for four treatments. Medical management was standardized across groups. The primary outcomes were patient adherence to therapy after four treatments (minutes used/60 minutes prescribed) and satisfaction. Secondary outcomes included change in Borg dyspnea score (≥ 1 unit indicates a clinically significant change), spontaneously expectorated sputum volume, and forced expired volume in 1 second.

Results

Fifty-two participants were randomized to active (n = 25) or sham (n = 27) treatment. Patient adherence was similarly high in both groups (91% vs. 93%; p = 0.70). Patient satisfaction was also similarly high in both groups. After four treatments, a higher proportion of patients in the active treatment group had a clinically significant improvement in dyspnea (70.8% vs. 42.3%, p = 0.04). There were no significant differences in other secondary outcomes.

Conclusions

HFCWO is well tolerated in adults hospitalized for acute asthma or COPD and significantly improves dyspnea. The high levels of patient satisfaction in both treatment groups justify the need for sham controls when evaluating the use of HFCWO on patient-reported outcomes. Additional studies are needed to more fully evaluate the role of HFCWO in improving in-hospital and post-discharge outcomes in this population.

Trial Registration

ClinicalTrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT00181285","term_id":"NCT00181285"}}NCT00181285     

Predicting outcomes of prostate cancer immunotherapy by personalized mathematical models

Background

Therapeutic vaccination against disseminated prostate cancer (PCa) is partially effective in some PCa patients. We hypothesized that the efficacy of treatment will be enhanced by individualized vaccination regimens tailored by simple mathematical models.

Methodology/Principal Findings

We developed a general mathematical model encompassing the basic interactions of a vaccine, immune system and PCa cells, and validated it by the results of a clinical trial testing an allogeneic PCa whole-cell vaccine. For model validation in the absence of any other pertinent marker, we used the clinically measured changes in prostate-specific antigen (PSA) levels as a correlate of tumor burden. Up to 26 PSA levels measured per patient were divided into each patient''s training set and his validation set. The training set, used for model personalization, contained the patient''s initial sequence of PSA levels; the validation set contained his subsequent PSA data points. Personalized models were simulated to predict changes in tumor burden and PSA levels and predictions were compared to the validation set. The model accurately predicted PSA levels over the entire measured period in 12 of the 15 vaccination-responsive patients (the coefficient of determination between the predicted and observed PSA values was R ² = 0.972). The model could not account for the inconsistent changes in PSA levels in 3 of the 15 responsive patients at the end of treatment. Each validated personalized model was simulated under many hypothetical immunotherapy protocols to suggest alternative vaccination regimens. Personalized regimens predicted to enhance the effects of therapy differed among the patients.

Conclusions/Significance

Using a few initial measurements, we constructed robust patient-specific models of PCa immunotherapy, which were retrospectively validated by clinical trial results. Our results emphasize the potential value and feasibility of individualized model-suggested immunotherapy protocols.     

Should the Arteriovenous Fistula Be Created before Starting Dialysis?: A Decision Analytic Approach

Background

An arteriovenous fistula (AVF) is considered the vascular access of choice, but uncertainty exists about the optimal time for its creation in pre-dialysis patients. The aim of this study was to determine the optimal vascular access referral strategy for stage 4 (glomerular filtration rate <30 ml/min/1.73 m²) chronic kidney disease patients using a decision analytic framework.

Methods

A Markov model was created to compare two strategies: refer all stage 4 chronic kidney disease patients for an AVF versus wait until the patient starts dialysis. Data from published observational studies were used to estimate the probabilities used in the model. A Markov cohort analysis was used to determine the optimal strategy with life expectancy and quality adjusted life expectancy as the outcomes. Sensitivity analyses, including a probabilistic sensitivity analysis, were performed using Monte Carlo simulation.

Results

The wait strategy results in a higher life expectancy (66.6 versus 65.9 months) and quality adjusted life expectancy (38.9 versus 38.5 quality adjusted life months) than immediate AVF creation. It was robust across all the parameters except at higher rates of progression and lower rates of ischemic steal syndrome.

