PSA Doubling Time
Dear OncoLink "Ask The Experts,"
Can you please explain PSA doubling time?
Richard Whittington, MD, Associate Professor of Radiation Oncology at the University of Pennsylvania School of Medicine, responds:
This is actually a fairly difficult question. PSA doubling time is supposed to reflect tumor growth, so the doubling time should reflect the time it takes for the number of tumor cells to double. The straightforward answer is that it is the time it takes for the PSA to go from X to 2X. This is absolutely true after prostatectomy, because there is no other source of PSA.
In a patient who still has a prostate in place (i.e., after radiation, brachytherapy, or hormone therapy) it is more difficult to interpret this value because there are two sources of PSA, the benign and malignant prostate tissue. However, the tumor doubling time is affected by the contribution from malignant portion only.
Imagine a situation where the baseline PSA from a benign prostate is 3.6, and it rises to 4.0 because of a new carcinoma (i.e. the contribution from the cancer is 0.4). For the PSA to go to 7.2 (which would be double the original PSA of 3.6), there would have to be a rise in PSA of an additional 3.2, which is actually 3 doublings. In other words, the time it takes for the malignant component to go from 0.4 to 0.8, from 0.8 to 1.6, and from 1.6 to 3.2. Later, when the PSA is 20, the malignant component is 16.4, so a doubling to 40 is a rise of 20, or 1.2 (20/16.4) doublings. This is why it is tougher to evaluate PSA doubling times in patients who have chosen watchful waiting or radiation.
Just to further keep things from seeming straightforward and sensible, some drugs, notably finasteride, will decrease the rate at which tumor leaks PSA into the blood. So, a patient may have a PSA of 6, which goes to 3 on finasteride, and will take 2 doublings to get to 12 and double the PSA.
Finally, prostate cancer treated with radiation therapy or hormones tends to be more anaplastic, which means it is very different from normal prostate and does not make as much PSA pound for pound as treatment-naive tumor, so doubling time after RT or hormones is frequently longer than in the treatment-naive group, even though the tumor is more rapidly growing.