Tigers or Pussycats?

Research to identify men who will benefit from radical treatment

Prostate Research Campaign UK is funding important research being carried out at University College London.  Professor John Masters, who leads the team, explains his research to Update.

'The way in which prostate cancer develops in an individual depends both on environmental factors (diet, geography) and more personal factors (age, family history, race, hormonal balance).  Consequently, the prognosis of the disease is very variable.  Some cancers are aggressive and fast growing.  Others grow very slowly and may require no treatment at all.  Differentiating the tigers from the pussycats is difficult and we need more research in this area.  The prognosis is known to depend on the stage and grade of the tumour at the time of diagnosis.  Only localised cancer, that is cancer confined to the prostate, can be reliably cured and this requires radical treatment.

Currently, there are a number of tools which help to predict the stage of the cancer at the time of diagnosis - blood tests, digital rectal examination, biopsy, and various scanning techniques.  Whether used singly or together, they do not, however, do a particularly good job of predicting the future on a case by case basis.

Many genetic changes associated with prostate cancer have been identified, but their clinical significance is, as yet, unknown.  In the research we are undertaking at UCL, we will examine the three most common types of genetic change; deletion of genetic material, duplication of genetic material and gene inactivation by a process called methylation.  The aim of our study is to identify which genetic changes are related to the outcome of patients with prostate cancer.  Our hypothesis is that by identifying specific genetic changes we will be able to provide more accurate markers to predict prognosis.  This will enable more appropriate selection of treatment for patients with prostatic carcinoma.'

Professor John Masters and his colleagues already have a database on which details of 712 radical prostatectomy patients are recorded.  Prostate Research Campaign UK has been funding the build up of this database over the past two years so that it now represents the largest series available in the UK.

'The next step' explains Professor John Masters, 'is to perform a number of outcome studies using this data including pre and post operative staging, the effect of radiotherapy on subsequent PSA recurrence, positive urethral margins compared with other positive surgical margins and subsequent PSA rise.  The research will also examine data on those patients who have undergone radical prostatectomy and who had repeated negative prostate biopsies before the correct diagnosis was made'.

The plan for the research is to select a subgroup of patients (30 in the first instance) who relapsed after surgery and match these with controls who have been untreated and disease-free for at least 3 years since surgery.  The cases will be selected from those who relapsed within 2 years of radical prostatectomy.  Normal and cancerous tissue, obtained at the time of the operation is available from these patients.  The DNA samples will be examined to identify genetic differences between the relapsed and the control group of matched patients.  The hope is that there will turn out to be sufficiently large differences that examination of DNA at the time of diagnosis may become an additional (and more effective) staging tool than those the medical profession has today'.