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. 

March 2016

1. Efficacy and potential benefits of intermittent versus continuous androgen deprivation therapy

The ICELAND study, a multicentre phase 3 randomised study was conducted in 20 European countries, investigated the efficacy and safety profile of intermittent androgen deprivation (IAD) compared with continuous androgen deprivation (CAD) therapy in patients with non-metastatic prostate cancer. 700 patients were randomly assigned to either IAD or CAD therapy with leuprorelin acetate. Leuprorelin is also called Prostap or Lutrate and is a type of hormone therapy for prostate cancer.

Results from this study indicate no statistically significant or clinically relevant difference between the IAD or CAD groups for time to PSA progression, PSA progression free survival and mean PSA levels over time or quality of life in patients with non-metastatic locally advanced or relapsing prostate cancer.

The authors concluded the main potential benefit of IAD compared with CAD was reduced drug costs with comparable overall survival rates. 

2. Prostate Cancer Survival in men with metastatic castration-resistance prostate cancer

Several studies have identified the presence of visceral disease as an important adverse prognostic factor of overall survival (OS) in men with metastatic castration-resistant prostate cancer (mCRPC).  In this study, Halabi and colleagues analysed the data of nine phase 3 clinical trials involving over 8,000 men with metastatic prostate cancer, who had been treated with the chemotherapy drug docetaxel.

In the study patients were classified into four groups based on where their prostate cancer had spread to: the lymph nodes only, the lung, the liver (without the lung) or the bone (with or without lymph nodes and no metastases to other organs). 

Men whose cancer had spread to the lymph nodes only had the longest median survival, at 32 months, while those whose cancer had spread to the liver had the shortest median survival, at 14 months.  Men with bone metastasis was associated with a median survival of just over 21 months, while men whose prostate cancer had spread to the lung had a median survival of 19 months.  In conclusion the authors suggested further research and study is needed to understand the development of different metastatic patterns of disease, and a need to biopsy patients with recurrences to identify underlying mechanisms and treatment approaches for men with mCRPC.

3. Impact of radiation therapy dose escalation

American researchers, Zaorsky and colleagues, carried out a meta-analysis looking at how increasing the dose of external radiation therapy (RT) is related with biochemical failure free survival (BFFS) and other overall patient outcomes, including distant metastasis, overall survival (OS) and cancer-specific mortality. Data from almost 7,000 patients with localised and locally advanced prostate cancer from 12 randomised-controlled trials was included in the analysis.

The authors reported although BFFS rates improved with increasing radiotherapy dose, overall patient outcomes (i.e. distant metastasis, cancer-specific mortality, OS) did not improve.  They also reported that increasing dose was not associated with worse treatment toxicity, suggesting that current practices are safe. In conclusion the authors suggested their meta-analysis indicated that reliance on the PSA test as a proxy for patient outcomes may not as useful as previously though, and this results from this study may have broad implications for the design of future clinical trials and the interpretation studies.

4. Is radical Prostatectomy linked with favourable outcomes?

Carlsson et al., conducted a prospective analysis of oncological and functional outcomes 12 months after treatment of very-low-risk prostate cancer with radical prostatectomy in men who could have been candidates for active surveillance. Of the 4000 men from 14 participating centres in Sweden, 338 men fulfilled the criteria for very-low-risk prostate cancer and were included in the study analysis.

Results of the study of men with very-low-risk prostate cancer undergoing open or robot-assisted radical prostatectomy showed that there were favourable oncological outcomes in approximately two-thirds. Of the 338 men, 35% experienced upgrading, defined as pT3 or post-operative Gleason sum of at least 7, while positive surgical margins were present in 16%. Only 2.1% of the men in the study were found to have a PSA concentration of greater than 0.1ng/mL 6-12 weeks postoperatively.  Additionally, urinary continence was observed in 84% of the men 12 months postoperatively, and 44% reported good erectile function 1 year after surgery.

From the results of their study, the authors concluded that choosing surgery as the primary treatment for this set of men in Sweden, men with very-low-risk prostate cancer, will result in a favourable oncological outcome for about two-thirds of the cases, but is likely to jeopardise a man's sexual and urinary health to a great extent.

The authors also said their results provided additional support for the use of active surveillance in men with very-low-risk prostate cancer, but the group of men with risk of upgrading and upstaging is not negligible - highlighting improved stratification in the future with more advanced mpMRI and target biopsies is urgently needed.

