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. 

January 2016

1. Fatal attraction: new research reveals link between obesity and cancer progression

French scientists have discovered how fat cells and cancer cells attract each other, causing aggressive tumours to spread beyond the prostate.

The study used experiments in cells and mice to investigate a potential new pathway, regulated by obesity, implicating periprostatic adipose tissue (PPAT) in prostate cancer progression and aggressiveness. PPAT surrounds the prostate gland, and, like other fat depots is an active endocrine organ. They found that these fat cells, surrounding the prostate, release a protein called CCL7 which is attracted to and sticks to a molecule on the surface of prostate cancer cells called CCR3 – in the mouse models this interaction enabled the cancerous cells to move and spread - a key step in the change between a localised prostate cancer cell and aggressive prostate cancer which can spread around the body.

CCL7 has been reported to be over-expressed in adipose tissue in a context of obesity, the researchers confirmed this when they assessed tissue samples of obese individuals and mice. To mimic the effects of obesity, some mice were fed a high fat diet whole others were kept on a normal diet. The migration of prostate cancer cells in response to mouse fat cells was significantly higher when cells migrate towards fat cells obtained from the obese mice compared with that of lean animals. In tissue samples, from men with prostate cancer, the investigators were also able to show that higher levels of the CCR3 molecule were more common in more aggressive forms of the disease.

Dr Iain Frame, Director of Research at Prostate Cancer UK said; “There is a known link between obesity and developing aggressive prostate cancer, and this research starts to fill in some of the blanks as to why this link might exist. “Prostate cancer is often symptomless in its early stages when it is most treatable and so awareness of risk is crucial. We already know that men over 50, black men and men with a family history of prostate cancer face a greater danger of developing the disease. Being overweight is an important new warning sign to be aware of.”

To read more about this research check out our News and Views page here

2. Regular aspirin use and the risk of lethal prostate cancer in the Physicians' Health Study

A study presented at the American Society of clinical Oncology 2016 Genitourinary Cancers Symposium, in San Francisco, reported that men who take aspirin regularly may have a lower risk of dying from prostate cancer.

As part of the prospective Physicians' Health Study 22,071 male physicians were enrolled and followed from 1982-2009. The investigators evaluated the relationship between regular aspirin intake (more than 3 tablets per week) and lethal prostate cancer (metastases or prostate cancer death), as well as looking at the incidence of total, high-grade (Gleason 8-10), and advanced cancers.

After adjusting for differences in age, race, body mass index, and smoking status analysis the researchers found that men who regularly took aspirin had a 24% lower risk of developing lethal cancer after being diagnosed with an early stage of the disease, and a 39% reduced risk of dying from prostate cancer.

But aspirin had little effect when researchers looked at overall incidence of prostate cancer among the participants. Although regularly taking aspirin seemed to affect the development of prostate cancer in men already diagnosed, it did not appear to affect the likelihood of being diagnosed with total prostate cancer, high-grade prostate cancer, or locally advanced prostate cancer.

The biological basis for this potential protective effect against prostate cancer progression is unknown and more research is needed to determine which men in particular would benefit from regular aspirin and what the optimal dose of aspirin is.

Regular aspirin use is also associated with protection against colorectal cancer and cardiovascular disease, but it comes with gastro-intestinal side effects including bleeding that can cause serious complications in some people. Patients considering an aspirin strategy to prevent progression of prostate cancer should discuss the risks and benefits with their doctors.

This information above is from an abstract presented at an annual conference/symposium and has not yet been published in a peer-reviewed journal. Data presented may not be complete and findings should be treated with caution.

3. Urinary Toxicity Due to Brachytherapy for Prostate Cancer

According to Initial findings, presented at the American Society of Clinical Oncology 2016 Genitourinary Cancers Symposium, brachytherapy for prostate cancer controls spread of the disease, and urinary complications from the procedure appear to resolve after 1 year.

Meek at colleagues from Washington University School of Medicine reviewed medical records of patients with localised prostate cancer treated with low dose rate (LDR) brachytherapy from 1997-2011. The median follow-up was 5.8 years. Patient-reported genitourinary (GU) toxicity was evaluated by the American Urological Association Symptom Score (AUAS), at, 1, 6, and 12 months following brachytherapy treatment.

At 9 years, the biochemical relapse-free survival (bRFS) among the 400 patients in the study was 92.8%. In addition, the metastasis-free survival was 97.8% and the overall survival was 79.9%.

AUAS scores rose from 6 to 14 at 1 month following brachytherapy, but did not change from month 1 to month 6. However, scores decreased to a median of 8 by 12 months after brachytherapy. In the 69 patients with all values (17%), no factors were found significant for change in AUAS scores.

The investigators conclude LDR brachytherapy for localised prostate cancer offers excellent bRFS, metastatic-free survival and overall survival. Genitourinary toxicity, assessed by AUAS scores, appears to return to pre-treatment baseline by 12 months post-brachytherapy, and older age and neoadjuvant androgen deprivation therapy use may be associated with higher AUAS scores.

This information above is from an abstract presented at an annual conference/symposium and has not yet been published in a peer-reviewed journal. Data presented may not be complete and findings should be treated with caution.

4. Even after anti-androgen therapy, docetaxel remains useful in prostate cancer

In an abstract presented at the 2016 Genitourinary Cancers Symposium reported 40 percent of patients with castration-resistant metastatic prostate cancer (mCRPC) treated with docetaxel following abiraterone had a reduction in prostate specific antigen (PSA).

