Tumor marker Doubling Time DT

Miyamoto [19] studied the growth of hepatic metastases in colorectal cancer patients. He established that a tumor marker could accurately reflect tumor volume and its changes. Using the CEA tumor marker he reported an almost equal and parallel correlation between CEA doubling time and hepatic tumor volume doubling time.

PSA-DT Figure 4 is the time it takes for the serum PSA to double. Evidence indicates PSA-DT closely mirrors prostate tumor volume doubling time. Kato et al. in 2008 [20] undertook an attempt to correlate prostate tumor volume to serum PSA level. Kato's group calculated that for each ng/ml increment of serum PSA, there was a 0.302 cc increase in total tumor volume and a 0.7% increase in relative tumor volume. Total tumor volume in cc was given as V(cc) = 3.476 + 0.302 X PSA (ng/ml) while the percent tumor volume Volume(%) = 11.331 + 0.704 X PSA (ng/ml).

Babaian et. al. [21] reported that multivariate regression analysis of tumor volume as a function of PSA, grade and stage demonstrated that log PSA had the strongest association with tumor volume. Tanaka [22] reported that among significant preoperative and postoperative parameters, calculated cancer volume remained an independent predictive parameter in multivariate analysis (P <0.01). Tumor volume, as calculated by preoperative parameters, was an independent predictor of biochemical recurrence in patients who had undergone radical prostatectomy. Vollmer et al. [23] used a compartmental model and first order kinetics to develop the calculation necessary to relate serum PSA to tumor volume. They found that the resulting model was a good fit to the observed kinetic data of PSA measured after biopsy or prostatectomy. The model also predicted a linear relationship between PSA and the sum of volumes of benign and malignant tissues.

Until evidence to the contrary, it is assumed that similar to colorectal tumors and CEA, there is a reasonable relationship between serum PSA and its kinetics allowing its use as a predictor of changes of prostate tumor volume and growth kinetics.

An important point when using serum PSA in calculations is that an exact interval for testing remains controversial, some investigators stress that the interval between PSA-DT determinations should approach 3-6 months [24] to limit error due to random variation of PSA values. Using a third generation highly sensitive PSA assay, our laboratory changes in PSA are precise to the third decimal point and allow educated decision-making based on monthly determinations.

Figure 4. This figure is a semi-log plot of logs PSA (y-axis) vs. time (x-axis) [26]. Note the linear relationship, indicating that the rise of PSA values follows an exponential expansion of PSA.

Historically, PSA kinetics for watchful waiters included PSA-DT. A PSA-DT of >10 yr. can be considered favorable; a PSA-DT of <3-4 yr. suggests a change in biology and consideration should be given to an alternative therapy [25]. PSA kinetics should always be combined with other diagnostics such as endorectal ultrasound; endorectal MRI, digital rectal exam and repeat prostate biopsies approximately every 6-12 months.

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