In the October issue of European Urology there was an interesting “consensus statement” about the role of radiation therapy as adjuvant or salvage therapy for men who are at significant risk for recurrence of their prostate cancer after first-line treatment with radical prostatectomy.
A review article by Stephenson et al. was co-authored by several leading experts on the role of radiation therapy in the management of localized prostate cancer — from the USA and Europe. The article makes the following key points:
- Between 15 and 25 percent of men who are given a radical prostatectomy for localized prostate cancer will have recurrence of their cancer.
- Three groups of men are recognized to be at particularly high risk:
- Those with poorly differentiated forms of cancer
- Those with non-organ-confined disease
- Those with pathologically evident positive surgical margins
- Three somewhat different, randomized, Phase III clinical trials have compared the value of immediate adjuvant radiation therapy to observation and subsequent salvage radiation therapy in high-risk patients post-surgery:
- The Southwest Oncology Group (SWOG) 8794 trial
- The European Organization for Research and Treatment of Cancer (EORTC) 22911 trial
- The German Cancer Society (ARO 96-02) trial
- The results of these trials are not uniform, but there is consensus that:
- Outcomes of men receiving post-surgical radiation therapy are best when their PSA levels are at the lowest possible levels.
- Adjuvant radiation therapy can have a favorable impact on systemic progression, prostate cancer-specific mortality, and overall survival.
What is still not clear at this time is whether long-term outcomes can be achieved by the use of immediate, adjuvant radiation therapy (as opposed to observation and salvage therapy) among all high-risk patients who have an undetectable PSA level following first-line surgery.
The authors conclude that — in light of this lack of clarity — what is important for such high-risk patients is an approach that involves a full discussion of the available information, multidisciplinary input, and shared decision-making among patients, urologists, and radiation oncologists.
The appropriate decision for the individual patient needs to take full account of his individual risk factors as well as the advantages and disadvantages of each approach.
Filed under: Living with Prostate Cancer, Management, Treatment | Tagged: "high risk", adjuvant, post-surgery, radiation therapy, salvage |
THE "NEW" PROSTATE CANCER INFOLINK 
I had that full discussion. We discussed the following after my pT3bN0Mx Gleason 4 + 3 = 7 post-op pathology. The staging was based on the AJCC 2002 manual so pT3b includes seminal vesicle invasion.
(1) I was 44 years old and available study data did not provide me adequate assurances using the wait and see approach.
(2) I had 10 lymph nodes dissected and that would only account for 25% of the nodes at most in the pelvic region.
(3) Studies from Harvard and Stanford were underway but only at 6 years (in 2007) of maturity. They were studying tyher use of hormone therapy with adjuvant RT and hitting additional lymph nodes in the pelvic region. These studies showed remarkable improvement in PSA control over patients that chose the wait and see approach.
(4) The final discussion was whether to add an LHRH agonist with an anti-androgen.
I voted yes. Almost 5 years after surgery, 4.5 years after radiation, and 2 years after completion of hormonal therapy, my PSA sits at zero. I know we still have a long time to go, but I believe that we did the right things.
I have a similar decision to make. Robotic surgery 5/2012 for T3b, Gleason 9 cancer; degarelix for 6 weeks before surgery; and now a recurrent PSA of 0.12 ng/ml 5 months post-surgery. I have elected to have salvage radiation therapy and hormone therapy but haven’t decided on which hormone treatment and for how long, Any suggestions. Start radiation next week.
pMikey
Dear Dr. Kaihlanen:
The use of degarelix in combination with external beam radiation as salvage therapy following biochemical progression after first-line surgery has never (as far as I am aware) been formally tested in large scale clinical trials, so it is hard to know what the effectiveness of such a therapy might be. … However, “applied logic” suggests that it should work just as well as an LHRH receptor agonist alone or even the combination of an LHRH receptor agonist with an antiandrogen like bicalutamide.
I am actually a little surprised that your doctors are willing to consider treating you with only 6 months of hormone therapy as well as the radiation, given your relatively fast biochemical progression after surgery, but I am certainly not trying to imply that this is not a long enough period of hormone therapy. This is very much a clinical judgment call.
It is now 12 months since my last contact with you. I am 17 months post-robotic surgery and 10 months since the end of salvage IBRT. I continue adjuvant ADT with degarelix. I will finish ADT treatment in 2 weeks after receiving it for 12 months. Since surgery I had three PSA readings of zero but then one PSA of 0.12 ng/ml, 5 months after surgery. This prompted starting salvage IBRT. IBRT ended on December 31, 2012 and then I had zero PSAs in February, May, and Augugust. I feel rather optimistic with the zero nadir but worry what the PSA will do when the degarelix is stopped next month. Is 12 months enough or should I continue longer? I had T3b with a Gleason of 9. No nodes. My testosterone is 10 and I have moderate fatigue and hot flashes. Hoping for the best.
Dr. K
Dear Dr. K:
Every patient who understands how the combination of salvage radiation and ADT actually works starts to worry about what is going to happen when the ADT is stopped, so from that perspective you are in good company.
What is much harder to determine is the optimal length of time for someone like you to stay on ADT, and I am sorry to say that I don’t have a good answer for you. Some specialists would say 12 months may well be enough; others are going to argue that 18 months to 2 years of ADT would be better; and the most conservative phyicians would say that the only data we have that actually confirms a survival benefit is 3 years of ADT. Arguably, they may all be correct!
By contrast, one has to consider the quality of life factors. The longer the patient is on ADT, the greater the time it take to recover something approaching normal serum T levels after the ADT is stopped and the greater the risk for really significant side effects of ADT to kick in (such as difficulties with mental acuity and the ability to think about how to do more than one thing at a time).
At the end of the day, this is a decision that I think you need to talk through with the doctor who has been treating you so that you can come to a shared decision about what you and he/she feel is really in your best interests. Whatever you decide to do, there is going to be some chance that the cancer will recur, so the hard question to answer is always going to be “when do I pull the rip-cord” and find out whether your PSA is going to stay down within the undetectable range.
Thanks for the prompt response. The reason for my optimism is an article by Crevosier et al. in Annals of Oncology, 2010, where he states that a PSA of 0.12 whose PSA 6 weeks after the start of IMRT was zero and 3 months after the start of neo-adjuvant ADT the PSA was zero. Am I missing something here? My only real concern is my 10-year prostate cancer-specific survival.
Dr. K
Dear Dr. K:
I am not familiar with the specific paper you refer to, but I assume that it is this one by de Crevosier et al., which (in the abstract) concludes that “A PSA decline 6 weeks after the start of EBRT when used as monotherapy and 3 months after the start of ADT in patients treated with combined ADT and EBRT is predictive of progression and specific survival.”
I have not read the complete text of this paper (which appears to be based on a series of patients from one specific institution). As a consequence, I am in no position to comment on whether this specific paper is well-founded in its conclusions, but I am always cautious about papers like this — because there have been dozens of them over the years. This type of retrospective analysis is easy to do, but unless the authors’ hypothesis is subsequently tested against an independent set of patients and is able to accurately predict the outcomes of those patients, it really is no more than an hypothesis — and I don’t get the impression that such a confirmatory study has been done based on this hypothesis.
I think we need to distinguish with care between a reasonable degree of optimism on your part based on your data to date, and the inevitable caveat that we are dealing with probabilities, and probabilities are great when they pan out and a disaster when they don’t. (Just ask any professional gambler.) I would repeat my prior suggestion that you have a serious conversation with your own doctors … but by all means take the full text of the paper by de Crevosier to the meeting and ask him what he thinks of it!