An article published on-line in BJU International suggests that there are limits to the degree to which PSA density is accurately predictive of risk for upstaging of clinically localized prostate cancer.
It is well understood that the biopsy-based Gleason score of a man with clinically localized prostate cancer can easily be underestimated — because of sampling error and because of the inexperience of non-specialist pathologists. Clearly, this presents the risk that a man assigned (say) a biopsy-based Gleason score of 3 + 3 = 6 may be inappropriately referred for active surveillance if his actual Gleason score is (say) 4 + 3 = 7. Previous studies have shown, however, that (under appropriate circumstances) PSA density may be an appropriate and accurate predictor of post-surgical upgrading in patients initially diagnosed with localized prostate cancer.
Corcoran et al. set out to study whether the PSA density of men initially diagnosed with with low- and intermediate-risk disease could be used accurately to predict their post-surgical Gleason score after radical prostatectomy. To do this, they used data from patients with matching biopsy and post-surgical Gleason scores (as well as PSA values, prostate volumes, and other relevant data such as numbers of biopsy cores, and assigned clinical stages) from two prospectively collected databases.
The authors categorized their patients into three different groups:
- Those with a biopsy score of 3 + 3 = 6 that was later upgraded to ≥ 7 (Group A)
- Those with a biopsy score of 3 + 4 = 7 that was later upgraded to 4 + 3 = 7 (Group B)
- Those with a biopsy score of 7 that was later upgraded to ≥ 8 (Group C)
Here are their core findings:
- From the available data on 1,516 patients, 435 men (29 percent) demonstrated an upgrade in the Gleason score from biopsy to post-surgical pathology.
- Among these 435 men
- For men in Group A, PSA density was the strongest predictor of a tumor upgrade (odds ratio [OR] = 1.46)
- For men in Group B, PSA density was again the strongest predicator of a tumor upgrade (OR = 1.37)
- For men in Group C, PSA density was not predictive of a tumor upgrade (but clinical stage and number of positive biopsy cores were significant independent predictors)
- There was a strong association between Gleason score and tumor volume.
- The average (median) volume of tumors of post-surgical Gleason score 7 was twice that of tumors of post-surgical Gleason score 6.
- The median volume of tumors of post-surgical Gleason score > 7 was four times that of tumors of post-surgical Gleason score 6.
- The median serum PSA level per milliliter of tumor volume decreased with increasing grade
- From 5.4 ng/ml for patients with tumors of post-surgical Gleason score 6
- To 2.1 ng/ml for patients with tumors of post-surgical Gleason score > 7
The authors conclude that:
- There is a strong correlation between Gleason score and tumor volume in men with well-differentiated (Gleason 6) and intermediately differentiated (Gleason 7) tumors.
- In men with Gleason 6 disease on biopsy, a high PSA density is the strongest single predictor of risk for tumor upgrading to a Gleason score of > 6.
- In men with Gleason 3 + 4 = 7 disease on biopsy, a high PSA density is the strongest predictor of risk for tumor upgrading to a Gleason score of 4 + 3 = 7.
- However, PSA density is not capable of accurately prediting risk for upgrading in men with a biopsy Gleason score of 7 as a whole.
Clearly this study has its greatest benefit in being able to show risk for upgrading in men with Gleason 6 and Gleason 3 + 4 = 7 disease who might be considering active surveillance (AS) as a management strategy. For these patients, PSA density may be a valuable indicator of whether risk for upgrading is significant and indicative of the importance of very close monitoring if AS is to be undertaken or should be considered inappropriate for some patients.
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Anyone ever address the value of PSA density as an indicator in cases where there’s also evidence of chronic bacterial prostatitis? Also, has it proven to have any value of a predictor of prostate cancer before prostate cancer is diagnosed via biopsy?
I quote from About.com …
“There is evidence that a high PSA density indicates a higher risk of prostate cancer.
“There is not, however, quite as good evidence that this likely higher risk of prostate cancer really changes the proper diagnosis or treatment for those found to have a high PSA density. Not all experts agree that PSA density should change the way that a physician diagnoses, monitors, or treats prostate cancer. Some doctors feel that PSA density is simply not helpful to them when making decisions and choose to ignore it.”
I am not aware of any good data on an association between PSA density and risk for chronic prostatitis/CPPD.
I’d understood PSA density to be calculated as the ratio of PSA to gland volume, and a useful predictor of suitability for active surveillance. One cutpoint being 0.15 ng/ml/ml – anything less being OK for AS.
This study appears to consider PSA density as ratio of PSA to tumour volume.
Could anyone please clarify this?
Richard:
In my interpretation (based only on the abstract of the paper), the authors are measuring PSA density in the classic way — as a ratio of PSA ledvel to gland volume. (It would be almost impossible to assess PSA density in terms of tumor volume until after you took the prostate out and sectioned it.)
The reference to the volume of tumor in the gland is not a reference to PSA density per se. It is a reference to the association between tumor volume, tumor grade, and PSA level and the fact that PSA density does not appear, in this study at least, to be an accurate predictor of risk for upgrading from Gleason 7 on biopsy to Gleason 8 or higher on pathologic examination post-surgery.
Thanks, that makes sense. I was distracted by the three occurrences of the phrase PSA per tumour volume, in the abstract, which is also PSA density, although not the “classic” definition.
Like Richard I too was confused throughout the article. But the statements that:
“The median serum PSA level per milliliter of tumor volume decreased with increasing grade
— From 5.4 ng/ml for patients with tumors of post-surgical Gleason score 6
— To 2.1 ng/ml for patients with tumors of post-surgical Gleason score > 7”
together with the above comment of 0.15 ng/ml for “classic definition” values makes more sense. From 2.1 to 5.4 would relate to the post-operative measurement of the tumor, and as such are much higher ratios.