Prostate Cancer Divided Into Five Distinct Types

Medscape Medical News > Oncology
Prostate Cancer Divided Into Five Distinct Types

Zosia Chustecka
August 03, 2015


The great hope in prostate cancer is for a test that would differentiate between patients with aggressive disease who need intensive treatment from those patients with mild forms of the disease, who may not need treatment. Much effort has gone into looking for genetic markers that could do this, and now a team of researchers from the United Kingdom says they have made a breakthrough. They have identified five distinct genetic types of prostate cancer, and say that their classification performs better than previously reported genetic signatures and that it is better at identifying the most aggressive cancers than established clinical measures such as prostate-specific antigen (PSA) levels and Gleason score.

"Our exciting results show that prostate cancer can be classified into five genetically different types. These findings could help doctors decide on the best course of treatment for each individual patient, based on the characteristics of their tumor," said study author Alastair Lamb, MD, from the Department of Urology, Addenbrooke's Hospital, and the Cancer Research UK Cambridge Institute at the University of Cambridge, United Kingdom. "The next step is to confirm these results in bigger studies," he said in a statement.

The findings were published online July 29 in EBioMedicine.

"Our refined 100-gene set seems, in our analysis, to be more informative than any other published signature to date, and as such presents a practically useful, robust tool to help clinicians distinguish good and poor outcome disease," the authors conclude.

However, approached for comment on the study, an expert who was not involved in the research warned that there was much work yet to be done.

This is a "very sophisticated genomic analysis that underscores the complexity prostate cancer," said Marc Garnick, MD, Gorman Brothers Professor of Medicine at Harvard Medical School (HMS) and the Beth Israel Deaconess Medical Center in Boston, and editor-in-chief of the HMS Annual Report on Prostate Diseases.

"This is great news and provides optimism that the years of research in trying to dissect out genomic predictors of clinical behavior are beginning to see the light at the end of the tunnel. But how long is that tunnel? Right now, pretty far away," he told Medscape Medical News.

"While the authors portray great excitement about their work, its limitations need to be acknowledged. The numbers in each of the cohorts are small and the follow-up is very short — woefully short — for any claims of superiority of existing data. There is no comparison to already better-established genomic predictors of either behavior or pathology, and there is no comparison to a multitude of bedside, clinically available metrics that are easily used in clinical practice for decision making, such as PSA doubling time, time to relapse, initial Gleason score, initial PSA level," Dr Garnick commented.

"These data, along with that of other genomic research compilations from prostate cancer tissues, are exciting for both basic and clinical research. As such, it should be a call to action for the integrated efforts of research teams to band together and provide the correct clinical protocols that provide adequate patient numbers, with adequate follow-up so the relative importance of these profiles can be put into their proper context," he said.

Study Details

For the study, the researchers studied a total of 482 tissue samples from 259 men with primary prostate cancer, which included both prostate cancer tissue and benign prostate tissue.

The work was carried out in two steps, as explained in a Cancer Research UK blog.

In the first step, the team analyzed tumor samples from 156 men who had undergone prostatectomy in Cambridge. They then confirmed their findings in another group 103 men who had undergone surgery in Sweden.

The team used a combined approach of looking both for abnormal chromosomes (copy-number alterations) and measuring gene activity (messenger RNA levels), and developed a refined 100-gene signature that showed five distinct patterns of genomic activity, as follows:

One group of patients had many DNA deletions and consequently low activity of certain genes.

Another group had high amounts of DNA repetition, which resulted in increased activity of specific genes.

Two more groups had very few copy-number alterations or changes in activity.

The fifth and final group had some — but not too many — copy-number alterations.

Next, the team traced the subsequent medical history for both sets of patients. They found that men in the subgroups with greater numbers of gene changes were more likely to relapse, compared with patients who had fewer changes.

Dr Lamb says that these gene signatures could be used alongside clinical tests to provide a more accurate idea of prognosis. "By combining the molecular information provided by this gene signature with existing clinical information, doctors might be able to identify those most at risk of relapse and treat them accordingly. For example, if a man had a low Gleason score but high levels of genetic alteration, he would be considered to be at a moderate to high risk of relapse," he explained in the blog.

Dr Lamb also discussed several caveats to the findings in the blog. The hope is that these findings will help to guide treatment at diagnosis, and for that the analysis would be done on tissue samples taken from a diagnostic biopsies, whereas this study used tissue samples taken from prostatectomies. There are questions whether the diagnostic biopsy would provide enough tissue to perform this genetic analysis, and there is also the issue of tumor heterogeneity, although new techniques such as MRI-guided targeted biopsy could help to ensure that the biopsy represents the majority of cancer cells in the tumor, he suggested.

"We still need to do more research to see if this technique can be used routinely by doctors in the hospital. We also need to confirm that it can change how we manage patients' treatment for the better, and reduce the number of men relapsing after prostate surgery," he added.

Dr Garnick also emphasized the need for more work before these findings can be used in a clinical setting. "We are beginning to see the light at the end of the tunnel," he commented, but added: "Right now, we are now just entering that tunnel, whose length, unfortunately, is unknown.

EBioMedicine. Published published online July 29, 2015. Abstract