3.28.07 Relapse After Radical Prostatectomy As Prostate Cancer Treatment

Radiation therapy, with or without hormonal therapy, is the most commonly used treatment for prostate cancer that recurs after radical prostatectomy. This practice is largely based on small studies and uses a wide range of radiation therapy techniques and doses. More importantly, the studies do not include a randomization comparison with the observation arm only as advocated by the Johns Hopkins group. Thus, this is not a proven treatment option. Of even greater concern is the fact that it is technically difficult to give enough radiation without risk of significant damage to bladder, bowel and loss of any sexual function that might have survived surgery. The situation seems to have improved considerably with the advent of IMRT as it allows for higher radiation doses in the neighborhood of 6,500 cGy while lessening side effects, particularly rectal complications. In sum, we have a treatment with potentially severe side effects whose therapeutic value has yet to be proven. This fact has led a number of the leading figures in urologic surgery, in addition to the Johns Hopkins group, to question the value of this approach. As you will see, my own assessment is more positive, if still guarded.

Short of actually having a randomized controlled trial, there is one large series that I think represents the most accurate assessment of those patients most likely to benefit. This paper pooled results from a large number of leading prostate cancer treatment centers, including Memorial Sloan Kettering, Cleveland Clinic, Baylor, University of Texas-Southwestern Medical Center, and University of Florida, Gainesville. In this analysis, patients most likely to be in remission at 45 months following radiation were those with a PSA doubling time of greater than 10 months, with a Gleason score of 7 or less, a PSA at the time of radiation of 2 ng/ml or less. For patients with no adverse features, 77% were still in remission at 45 months. PSA doubling time again was quite important because men with Gleason scores of 8-10 who had a PSA doubling time of greater than 10 months had an 81% chance of not developing progressive disease compared with only 37% of those with a doubling time faster than 10 months. In the wake of these and other studies, Lee and D’Amico nicely summarized the results: “Therefore, the optimal candidate for local-only salvage therapy is a man whose pretreatment PSA velocity was 2 ng/mL/year or less, interval to PSA failure exceeds 3 years, and post-treatment PSA doubling time is at least 12 months, and who did not have biopsy or prostatectomy Gleason score of 8 to 10 or seminal vesicle or lymph node involvement.” While I have not asked Drs. Partin or Walsh, I suspect they would respond that this is also a group that in their hands did well over a ten- year time period with no treatment at all.

One problem with radiation therapy in this setting is that we really do not know if the cancer is present in the prostate bed or has already spread to adjacent lymph nodes or even to remote areas like bone and lymph nodes outside the pelvis. One attempt to improve this situation is the ProstaScint scan. This technique uses a radioactive antibody that binds to prostate cancer cells in order to identify where the cancer is located. In the clinical trial leading to FDA approval of the ProstaScint scan, if the scan failed to identify cancer outside the prostate bed, 70% of the patients experienced long-term control with radiation therapy to the prostate bed. Unfortunately, ProstaScint scans are difficult to perform and difficult to read. The recent move to fuse the ProstaScint scan with the CT scan appears to significantly reduce these problems and the resulting fused images provide the radiation therapists well-defined anatomical landmarks that identify the location of the cancer. It is our practice here at AIDP to refer patients to centers that fuse the ProstaScint scan with the CT scan and that have experts capable of reading these images appropriately. At the top of our list of ProstaScint experts is Dr. Sodee at Case Western Reserve, who has done more than anyone else to improve the usefulness of this technique. Nevertheless, it would be useful to have a means of visualizing cancer in the prostate bed and elsewhere that could be reliably used at the community level rather than in a few select centers with well-trained experts.

The rest of this article can be read in volume 9:10 of Prostate Forum. Click here to download this issue now.