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Every month we collate a selection of the latest clinically-relevant research to help you keep up to date with the most important developments in the field of prostate cancer.

Articles have been selected based on impact factor of the journal, relevance to UK clinical practice and general interest. You may be able to access the full text from your Trust's library service or via ATHENS registration. Information from PubMed explains other ways to access full text articles. 

July 2015

Research round up from the clinic - top four articles from July 2015:

1. Could targeting the protein DNA-PKcs prevent the spread of prostate cancer?

In this study, Goodwin et al. aimed to determine the molecular basis of DNA-PKcs function and the contribution of DNA-PKcs-mediated transcriptional regulation on tumour phenotypes. The DNA-dependent protein kinase (DNA-PK) is composed of two units, including a catalytic subunit (DNA-PKcs) that plays an important role in the DNA damage response and maintenance of genomic stability. This research, which was carried out in the United States, involved mouse models and clinical analysis of tumour samples from 232 patients. Samples were obtained using a case-cohort study design to randomly sample 20% of patients for analysis, in addition to all in whom metastases developed, from a cohort of 1,010 high-risk men who underwent radical prostatectomy between 2000 and 2006.

The authors identified DNA-PKcs as a key contributor to metastatic progression, and the findings support a model wherein the transcriptional regulatory functions of DNA-PKcs induce a signalling program that drives tumour metastases and lethal disease. Dr Iain Frame, director of research at Prostate Cancer UK said “Getting to grips with how and why cancer cells spread around the body is one of the biggest challenges we face today. The answer to this question will allow us to not only predict which early stage prostate cancers may go on to spread and become dangerous, but also develop new treatments to stop the cells spreading in the first place. Although this research could provide us with some of the answers we desperately need, it's still early days. We look forward to further results of this trial and hope they lead to better ways to prevent and treat advanced prostate cancer.”

2. Are surveillance strategies effective for men with low-risk prostate cancer?

Many men diagnosed with localised, low-risk prostate cancer, which may not be lethal, undergo primary treatment with surgery or radiation. These treatments can affect health-related quality of life (HRQOL), including longstanding side effects such as erectile dysfunction and impaired urinary function. This review, by Filson and colleagues from UCLA in the United States, describes the current surveillance protocols (e.g. active surveillance and watchful waiting), and reviews the outcomes for each of these strategies in terms of cancer survival and quality of life. Additionally the review addresses the novel technologies such as prostate MRI and fusion biopsies that may prove beneficial for surveillance patients.

The authors concluded active surveillance and expectant management strategies can produce excellent long-term disease-specific survival and minimal morbidity for men with prostate cancer. Questions remain regarding both the identification of optimal candidates for surveillance, as well as understanding the ideal monitoring strategy. Despite increased adoption of expectant management, active surveillance still remains broadly underused and more data will be needed to clarify the factors contributing to the findings of the review at a population level.

3. Novel Biomarker Signature may predict aggressive prostate cancer in African-Americans

Researchers from the United States and Canada evaluated whether genetic factors could affect ethnic disparities in prostate cancer development and disease progression. The study looked at the ethnicity-specific expression of 20 prostate cancer-associated biomarkers in 154 African Americans and 243 European American patients. The researchers analysed these samples to find out which of the 20 validated genes—some of which initiate and some which drive cancer - were expressed in high or low quantities in the two populations of men. The authors identified a subtype which they called "triple negative prostate cancer," and defined as the absence or low levels of three genes called ERG, ETS, and SPINK1.

They reported African American men with high disease severity and risk of recurrence (this was calculated using a validated scoring system known as CAPRA-S) and more advanced Gleason grade disease at diagnosis were more likely to be triple negative when compared to European American men with a similar disease scores at diagnosis. In addition, the researchers also found other genes that were expressed at different levels in African American versus European American men. Further studies are already underway to validate the significance of this trend. The authors concluded that the subset of prostate cancer biomarkers they identified may explain in part the biologic contribution to ethnic disparity in prostate cancer outcomes between African American and European American men. In a clinical setting, it may suggest that some African American men with prostate cancer might have a better shot at survival if they are treated with a different approach than standard of care, however more research and investigation is required to refine the biomarkers that will capture these differences and develop approaches that help reduce the disparities in outcomes.

