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. 

October 2016

1: Baseline PSA levels predict for future development of lethal prostate cancer

An American study published in the Journal of Clinical Oncology has shown that baseline PSA levels taken in midlife were strongly associated with future risk of lethal prostate cancer (PCa). Researchers measured baseline PSA levels in blood samples, collected between 1982 and 1984, from men then aged 40-59 years. Men were divided into two categories: 234 cases (men who were diagnosed with PCa between 1982 and 1993) and 711 matched controls. During follow up, 60 out of the 234 men (26%) originally diagnosed with PCa died of the disease, whereas 11 out of 711 men (2%) selected as controls also developed lethal PCa.

Across all age groups, men with baseline PSA levels above the age-specific median had increased risk of developing PCa compared to men with PSA levels at or below the median. The ORs were 7.3 (95% CI, 2.4 to 21.8) for 40-49 years, 7.6 (95% CI 3.4-17.2) for 50-54 years and 10.1 (95% CI, 5.2 to 19.6) for 55-59 years. The risk of developing lethal PCa was also strongly associated with baseline PSA levels, with 86% of lethal cases occurring in men with PSA measurements above the median level. These results are consistent with previous research and suggest that there may be limited benefit in re-testing men who have no additional risk factors and a PSA less than 1.0ng/ml at 60 years. While significant, this was a small study and future research will be important to confirm these results. For more information about Prostate Cancer UK's position on PSA testing please see our PSA Consensus Statements

2: Androgen deprivation treatments associated with higher risk of dementia

A retrospective analysis of 9272 men with prostate cancer found that men who received androgen deprivation treatment (ADT) had a small but significant increased rate of dementia at 5 years. Men who received ADT had a 7.9% absolute risk of developing dementia compared to 3.5% for men who were not treated with ADT. Men receiving ADT were significantly older and had more co-morbidities. These factors were adjusted for in the analysis, however do raise the possibility that there may be other aspects of poor health that were not accounted for in the ADT treatment group. This data is consistent with previous research from the same group showing a link between ADT treatment and Alzheimer’s disease, as well as work suggesting that lower levels of testosterone in men may be predictive for developing dementia.

Despite the possible increased dementia risk, ADT remains a highly effective treatment. Therefore, while these risks may form part of a risk-benefit conversation, the study does not support changing current clinical practice. 

3: Chemotherapy-naive patients may have greater benefit from treatment than post-chemotherapy patients 

Preliminary data from Janssen EMEA’s Prostate Cancer Registry was presented this month at the annual European Society for Medical Oncology Congress (ESMO 2016). The early data (Abstact# 746P) from men with metastatic castration-resistant prostate cancer (mCRPC) shows that chemotherapy-naïve men have a longer time to next treatment when treated with androgen receptor-targeted agents than post-chemotherapy patients. Median time to next therapy for chemotherapy-naïve men was 601 days for abiraterone acetate and 503 days for enzalutamide compared to 428 days for abiraterone acetate and 366 days for enzalutamide for post-chemotherapy patients. The Prostate Cancer Registry has enrolled over 3000 patients across 16 countries and ongoing data collection aims to provide insights into real world management of mCRPC.

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.