UroToday - Editorial - Current Applications for Prostate Specific Antigen Doubling Time

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Thursday, 26 June 2008

BERKELEY, CA (UroToday.com) - In the online version of European Urology, Dr.

and colleagues from UC discuss present applications

of PSA doubling time (PSADT). Where PSADT is most applicable in managing

patients with prostate cancer is emphasized.

Derived from the same data as PSA velocity (PSAV), which measures the

absolute rate of change and is calculated as the slope of a linear

regression of PSA measurements over time (ng/ml/yr), PSADT represents the

relative rate of PSA change over time and is defined as the time needed for

the PSA value to double. As opposed to PSAV, which is related to tumor

volume, PSADT takes into account the exponential nature of neoplastic growth

and requires logarithmic analysis. It is independent of the baseline PSA

value and should therefore be used when comparing different patient

populations.

Before diagnosis, PSADT has not been shown to be of additional value to

current screening and diagnostic methods. However, it may be helpful in

determining which patients with initial negative biopsy actually harbor

prostate cancer. Prior to definitive therapy, PSADT usefulness is limited by

the inherent biologic variability of PSA from the intact prostate. Alternate

methods for calculating PSADT may partially compensate, but this has yet to

be demonstrated. Only until pretreatment PSADT is proven to have a greater

predictive power than PSA alone should it be implemented in clinical

practice. Nevertheless, accumulating evidence indicates that men who have a

continual rise in PSA are more likely to have disease progression, and if

the rise is rapid, prognosis is more ominous. Therefore, PSADT, in

combination with other variables, may be useful in risk stratification,

although parameters for observation and intervention are the subject of

controversy.

After definitive therapy, PSADT is an important determinant of the presence

and pattern of disease recurrence, but optimal thresholds are still to be

established. Certainly those with a short PSADT represent clinically

important disease that should be treated aggressively, but for the majority

of patients, those with longer doubling times, the benefits of therapy need

to be better defined. Most likely, levels reflect a continuum of degree of

risk without exact cut-off points. Given the heterogeneity that exists

within each stage of prostate cancer, management should be dictated by a

combination of variables, PSADT being a highly reliable predictor. Following

androgen deprivation therapy, PSADT maintains its value as a significant

prognostic indicator and is now being included in nomograms for this patient

subset. It is possible that PSADT is also a predictor for certain therapies

in the androgen independent setting, as well as a suitable criterion in

selecting patients for new therapeutic clinical trials. Finally, the use of

PSADT as a surrogate for CSS has not yet been confirmed, but because data

are promising and other applicable end points are lacking to evaluate the

often extended course of prostate cancer, many short-term trials are

alternatively using PSADT. Prospective, randomized trials and meta-analysis

to determine optimal cut-off points in the above-listed categories could

improve validity and bring clarity to conflicting data in the literature.

Ramírez ML, EC, Devere White RW, Lara PN Jr, CP.

Eur Urol. 2008 Apr 11. Epub ahead of print.

doi: 10.1016/j.eururo.2008.04.003

PubMed Abstract

PMID: 18439749