Conclusions

Early creation of an AVF, as recommended by most guidelines, may not be the preferred strategy in all pre-dialysis patients. Further research on cost implications and patient preferences for treatment options needs to be done before recommending early AVF creation.     

Polymorphisms of an Innate Immune Gene,Toll-Like Receptor 4, and Aggressive Prostate Cancer Risk: A Systematic Review and Meta-Analysis

Background

Toll-like receptor 4 (TLR4) is one of the best known TLR members expressed on the surface of several leukocytes and tissue cells and has a key function in detecting pathogen and danger-associated molecular patterns. The role of TLR4 in the pathophysiology of several age-related diseases is also well recognized, such as prostate cancer (PCa). TLR4 polymorphisms have been related to PCa risk, but the relationship between TLR4 genotypes and aggressive PCa risk has not been evaluated by any systematic reviews.

Methods

We performed a systematic review and meta-analysis of candidate-gene and genome-wide association studies analyzing this relationship and included only white population. Considering appropriate criteria, only nine studies were analyzed in the meta-analysis, including 3,937 aggressive PCa and 7,382 controls.

Results

Using random effects model, no significant association was found in the ten TLR4 SNPs reported by at least four included studies under any inheritance model (rs2737191, rs1927914, rs10759932, rs1927911, rs11536879, rs2149356, rs4986790, rs11536889, rs7873784, and rs1554973). Pooled estimates from another ten TLR4 SNPs reported by three studies also showed no significant association (rs10759930, rs10116253, rs11536869, rs5030717, rs4986791, rs11536897, rs1927906, rs913930, rs1927905, and rs7045953). Meta-regression revealed that study type was not a significant source of between-study heterogeneity.

Conclusions

TLR4 polymorphisms were not significantly associated with the risk of aggressive PCa.     

The Hepatitis C Cascade of Care: Identifying Priorities to Improve Clinical Outcomes

Background

As highly effective hepatitis C virus (HCV) therapies emerge, data are needed to inform the development of interventions to improve HCV treatment rates. We used simulation modeling to estimate the impact of loss to follow-up on HCV treatment outcomes and to identify intervention strategies likely to provide good value for the resources invested in them.

Methods

We used a Monte Carlo state-transition model to simulate a hypothetical cohort of chronically HCV-infected individuals recently screened positive for serum HCV antibody. We simulated four hypothetical intervention strategies (linkage to care; treatment initiation; integrated case management; peer navigator) to improve HCV treatment rates, varying efficacies and costs, and identified strategies that would most likely result in the best value for the resources required for implementation.

Main measures

Sustained virologic responses (SVRs), life expectancy, quality-adjusted life expectancy (QALE), costs from health system and program implementation perspectives, and incremental cost-effectiveness ratios (ICERs).

Results

We estimate that imperfect follow-up reduces the real-world effectiveness of HCV therapies by approximately 75%. In the base case, a modestly effective hypothetical peer navigator program maximized the number of SVRs and QALE, with an ICER compared to the next best intervention of $48,700/quality-adjusted life year. Hypothetical interventions that simultaneously addressed multiple points along the cascade provided better outcomes and more value for money than less costly interventions targeting single steps. The 5-year program cost of the hypothetical peer navigator intervention was $14.5 million per 10,000 newly diagnosed individuals.

Conclusions

We estimate that imperfect follow-up during the HCV cascade of care greatly reduces the real-world effectiveness of HCV therapy. Our mathematical model shows that modestly effective interventions to improve follow-up would likely be cost-effective. Priority should be given to developing and evaluating interventions addressing multiple points along the cascade rather than options focusing solely on single points.     

Development and Evaluation of a Pilot Nurse Case Management Model to Address Multidrug-Resistant Tuberculosis (MDR-TB) and HIV in South Africa

Setting

Multidrug-resistant tuberculosis (MDR-TB) unit in KwaZulu-Natal, South Africa.

