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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 2016

1. Both robotic and open surgery achieve similar results at 3 months

The first stage of a two year study published in the Lancet, reports that both robot-assisted laparoscopic prostatectomy (RALP) and radical retropubic prostatectomy (open) surgery for localized prostate cancer achieve similar outcomes at 3 months. This Australian study, composed of 308 men, is the first randomised controlled trial to compare robotic vs open surgery for the treatment of localized prostate cancer. There was no significant difference between open vs RALP groups at 12 weeks post surgery for urinary (83.80 vs 82.50; p=0.48) or sexual (35.00 vs 38.90; p=0.18) function or proportion of positive surgical margins (10% vs 15%; p=0.21).  There was a tendency, which did not reach statistical significance (p=0.052), towards lower postoperative complications in the RALP group (2%) compared to open surgery (8%). According to the 2014 BAUS Surgical audit of radical prostatectomies in the UK, RALP accounted for 59% of surgeries, while open surgeries were performed in 13.4% of the cases. Reporting on longer-term follow, at 24 months post-surgery, is expected, and will include analysis of urinary and sexual function and oncological outcomes including positive surgical margin status and evidence of progression. This will be important to fully assess the efficacy of both treatments in terms of long-term side-effects and cancer survival.

You can read more about this study on the news section of our website here.

2. Men with advanced prostate cancer more likely to inherit gene mutations than men with localised disease

A new study published in the New England Journal of Medicine has shown that men with metastatic prostate cancer have a much greater chance of carrying a germline mutation in DNA-repair genes such as BRCA1/2 and ATM than those with localized disease. The ICR team, led by Prof. Johann de Bono, sequenced 20 DNA-repair genes that are associated with cancer-predisposition from 700 men with aggressive disease. These men had an 11.8% chance of carrying a germline mutation in genes that are responsible for maintaining DNA integrity compared to a 4.6% chance in men with localized prostate cancer. Significantly 71% of men with DNA-repair gene mutations had a first-degree relative with a cancer other than prostate cancer compared to only 50% of men without the DNA-repair gene mutations. Although these are early results this study has two clear implications. Firstly, testing men with prostate cancer for the presence of these mutations may allow their treatment to be personalized, for instance with the addition of PARP inhibitors which have been shown to have anti-tumour effects in other cancers with DNA-repair mutations. Secondly, just as BRCA1/2 mutations are used to screen for women at high risk of developing breast cancer, men who have a close family member with advanced prostate cancer may be tested for these mutations which would identify if they have a higher risk of developing prostate cancer themselves.

You can read more about this study on the news section of our website here.   

3. Patients taking statins are almost half as likely to die of prostate cancer

Adding to the growing evidence about the cancer-preventing properties of statins, a study of 22 667 cancer patients out of Aston University in Birmingham found that patients who were on the cholesterol lowering drug were up to 47% less likely to die of their disease. The study presented at Frontiers in CardioVascular Biology (FCVB) 2016 prospectively examined the outcomes of people who had been admitted to hospital between 2000 and 2013 with prostate, breast, bowel and lung cancers. The largest effect was seen in prostate cancer, where after taking into account factors such as age, gender or ethnicity, researchers found that prostate cancer patients who had previously been diagnosed with high-cholesterol were 47% less likely to die than patients with normal cholesterol levels. As 9 out of 10 patients with high cholesterol were taking statins, the authors propose that increased survival is linked to statin usage and call for a clinical trial to more closely examine the connection between statins or other cholesterol-reducing drugs and cancer. While there is currently no evidence to support this, future research will be important to explore if statins could be effective in patients without high cholesterol levels.

June 2016

1. Hypofractionated radiotherapy to become the new standard of care – 5 year results from the CHHiP trial

The long-awaited CHHiP (Conventional or hypofractionated high dose intensity modulated radiotherapy for prostate cancer) trial results were published last month in Lancet Oncology. The phase 3 non-inferiority trial, led by the ICR’s Prof David Dearnaley and involving 3,163 participants, showed that hypofractionated radiotherapy using 60 Gy in 20 fractions is non-inferior to conventional fractionation using 74 Gy in 37 fractions. The study recommended this as a new standard of care for external-beam radiotherapy of localised prostate cancer (since men can now make 17 fewer hospital trips without compromising on effectiveness) and we are working with Prof Dearnaley’s team to ensure widespread roll-out.

