A new review by Ganswindt et al. proposes that patients at high risk for local relapse following first-line radiacal prostatectomy (RP) should receive immediate external beam radiotherapy (EBRT), especially including those patients with positive surgical margins. This seems like a rather provocative recommendation to The “New” Prostate Cancer InfoLink.
The authors state that “after radical prostatectomy … pathologically advanced disease is detected in 38% to 52% of patients.” They go on to note that available retrospective data on the role of postoperative radiotherapy are controversial. They therefore set out to clarify the extent to which adjuvant radiation treatment affects patient outcome in those patients with “locally advanced disease.”
They examined the data from three major randomized clinical trials:
- The European Organization for Research and Treatment of Cancer (EORTC) trial number 22911
- Southwest Oncology Group (SWOG) trial number 8794, and
- German Intergroup trial ARO 96-02/AUO AP 09/95
These three trials all randomized patients to receive adjuvant EBRT post-surgery at levels between 60 and 64 Gy. The majority of patients had undetectable PSA levels following their RP.
According to Ganswindt et al., the data show that:
- Adjuvant EBRT improved biochemical progression-free survival rates in all three trials
- EORTC 22911 — biochemical progression-free survival rate after 5 yr was 74.0 percent with adjuvant EBRT vs 52.6 percent without adjuvant EBRT
- SWOG 8794 — biochemical progresssion-free survival after 5 yr was ~ 73 percent with adjuvant EBRT vs ~ 44 percent without adjuvant EBRT
- ARO 96-02/AUO AP 09/95 — biochemical progresssion-free survival after 5 yr was 72 percent with adjuvant EBRT vs 54 percent without adjuvant EBRT).
- The EORTC trial showed improved local control of cancer progression (p<0.0001) for treated patients.
- At 5 years the SWOG trial demonstrate an reduced need for hormonal therapy (79 percent in patients receiving adjuvant EBRT compared to 90 percent in patients not receiving adjuvant EBRT).
- There was no statistically significant benefit with regard to metastasis-free survival or overall survival. was not seen.
- Major genitourinary and gastrointestinal toxicities were moderate, with late side-effects ≥ grade 3 ranging from 3 percent (in the ARO 96-02 trial) to <5% (in the EORTC trial).
The consistency of the results in these three trials is certainly clear evidence for a consistent effect on something. However, there are several issues that need to be addressed before we can possibly conclude that these data support an argument favoring adjuvant EBRT as a “new standard of care:”
- Does the lack of any form of survival benefit negate the hypothesis from the beginning? What is the actual value of adjuvant EBRT to the patient if it does not offer a survival benefit? We know that we can still give EBRT later if the patient’s PSA starts to rise. Is early radiation just one more means to simply “manage PSA levels”?
- What is a positive surgical margin (PSM), and do all positive surgical margins predispose the patient for risk? This itself is a matter of considerable debate. The conclusion that all patients with positive PSMs are at particular risk is certainly open to question.
- Are the trials reviewed by the authors actually representative of current EBRT? It would seem to The “New” Prostate Cancer InfoLink that the quality of EBRT had improved significantly since the design and initiation of the three trials referenced. Hgher doses, greater accuracy of delivery, and (potentially) greater efficacy of EBRT would all seem to be available today than the several years ago when the three trials were designed. On the one hand this allows the argument that safer and higher quality radiotherapy can now be delivered as adjuvant therapy. On the other hand, there is the equally compelling argument that safer and higher quality radiotherapy can now be delivered when the patient’s PSA starts to rise.
On the whole, The “New” Prostate Cancer InfoLink is not yet ready to embrace the idea of adjuvant EBRT as a standard of care for “all patients at high risk for local relapse following first-line radical prostatectomy” — or at least, not until the definition of “high risk” in this context is a great deal more clear.
Filed under: Management, Treatment
Among the many reports at the AUA conference earlier this year was that included in SWOG 8794 regarding radiation as adjuvant therapy following radical prostatectomy to patients with high risk disease. Well known Medical Oncologist Charles E. “Snuffy” Myers of the American Institute Diseases of the Prostate posted these remarks on the ProstateProblemsMailList back in May:
“From the comments, it is clear folks did not really appreciate the full impact of this study. This was not about salvage radiation, which is a whole different issue. This is about adjuvant radiation given shortly after surgery to those with high risk disease. I am neither a radiation oncologist nor a surgeon, but to me the results are stunning. Radiation given shortly after surgery dramatically and significantly reduced the risk of bone metastases. This is huge. It means that in these men, the cancer cells that ultimately would cause bone mets were still in the pelvis and sensitive to radiation! By the time you are talking about salvage radiation, that opportunity is gone and those cancer cells are already out at the bone site in those with high risk disease. Salvage radiation, on the other hand, only really works well for those with indolent, slow growing disease: PSA doubling time greater than 9 months, Gleason score 7 or less. Bottom line is that surgery followed by adjuvant radiation therapy will offer many men with high-risk disease a chance at being disease free long-term - perhaps even cured.
“I would point out that the same issues hold for adjuvant hormonal therapy after surgery rather than waiting to give hormonal therapy when metastatic disease appears.”