February 2016

1. Can phytochemical agents manage prostate cancer morbidity and mortality?

A systematic review, published in the British Journal of Urology International (BJUI) evaluated the evidence from randomised trials of phytotherapeutic interventions in the management of prostate cancer recurrence and disease progression. Phytochemicals are compounds that are produced by plants and the researchers of this review assessed 23 articles, with only five meeting the criteria for inclusion. The interventions investigated looked at phytochemical agents including lycopene, soy protein, pomegranate extract, green tea and broccoli sprouts.

The results from the review indicated there is limited evidence that the phytochemicals such as sulphoraphane, lycopene, soy isoflavones, and pomegranate extracts (e.g. POMx, and Pomi-T) can affect PSA dynamics, although the data indicates they are safe and well-tolerated. In conclusion the authors stated no recommendation can be made for the use of these agents in managing prostate cancer morbidity and mortality until high-quality, fully powered, placebo-controlled studies are available.

2. Systematic review of MRI/US-fusion biopsy in prostate cancer detection

The current ‘gold standard’ for the diagnosis of prostate cancer is ultrasonography (US) guided systematic biopsies. This technique has several limitations. Recent research has been focussing on targeted prostate biopsies using magnetic resonance imaging (MRI) and ultrasonography (MRI/US)-fusion platforms. The aim of this systematic review published in the BJUI was to assess the cancer detection rates of different MRI/Ultrasound (US)-fusion platforms for taking prostate targeted biopsies from the published literature.

The researchers identified over 2000 records during the literature search and in total 11 studies met the inclusion criteria for analysis. The results of the systematic review indicated no clear advantage of MRI/US-fusion guided targeted biopsies was seen for cancer detection rates of all prostate cancers. However, the technique tended to give higher detection rates for clinically significant prostate cancers. In their conclusion the authors also highlighted general limitations in assessing the value of MRI/US-fusion targeted biopsies, which included the quality of taking biopsies and experience of the radiologist and physician performing the biopsy which may determine the quality of the biopsy cores and ultimately determines the detection rates. The authors also highlighted the need for more prospective studies on the effectiveness of MRI/US-fusion TB for prostate cancer diagnosis. 

3. Can pelvic floor training before post-prostatectomy help incontinence?

Urinary incontinence is one of the most common side effects of radical prostatectomy (RP) and can substantially affect a man's quality of life. Reported rates of urinary incontinence after radical prostatectomy have been as high as 87% at one-month postoperatively, but generally improving after a year. A meta-analysis and systematic review, conducted by Chang and colleagues at the University of Sydney assessed almost 20 articles, and included 11 in their systematic review and 7 in their meta-analysis. Their meta-analysis demonstrated a significant 36% reduced risk of postoperative incontinence at 3 months after radical prostatectomy if pelvic floor muscle exercise was taken. Although no significant difference was seen at 1- or 6 months.

In conclusion the authors stated, based on their systematic review and meta-analysis, preoperative pelvic floor muscle exercise might aid early urinary incontinence recovery and increase the QoL of patients after RP. This systematic review and meta-analysis did not investigate how pelvic floor muscle exercise improves incontinence. The researchers also acknowledged their study was limited by the small number of studies and patients that were available for analysis, as well as the difference in pelvic floor exercise regimens and definitions of continence and quality of life tools across the available studies.

4. Cancer control outcomes following robotic-assisted laparoscopic radical prostatectomy

This multi-institutional study, involving researchers from the USA, Germany and Italy, investigated cancer control outcomes in over 5,500 prostate cancer patients following robot-assisted radical prostatectomy between 2001 and 2010. The study examined recurrence-free survival (BCRFS), clinical recurrence-free survival (CRFS), and cancer-specific survival (CSS) at least 5-years following RARP. At 5-year follow up BCRFS, CRFS and CSS were 3.3, 98.6, and 99.5 %, respectively. Less than 2% of patients received any adjuvant treatment. Independent clinical predictors of BCRFS, CRFS and CSS included preoperative PSA and biopsy gleason score.

The authors concluded data from their study suggests despite low overall rate of adjuvant treatment, cancer control outcomes of RARP are comparable to those reported for open and laparoscopic RP in previous literature.

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.