Read about the trial results in more detail on our website here.

2. mpMRI scans will help men avoid unnecessary prostate biopsy – results from PROMIS

An ASCO 2016 highlight was the much anticipated PROMIS (PROstate MRI Imaging Study) results, led by Prof Mark Emberton and Dr Hashim Ahmed from UCL. The results from 576 men showed the mpMRI sensitivity was 93% [95%CI 88-96], specificity was 41% [36-46], PPV was 51% [45-56] and NPV was 89% [83-94]. This means that using mpMRI as a triage test would, at a minimum, avoid a primary biopsy in 158 (27%) men with 14 (2%) fewer cases of clinically significant cancer detected. Second, if biopsy targeted to mpMRI findings achieves the sensitivity of TPM-biopsy, triage with mpMRI would again avoid primary biopsy in 158 (27%) but detect 17 (3%) more cases of clinically significant cancer than the standard TRUS-biopsy. Read about the trial results in more detail on our website here.

The results still need to be confirmed in a peer-reviewed publication but here’s how we’ve already been working to turn the results into reality for men.

3. Evidence base linking weight to aggressive prostate cancer continues to grow – results from EPIC

EPIC (European Prospective Investigation into Cancer and Nutrition) released new data at the European Obesity Summit (abstract PO1.857) last month which supports previously published research by the WCRF. After 14 years of follow-up with 142,239 men, EPIC has shown a 10% increased risk of getting aggressive (high-grade) prostate cancer per 5kg/m2 (BMI) and a 13% increased risk per 10cm of waist circumference. The latest results also show a 14% increased risk of dying from aggressive prostate cancer per 5kg/m2 and 18% increased risk per 10cm of waist circumference.

These findings may give health professionals another warning sign to look out for. Importantly, unlike the other known risk factors, being overweight is a risk factor that men can proactively do something to change.

May 2016

1. Short-term hormone therapy associated with radiotherapy as salvage treatment after radical prostatectomy: results of the GETUG-AFU 16 phase III randomized trial

Results of the GETUG-AF 16 randomised multicentre phase 3 trial were published in the Lancet this month. The trial investigated the addition of short-term androgen suppression to salvage radiotherapy (RT) on survival in men with rising PSA concentrations after radical prostatectomy.

Over 700 patients were enrolled in the study and randomly assigned to receive RT alone or RT plus goserelin. The average age of both groups was 67 years. All patients received 3D conformal radiotherapy or intensity modulated radiotherapy (IMRT). Patients in the RT plus goserelin group were given goserelin acetate by subcutaneous injection on the first day of irradiation and again after 3 months. Primary endpoints were progression-free survival (clinical or biological progression, or both) and death from any cause.

At final analysis, follow-up was around 5 years. The authors reported no additional serious acute or late genitourinary, gastrointestinal, or cardiovascular toxicities in the RT plus goserelin group. 5-year progression-free survival in the radiotherapy plus goserelin group was significantly higher than in the radiotherapy alone group (80% vs. 62%, respectively). The median duration to relapse was significantly different between the two groups (22 months in the radiotherapy alone group vs. 32 months in the RT plus goserelin group). The results showed no significant differences in health-related quality of life between the two groups. The authors acknowledged the need for longer follow-up, in order to establish the effect of this therapeutic strategy on overall survival, and suggested that combined RT and goserelin treatment could delay the need for more aggressive therapy.

2. Systematic review and meta-analysis indirectly comparing abiraterone acetate and enzalutamide for the treatment of metastatic CRPC

This literature‑based systematic review and meta‑analysis evaluated the efficacy, tolerability, and sequential administration of abiraterone acetate (AA) and enzalutamide (Enz) for metastatic castration‑resistant prostate cancer (mCRPC).

