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. 

April 2016

1. Can radium-223 improve quality of life for men with CRPC?

Nillson and colleagues analysed health-related quality of life (QOL) data from the phase III multi-centre ALSYMPCA trial to determine the effects of radium-223 on patient experience of QOL. The ALSYMPCA trial was a randomised, double-blind, placebo-controlled trial which looked at radium-223 dichloride (radium-223) plus standard of care (SOC) compared to a placebo plus SOC for men with castration-resistant prostate cancer (CRPC). The trial demonstrated radium-223 versus placebo prolonged overall survival (OS) by 3.6 months and prolonged time to first symptomatic skeletal event (SSE) by 5.8 months. Radium-223 specifically targets prostate cancers that have spread to the bone. While radium-223 after chemotherapy is available on the NHS in England, NICE are currently considering whether it should also be available pre chemotherapy. In Scotland men with advanced prostate cancer can access the drug whether or not they have had chemotherapy.

For this study, the authors analysed data from two validated QOL questionnaires, the general EuroQoL 5D (EQ-5D) and the prostate-specific Functional Assessment of Cancer-Prostate (FACT-P). The questionnaires were completed by patients at randomisation (0), whilst on treatment at weeks 16 and 24, and at study discontinuation. The authors assessed the data for percentage of patients experiencing improvement, experiencing worsening and mean QOL scores during the study.

Results of the analysis demonstrated in patients receiving radium-223 a significantly higher percentage experienced meaningful improvement in QOL and a lower percentage experienced of pa meaningful worsening in QOL compared to patients who received placebo. Radium-223 treatment appeared to result in higher mean QOL scores on study versus placebo, and appeared to extend across multiple QOL domains. In conclusion, the authors stated their analysis of EQ-5D and FACT-P data from the ALSYMPCA trial demonstrated clinically meaningful QOL benefits, which accompanies improved survival results from analysis of earlier ALSYMPCA trial analysis.

2. Does a shortened radiotherapy schedule benefit low-risk prostate cancer patients?

The aim of this trial, by Lee and colleagues, was to assess the efficacy of a hypofractionated, also known as shortened, radiotherapy (H-RT) treatment schedule compared to a conventional radiotherapy (C-RT) schedule in men with low-risk prostate cancer. Conventional schedules typically require 40 to 45 treatments that take place from 8 to 9 weeks (>73Gy), whilst H-RT involves 28 treatments over 5-6 weeks (70 Gy).

Over 1,000 men with low-risk prostate cancer were enrolled in the study, received radiotherapy and were treated according to the study protocol. 542 men were assigned to C-RT and 550 to the H-RT protocol. The primary aim of the study was to compare disease-free survival rate, including local progression and distant metastatic progression, between H-RT and C-RT. Additionally the study looked at overall survival, prostate cancer-specific survival and time to biochemical recurrence. The authors reported treatment efficacy was similar between the C-RT and H-RT groups. Men treated with the shorter regimen (H-RT) were reported to experience more mild side effects, although late grade 2 and 3 gastrointestinal (GI) and genitourinary adverse events were increased this group compared to C-RT.

In conclusion the authors reported their data on men with low-risk prostate cancer and demonstrated the efficacy of their H-RT schedule was not inferior to C-RT, although an increase in late GI/genitourinary adverse events was observed in patients treated with H-RT.

3. Fitness outcomes from a randomised controlled trial of exercise training for men with prostate cancer

The main purpose of this study was to investigate the effects of a 12-week, clinician-referred, community-based exercise training program for improving exercise levels and quality of life for men with prostate cancer. The secondary purpose was to determine whether androgen deprivation therapy (ADT) modified responses to exercise training.

119 patients who had been diagnosed with prostate cancer and had completed active treatment within the previous 3-12 months provided data for this analysis. Of these patients, 53 were referred to the intervention (exercise) condition and 66 to the control condition. Outcome measures included fitness and physical function, anthropometrics, resting heart rate, and blood pressure. 85 % of the men in the intervention condition undertook at least 18 of the 24 supervised sessions in their local community gym.

Statistically significant differences between the two conditions were observed, in favour of men in the intervention condition for all measures of physical function. For example, compared to the control condition, men in the intervention significantly improved their 6-min walk distance, leg and chest strength and 30-s sit-to-stand result. The resting heart rates of the men in the intervention condition decreased by 3.76 beats/min more than those of men in the control condition. In addition ADT did not appear to modify responses to exercise training. Anthropometric differences between the conditions were minimal and were not statistically significant.

The authors concluded their analysis demonstrated that the fitness and physical functioning of men with prostate cancer can be enhanced through a community-based exercise training program. IN addition, the authors noted that improvement in strength, physical functioning, and, potentially, cardiovascular health. They also highlighted their findings suggest that favourable outcomes were gained irrespective of whether or not men were treated with ADT. The authors also acknowledged a limitation of their trial was that men recruited were more physically active than those reported in other studies, and this may have lessened the magnitude of the effects that may have other wise been achieved through the exercise training program.

4. Prostate cancer mortality declined along with cigarette smoking in the US

Researchers in the United States examined prostate cancer mortality rates in relation to changes in cigarette smoking. As in the UK, smoking rates in the US have declined and this is associated with a population-level reduction in incidence and mortality from many smoking associated diseases, including cardiovascular disease and lung cancer.

The study included analysis of smoking rates and prostate cancer mortality in men aged 35 years or older in California, Kentucky, Maryland, and Utah from 1999 through to 2010. The data came from the Behavioural Risk Factor Surveillance System and the Centres for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database.

Across the duration of the data analysed smoking rates declined in each of the four states studied (range 3.0-3.5% across states), although this decline was not significant in Maryland. Prostate cancer mortality rates also declined across all four states (2.1-3.5% across states). The researchers further analysis looking at the populations by ethnicity, found that while smoking rates declined significantly among white men in all four states, the prevalence declined significantly among black men in one state (out of three analysed at ethnicity level).

The authors noted that this study was an ecological analysis and was therefore unable to conclude any causal association between smoking and prostate cancer mortality. The authors also highlighted that the decreases in prostate cancer mortality occurred in spite of increasing obesity prevalence over the study period.
In conclusion the authors stated their findings support the need for targeted smoking cessation efforts, which could reduce prostate cancer mortality rates in this population burdened by both higher rates of prostate cancer and an elevated prevalence of cigarette smoking.

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.