The PSA “bump” some men see after brachytherapy for prostate cancer is puzzling enough—a transient PSA rise that's not a sign of recurrence (OT, 7/00, p 1). The situation is now even more confused by a recent report of another phenomenon—a post-brachytherapy biopsy that is positive but that also does not indicate cancer has recurred.
The two phenomena are causally related in that a rising PSA after implant often prompts a repeat biopsy. But the author of the new report in the August issue of the International Journal of Radiation Oncology Biology Physics (2001;50:1207–1211) says 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 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.
He acknowledges that his study lacks a denominator; not every man has a biopsy after brachytherapy, so it is not possible to say how common it is to have both a bump and a positive biopsy. “But it is common enough so that people need to know about it,” he said.
He is currently following six men who had PSA bumps and also positive repeat biopsies, but whose PSA levels have since fallen and are consistent with long-term cancer control. “This is a real problem because common sense would tell us we've got to operate on these people,” Dr. Wallner said. “But because there's no clear answer, we are saying you should think long and hard before recommending a salvage prostatectomy.”
Residual Tumor Cells
Dr. Wallner hypothesizes that a repeat biopsy after radiation might be positive because of residual tumor in the prostate. “We know it takes a couple of years to clear cancer after high-dose radiation, so for the first two years or so you can see residual cancer in the prostate. But you don't know if it is still viable or not,” he said.
The author of a paper cited by Dr. Wallner agrees, adding that prostate biopsies done within three years after external-beam or radiation or brachytherapy are difficult to interpret. “The older literature is fraught with misreadings of biopsies done too soon—within 12 to 18 months postradiation treatment,” said Bradley R. Prestidge, MD, a radiation oncologist in private practice at the Cancer Therapy and Research Center in San Antonio, TX. “Cancer cells take a while to die off, and even though some may look like cancer architecturally, they are not dividing.”
Especially after brachytherapy, he said, prostate cells labeled “indeterminate” on biopsy may look cancerous because of background radiation effects. These can later convert to an interpretation of benign.
“It's subtle—prostate biopsies after radiation aren't easy to read,” Dr. Prestidge explained in an interview, “but I think if they were rebiopsied, a lot of them would be negative.”
Dr. Prestidge feels that prostate cancer patients should simply not be biopsied in the 12- to 18-month time frame after radiation. “Do not rush into this,” he said.
If a PSA level does not nadir after brachytherapy and rises, Dr. Prestidge advises going back to look at the radiation dosimetry to determine the quality of the implant. If coverage was suboptimal, a repeat brachytherapy may be necessary.
Three patients referred to Dr. Prestidge recently because of rising PSA after brachytherapy had positive biopsies in areas of the prostate that had no seeds, he said. The men were reimplanted, and the PSA levels dropped.
If the patient has had complete implant coverage, as can be assumed for the men in Dr. Wallner's report, a rising PSA level could be due to prostatitis, recurrent localized cancer, metastatic cancer, or the mysterious “bump.”
Dr. Wallner said that although prostatitis in these cases is usually viral and does not respond to antibiotics, it is still reasonable to try antibiotics. “But mostly you just have to give it some time,” he said. “If the patient has a rising PSA in the first couple of years after an implant, don't do anything.”
Dr. Wallner said he personally would wait for three years for the PSA to decline after brachytherapy. He admits this is a tough option to recommend, because some men will indeed have recurrent cancer and should have a prostatectomy.
“But if I had done a salvage prostatectomy on these men [in his report], I would have done them a big disservice,” he said.
After Dr. Wallner and colleagues described the bump phenomenon in a 1997 publication, a 2000 study from the Radiotherapy Clinics of Georgia found that it was experienced by 35 percent of men treated with external-beam and brachytherapy radiation for T1T2N0 prostate cancer.
The study of 779 men, by Frank Critz, MD, and colleagues, found that the median PSA rise was 0.4 ng/ml above the median pre-bump PSA of 0.7 ng/ml. For 10 to 20 percent of these men, the rise was 2.0 ng/ml during the bump. In one case the PSA level reached 15.8 ng/ml before dropping.
The median time to the rise was 18 months from the time of implant, and in 92 percent of men it was observed within 36 months.
Dr. Critz defined a bump (which he called a “bounce” in his report) as a PSA rise above 0.5 ng/ml with a subsequent fall to less than 0.5 ng/ml, for men who had a post-treatment PSA nadir of 0.5 ng/ml or less. For men with a pre-bump PSA of greater than 0.5 ng/ml, a bump was a rise of 0.1 ng/dl or more with a subsequent fall below the pre-bump PSA level. He noted, however, that one percent of men have a bump with the very first PSA assay taken after treatment.
The mechanism of PSA bounce after radiotherapy and its relevance to long-term survival were unknown, Dr. Critz said, in an interview for the article in the May 2000 OT. But he noted that curative surgery for prostate cancer differs from curative radiotherapy, in that time must be allowed after successful irradiation for malignant and benign prostate epithelium to disintegrate.
It may be this process that causes a clinical or sub-clinical prostatitis and leads to the temporary PSA rise, he speculated.
Smathers S, Wallner K, Sprouse J, True L. Temporary PSA rises and repeat prostate biopsies after brachytherapy. Int J Radiat Oncol Biol Phys 2001;50:1207–1211.
Prestidge BR, Hoak DC, Grimm PD, Ragde H, Cavanagh W, Blasko JC. Posttreatment biopsy results following interstitial brachytherapy in early-stage prostate cancer. Int J Radiation Oncol Biol Phys 1997;37:31–39.
Wallner KE, Blasko J, Dattoli MJ. Evaluating cancer status. In: Wallner KE, Blasko J, Dattoli MJ, editors. Prostate brachytherapy made complicated. Seattle: SmartMedicine Press; 1997. pp 14.1–14.15.
Critz FA, Williams WH, Benton JB, Levinson AK, Holladay CT, Holladay DA. Prostate specific antigen bounce after radioactive seed implantation followed by external beam radiation for prostate cancer. J Urol 2000;163:1085–1089.© 2001 Lippincott Williams & Wilkins, Inc.
More on ONCOLOGY-TIMES.com...