Research round up from the clinic - top four articles from June 2015:
1. Cigarette smoking is associated with increased risk of biochemical recurrence following prostatectomy
For the first time, an international study led by MedUni Vienna and Basle University Hospital, has provided evidence of a link between smoking and biochemical recurrence (BCR) of prostate cancer after prostatectomy. In a study of 6,538 patients, Rieken and colleagues showed a significant 63% and 80% increased risk of BCR in ex-smokers and current smokers, respectively, compared to ‘never smokers’. The research also showed that the negative impact of smoking on the risk of BCR is reduced to that of ‘never smokers’ after 10 years of not smoking.
2. Phase III trial shows adding docetaxel and estramustine to ADT improves relapse-free survival for high-risk localised prostate cancer patients
The GETUG-12 trial published results of the addition of docetaxel and estramustine to ADT, compared to ADT alone, in patients with non-metastatic high-risk localised disease. (Last month, we reported on the STAMPEDE trial results from ASCO 2015 which looked at metastatic patients – see here). In GETUG-12, Fizazi et al used the primary end point of ‘relapse-free survival’ which, after 8 years, was 62% in the men on ADT + docetaxel and estramustine, compared to 50% in the men on ADT alone. However, since this trial's inception in 2002, estramustine has fallen out of favour as a treatment for prostate cancer because of a lack of additive effects with docetaxel and its gastrointestinal toxic effects, and prostate-specific antigen endpoints are accorded less importance, limiting the generalisability of the results. At present, docetaxel should be reserved for metastatic disease either in the castration-sensitive setting, such as was assessed in CHAARTED and STAMPEDE, or for castration-resistant disease.
3. Scientists unveil the ‘Rosetta Stone’ of prostate cancer
An international team of scientists, led by the ICR in London, analysed the genetic codes of metastatic tumours from the bone, soft tissues, lymph nodes and liver of 150 patients with advanced prostate cancer. This enabled Robinson et al to produce a comprehensive genetic map of the mutations in prostate cancers that have spread round the body. The mutations found included some already known (eg in the BRCA1/2 genes) as well as previously undetected mutations in prostate cancer (eg in the PI3K and RAF gene families). They discovered that almost 90% of men with advanced prostate cancer carry genetic mutations in their tumours that could be targeted by either existing or new cancer drugs.
4. Increased prevalence of metabolic syndrome associated with ADT
Morote and colleagues conducted an observational prospective study involving 539 prostate cancer patients scheduled to receive three-month depot LHRH analogs for longer than 12 months. The authors examined the prevalence of full metabolic syndrome, assessed according to different definitions, and its components and found that at six and 12 months after ADT initiation there were significant increases in waist circumference, BMI, fasting glucose, triglycerides, total cholesterol, and high- and low-density lipoprotein cholesterol. At 12 months there were significant increases in metabolic syndrome prevalence. The authors concluded that counselling patients on the prevention, early detection, and treatment of specific metabolic alterations is recommended.