AA and Enz are two new agents that block androgen synthesis. Recent studies have demonstrated that tumour progression after androgen deprivation therapy commonly remains hormone driven, thus, therapies targeting residual androgen production may be promising and well‑tolerated alternatives to standard chemotherapy. In this study a literature search of the PubMed, Embase, and Web of Science databases in 2015 to identify relevant studies was carried out. Using the defined search criteria analysis of ten manuscripts on phase III trials for the indirect comparisons between AA and Enz as treatments for mCRPC, and 8 case series studies and 1 case–control study were used to evaluate the optimal sequencing of AA and Enz.

The authors reported results of indirect comparisons from their analysis and review demonstrated improvement in overall survival (OS) was not significantly different between AA and Enz. However, they reported the results suggested a potential advantage of Enz over AA in most secondary endpoints, including time to PSA progression, radiographic progression free survival (PFS), PSA response rate, time to health-related quality of life (HRQoL) deterioration, and time to initiation of chemotherapy (chemotherapy‑naive patients). However, the authors also highlighted that their review had not shown any head‑to‑head comparison. They acknowledged several limitations of the study, particularly the differences in baseline characteristics among the trials – including the inclusion of patients with visceral disease in some (but not all) of the trials and the inclusion of case series studies for evaluating optimal sequencing, which have relatively low methodological quality.

In conclusion it was reported that AA and Enz demonstrated similar survival benefits in patients with mCRPC before and after chemotherapy, whilst Enz may be advantageous for secondary endpoints including time to PSA progression, radiographic PFS, PSA response rate, time to HRQoL deterioration, and time to initiation of chemotherapy (chemotherapy‑naive patients).

3. The role of targeted biopsy in active surveillance

Prostate-specific antigen (PSA) testing is associated with higher prevalence of favourable-risk prostate cancer. Active surveillance (AS) can reduce over-treatment of men with favourable disease. Advances in multiparametric magnetic resonance imaging (mpMRI) allow high-quality visualization of the prostate and improved identification of prostate cancer. Some studies have shown that mpMRI/TRUS fusion biopsy (targeted biopsy) is associated with greater detection of high-risk cancer and lower detection of low-risk cancer when compared to SB. The authors of this study sought to assess the use of targeted biopsy among active surveillance candidates.

In this study retrospective evaluation of 12-core transrectal ultrasound-guided prostate biopsy (TRUS biopsy) and targeted biopsy among 230 men was conducted (103 AS men undergoing surveillance biopsy, 54 men undergoing confirmatory biopsy (CB), and 73 men referred for diagnostic biopsy (DB; comparison group)). The mpMRI protocol was performed using a 3.0-T whole body scanner, and T2-weighted imaging, diffusion weighted imaging and dynamic contrast enhanced imaging were interpreted by a radiologist. PI-RADS version 2 was used to score regions of interest, and scores ≥3 were considered positive and targeted on biopsy.

Gleason score (GS) ≥7 was detected by either of the two biopsy methods in 24% of men in the AS group, 22% in the CB group, and 75% in the DB group. GS ≥7 was found in 24.3% by SB + TB versus 20.4% by SB in the AS group (p = 0.13); in 22.2% by SB + TB versus 16.7% by SB in the CB group (p = 0.25); and in 75.3% by SB + TB versus 58.9% by SB in the DB group (p = 0.002).

The sensitivity for GS ≥7 detection was lower for TB than for SB (p = 0.006) in the AS cohort (relative sensitivity ratio 0.33, 95% confidence interval 0.16–0.71). Higher PI-RADS score (4 vs 3, odds ratio [OR] 2.00, p = 0.04; 5 vs 3, OR 4.74, p = 0.02), lower MRI-estimated prostate volume (OR 1.20 per 10-cm3 lower volume, p = 0.01), larger ROI (OR 1.04 per mm, p = 0.02), and right-sided ROI (OR 2.27, p = 0.01) were associated with finding cancer on TB. A potential limitation is that not all men who presented for biopsy underwent targeted biopsy and the urologist was not blinded to MRI results before TRUS biopsy.

In summary the authors indicated that image-guided prostate biopsy alone may not be informative for men enrolled in an active surveillance program for prostate cancer, and TRUS biopsy should still be performed on this group.