Could “single cell genomics” replace Gleason grading in prostate cancer risk evaluation?


According to a study just published in Cancer Research, a completely new technique referred to as “single cell genomics” may be able to improve the accuracy of diagnosis of prostate cancer based on biopsy tissue.

The new paper by Alexander et al. describes how researchers at the Cold Spring Harbor Laboratory on Long Island have developed a technique that would use hundreds of prostate cancer cells from prostate biopsy specimens to provide a superior assessment of prostate cancer risk.

Basically, the results of single cell genomics would give data that was more closely replicative of the post-surgical Gleason score than the biopsy-based, pre-surgical Gleason score.

As described in a news story on the CSHL website,

A team at CSHL reports success in a small-scale test of a new analytical method to improve the early detection of potentially lethal prostate cancer. Based on diagnostic biopsy samples, the method promises to more accurately parse men who need surgery from those who do not.

Now the initial scientific premise is certainly interesting, and the current pilot study data (based on analysis of specimens from just eight patients) reported by Alexander et al. endorses the initial hypothesis. However, we are going to need a prospective study from many more patients, followed over time, to accurately confirm the potential of this new technique. The initial assessment of probability can presumably be conducted using biopsy tissue and pathology tissue from a retrospective cohort of (say) 100 or so patients whose original biopsy and surgical samples have been carefully preserved.

The downside to the technique described by Alexander et al., is that it is still a prognostic test based on random biopsy samples. The upside is that if it really can much more accurately indicate the true pathological Gleason score than the clinical biopsy-based Gleason score, then it should save men who don’t need treatment from having it (at least immediately) so that they can be monitored on active surveillance, while simultaneously allowing us to make better decisions about who really must have treatment early.

It is unlikely that this test will actually replace Gleason grading (at least in the near term), but it might be able to do so in the long-term … if it could clearly be proven to provide data that could act as surrogates for the pathological Gleason grades and Gleason scores.

2 Responses

  1. This is an interesting topic. This method still requires a biopsy to be able to genetically analyze the cells. This is in contrast to new developments in liquid biopsy research which is trying to detect prostate cancer through urine and/or blood and determine risk as well. The method here is to get circulating tumor DNA (ctDNA) without a biopsy and all the risks of a biopsy.

    This article and this one were both in the ASCO Post last July. And last May a company issued a press release indicating that they do, in fact, have some success with it.

    It will be interesting to see the day when patients start making decisions without a Gleason score. That day may be closer than we might expect — but it’s still a ways off. It will take time conducting trials to verify efficacy.

  2. Perhaps the most significant improvement, if and when innovated, is that this gene-based approach is objective rather than the subjective assessment of a Gleason number.

    W.r.t. Tony’s comment, the issue with liquid biopsies surrounds harvesting CTCs in men with low or very low tumor burdens — as is the case with the majority of newly diagnosed men.

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