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. 

September 2016

1: 10-yr survival is the same for men following active monitoring, surgery or radiotherapy 

The ProtecT trial, published this month in the New England Journal of Medicine, has reported that men with localised prostate cancer who participated in ‘active monitoring’ had the same 10 year survival as men who had either radical prostatectomy or external-beam radiotherapy. 1643 men were randomised to the three treatment arms and followed for a median of 10 years; by the end of the study approximately 50% of men assigned to active monitoring had undergone either surgery or radiotherapy as their disease progressed. There was no difference in prostate cancer specific survival between any of the arms. However as survival was very high (over 98.8%) in all three groups it will be important to see the results of the planned follow up in 5 years, to see if any of the treatments affect mortality at later time periods. Most of the men who took part in the trial had low risk disease (median PSA 4.6 ng/mL, 77% had Gleason 6) and if currently diagnosed would already be encouraged to undergo active surveillance. This trial did not include enough men with higher-risk localised disease (i.e. Gleason 7) to draw a conclusion about the effectiveness of active monitoring for men in this risk category.

Despite having similar survival, men who were on the active monitoring arm had higher rates of disease progression (112 men in the active monitoring, 46 men in the surgery and 46 men in the radiotherapy group, p<0.001) and metastatic disease (33 men in the active monitoring, 13 men in the surgery and 16 men in the radiotherapy group, p<0.004). During the trial, men in active monitoring were followed by PSA kinetics. This is quite different than current active surveillance protocols, which recommend including mpMRI staging and scheduled repeat biopsies, and it is likely that this more active method may result in decreased rates of disease progression for men currently under active surveillance protocols.

When taken together with the patient-reported outcomes (published concurrently and described below) this study supports the use of active monitoring for men with localised prostate cancer and will help men make a more informed treatment choice that is right for them.  

2: Patient-reported outcomes following active monitoring, surgery or radiotherapy 

As described above, the ProtecT trial showed no difference in 10 year survival for men with localised prostate cancer who were assigned to either active monitoring, surgery or radiotherapy. Men also completed questionnaires (at 6 and 12 months after randomisation and annually thereafter) that aimed to measure urinary, bowel and sexual function and quality of life. These results, published concurrently in the New England Journal of Medicine, describe different levels of severity and recovery of urinary, bowel and sexual function among the treatment arms. Interestingly, there was no significant difference with respect to men’s anxiety, depression or over-all health-related quality of life between the treatment groups.

Of the three treatments, prostatectomy had the largest negative effect on sexual and urinary function. This was greatest at 6 months and, while there was recovery over time, this group maintained worse function throughout the trial compared to radiotherapy or active monitoring (p<0.001 for either sexual or urinary function). There was also a gradual decline in sexual and urinary function in men in the active monitoring group as increasing numbers received surgery/radiotherapy or underwent age-related changes. 

At 6 months, men in the radiotherapy group experienced almost as much sexual dysfunction as the surgery group, and had worse bowel function than either of the other arms. However, there was considerable improvement over time for all measures except frequent bloody stools (p<0.001). Finally, overall health-related quality of life (including measures for anxiety and depression) was the same amongst all groups.

It has long been thought that an active monitoring/surveillance approach leads to increased levels of anxiety in men, compared to radical treatment. This study suggests that this is not in fact the case and that men who undergo active monitoring may overall experience less negative side effects.

August 2016

1: High dose radiation as effective as radical prostatectomy for aggressive prostate cancer

In a study published this month in the European Journal of Urology, researchers from UCLA performed a retrospective analysis to compare the outcomes for 487 men with Gleason scores of 9 or 10 treated with either radiation or surgery. Clinical outcomes were measured for men treated between 2000-2013 with either EBRT (extremely-dose escalated radiotherapy) [230 men], EBRT + BT (Brachytherapy) [87 men] or RP (radical prostatectomy) [170 men], with a median follow-up of 4.6 years.

While 5-yr and 10-yr cancer specific survival and overall survival was similar for all three treatment groups, there was a significant increase in 5-yr and 10-yr distant metastasis-free survival in men who received EBRT + BT (94.6%, 89.8%) compared to EBRT alone (78.7%, 66.7%, p<0.0005) or RP (79.1%, 61.5%, p<0.0001). In addition, there was increased local and systemic salvage associated with RP (49.0%, 30.1%) compared to EBRT (0.9%, 19.7%) or EBRT + BT (1.2%, 16.1%, p<0.001).

This study provides both clinicians and patients with more evidence about the efficiency of these common treatments and indicates that while both radiation and surgery are effective treatments for aggressive prostate cancer, EBRT + BT may provide the best chance of preventing metastatic disease.

2: Addition of radiotherapy to hormone therapy increases survival in men with newly diagnosed metastatic prostate cancer

Androgen deprivation therapy (ADT) is first line therapy for newly diagnosed metatastic prostate cancer (mPCa). Following up on recent studies that have shown improved survival when ADT is combined with prostatectomy, an American study published in the Journal of Clinical Oncology has examined the benefits of combining ADT with radiotherapy (RT). 6382 men were identified within the National Cancer Database (NCDB) who were diagnosed with mPCA between 2004 and 2012. Of these, 538 men received RT. With a median follow-up of 5.1 years, there was significantly improved overall survival for men receiving RT + ADT compared to ADT alone (hazard ratio, 0.624; 95% CI, 0.551-0.706; p<0.001).

Analysis of a sub-set of long-term survivors showed increased overall survival at ≥1, ≥3 and ≥5 years (all p<0.05) with the addition of RT to ADT. There was no difference in overall survival between Prostatectomy + ADT compared to RT + ADT, while both combinations were superior to ADT alone. This study adds to growing evidence supporting the use of ADT in combination with local treatment strategies such as surgery or RT.

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.