Retreatment for recurrent prostate cancer
Dear OncoLink "Ask The Experts,"
A 62 year old friend of mine had a prostatectomy (age 57) for a grade 6 Gleason tumor 5 years ago. His PSA has increased from undetectable (<0.1ug/ml) to 0.2ug in the past year. His surgical specimen 5 years ago showed what appeared to be a positive surgical margin however he decided not to proceed with adjuvant radiotherapy. Would you consider salvage radiotherapy in this man? If so, at what PSA value? When would you advocate additional tests? Do you use a higher then conventional dose of radiation and would you radiate the pelvic bed as well in a Gleason 6 tumor?
Richard Whittington, MD, Associate Professor of Radiation Oncology at the University of Pennsylvania School of Medicine, responds:
We have a paper awaiting final publication regarding this issue. We have had about 10% of men have a PSA reach 0.2 ng/ml and spontaneously resolve without therapy. We don't know why for sure, but we think the small bump in PSA comes from urethral glands and may be associated with inflammation. A man with a focally positive margin at prostatectomy only has a 20% risk of recurrence anyway. I have one man that had a PSA of 0.3 ng/ml right after passing a kidney stone that also cleared, so my threshold to treat is 0.4 ng/ml. The salvage rate is 65% when the PSA is less than 1.0 ng/ml, although Kupelian in Cleveland argues that 1.5 ng/ml PSA's are also OK. For a PSA of 4 ng/ml there is only a 14% salvage and 0% for a PSA >10.0 ng/ml. It seems that many of these men metastasize from the recurrence and not the initial tumor.
As for the work up, we recommend a bone scan and CT to rule out distant metastasis and positive lymph nodes. Biopsy is useful if it is positive but even if negative, we treat the prostate bed. The likelihood the PSA will fall when we treat the bed after a negative biopsy of the bed/anastamosis is 97%, with 91% developing an undetectable PSA and 65% free of relapse 8 years later. With a positive biopsy we do about the same. The prognositc factors are important. The good factors are a time to recurrence >18 mos, a PSA < 1.0 ng/ml, A Gleason Score of 7 or less, and a positive margin or extracapsular extension.
If this gentleman has recurred, and I am not sure he has, he has every reason to be optimistic. I looked at the data from Wisconsin that uses adjuvant RT in this setting versus salvage RT as we do and I don't think there is any difference in survival or disease free survival by waiting until there is biochemical evidence of recurrence. If you treat everybody, it looks better, but out of 100 men they treat 100 and 95 are cured. For the same 100 men we would treat 20 and cure 15 and the surgery cures 80. So either way, 95 are alive and well but only 20 have radiation side effects which include a 5% risk of rectal ulcer and a 1% risk of worsening continence. The dose of radiation is actually lower then patients that never had surgery. We treat only the prostate bed and anastamosis to a dose of 66 Gy as opposed to 78 Gy in definitive cases. With this regimen, the risk of palpable recurrence in the bed is 0 out of 189. With 60 Gy I had 2 recurrences in the fossa in 10 patients. Nothing magic about the dose other than 60 Gy isn't enough and 66Gy isn't too much. Hope this helps.