4. Black men are twice as likely to die from prostate cancer as white men

A study recently published in BMC Medicine, by researchers at Prostate Cancer UK and Public Health England, looked at the absolute risk figures to help men of different ethnicities better understand their risk of being diagnosed with, and dying from, prostate cancer. Previous research has estimated that a UK man’s lifetime risk of being diagnosed with prostate cancer is 1 in 8, and prostate cancer incidence rate data in England shows that Black men are significantly more likely, and Asian men significantly less likely, to be diagnosed with the disease compared to White men. The authors of this current study analysed prostate cancer incidence and mortality data of over 100,000 men, along with population and ethnicity figures from a combination of sources, to calculate the lifetime risk of being diagnosed with, and dying from, prostate cancer by ethnic group.

The study reported the lifetime risk of being diagnosed with prostate cancer is approximately 1 in 4 for Black men, 1 in 8 for white men and 1 in 13 for Asian men. In addition, the article reports the lifetime risk of dying from prostate cancer – approximately 1 in 12 for Black men, 1 in 24 for White men and 1 in 44 for Asian men. The authors conclude the findings should be used for targeted awareness-raising, but raise the fact that other risk factors can also affect an individual man’s risk of prostate cancer (including family history, weight and age). In addition, they recommend that further work is needed to understand the mechanisms behind the higher than average risk in Black men.

June 2015

Research round up from the clinic - top four articles from June 2015:

1. Cigarette smoking is associated with increased risk of biochemical recurrence following prostatectomy

For the first time, an international study led by MedUni Vienna and Basle University Hospital has provided evidence of a link between smoking and biochemical recurrence (BCR) of prostate cancer after prostatectomy. In a study of 6,538 patients, Rieken and colleagues showed a significant 63% and 80% increased risk of BCR in ex-smokers and current smokers, respectively, compared to ‘never smokers’. The research also showed that the negative impact of smoking on the risk of BCR is reduced to that of ‘never smokers’ after 10 years of not smoking.

2. Phase III trial shows adding docetaxel and estramustine to ADT improves relapse-free survival for high-risk localised prostate cancer patients

The GETUG-12 trial published results of the addition of docetaxel and estramustine to ADT, compared to ADT alone, in patients with non-metastatic high-risk localised disease. (Last month, we reported on the STAMPEDE trial results from ASCO 2015 which looked at metastatic patients – see here). In GETUG-12, Fizazi et al used the primary end point of ‘relapse-free survival’ which, after 8 years, was 62% in the men on ADT + docetaxel and estramustine, compared to 50% in the men on ADT alone. However, since this trial's inception in 2002, estramustine has fallen out of favour as a treatment for prostate cancer because of a lack of additive effects with docetaxel and its gastrointestinal toxic effects, and prostate-specific antigen endpoints are accorded less importance, limiting the generalisability of the results. At present, docetaxel should be reserved for metastatic disease either in the castration-sensitive setting, such as was assessed in CHAARTED and STAMPEDE, or for castration-resistant disease.

3. Scientists unveil the ‘Rosetta Stone’ of prostate cancer

An international team of scientists, led by the ICR in London, analysed the genetic codes of metastatic tumours from the bone, soft tissues, lymph nodes and liver of 150 patients with advanced prostate cancer. This enabled Robinson et al to produce a comprehensive genetic map of the mutations in prostate cancers that have spread round the body. The mutations found included some already known (e.g. in the BRCA1/2 genes) as well as previously undetected mutations in prostate cancer (eg in the PI3K and RAF gene families). They discovered that almost 90% of men with advanced prostate cancer carry genetic mutations in their tumours that could be targeted by either existing or new cancer drugs.

4. Increased prevalence of metabolic syndrome associated with ADT

Morote and colleagues conducted an observational prospective study involving 539 prostate cancer patients scheduled to receive three-month depot LHRH analogs for longer than 12 months. The authors examined the prevalence of full metabolic syndrome, assessed according to different definitions, and its components and found that at six and 12 months after ADT initiation there were significant increases in waist circumference, BMI, fasting glucose, triglycerides, total cholesterol, and high- and low-density lipoprotein cholesterol. At 12 months there were significant increases in metabolic syndrome prevalence. The authors concluded that counselling patients on the prevention, early detection, and treatment of specific metabolic alterations is recommended.

