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. 

November 2016

1: Early diagnosis of advanced prostate cancer may improve men's survival

Follow-up analysis from the ProtecT trial suggests that PSA testing of asymptomatic men can lead to early detection of advanced prostate cancer and may improve survival. This study examined outcomes for 492 men (ProtecT cohort), who after PSA testing, were diagnosed with metastatic, locally advanced (cT3-4) disease and/or had PSA ≥ 20ug/l and were excluded from randomisation in the ProtecT trial. Prostate cancer specific and overall survival was compared between this group of men and a cohort of men from the UK Anglia Cancer Network (ACN) (control cohort) who were matched in terms of age, year of diagnosis and disease severity.

Men within the ProtecT cohort had a reduced risk of death from prostate cancer (HR 0.29, 95% CI 0.38-0.53, p<0.0001) compared to ACN controls at 7.6 years. This difference was due to the lower risk of death among men who received non-radical treatment; there was no difference in the risk of death from prostate cancer among men who received radical treatment (radical prostatectomy or radiotherapy). Men in the ProtecT cohort had been invited to attend PSA testing and this suggests that wider PSA testing for asymptomatic men may be beneficial to diagnose advanced cancers at an earlier stage.

There are some key limitations of this study. Most importantly, this is an observational, non-randomized study. The control group was from a single region and was less fit overall then the ProtecT cohort. Although the authors tried to adjust for these differences, they acknowledge that lead-time and selection bias cannot be ruled out. Future controlled studies including the CAP trial (cluster randomised trial of PSA testing) which is expected to publish in 2017, will be critical to clarify the potential impact of wider PSA testing in the community. 

2: Meta-analysis finds link between alcohol consumption and risk of developing prostate cancer

A new meta-analysis, published in the BMC, has concluded that there may be a small dose-response relationship between alcohol intake and prostate cancer risk. Researchers analysed data from 27 out of a possible 340 studies and found that the relative risk of prostate cancer was 1.08 (p<0.001), 1.07 (p<0.01), 1.14 (p<0.001) and 1.18 (p<0.001) for low, medium, high, and higher volume drinkers respectively, compared to non-drinkers. This was a significant dose-response rate (ptrend<0.01).

This study statistically corrected for misclassification or abstainer bias which can occur when former and occasional drinkers are counted as non-drinkers. It has been shown that this can lead to an underestimate of alcohol risk as former/occasional drinkers are often in poorer health than the general population and may include people who have stopped or reduced alcohol consumption as they age or face poor health. In fact, a sub-analysis that only included studies without abstainer bias, showed a stronger relative risk of 1.22 (p<0.05) for drinkers versus abstainers.

Taken together this study indicates that increased alcohol consumption may increase the risk of developing prostate cancer. The increase in risk however is small, and the limited number of studies included in the analysis may weaken the robustness and and reproducibility of the results. It will be important to see if future studies and meta-analysis also support this conclusion. 

 

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.