Objective

To develop and evaluate a nurse case management model and intervention using the tenets of the Chronic Care Model to manage treatment for MDR-TB patients with a high prevalence of human immunodeficiency virus (HIV) co-infection.

Design

A quasi-experimental pilot programme utilizing a nurse case manager to manage care for 40 hospitalized MDR-TB patients, 70% HIV co-infected, during the intensive phase of MDR-TB treatment. Patients were followed for six months to compare proximal outcomes identified in the model between the pre- and post-intervention period.

Results

The greatest percent differences between baseline and six-month MDR-TB proximal outcomes were seen in the following three areas: baseline symptom evaluation on treatment initiation (95% improvement), baseline and monthly laboratory evaluations completed per guidelines (75% improvement), and adverse drug reactions acted upon by medical and/or nursing intervention (75% improvement).

Conclusion

Improvements were identified in guideline-based treatment and monitoring of adverse drug reactions following implementation of the nurse case management intervention. Further study is required to determine if the intervention introduced in this model will ultimately result in improvements in final MDR-TB treatment outcomes.     

The Representation of Risk in Routine Medical Experience: What Actions for Contemporary Health Policy?

Background

The comprehension of appropriate information about illnesses and treatments, can have beneficial effects on patients’ satisfaction and on important health outcomes. However, it is questionable whether people are able to understand risk properly.

Aim

To describe patients’ representation of risk in common medical experiences by linking such a representation to the concept of trust. A further goal was to test whether the representation of risk in the medical domain is associated to the level of expertise. The third goal was to verify whether socio-demographic differences influence the representation of risk.

Methods

Eighty voluntary participants from 6 health-centers in northern Italy were enrolled to conduct a semi-structured interview which included demographic questions, term-associations about risk representation, closed and open questions about attitudes and perception of risk in the medical context, as well as about medical expertise and trust.

Results

The results showed that people do not have in mind a scientific definition of risk in medicine. Risk is seen as a synonym for surgery and disease and it is often confused with fear. However, general knowledge of medical matters helps people to have a better health management through risk identification and risk information, adoption of careful behaviors and tendency to have a critical view about safety and medical news. Finally, trust proved to be an important variable in risk representation and risk and trust were correlated positively.

Conclusions

People must receive appropriate information about the risks and benefits of treatment, in a form that they can understand and apply to their own circumstances. Moreover, contemporary health policy should empower patients to adopt an active self-care attitude. Methodologies to enhance people’s decision-making outcomes based on better risk communication should be improved in order to enable low literacy population as well elderly people to better understand their treatment and associated risk.     

Predictive Value of Clinical Judgment of Tumour Progression in Phase II Trials

Background

The diagnosis of tumour progression or progressive disease (PD) is a key element for designing and interpreting contemporary phase II trials. In some cases, PD is stated by the physician and is not formally confirmed by imaging.

Purpose

In this study, we intend to analyze the value of the PD based on clinical judgment and the risk of overestimating the occurrence of PD by clinical judgment.

Methods

We have conducted a single-centre retrospective study to analyse the diagnostic accuracy of this clinical judgment compared to planned imaging including all patients enrolled in our institution in phase II trials investigating systemic treatments for advanced solid tumours between January 2008 and November 2010.

Results

The positive predictive value (PPV) and the specificity of clinical judgment of PD was very high (>90%).

Conclusions

According to this study, the clinical judgment of PD is highly predictive of radiological PD as assessed, for example, by RECIST. Physicians do not overestimate PD occurence. Clinical judgment of PD could be taken into account in the definition of PD.     

Serum early prostate cancer antigen (EPCA) level and its association with disease progression in prostate cancer in a Chinese population

Background

Early prostate cancer antigen (EPCA) has been shown a prostate cancer (PCa)-associated nuclear matrix protein, however, its serum status and prognostic power in PCa are unknown. The goals of this study are to measure serum EPCA levels in a cohort of patients with PCa prior to the treatment, and to evaluate the clinical value of serum EPCA.