To assess treatment patterns after abiraterone, researchers from the United States analysed data from the clinical trial COU-AA-302 (chemotherapy-naïve men with mCRPC, abiraterone acetate plus prednisone (AA) significantly improved radiographic progression-free survival and overall survival vs placebo plus prednisone (P)). This multi-institution study conducted post-hoc analysis of patients in the abiraterone acetate plus prednisone (AA) arm (546 patients) who progressed.

The post hoc analysis, presented at the symposium earlier this year, indicates that treatment with subsequent therapy was common (67% and 80%) in patients with chemotherapy-naïve mCRPC who progressed with AA or P, respectively. 36 percent of patients in the AA arm received two additional therapies and 15 percent receiving three or more subsequent therapies. About half of all abiraterone-treated patients on the study were treated with docetaxel in the next subsequent line of therapy. Of these patients treated with docetaxel immediately after abiraterone, 40 percent had PSA decline by more than half, demonstrating the effectiveness of this chemotherapy even after treatment with androgen-deprivation therapy.

Despite limitations of a retrospective analysis, these data support further assessment of subsequent therapy following AA treatment for mCRPC.

This information above is from an abstract presented at an annual conference/symposium and has not yet been published in a peer-reviewed journal. Data presented may not be complete and findings should be treated with caution.

December 2015

1: Giving docetaxel at the same time as ADT to men with metastatic prostate cancer extends overall survival by an average of 15 months – results from STAMPEDE

The much anticipated official results of the docetaxel arm of the STAMPEDE trial have been published in the Lancet. The trial reported an almost unprecedented survival benefit for men newly diagnosed with metastatic prostate cancer, when they were given docetaxel chemotherapy as a first line treatment alongside ADT. On average, men receiving ADT + docetaxel lived 15 months longer than those receiving ADT alone, the current standard of care.

Find out more about how we’ve been working with NHS England to ensure this research leads to a change in clinical practice here.

2: Prostate cancer patients are more likely to survive if they undergo surgery rather than radiation

A systematic review and meta-analysis of 19 studies and 118,830 patients has found that radiotherapy is associated with an increased risk of overall and prostate cancer-specific mortality compared with surgery, in men with localised prostate cancer.

Both treatment approaches should be discussed with patients prior to the start of therapy. The important thing about this research is that it gives clinicians and patients additional information to consider when making the decision about how to treat localised prostate cancer.

The randomised controlled trial ProtecT, due to report next year, will provide definitive evidence for the best treatment for men with localised prostate cancer.

November 2015

Research round-up from the clinic - top three articles from November 2015:

1. STHLM3 model could reduce unnecessary biopsies without compromising the ability to diagnose prostate cancer

In a study of 58,818 men aged 50-69 published in The Lancet Oncology, researchers found that a test, known as STHLM3, reduced the number of biopsies given to men who received it by 27%, compared to relying solely on PSA measurement. The scientists at the Karolinska Insitute in Sweden combined PSA measurement and a prostate exam, along with analysis of more than 200 genetic markers linked to prostate cancer, and clinical information such as age and family history, to try to develop a more accurate test.

The researchers found that the S3M test was much better than PSA alone at detecting potentially dangerous prostate cancers (those with a Gleason score of 7 or more), and every independent step of the assessment process – from risk assessment, through biomarker panel to prostate exam – added an extra level of prediction to the test. These results give compelling evidence that the S3M risk assessment model can dramatically reduce the number of men undergoing unnecessary biopsies, without compromising the safety of men who do have an aggressive form of prostate cancer.

Prostate Cancer UK believe that men need a better test of their risk as soon as possible. That’s why we’re funding an international team of scientists to develop a risk assessment tool for use within primary care in the UK. These plans are still going full-steam ahead, and we expect to have more to say about this in the New Year. That work will accommodate this new Stockholm model when we’ve shown that it’s effective in the UK.

2. Radiotherapy trial shows fewer, higher doses don't worsen patient side effects and could save the NHS millions per year

Research from the Institute of Cancer Research presented at the National Cancer Research Institute (NCRI) Cancer Conference showed the effectiveness of using IMRT in higher doses over fewer hospital visits than is currently recommended on the NHS. After 5 years of follow-up with 3,216 men, the phase III CHHiP trial has shown that treatment with fewer, higher doses (20 x 3Gy/day) than currently offered by the NHS (27 x 2Gy/day) delays progression of prostate cancer at least as effectively as greater numbers of lower doses. The new regime is just as good for quality of life as the longer, lower-dose regime, and is associated with less than half the rate of side-effects of older conformal radiotherapy.

The new regime for prostate cancer would save each patient 17 fatigue-inducing hospital trips and complex radiotherapy treatments, leading to a reduction nationally of more than 150,000 visits per year.

Note: these results are yet to be published in a peer-reviewed journal.

3. Enzalutamide is effective and well tolerated in elderly patients – an analysis from the PREVAIL trial

In the double-blind, international PREVAIL trial, 1717 chemotherapy-naïve men with mCRPC were randomly assigned to receive enzalutamide 160 mg orally daily or placebo. Of those, 609 patients (35%) were elderly (75+). An further analysis by Graff et al, has shown that overall survival was 32.4 months among the elderly patients taking enzalutamide, compared to 25.1 months in the elderly placebo group (7.3 months survival benefit). In regard to safety, the incidence of adverse events was similar in both treatment arms, but there was an overall higher incidence of falls among elderly patients compared with younger patients and among elderly patients receiving enzalutamide vs those receiving placebo.