May 2015

Research round up from the clinic - top five articles from May 2015:

1. Earlier chemotherapy treatment can keep men with advanced prostate cancer alive for longer

A press release from the UK-led trial STAMPEDE trial was recently published ahead of a presentation of the results at ASCO’s annual meeting in June 2015. The STAMPEDE trial found that adding docetaxel chemotherapy to standard hormone therapy markedly improves survival for men with newly diagnosed advanced prostate cancer not previously treated with hormone therapy (hormone-naïve). Men who received docetaxel plus standard therapy lived on average ten months longer than those who received only standard therapy. Director of Research, Dr Iain Frame, said: “The findings of this trial are potentially game-changing – we can’t wait to see the full results at ASCO.” Read Prostate Cancer UK’s comment on the preliminary results from the STAMPEDE trial here. We’ve tried to address some of the key questions the research has raised for men with prostate cancer have been answered here.

2. Prostate cancer gene map could help targeted drugs

Robinson and his colleagues conducted a prospective study, sequencing the genetic codes of bone, soft tissues, lymph nodes and liver from 150 patients with metastatic prostate cancer. The scientists, based in the UK and US, used this information to create a comprehensive map of the genetic mutations within lethal prostate cancers that have spread around the body. The study revealed that almost 90% of men with advanced prostate cancer carry genetic mutations in their tumours that could be targeted by either existing or new cancer drugs. Nearly two thirds of men in the study had mutations in a molecule that interacts with the male hormone androgen which is targeted by current standard treatments. Mutations in the BRCA1 and BRCA2 genes, often know for their roles in breast cancer, were found in nearly 20% of patients. The scientists also reported new mutations, previously never detected in prostate cancer, but which do occur in other cancers. Almost 90 per cent of men with advanced prostate cancer carry genetic mutations in their tumours that could be targeted by either existing or new cancer drugs. The study also reported some evidence which may strengthen the case for genetic screening for people with a family history of the disease. The scientists believe the results of this study provide evidence that clinical sequencing in advanced prostate cancer is feasible and could impact treatment decisions in significant numbers or patients. In response to the publication of this exciting and ground-breaking research Dr Iain Frame, Director of Research at Prostate Cancer UK said: “This could provide the information about the best routes of attack in each individual case, which is crucial if we are to reduce the number of men dying needlessly from this disease. What’s more, many of the genetic changes they have identified could potentially be targeted by existing drugs.” More information and news on the study results can be found on the Institute of Cancer Research website (here).

3. Can statins slow the progress of prostate cancer?

Researchers from Boston, Harshman et al., investigated the effects of statins in men being treated with hormone therapy. The researchers looked at the clinical records of 926 men whose prostate cancer had either returned after treatment, or who had been diagnosed with prostate cancer that had already started to spread. Almost one third of those men were already taking some form of statin at the time that they initiated hormone therapy. The results also showed that it took longer for the cancer to progress in men who were taking statins at the same time as hormone therapy than in those who weren’t. Dr Iain Frame, Director of Research at Prostate Cancer UK said: “Whilst we continue to explore why men’s cancers stop responding to hormone therapies, this study suggests that taking statins alongside established treatments could be an effective and affordable way to extend the time that they can keep the cancer in check.” Read Prostate Cancer UK's comment on the research here.

4. Benefits of exercise for prostate cancer survivors

Phillips and colleagues from the United States assessed the relationships between types and intensities of activity and sedentary behaviour and the quality of life of almost 2,000 men diagnosed with non-metastatic prostate cancer. After controlling for potential confounders (e.g. pre-diagnosis physical activity and sedentary time) the researchers reported findings indicating higher duration of total, non-vigorous activity and walking, were associated with better hormone/vitality functioning (e.g. hot flushes, depression and changes in body weight). It was also noted that the data suggests engaging in just 90 min of normal/brisk walking per week may provide some benefits. The relationship between activity and hormone/vitality function appeared to be even stronger in longer-term survivors, and those who have chronic conditions and were diagnosed with more advanced disease indicating that targeting programmes and treatments at these groups may be particularly beneficial for improving prostate cancer-specific health-related quality of life.

5. Obesity link to prostate cancer may vary by race

In this prospective study, Barrington and colleagues investigated whether the association between obesity and prostate cancer risk differs by race. Data from over 3,000 African-American and more than 22,000 non-Hispanic white men were analysed. The reported body mass index (BMI) was positively associated with prostate cancer risk among African-American men, but there was no association of BMI and risk among non-Hispanic white men. African-American men considered to be severely obese (>35 kg/m2) were twice as likely (103% or a hazard ratio of 2.03) to be diagnosed with prostate cancer, compared to non-Hispanic white men. The study also looked at the association of body mass and race on the grading of prostate cancer (e.g. Gleason score). The researchers identified the need to understand the mechanisms underpinning the associations, although they also suggest that reducing obesity among African-American men could reduce the racial disparity in cancer incidence.