Methods

Pretreatment serum EPCA levels were determined with an ELISA in 77 patients with clinically localized PCa who underwent radical prostatectomy and 51 patients with locally advanced or metastatic disease who received primary androgen deprivation therapy, and were correlated with clinicopathological variables and disease progression. Serum EPCA levels were also examined in 40 healthy controls.

Results

Pretreatment mean serum EPCA levels were significantly higher in PCa patients than in controls (16.84±7.60 ng/ml vs. 4.12±2.05 ng/ml, P<0.001). Patients with locally advanced and metastatic PCa had significantly higher serum EPCA level than those with clinically localized PCa (22.93±5.28 ng/ml and 29.41±8.47 ng/ml vs. 15.17±6.03 ng/ml, P = 0.014 and P<0.001, respectively). Significantly elevated EPCA level was also found in metastatic PCa compared with locally advanced disease (P<0.001). Increased serum EPCA levels were significantly and positively correlated with Gleason score and clinical stage, but not with PSA levels and age. On multivariate analysis, pretreatment serum EPCA level held the most significantly predictive value for the biochemical recurrence and androgen-independent progression among pretreatment variables (HR = 4.860, P<0.001 and HR = 5.418, P<0.001, respectively).

Conclusions

Serum EPCA level is markedly elevated in PCa. Pretreatment serum EPCA level correlates significantly with the poor prognosis, showing prediction potential for PCa progression.     

Incidence of Second Malignancies for Prostate Cancer

Introduction

There is a need to assess risk of second primary cancers in prostate cancer (PCa) patients, especially since PCa treatment may be associated with increased risk of second primary tumours.

Methods

We calculated standardized incidence ratios (SIRs) for second primary tumours comparing men diagnosed with PCa between 1980 and 2010 in the Canton of Zurich, Switzerland (n = 20,559), and the general male population in the Canton.

Results

A total of 1,718 men developed a second primary tumour after PCa diagnosis, with lung and colon cancer being the most common (15 and 13% respectively). The SIR for overall second primary cancer was 1.11 (95%CI: 1.06–1.17). Site-specific SIRs varied from 1.19 (1.05–1.34) to 2.89 (2.62–4.77) for lung and thyroid cancer, respectively. When stratified by treatment, the highest SIR was observed for thyroid cancer (3.57 (1.30–7.76)) when undergoing surgery, whereas liver cancer was common when treated with radiotherapy (3.21 (1.54–5.90)) and kidney bladder was most prevalent for those on hormonal treatment (3.15 (1.93–4.87)). Stratification by time since PCa diagnosis showed a lower risk of cancer for men with PCa compared to the general population for the first four years, but then a steep increase in risk was observed.

Conclusion

In the Canton of Zurich, there was an increased risk of second primary cancers among men with PCa compared to the general population. Increased diagnostic activity after PCa diagnosis may partly explain increased risks within the first years of diagnosis, but time-stratified analyses indicated that increased risks remained and even increased over time.     

MicroRNA expression characterizes oligometastasis(es)

Background

Cancer staging and treatment presumes a division into localized or metastatic disease. We proposed an intermediate state defined by ≤5 cumulative metastasis(es), termed oligometastases. In contrast to widespread polymetastases, oligometastatic patients may benefit from metastasis-directed local treatments. However, many patients who initially present with oligometastases progress to polymetastases. Predictors of progression could improve patient selection for metastasis-directed therapy.

Methods

Here, we identified patterns of microRNA expression of tumor samples from oligometastatic patients treated with high-dose radiotherapy.

Results

Patients who failed to develop polymetastases are characterized by unique prioritized features of a microRNA classifier that includes the microRNA-200 family. We created an oligometastatic-polymetastatic xenograft model in which the patient-derived microRNAs discriminated between the two metastatic outcomes. MicroRNA-200c enhancement in an oligometastatic cell line resulted in polymetastatic progression.

Conclusions

These results demonstrate a biological basis for oligometastases and a potential for using microRNA expression to identify patients most likely to remain oligometastatic after metastasis-directed treatment.