A new report from the prostate cancer research team at Johns Hopkins has offered data suggesting a strong association between the structure of the nucleus of prostate cancer cells in individual patients and the risk for more aggressive prostate cancer. The report is based on data with a follow-up time of up to 25 years.
The nucleus of an individual cell is a highly structured part of the cell which contains each patient’s genetic material his chromosomes and the associated DNA. It has been known for many years that the structure of the nucleus of cancer cells can be significantly different compared to the structure of equivalent non-cancerous cells, and there has been research into the relationship between “nuclear roundness” and the aggressiveness of prostate cancer going back to the 1990s. However, much of that research was inconclusive.
Veltri et al. have now reported on the relationship between nuclear roundness variance (NRV) and actual clinical outcomes for a cohort of 116 men all diagnosed in 1992-93 and treated by radical prostatectomy.
The NRV is a reflection of the degree of variation from a perfect circle. For each individual patient, the actual nuclear roundness was calculated by evaluating the roundness of 150 nuclei from prostate cancer cells in the radical prostatectomy specimen post surgery. All the cells were examined under a microscope at high magnification to assess the nuclear roundness according to an established formula:
The variation in nuclear roundness was then calculated as an average for all the 150 cells from each individual patient, and the NRV data were correlated with the available clinical, pathologic, and follow-up data for the same 116 patients in 2009.
The results from this analysis are quite striking:
- Median follow-up time after RP for all patients was 19 years (range: 1-25 years, mean: 17 years).
- NRV was the most significant parameter for prediction of three long-term outcomes.
- NRV was significantly better than the Gleason score in predicting both metastasis-free and prostate cancer-specific survival.
- NRV was also better than the Gleason score in predicting biochemical progression-free survival, but this improvement was not statistically significant.
The authors conclude that NRV is better than the Gleason score at predicting the presence of an aggressive phenotype of prostate cancer (based on tissue data available after a radical prostatectomy).
The question that immediately comes to mind, of course, is whether sufficient cells are available from biopsy specimens to make accurate computation of the NRV for individual patients after a biopsy, and what the cost would be to compute the NRV for each individual patient based on biopsy tissues. If the NRV is a significantly more accurate prognostic marker for metastasis-free survival than the Gleason score, and it is reasonably possible to compute the NRV based on data from biopsy tissues, then the next question is, does inclusion of NRV data into predictive models significantly improve our ability to determine who actually needs treatment for low-, intermediate-, and high-risk prostate cancer?
It would seem that several things will need to be done to advance this possibility. The first of these would be for another laboratory to see if they can reproduce the data just published by the team at Johns Hopkins based on a similar series of patients with long-term follow-up. The second would be to determine whether it is possible and reasonable to determine nuclear roundness variance with accuracy based on biopsy specimens.
A new report from the prostate cancer research team at Johns Hopkins has offered data suggesting a strong association between the structure of the nucleus of prostate cancer cells in individual patients and the risk for more aggressive prostate cancer. The report is based on data with a follow-up time of up to 25 years.
The nucleus of an individual cell is a highly structured part of the cell which contains each patient’s genetic material his chromosomes and the associated DNA. It has been known for many years that the structure of the nucleus of cancer cells can be significantly different compared to the structure of equivalent non-cancerous cells, and there has been research into the relationship between “nuclear roundness” and the aggressiveness of prostate cancer going back to the 1990s. However, much of that research was inconclusive.
Veltri et al. have now reported on the relationship between nuclear roundness variance (NRV) and actual clinical outcomes for a cohort of 116 men all diagnosed in 1992-93 and treated by radical prostatectomy.
The NRV is a reflection of the degree of variation from a perfect circle. For each individual patient, the actual nuclear roundness was calculated by evaluating the roundness of 150 nuclei from prostate cancer cells in the radical prostatectomy specimen post surgery. All the cells were examined under a microscope at high magnification to assess the nuclear roundness according to an established formula:
The variation in nuclear roundness was then calculated as an average for all the 150 cells from each individual patient, and the NRV data were correlated with the available clinical, pathologic, and follow-up data for the same 116 patients in 2009.
The results from this analysis are quite striking:
The authors conclude that NRV is better than the Gleason score at predicting the presence of an aggressive phenotype of prostate cancer (based on tissue data available after a radical prostatectomy).
The question that immediately comes to mind, of course, is whether sufficient cells are available from biopsy specimens to make accurate computation of the NRV for individual patients after a biopsy, and what the cost would be to compute the NRV for each individual patient based on biopsy tissues. If the NRV is a significantly more accurate prognostic marker for metastasis-free survival than the Gleason score, and it is reasonably possible to compute the NRV based on data from biopsy tissues, then the next question is, does inclusion of NRV data into predictive models significantly improve our ability to determine who actually needs treatment for low-, intermediate-, and high-risk prostate cancer?
It would seem that several things will need to be done to advance this possibility. The first of these would be for another laboratory to see if they can reproduce the data just published by the team at Johns Hopkins based on a similar series of patients with long-term follow-up. The second would be to determine whether it is possible and reasonable to determine nuclear roundness variance with accuracy based on biopsy specimens.