Prostate Cancer Subtypes

It's an axiom that's as valid for doctors as it is for generals. In the war on prostate cancer, our side has just received some new intel.  Scientists have identified and validated three distinct molecular subtypes of prostate cancer that correlate with distant metastasis-free survival and which will be extraordinarily useful in future research to determine how patients will respond to treatment.  It was the largest study of its kind today to date.

Currently, doctors use a variety of tools when diagnosing prostate cancer, including prostate specific antigen level blood tests, digital rectal examinations, and tumor biopsies. By sub-typing tumor cells, doctors will be able to better individualize care and adapt their treatments to the actual biochemistry of each patient's specific ailment.

"Tumors that appear similar under a microscope can behave very differently, from a clinical standpoint," said Daniel E. Spratt, MD, lead author of the study and Chief of the Genitourinary Radiotherapy Program at the University of Michigan in Ann Arbor, Michigan. "One promise of genomic analyses is to elucidate subtypes of cancer based on the genetics of the tumor rather than merely how they look or what size they are."

The results of the study were presented at the American Society for Radiation Oncology 2016 Annual Meeting.

4,236 samples from nine separate groups of men treated with radical prostatectomy for localized prostate cancer were analyzed by Spratt and his team to develop the new profiles. After some pruning and parsing of the datasets, the researchers identified three molecular subtypes of prostate cancer that could be characterized through a profile of 100 distinct genes.

"We were surprised to find that prostate cancer subtyped into only three very distinct subtypes," said Dr. Spratt. "We knew that primary prostate cancer was a relatively quiet tumor, genomically, but similar cancers that are endocrine-driven, like breast cancer, have been shown to be able to be clustered into a finite number of subtypes."

The scientists validated the subtypes across six additional retrospective cohorts that represented a wide spectrum of RNA sequencing platforms and tissue storage methods. They also drew upon the data of two prospective cohorts comprising 2,610 patients.

"We have discovered and independently validated a highly stable 100-gene intrinsic molecular profile of prostate cancer that is both prognostic and predictive for radiation therapy," said Dr. Spratt. "We believe that these subtypes reflect truly distinctive underlying biology and that this work represents a significant advance in our understanding of prostate cancer biology. Moreover, our findings identify numerous genes and enriched biologically active pathways in prostate cancer that have been underappreciated to date but may be potential targets to improve cure rates in this disease by developing new targeted therapies."