Friday, November 2, 2012

Post-Treatment PSA Increases: Another Cause for Concern?

Alas, the more one reads concerning the aftermath of radiation treatment for prostate cancer, the more one wishes he didn’t! Having now just completed my 1-month report on side effects to my radiation oncologist at UCSF I now am faced with getting a PSA test next month to check on the efficacy of the high dose brachytherapy treatment.

Googling- reading disclosed a number of disconcerting aspects:

- In some 17% or more of men (depending on the study)  there is an uptick in PSA following treatment at some point or what is called a “PSA bounce”.

- If this uptick is repetitive, i.e. the PSA doesn’t go back down to 0.2 ng/ml or less, it could signal “treatment failure” and the potential for further biopsies, treatments

- These further biopsies could cause the oncologist to prescribe surgery, hormone treatment (androgen deprivation therapy) or other further interventions.

All of this makes me nervous as hell, especially as any surgery (i.e. radical prostatectomy) would be hideously complicated given that after radiation (especially high dose) there is residual scarring that makes a clean extraction difficult if not impossible. The other alternative, hormone treatment therapy, is almost as disturbing with all kinds of effects no male in his right mind wishes to remotely contemplate! See also the video:

Hence, I am approaching next month’s PSA blood test with some degree of trepidation.

The PSA bump some men experience after brachytherapy for prostate cancer is puzzling enough- basically a PSA rise that's not a sign of recurrence (Oncology Times, 7/2000, p 1). The situation is rendered even more confused by a recent report of another phenomenon: post-brachytherapy biopsies that are positive but that don’t indicate cancer has recurred!

The two phenomena are causally related in that when an oncologist or urologist sees a rising PSA after prostate implant it often prompts a demand for repeat biopsy. But the author of one report in the August, 2001, issue of the International Journal of Radiation Oncology Biology Physics (Vol. 50:1207-1211) insists a rising PSA and a positive biopsy can be entirely coincidental. Kent Wallner, MD, Associate Professor in the Radiation Oncology Department at the University of Washington Medical Center and Chief of Radiation Oncology at Puget Sound Veterans Hospital in Seattle, reported three cases of men who had temporary self-limited PSA rises as well as post-implant biopsies showing histologic evidence of persistent cancer. The patients declined to have salvage prostatectomy, and subsequently all have had PSA levels fall.

In an “Oncology Times” interview, Dr. Wallner noted that he has met with skepticism when describing these cases, because it defies common sense to have a rising PSA and a positive biopsy and not have cancer, he said.

“We've known about the 'bump' for some years now, but this muddies the water even more. The positive biopsy along with the bump had not yet been described.”

Since approximately one third of men will have rising PSAs sometime after brachytherapy, Dr. Wallner said, a fairly large percentage of them might have unnecessary repeat biopsies. If positive, these could lead to unnecessary surgery.

To say this is distressing is putting it mildly! Then, to add to that, there seems to be –incredibly! – a movement afoot to judge treatment failure and post—procedure PSA results along the same lines as for radical prostatectomy! For one thing, in radiation therapy the prostate gland remains in place and hence the remaining (normal) cells will continue to produce prostate –specific antigen so it’s nuts or at least irrational to expect PSA level to decline to “undetectable” levels (i.e. < 0.1 ng/ml).

Moreover, on account of this fundamental difference, PSA levels will only over time tend to decrease to the levels seen relatively quickly after radical prostate surgery. Some papers cite a 2-year minimum to reach 0.1 ng/ml and another cites a median interval of 40 months – which may include PSA intermittent rises in between.

In their article, ‘PSA Kinetics After Prostate Brachytherapy: PSA Bounce Phenomenon and its Implications for PSA Doubling Time’ (Journal of Radiation Oncology Biological Physics, Feb. 2006, p. 512) Ciezki et al found in their post-procedure analysis of 162 patients who’d received prostate cancer brachytherapy treatment a “PSA bounce” by 75 or 46.3 %.

Interestingly, patients found to have experienced a PSA bounce (uptick in their PSA readings after procedure) were less likely to have been deemed to have a “biochemical failure” irrespective of the definition used for such failure.

What factors, if any, affect or may contribute to PSA level bounces post-treatment? They include:

1. Prostate size: the larger the size the more likely the patient is to have a PSA level rise

2. Patient age and isotope used: Those under 62 are more likely to experience a PSA spike, while those subjected to Iodine -125 radiation are 3 times more likely to see a PSA rise. It is less likely for those receiving dosage from Iridium-192 as I have.

3. Implant dose: the higher the dose received at implant the less likely the PSA rise since more cells will have been killed.

4. PSA Nadir: The PSA nadir following brachytherapy is a predictor for subsequent PSA spike. The nadir is the lowest measurable PSA before a spike would occur. Patients with a nadir of 0.2 ng/ml or less are less likely to develop a PSA spike (Merrick et al., 2002). The median time to achieve nadir is 27 months. When nadir occurs within this time frame, it indicates that there is little to no viable prostate epithelium present; hence, the absence of residual malignancy. A PSA spike, therefore, is uncommon after a nadir of less than 0.2 ng/ml is reached.

What will my strategy be in the event of a PSA spike, assuming such occurs? First, not to hit the panic button since as numerous graphs in oncology papers show, there’s about a 1 in 3 chance this will take place at some point. If further rises continue, I will decline any biopsies, since the paradox earlier noted is plausibly the basis. I also most certainly will decline any recommended surgery after the fact. If any other treatment is considered it’ll most like be the “intermittent hormone treatment” described in the earlier video link.

Anyway, we will see what happens!

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