In a recent article Journal of National Cancer Institute the authors reach the conclusion that PSA velocity has no merit. They state:
Results Incorporation of PSA velocity led to a very small increase in area under the curve from 0.702 to 0.709. Improvements in predictive accuracy were smaller for the endpoints of high-grade cancer (Gleason score of 7 or greater) and clinically significant cancer (Epstein criteria). Biopsying men with high PSA velocity but no other indication would lead to a large number of additional biopsies, with close to one in seven men being biopsied. PSA cut points with a comparable specificity to PSA velocity cut points had a higher sensitivity (23% vs 19%), particularly for high-grade (41% vs 25%) and clinically significant (32% vs 22%) disease. These findings were robust to the method of calculating PSA velocity.
Conclusions We found no evidence to support the recommendation that men with high PSA velocity should be biopsied in the absence of other indications; this measure should not be included in practice guidelines.
As reported in Eureka:
As expected, the authors found a statistical association between PSA velocity and biopsy outcome. But when they adjusted for other risk indicators, such as age, race, PSA levels, and digital rectal exam, there was virtually no association between PSA velocity and biopsy outcome.
"There was little evidence that PSA velocity adds an important level of predictive accuracy to either standard predictors or to PSA alone," they write.
The authors also evaluated guidelines stating that men with a rapid rise in PSA should have a biopsy even if their PSA is low and there are no abnormal findings on a clinical exam. The vast majority of the men who fell into this category (about 80%) did not have cancer, suggesting that use of PSA velocity would lead to many unnecessary biopsies. PSA alone was a better predictor of biopsy outcome in these men than PSA velocity.
"In other words," they write, "if a clinician feels that the current PSA thresholds are insufficiently sensitive, he or she would be better off identifying patients to biopsy by using low PSA thresholds than by adding PSA velocity as a criterion for biopsy."
The authors conclude that PSA velocity should not be included in prostate cancer screening guidelines.
In an accompanying editorial, Siu-Long Yao, M.D., and Grace Lu-Yao, Ph.D., of the Cancer Institute of New Jersey agree that the findings suggest that PSA velocity does not help doctors and patients decide what to do about screening results.
"PSA velocity measurements take time to acquire, and recognizing that such data add relatively little information may help prevent inappropriate postponement of follow-up in affected patients," they write. "Avoiding the wait to acquire subsequent PSA values may also help reduce some of the anxiety associated with testing." They go on to say that the results of this study serve to "remind us that the use of PSA as a screening tool still leaves much to be desired."
We would argue that there analysis has certain issue requiring further analysis:
1. PSA velocity is a long measurement subject to substantial errors due to the variability in PSA measurements. For example, if we measure PSA over 20 years we may go through a dozen or more different assays and they each have substantial variability between each other. Also the PSA has its own variability depending or many personal factors independent of cellular type and density.
2. To obtain a reasonable PSA velocity one needs at least ten years of data taken on about a yearly basis at least. Biases must be addressed by also knowing the types of assays employed.
3. The approach we have developed above takes into account the dynamics of both cellular growth and PSA density. We believe that this temporal factor must be included. However the approach lacks substantial clinical validation.
4. PSA and PSA velocity should always be used with many other factors. Yet a biopsy is often worthwhile especially if there is a family history. Yet despite biopsies we also know that there is a 20-30% probability that a cancer may be missed. Thus a benign biopsy is not indicative of a non cancerous prostate.
Clearly more must be done here but a summary dismissal is less than productive, in my opinion.
The underlying issue is that of understanding the genetic dynamics of PCa. Current work seems to address the issue of what genes are activated in a mass of PCa cells. However as we have argued before, the mass may be a mix of genetic wiring. The PCa stem cell may be the master controller and as such it is that cell which should be examined. The non stem cell daughters of the PCa CSC may contain other genetic profiles and thus performing an analysis on the collection may be deceptive. Moreover the dynamics of the genetic pathways must also be understood. Finally we have the issue of intercellular signaling. In short we still face a very complex issue and we should use the tools that are available. The most valuable statistic is still family history, albeit not 100% is is highly suggestive.
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